Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies.

PubMed

Kelly, Peter J; Albers, Gregory W; Chatzikonstantinou, Anastasios; De Marchis, Gian Marco; Ferrari, Julia; George, Paul; Katan, Mira; Knoflach, Michael; Kim, Jong S; Li, Linxin; Lee, Eun-Jae; Olivot, Jean-Marc; Purroy, Francisco; Raposo, Nicolas; Rothwell, Peter M; Sharma, Vijay K; Song, Bo; Tsivgoulis, Georgios; Walsh, Cathal; Xu, Yuming; Merwick, Aine

2016-11-01

Identification of patients at highest risk of early stroke after transient ischaemic attack has been improved with imaging based scores. We aimed to compare the validity and prognostic utility of imaging-based stroke risk scores in patients after transient ischaemic attack. We did a pooled analysis of published and unpublished individual-patient data from 16 cohort studies of transient ischaemic attack done in Asia, Europe, and the USA, with early brain and vascular imaging and follow up. All patients were assessed by stroke specialists in hospital settings as inpatients, in emergency departments, or in transient ischaemic attack clinics. Inclusion criteria were stroke-specialist confirmed transient ischaemic attack, age of 18 years or older, and MRI done within 7 days of index transient ischaemic attack and before stroke recurrence. Multivariable logistic regression was done to analyse the predictive utility of abnormal diffusion-weighted MRI, carotid stenosis, and transient ischaemic attack within 1 week of index transient ischaemic attack (dual transient ischaemic attack) after adjusting for ABCD2 score. We compared the prognostic utility of the ABCD2, ABCD2-I, and ABCD3-I scores using discrimination, calibration, and risk reclassification. In 2176 patients from 16 cohort studies done between 2005 and 2015, after adjusting for ABCD2 score, positive diffusion-weighted imaging (odds ratio [OR] 3·8, 95% CI 2·1-7·0), dual transient ischaemic attack (OR 3·3, 95% CI 1·8-5·8), and ipsilateral carotid stenosis (OR 4·7, 95% CI 2·6-8·6) were associated with 7 day stroke after index transient ischaemic attack (p<0·001 for all). 7 day stroke risk increased with increasing ABCD2-I and ABCD3-I scores (both p<0·001). Discrimination to identify early stroke risk was improved for ABCD2-I versus ABCD2 (2 day c statistic 0·74 vs 0·64; p=0·006). However, discrimination was further improved by ABCD3-I compared with ABCD2 (2 day c statistic 0·84 vs 0·64; p<0·001) and ABCD2-I (c statistic 0·84 vs 0·74; p<0·001). Early stroke risk reclassification was improved by ABCD3-I compared with ABCD2-I score (clinical net reclassification improvement 33% at 2 days). Although ABCD2-I and ABCD3-I showed validity, the ABCD3-I score reliably identified highest-risk patients at highest risk of a stroke after transient ischaemic attack with improved risk prediction compared with ABCD2-I. Transient ischaemic attack management guided by ABCD3-I with immediate stroke-specialist assessment, urgent MRI, and vascular imaging should now be considered, with monitoring of safety and cost-effectiveness. Health Research Board of Ireland, Irish Heart Foundation, Irish Health Service Executive, Irish National Lottery, National Medical Research Council of Singapore, Swiss National Science Foundation, Bangerter-Rhyner Foundation, Swiss National Science Foundation, Swisslife Jubiläumsstiftung for Medical Research, Swiss Neurological Society, Fondazione Dr Ettore Balli (Switzerland), Clinical Trial Unit of University of Bern, South Korea's Ministry for Health, Welfare, and Family Affairs, UK Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rates and predictors of stroke-associated case fatality in black Central African patients.

PubMed

Longo-Mbenza, B; Lelo Tshinkwela, M; Mbuilu Pukuta, J

2008-01-01

To identify case fatality rates and predictors of stroke in a private clinic in Kinshasa, Democratic Republic of Congo. Two hundred and twelve black Africans were consecutively admitted to a clinic and prospectively assessed during the first 30 days by CT scan-proven stroke types and outcome. Univariate and multivariate analyses were used to estimate the in-hospital mortality risk for the following baseline characteristics: age, gender, education, arterial hypertension, diabetes, stroke types, leukocyte count, and haematocrit, blood glucose, uric acid, fibrinogen and total cholesterol levels. Haemorrhagic and ischaemic strokes were present in 52 and 48% of the study population, respectively; and 44% of all stroke type patients, 29% of haemorrhagic stroke and 31% of ischaemic stroke patients died. Compared to the survivors, deceased patients were significantly (p < 0.001) older with higher leukocyte counts and haematocrit, haemoglobin and fibrinogen levels, but lower glycaemic levels. The variable significantly associated with all stroke type mortalities in the multivariate model was ischaemic stroke (HR = 4.28, p < 0.001). The univariate risk factors of mortality in patients with ischaemic stroke were higher fibrinogenaemia (RR = 6.4; 95% CI = 4.8-8.2 for tertile 3 and RR = 12.9; 95% CI = 7.8-18.4 for tertile 4; p < 0.001) and higher glycaemia (RR = 3.3; 95% CI = 1.4-5.7 for tertile 3 and RR = 6.7; 95% CI = 5.2-9.2 for tertile 4; p < 0.001). We have shown that all acute stroke types remain a deadly nosological entity, and ischaemic stroke, baseline haematocrit and fibrinogen levels, and dependency on others' care were significantly associated with all stroke mortalities. Moreover, hyperfibrinogaemia and hyperglycaemia were the significant predictors of case fatality in ischaemic stroke patients. In Africa, the top priority for resource allocation for stroke services should go to the primary prevention of stroke.

Prevalence and long-term clinical significance of intracranial atherosclerosis after ischaemic stroke or transient ischaemic attack: a cohort study.

PubMed

Ovesen, Christian; Abild, Annemette; Christensen, Anders Fogh; Rosenbaum, Sverre; Hansen, Christine Krarup; Havsteen, Inger; Nielsen, Jens Kellberg; Christensen, Hanne

2013-10-21

We investigated the prevalence and long-term risk associated with intracranial atherosclerosis identified during routine evaluation. This study presents data from a prospective cohort of patients admitted to our stroke unit for thrombolysis evaluation. We included 652 with a final diagnosis of ischaemic stroke or transient ischaemic attack (TIA) from April 2009 to December 2011. All patients were acutely evaluated with cerebral CT and CT angiography (CTA). Acute radiological examinations were screened for intracranial arterial stenosis (IAS) or intracranial arterial calcifications (IAC). Intracranial stenosis was grouped into 30-50%, 50-70% and >70% lumen reduction. The extent of IAC was graded as number of vessels affected. Patients were followed until July 2013. Recurrence of an ischaemic event (stroke, ischaemic heart disease (IHD) and TIA) was documented through the national chart system. Poor outcome was defined as death or recurrence of ischaemic event. 101 (15.5%) patients showed IAS (70: 30-50%, 29: 50-70% and 16: >70%). Two-hundred and fifteen (33%) patients had no IAC, 339 (52%) in 1-2 vessels and 102 (16%) in >2 vessels. During follow-up, 53 strokes, 20 TIA and 14 IHD occurred, and 95 patients died. The risk of poor outcome was significantly different among different extents of IAS as well as IAC (log-rank test p<0.01 for both). In unadjusted analysis IAS and IAC predicted poor outcome and recurrent ischaemic event. When adjusted, IAS and IAC independently increased the risk of a recurrent ischaemic event (IAS: HR 1.67; CI 1.04 to 2.64 and IAC: HR 1.22; CI 1.02 to 1.47). Intracranial atherosclerosis detected during acute evaluation predicts an increased risk of recurrent stroke.

Neurological signs in 23 dogs with suspected rostral cerebellar ischaemic stroke.

PubMed

Thomsen, Barbara; Garosi, Laurent; Skerritt, Geoff; Rusbridge, Clare; Sparrow, Tim; Berendt, Mette; Gredal, Hanne

2016-06-07

In dogs with ischaemic stroke, a very common site of infarction is the cerebellum. The aim of this study was to characterise neurological signs in relation to infarct topography in dogs with suspected cerebellar ischaemic stroke and to report short-term outcome confined to the hospitalisation period. A retrospective multicentre study of dogs with suspected cerebellar ischaemic stroke examined from 2010-2015 at five veterinary referral hospitals was performed. Findings from clinical, neurological, and paraclinical investigations including magnetic resonance imaging were assessed. Twenty-three dogs, 13 females and 10 males with a median age of 8 years and 8 months, were included in the study. The Cavalier King Charles Spaniel (n = 9) was a commonly represented breed. All ischaemic strokes were located to the vascular territory of the rostral cerebellar artery including four extensive and 19 limited occlusions. The most prominent neurological deficits were gait abnormalities (ataxia with hypermetria n = 11, ataxia without hypermetria n = 4, non-ambulatory n = 6), head tilt (n = 13), nystagmus (n = 8), decreased menace response (n = 7), postural reaction deficits (n = 7), and proprioceptive deficits (n = 5). Neurological signs appeared irrespective of the infarct being classified as extensive or limited. All dogs survived and were discharged within 1-10 days of hospitalisation. Dogs affected by rostral cerebellar ischaemic stroke typically present with a collection of neurological deficits characterised by ataxia, head tilt, and nystagmus irrespective of the specific cerebellar infarct topography. In dogs with peracute to acute onset of these neurological deficits, cerebellar ischaemic stroke should be considered an important differential diagnosis, and neuroimaging investigations are indicated. Although dogs are often severely compromised at presentation, short-term prognosis is excellent and rapid clinical improvement may be observed within the first week following the ischaemic stroke.

[Outcomes of open endovascular operations on the internal carotid artery in acute stage of ischaemic stroke].

PubMed

Khripun, A I; Priamikov, A D; Mironkov, A B; Tiurin, I N; Asratian, S A; Suriakhin, V S; Simonov, O V; Sazhina, O A; Mikhaĭlenko, V P

The authors share their experience in diagnosis and treatment of patients with acute ischaemic stroke. The study included a total of 33 patients. Of these, 20 patients (Study Group) were operated on at terms ranging from 2 to 7 days after onset of acute cerebral circulatory impairment. The Control Group was composed of 13 patients with ischaemic stroke, having refused surgical prevention of recurrent stroke. Both groups were matched by age, gender, level of neurological deficiency and size of cerebral ischaemic foci. Surgical management in the Study Group consisted in either carotid endarterectomy (n=15) or stenting of the internal carotid artery (n=5). Depending on the severity of coronary artery lesion and the presence of accompanying therapeutic pathology, options of operative treatment with various anaesthesiological support were offered. At discharge, neurological deficit in the Study Group patients was lower - 1.2 points by the NIH Stroke Scale versus 2.7 points in the Control Group, however, this difference was not statistically significant (p=0.45). In the Study Group there were two complications: haematoma of the postoperative injury requiring its revision and a transient ischaemic attack during stenting of the internal carotid artery, having disappeared on the operation table after the distal cerebral protection device was removed. Significantly better results were obtained by the following parameters: in the Study Group the number of patients discharged with no neurological deficit (scoring 0 by the NIHSS scale) was significantly higher compared with the Control Group; 50% vs 7.7% (p<0.001). There were no lethal outcomes in either group. One patient (7.7%) from the Study Group developed recurrent ischaemic stroke, whereas neither intra- nor postoperative stroke was registered in the Control Group patients (p<0.001). In carefully selected patients with ischaemic stroke (neurological deficit not exceeding 3 points by the Rankin scale and not more than 11 points by the NIHSS, with the size of the ischaemic focus not exceeding 4 cm), surgical prevention of recurrent stroke within 7 days after the onset of an ischaemic event may be performed effectively and safely. Early operation effectively prevents relapsing ischaemic events at the in-hospital stage. Besides, reconstruction of brachiocephalic arteries during an acute stage of stroke in operated patients improves the neurological status in the postoperative period, decreases the degree of motor and sensory disorders and makes it possible in half of patients to completely eliminate neurological deficit present at admission.

Essential role of interleukin-6 in post-stroke angiogenesis

PubMed Central

Gertz, Karen; Kronenberg, Golo; Kälin, Roland E.; Baldinger, Tina; Werner, Christian; Balkaya, Mustafa; Eom, Gina D.; Hellmann-Regen, Julian; Kröber, Jan; Miller, Kelly R.; Lindauer, Ute; Laufs, Ulrich; Dirnagl, Ulrich; Heppner, Frank L.

2012-01-01

Ambivalent effects of interleukin-6 on the pathogenesis of ischaemic stroke have been reported. However, to date, the long-term actions of interleukin-6 after stroke have not been investigated. Here, we subjected interleukin-6 knockout (IL-6−/−) and wild-type control mice to mild brain ischaemia by 30-min filamentous middle cerebral artery occlusion/reperfusion. While ischaemic tissue damage was comparable at early time points, IL-6−/− mice showed significantly increased chronic lesion volumes as well as worse long-term functional outcome. In particular, IL-6−/− mice displayed an impaired angiogenic response to brain ischaemia with reduced numbers of newly generated endothelial cells and decreased density of perfused microvessels along with lower absolute regional cerebral blood flow and reduced vessel responsivity in ischaemic striatum at 4 weeks. Similarly, the early genomic activation of angiogenesis-related gene networks was strongly reduced and the ischaemia-induced signal transducer and activator of transcription 3 activation observed in wild-type mice was almost absent in IL-6−/− mice. In addition, systemic neoangiogenesis was impaired in IL-6−/− mice. Transplantation of interleukin-6 competent bone marrow into IL-6−/− mice (IL-6chi) did not rescue interleukin-6 messenger RNA expression or the early transcriptional activation of angiogenesis after stroke. Accordingly, chronic stroke outcome in IL-6chi mice recapitulated the major effects of interleukin-6 deficiency on post-stroke regeneration with significantly enhanced lesion volumes and reduced vessel densities. Additional in vitro experiments yielded complementary evidence, which showed that after stroke resident brain cells serve as the major source of interleukin-6 in a self-amplifying network. Treatment of primary cortical neurons, mixed glial cultures or immortalized brain endothelia with interleukin 6-induced robust interleukin-6 messenger RNA transcription in each case, whereas oxygen–glucose deprivation did not. However, oxygen–glucose deprivation of organotypic brain slices resulted in strong upregulation of interleukin-6 messenger RNA along with increased transcription of key angiogenesis-associated genes. In conclusion, interleukin-6 produced locally by resident brain cells promotes post-stroke angiogenesis and thereby affords long-term histological and functional protection. PMID:22492561

Bronchogenic adenocarcinoma presenting as a synchronous solitary lytic skull lesion with ischaemic stroke – case report and literature review

PubMed Central

O’Connell, David; Kaliaperumal, Chandrasekaran; Wyse, Gerald; McCarthy, Julie; Ryan, Aisling

2011-01-01

The authors describe a rare case of metastatic bronchogenic adenocarcinoma in a 55-year-old man presenting with concomittant solitary lytic skull lesion and ischaemic stroke. Metastatic bronchogenic carcinoma is known to present as lytic skull lesions. Primary brain tumours are also known to cause ischaemic brain injury. An underlying stroke risk may be exagerated by cranial tumour surgery. Patients with brain tumours are well known to be predisposed to an increased risk of developing thromboembolic disease. It is unusual to see metastatic bronchogenic adenocarcinoma presenting as ischaemic stroke with a background of concomittant cerebral metastasis. The aetio-pathogenesis of this rare occurrence is discussed with a review of literature. PMID:22669998

Acute post-stroke blood pressure relative to premorbid levels in intracerebral haemorrhage versus major ischaemic stroke: a population-based study

PubMed Central

Fischer, Urs; Cooney, Marie Therese; Bull, Linda M; Silver, Louise E; Chalmers, John; Anderson, Craig S; Mehta, Ziyah; Rothwell, Peter M

2014-01-01

Summary Background It is often assumed that blood pressure increases acutely after major stroke, resulting in so-called post-stroke hypertension. In view of evidence that the risks and benefits of blood pressure-lowering treatment in acute stroke might differ between patients with major ischaemic stroke and those with primary intracerebral haemorrhage, we compared acute-phase and premorbid blood pressure levels in these two disorders. Methods In a population-based study in Oxfordshire, UK, we recruited all patients presenting with stroke between April 1, 2002, and March 31, 2012. We compared all acute-phase post-event blood pressure readings with premorbid readings from 10-year primary care records in all patients with acute major ischaemic stroke (National Institutes of Health Stroke Scale >3) versus those with acute intracerebral haemorrhage. Findings Of 653 consecutive eligible patients, premorbid and acute-phase blood pressure readings were available for 636 (97%) individuals. Premorbid blood pressure (total readings 13 244) had been measured on a median of 17 separate occasions per patient (IQR 8–31). In patients with ischaemic stroke, the first acute-phase systolic blood pressure was much lower than after intracerebral haemorrhage (158·5 mm Hg [SD 30·1] vs 189·8 mm Hg [38·5], p<0·0001; for patients not on antihypertensive treatment 159·2 mm Hg [27·8] vs 193·4 mm Hg [37·4], p<0·0001), was little higher than premorbid levels (increase of 10·6 mm Hg vs 10-year mean premorbid level), and decreased only slightly during the first 24 h (mean decrease from <90 min to 24 h 13·6 mm Hg). By contrast with findings in ischaemic stroke, the mean first systolic blood pressure after intracerebral haemorrhage was substantially higher than premorbid levels (mean increase of 40·7 mm Hg, p<0·0001) and fell substantially in the first 24 h (mean decrease of 41·1 mm Hg; p=0·0007 for difference from decrease in ischaemic stroke). Mean systolic blood pressure also increased steeply in the days and weeks before intracerebral haemorrhage (regression p<0·0001) but not before ischaemic stroke. Consequently, the first acute-phase blood pressure reading after primary intracerebral haemorrhage was more likely than after ischaemic stroke to be the highest ever recorded (OR 3·4, 95% CI 2·3–5·2, p<0·0001). In patients with intracerebral haemorrhage seen within 90 min, the highest systolic blood pressure within 3 h of onset was 50 mm Hg higher, on average, than the maximum premorbid level whereas that after ischaemic stroke was 5·2 mm Hg lower (p<0·0001). Interpretation Our findings suggest that systolic blood pressure is substantially raised compared with usual premorbid levels after intracerebral haemorrhage, whereas acute-phase systolic blood pressure after major ischaemic stroke is much closer to the accustomed long-term premorbid level, providing a potential explanation for why the risks and benefits of lowering blood pressure acutely after stroke might be expected to differ. Funding Wellcome Trust, Wolfson Foundation, UK Medical Research Council, Stroke Association, British Heart Foundation, National Institute for Health Research. PMID:24582530

Dehydration is an independent predictor of discharge outcome and admission cost in acute ischaemic stroke.

PubMed

Liu, C-H; Lin, S-C; Lin, J-R; Yang, J-T; Chang, Y-J; Chang, C-H; Chang, T-Y; Huang, K-L; Ryu, S-J; Lee, T-H

2014-09-01

Our aim was to investigate the influence of admission dehydration on the discharge outcome in acute ischaemic and hemorrhagic stroke. Between January 2009 and December 2011, 4311 ischaemic and 1371 hemorrhagic stroke patients from the stroke registry of Chang Gung healthcare system were analyzed. The eligible patients were identified according to inclusion/exclusion criteria. In total, 2570 acute ischaemic and 573 acute hemorrhagic stroke patients were finally recruited. According to the blood urea nitrogen (BUN) to creatinine (Cr) ratio (BUN/Cr), these patients were divided into dehydrated (BUN/Cr ≥ 15) and non-dehydrated (BUN/Cr < 15) groups. Demographics, admission costs and discharge outcomes including modified Rankin scale (mRS) and Barthel index (BI) were examined. Data were analyzed using multivariate analysis of two-stage least squares including logistic and linear regression. Acute ischaemic stroke with admission dehydration had higher infection rates (P = 0.006), worse discharge BI (62.8 ± 37.4 vs. 73.4 ± 32.4, P < 0.001, adjusted P < 0.001), worse mRS (2.7 ± 1.6 vs. 2.3 ± 1.5, P < 0.001, adjusted P = 0.009) and higher admission costs (2470.8 ± 3160.8 vs. 1901.2 ± 2046.8 US dollars, P < 0.001, adjusted P = 0.013) than those without dehydration. However, acute hemorrhagic stroke with or without admission dehydration showd no difference in admission costs (P = 0.618) and discharge outcomes (BI, P = 0.058; mRS, P = 0.058). Admission dehydration is associated with worse discharge outcomes and higher admission costs in acute ischaemic stroke but not in hemorrhagic stroke. © 2014 The Author(s) European Journal of Neurology © 2014 EAN.

Acute pathophysiological processes after ischaemic and traumatic brain injury.

PubMed

Kunz, Alexander; Dirnagl, Ulrich; Mergenthaler, Philipp

2010-12-01

Ischaemic stroke and brain trauma are among the leading causes of mortality and long-term disability in the western world. Enormous endeavours have been made to elucidate the complex pathophysiology of ischaemic and traumatic brain injury with the intention of developing new therapeutic strategies for patients suffering from these devastating diseases. This article reviews the current knowledge on cascades that are activated after ischaemic and traumatic brain injury and that lead to progression of tissue damage. Main attention will be on pathophysiological events initiated after ischaemic stroke including excitotoxicity, oxidative/nitrosative stress, peri-infarct depolarizations, apoptosis and inflammation. Additionally, specific pathophysiological aspects after traumatic brain injury will be discussed along with their similarities and differences to ischaemic brain injury. This article provides prerequisites for understanding the therapeutic strategies for stroke and trauma patients which are addressed in other articles of this issue. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effect of Statin Intensity on the Risk of Epilepsy After Ischaemic Stroke: Real-World Evidence from Population-Based Health Claims.

PubMed

Lin, Fang-Ju; Lin, Hung-Wei; Ho, Yunn-Fang

2018-04-01

Statins possess neuroprotective effects. However, real-world evidence supporting their utility in post-stroke epilepsy (PSE) prevention is limited. The association between statin use, including timing of prescribing (pre-stroke vs post-stroke), type (lipophilicity, intensity of therapy) and dose intensity, and risk of developing PSE were investigated by studying Taiwanese health claims (2003-2013). Patients with new-onset ischaemic stroke were identified. The main outcome was a diagnosis of epilepsy after ischaemic stroke. According to pre-stroke statin use, groups of current users, former users, and non-users were compared using ANOVA. An extended Cox regression model was utilized to estimate the hazard ratio (HR) of PSE, with post-stroke statin use and certain comedications as time-dependent variables. Serial sensitivity analyses were performed to ensure study robustness. Of the 20,858 ischaemic stroke patients, 954 (4.6%) developed PSE. Post-stroke statin use (adjusted HR (aHR) 0.55; 95% confidence interval 0.46-0.67, p < 0.001), but not pre-stroke statin use was associated with a significantly reduced risk of developing PSE. A dose-response correlation was also observed between PSE risk reduction and quartiles of the statin cumulative defined daily dose (cDDD) (aHR 0.84, 0.67, 0.53, and 0.50 for the lowest, second, third, and highest quartiles of cDDD, respectively). Risk predictors and protectors against PSE were also characterized. The post-stroke use of statins after ischaemic stroke was associated with PSE risk reduction in a cDDD-dependent manner. Further clinical studies on the potential applications of statins for PSE prophylaxis, particularly among at-risk patients, are warranted.

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

PubMed Central

Traylor, Matthew; Farrall, Martin; Holliday, Elizabeth G; Sudlow, Cathie; Hopewell, Jemma C; Cheng, Yu-Ching; Fornage, Myriam; Ikram, M Arfan; Malik, Rainer; Bevan, Steve; Thorsteinsdottir, Unnur; Nalls, Mike A; Longstreth, WT; Wiggins, Kerri L; Yadav, Sunaina; Parati, Eugenio A; DeStefano, Anita L; Worrall, Bradford B; Kittner, Steven J; Khan, Muhammad Saleem; Reiner, Alex P; Helgadottir, Anna; Achterberg, Sefanja; Fernandez-Cadenas, Israel; Abboud, Sherine; Schmidt, Reinhold; Walters, Matthew; Chen, Wei-Min; Ringelstein, E Bernd; O'Donnell, Martin; Ho, Weang Kee; Pera, Joanna; Lemmens, Robin; Norrving, Bo; Higgins, Peter; Benn, Marianne; Sale, Michele; Kuhlenbäumer, Gregor; Doney, Alexander S F; Vicente, Astrid M; Delavaran, Hossein; Algra, Ale; Davies, Gail; Oliveira, Sofia A; Palmer, Colin N A; Deary, Ian; Schmidt, Helena; Pandolfo, Massimo; Montaner, Joan; Carty, Cara; de Bakker, Paul I W; Kostulas, Konstantinos; Ferro, Jose M; van Zuydam, Natalie R; Valdimarsson, Einar; Nordestgaard, Børge G; Lindgren, Arne; Thijs, Vincent; Slowik, Agnieszka; Saleheen, Danish; Paré, Guillaume; Berger, Klaus; Thorleifsson, Gudmar; Hofman, Albert; Mosley, Thomas H; Mitchell, Braxton D; Furie, Karen; Clarke, Robert; Levi, Christopher; Seshadri, Sudha; Gschwendtner, Andreas; Boncoraglio, Giorgio B; Sharma, Pankaj; Bis, Joshua C; Gretarsdottir, Solveig; Psaty, Bruce M; Rothwell, Peter M; Rosand, Jonathan; Meschia, James F; Stefansson, Kari; Dichgans, Martin; Markus, Hugh S

2012-01-01

Summary Background Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes. Methods We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls. Findings We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort. Interpretation Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes. Funding Wellcome Trust, UK Medical Research Council (MRC), Australian National and Medical Health Research Council, National Institutes of Health (NIH) including National Heart, Lung and Blood Institute (NHLBI), the National Institute on Aging (NIA), the National Human Genome Research Institute (NHGRI), and the National Institute of Neurological Disorders and Stroke (NINDS). PMID:23041239

Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: findings from the Global Burden of Disease Study 2010

PubMed Central

Krishnamurthi, Rita V; Feigin, Valery L; Forouzanfar, Mohammad H; Mensah, George A; Connor, Myles; Bennett, Derrick A; Moran, Andrew E; Sacco, Ralph L; Anderson, Laurie M; Truelsen, Thomas; O’Donnell, Martin; Venketasubramanian, Narayanaswamy; Barker-Collo, Suzanne; Lawes, Carlene M M; Wang, Wenzhi; Shinohara, Yukito; Witt, Emma; Ezzati, Majid; Naghavi, Mohsen; Murray, Christopher

2014-01-01

Summary Background The burden of ischaemic and haemorrhagic stroke varies between regions and over time. With differences in prognosis, prevalence of risk factors, and treatment strategies, knowledge of stroke pathological type is important for targeted region-specific health-care planning for stroke and could inform priorities for type-specific prevention strategies. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010. Methods We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010. We applied the GBD 2010 analytical technique (DisMod-MR) to calculate regional and country-specific estimates for ischaemic and haemorrhagic stroke incidence, mortality, mortality-to-incidence ratio, and disability-adjusted life-years (DALYs) lost, by age group (aged <75 years, ≥75 years, and in total) and country income level (high-income and low-income and middle-income) for 1990, 2005, and 2010. Findings We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). Worldwide, the burden of ischaemic and haemorrhagic stroke increased significantly between 1990 and 2010 in terms of the absolute number of people with incident ischaemic and haemorrhagic stroke (37% and 47% increase, respectively), number of deaths (21% and 20% increase), and DALYs lost (18% and 14% increase). In the past two decades in high-income countries, incidence of ischaemic stroke reduced significantly by 13% (95% CI 6–18), mortality by 37% (19–39), DALYs lost by 34% (16–36), and mortality-to-incidence ratios by 21% (10–27). For haemorrhagic stroke, incidence reduced significantly by 19% (1–15), mortality by 38% (32–43), DALYs lost by 39% (32–44), and mortality-to-incidence ratios by 27% (19–35). By contrast, in low-income and middle-income countries, we noted a significant increase of 22% (5–30) in incidence of haemorrhagic stroke and a 6% (–7 to 18) non-significant increase in the incidence of ischaemic stroke. Mortality rates for ischaemic stroke fell by 14% (9–19), DALYs lost by 17% (–11 to 21%), and mortality-to-incidence ratios by 16% (–12 to 22). For haemorrhagic stroke in low-income and middle-income countries, mortality rates reduced by 23% (–18 to 25%), DALYs lost by 25% (–21 to 28), and mortality-to-incidence ratios by 36% (–34 to 28). Interpretation Although age-standardised mortality rates for ischaemic and haemorrhagic stroke have decreased in the past two decades, the absolute number of people who have these stroke types annually, and the number with related deaths and DALYs lost, is increasing, with most of the burden in low-income and middle-income countries. Further study is needed in these countries to identify which subgroups of the population are at greatest risk and who could be targeted for preventive efforts. PMID:25104492

Predictors of early neurological deterioration after ischaemic stroke: a case-control study.

PubMed

Barber, Mark; Wright, Fiona; Stott, David J; Langhorne, Peter

2004-01-01

Early neurological deterioration after ischaemic stroke (stroke in progression) is reported to be common and associated with poor outcome or death. The causes of progressing stroke are, however, uncertain. To determine whether prior drug treatment (with anticoagulant or antiplatelet agents) or early adverse physiological features (pyrexia, hypoxia, dehydration or hyperglycaemia) are associated with progressing ischaemic stroke. The study used a case-control design. From a database of 873 consecutive acute stroke admissions, 196 cases of progressing ischaemic stroke (defined by point deterioration in components of the Scandinavian Stroke Scale or death over the first 72 h after hospital admission) were matched to 196 controls on the basis of age and stroke type. Univariate and conditional logistic regression techniques were used to explore predictors of progressing stroke. Cases and controls were well matched for baseline stroke severity. Warfarin use prior to admission was associated with a reduced risk of progressing stroke [odds ratio (OR) 0.10, p = 0.005]. Prior antiplatelet use was not related. A previous history of diabetes (OR 2.11, p = 0.039) and elevated systolic blood pressure on admission (OR 1.01 for each 1 mm Hg rise, p = 0.017) predicted progressing stroke. Although there were no differences in time to presentation or to brain imaging, a visible causative lesion on CT scanning was more common in the progressing stroke group (OR 2.30, p = 0.022). We found no evidence that adverse physiological features were associated with progressing stroke. Outcomes were worse in the progressing stroke group with 70% being dead or dependent by 30 days compared to 55% in the control group (p = 0.002). Prior warfarin use may be protective against progressing ischaemic stroke. A previous history of diabetes along with elevated admission systolic blood pressure predict deterioration. We found no evidence for an association between adverse physiological features and progressing stroke. Copyright 2004 S. Karger AG, Basel

Animal models of ischaemic stroke and characterisation of the ischaemic penumbra.

PubMed

McCabe, Christopher; Arroja, Mariana M; Reid, Emma; Macrae, I Mhairi

2018-05-15

Over the past forty years, animal models of focal cerebral ischaemia have allowed us to identify the critical cerebral blood flow thresholds responsible for irreversible cell death, electrical failure, inhibition of protein synthesis, energy depletion and thereby the lifespan of the potentially salvageable penumbra. They have allowed us to understand the intricate biochemical and molecular mechanisms within the 'ischaemic cascade' that initiate cell death in the first minutes, hours and days following stroke. Models of permanent, transient middle cerebral artery occlusion and embolic stroke have been developed each with advantages and limitations when trying to model the complex heterogeneous nature of stroke in humans. Yet despite these advances in understanding the pathophysiological mechanisms of stroke-induced cell death with numerous targets identified and drugs tested, a lack of translation to the clinic has hampered pre-clinical stroke research. With recent positive clinical trials of endovascular thrombectomy in acute ischaemic stroke the stroke community has been reinvigorated, opening up the potential for future translation of adjunctive treatments that can be given alongside thrombectomy/thrombolysis. This review discusses the major animal models of focal cerebral ischaemia highlighting their advantages and limitations. Acute imaging is crucial in longitudinal pre-clinical stroke studies in order to identify the influence of acute therapies on tissue salvage over time. Therefore, the methods of identifying potentially salvageable ischaemic penumbra are discussed. This article is part of the Special Issue entitled 'Cerebral Ischemia'. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Stroke and methamphetamine use in young adults: a review.

PubMed

Lappin, Julia M; Darke, Shane; Farrell, Michael

2017-12-01

Methamphetamine use and stroke are significant public health problems. Strokes among people aged below 45 years are much less common than in older age groups but have significant mortality and morbidity. Methamphetamine is a putative cause of strokes among younger people. A review of methamphetamine-related strokes was conducted. Bibliographic databases were searched until February 2017 for articles related to methamphetamine and stroke. Both haemorrhagic and ischaemic strokes were considered. Of 370 articles screened, 77 were selected for inclusion. There were 81 haemorrhagic and 17 ischaemic strokes reported in case reports and series. Both types were approximately twice as common in males. Route of administration associated with haemorrhagic stroke was typically oral or injecting, but for ischaemic stroke inhalation was most common. Haemorrhagic stroke was associated with vascular abnormalities in a third of cases. One quarter of individuals completely recovered, and a third died following haemorrhagic stroke. One-fifth completely recovered, and one-fifth died following ischaemic stroke. There is a preponderance of haemorrhagic strokes associated with methamphetamine use in young people, and methamphetamine-related stroke is associated with poor clinical outcomes. Mechanisms of methamphetamine-associated stroke include hypertension, vasculitis, direct vascular toxicity and vasospasm. In a period of rising worldwide methamphetamine use, the incidence of methamphetamine-related stroke will increase, with a consequent increase in the burden of disease contributed by such events. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Incidence, predictors and clinical characteristics of orolingual angio-oedema complicating thrombolysis with tissue plasminogen activator for ischaemic stroke.

PubMed

Hurford, Robert; Rezvani, Sean; Kreimei, Mohammad; Herbert, Annie; Vail, Andy; Parry-Jones, Adrian R; Douglass, Chris; Molloy, Jane; Alachkar, Hana; Tyrrell, Pippa J; Smith, Craig J

2015-05-01

Orolingual angio-oedema is a recognised complication of tissue plasminogen activator (tPA) for ischaemic stroke. We investigated its incidence, clinical characteristics and relationship with other factors in patients receiving tPA at a UK centre. 530 consecutive patients (median age 70 years) receiving tPA treatment for confirmed ischaemic stroke were included. Cases were defined as those developing angio-oedema within 24 h of initiation of tPA. Angio-oedema was retrospectively classified as mild, moderate or severe using predefined criteria. The primary analysis was the association between prior ACE inhibitor (ACE-I) treatment and angio-oedema. Orolingual angio-oedema was observed in 42 patients (7.9%; 95% CI 5.5% to 10.6%), ranging from 5 to 189 min after initiation of tPA (median 65 min). 12% of the angio-oedema cases were severe (1% of all patients treated with tPA), requiring urgent advanced airway management. 172 patients (33%) were taking ACE-I. In multifactorial analyses, only prior ACE-I treatment remained a significant independent predictor of angio-oedema (odds ratio (OR) 2.3; 95% CI 1.1 to 4.7). Angio-oedema occurs more frequently than previously reported and is associated with preceding ACE-I treatment. Angio-oedema may be delayed and progress to life-threatening airway compromise, which has implications for the assessment and delivery of thrombolysis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Utility of treatment with atorvastatin 40 mg plus ezetimibe 10 mg versus atorvastatin 80 mg in reducing the levels of LDL cholesterol in patients with ischaemic stroke or transient ischaemic attack].

PubMed

Palacio, Enrique; Viadero-Cervera, Raquel; Revilla, Marián; Larrosa-Campo, Davinia; Acha-Salazar, Olga; Novo-Robledo, Francisco; Oterino, Agustín

2016-03-01

After an ischaemic stroke, to reduce LDL cholesterol (LDLc) levels decreases the risk of recurrence. The risk of recurrence is lower with more intense reductions in LDLc levels. To evaluate the efficacy and security of atorvastatin 40 mg plus ezetimibe 10 mg after ischaemic stroke or transient ischaemic attack (TIA). We retrospectively evaluated stroke or TIA patients admitted to our hospital who received atorvastatin 40 mg plus ezetimibe 10 mg (n = 34) or atorvastatin 80 mg (n = 52) at discharge. We analyzed changes in lipid parameters and established as a primary outcome LDLc <= 70 mg/dL and/or reduction in LDLc >= 50%. Furthermore, safety parameters were assessed. Predictors associated with primary outcome achievement were treatment with atorvastatin 40 mg plus ezetimibe 10 mg (odds ratio: 11.94; 95% CI: 2.82-50.64; p = 0.001) and male (odds ratio: 4.76; 95% CI: 1.35-16.67; p = 0.02). Treatment with atorvastatin 40 mg plus ezetimibe 10 mg achieved significantly greater reductions in LDLc (p < 0.001), total cholesterol (p < 0.001) and non-HDLc (p < 0.001). Both treatments were safe and well tolerated, with a low number of secondary effects. Compared with atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg increases the likelihood of achieving LDLc goals after ischaemic stroke or transient ischaemic attack. Both treatments were safe and well tolerated.

Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis.

PubMed

Wiseman, Stewart; Marlborough, Fergal; Doubal, Fergus; Webb, David J; Wardlaw, Joanna

2014-01-01

The cause of cerebral small vessel disease is not fully understood, yet it is important, accounting for about 25% of all strokes. It also increases the risk of having another stroke and contributes to about 40% of dementias. Various processes have been implicated, including microatheroma, endothelial dysfunction and inflammation. A previous review investigated endothelial dysfunction in lacunar stroke versus mostly non-stroke controls while another looked at markers of inflammation and endothelial damage in ischaemic stroke in general. We have focused on blood markers between clinically evident lacunar stroke and other subtypes of ischaemic stroke, thereby controlling for stroke in general. We systematically assessed the literature for studies comparing blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-stroke controls or other ischaemic stroke subtypes. We assessed the quality of included papers and meta-analysed results. We split the analysis on time of blood draw in relation to the stroke. We identified 1,468 full papers of which 42 were eligible for inclusion, including 4,816 ischaemic strokes, of which 2,196 were lacunar and 2,500 non-stroke controls. Most studies subtyped stroke using TOAST. The definition of lacunar stroke varied between studies. Markers of coagulation/fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), fibrinogen, D-dimer) were higher in lacunar stroke versus non-stroke although fibrinogen was no different to non-stroke in the acute phase. tPA and PAI were no different between lacunar and non-lacunar stroke. Fibrinogen and D-dimer were significantly lower in lacunar stroke compared to other ischaemic strokes, both acutely and chronically. Markers of endothelial dysfunction (homocysteine, von Willebrand Factor (vWF), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule-1 (VCAM)) were higher or had insufficient or conflicting data (P-selectin, VCAM) in lacunar stroke versus non-stroke. Compared to other ischaemic stroke subtypes, homocysteine did not differ in lacunar stroke while vWF was significantly lower in lacunar stroke acutely [atherothrombotic standardized mean difference, SMD, -0.34 (-0.61, -0.08); cardioembolic SMD -0.38 (-0.62, -0.14)], with insufficient data chronically. Markers of inflammation (C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)) were higher in lacunar stroke versus non-stroke, although there were no studies measuring TNF-α chronically and the sole study measuring IL-6 chronically showed no difference between lacunar stroke and non-stroke. Compared to other ischaemic stroke subtypes, there was no difference (CRP) or insufficient or conflicting data (TNF-α) to lacunar stroke. IL-6 was significantly lower [atherothrombotic SMD -0.37 (-0.63, -0.10); cardioembolic SMD -0.52 (-0.82, -0.22)] in lacunar stroke acutely, with insufficient data chronically. Lacunar stroke is an important stroke subtype. More studies comparing lacunar stroke to non-lacunar stroke specifically, rather than to non-stroke controls, are needed. Prospective studies with measurements taken well after the acute event are more likely to be helpful in determining pathogenesis. The available data in this review were limited and do not exclude the possibility that peripheral inflammatory processes including endothelial dysfunction are associated with lacunar stroke and cerebral small vessel disease. © 2013 S. Karger AG, Basel

Do lacunar strokes benefit from thrombolysis? Evidence from the Registry of the Canadian Stroke Network.

PubMed

Shobha, Nandavar; Fang, Jiming; Hill, Michael D

2013-10-01

Lacunar infarcts constitute up to 25% of all ischaemic strokes. As acute intracranial vascular imaging has become widely available with computed tomographic angiography, thrombolysis of lacunar strokes has become contentious because an intracranial vascular lesion cannot be visualized. We studied the effect of thrombolysis on lacunar strokes compared to other clinical ischaemic stroke sub-types. Ischaemic stroke patients from phase 3 of the Registry of the Canadian Stroke Network data (July 2003-March 2008) were included. Lacunar stroke was defined as a lacunar syndrome supported by computed tomography brain showing a subcortical hypodense lesion with a diameter <20 mm. Clinical syndromes were used to define other stroke sub-types. The outcomes were mortality at 90 days, modified Rankin Scale score 0-2 at discharge, occurrence of intracranial haemorrhage as a complication of stroke in-hospital, and discharge disposition to home. A total of 11,503 patients of ischaemic stroke were included from the Registry of the Canadian Stroke Network 3 between July 2003 and March 2008. Lacunar strokes formed 19.1% of the total strokes. The total number of patients who received tissue plasminogen activator was 1630 (14.2%). A significant association was found between tissue plasminogen activator treatment and outcomes after controlling Oxfordshire Community Stroke Project types--for modified Rankin Scale at discharge and discharge to home, but not for mortality. A thrombolysis-by-Oxfordshire Community Stroke Project stroke sub-type interaction was observed due to lack of benefit among the posterior circulation stroke sub-types. Patients with lacunar strokes, partial anterior circulation stroke, and total anterior circulation strokes all benefited approximately equally from thrombolysis. Thrombolysis is associated with clinically improved outcome among patients with lacunar stroke syndromes. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Better adherence to antithyroid drug is associated with decreased risk of stroke in hyperthyroidism patients.

PubMed

Tsai, M-S; Chuang, P-Y; Huang, C-H; Shih, S-R; Chang, W-T; Chen, N-C; Yu, P-H; Cheng, H-J; Tang, C-H; Chen, W-J

2015-12-01

An increased risk for ischaemic stroke has been reported in young hyperthyroidism patients independent of atrial fibrillation (AF). However, whether the use of antithyroid drugs in hyperthyroidism patients can reduce the occurrence of ischaemic stroke remains unclear. A total of 36,510 newly diagnosed hyperthyroidism patients during 2003-2006 were identified from the Taiwan National Health Insurance Research database. Each patient was individually tracked for 5 years from their index date (beginning the antithyroid drugs) to identify those who suffered from new episode of ischaemic stroke. Medication possession ratio (MPR) was used to represent the antithyroid drug compliance. The association between the MPR and the risk of stroke was examined. The stroke incidence rates for hyperthyroidism patients with age < 45 years and age ≥ 45 years were 0.42 and 3.76 per 1000 person-years, respectively. The patients aged < 45 years with MPR < 0.2 (adjusted hazard ratio, HR, 2.30; 95% CI, 1.13-4.70; p = 0.02) and 0.2 ≤ MPR < 0.4 (adjusted HR, 2.24; 95% CI, 1.06-4.72; p = 0.035) had a significantly increased risk of ischaemic stroke as compared to those with ≥ 0.6. In patients of the age ≥ 45 years, only the patients with MPR < 0.2 (adjusted HR, 1.44; 95% CI, 1.03-2.01; p = 0.036) had a significantly higher risk of ischaemic stroke as compared to those with MPR ≥ 0.6. In hyperthyroidism patients without AF, good antithyroid drugs compliance also reduced the incidence of stroke significantly (adjusted HR, range: 1.52-1.61; p = 0.02); but not in hyperthyroidism with AF. Hyperthyroidism patients with good antithyroid drug compliance had a lower risk of ischaemic stroke than patients with poor compliance. © 2015 John Wiley & Sons Ltd.

High serum uric acid levels are a protective factor against unfavourable neurological functional outcome in patients with ischaemic stroke.

PubMed

Wang, Yu-Fang; Li, Jiao-Xing; Sun, Xun-Sha; Lai, Rong; Sheng, Wen-Li

2018-05-01

Objective We aimed to evaluate the association between serum uric acid levels at the onset and prognostic outcome in patients with acute ischaemic stroke. Methods We retrospectively analysed the outcomes of 1166 patients with ischaemic stroke who were hospitalized in our centre during August 2008 to November 2012. Correlations of serum uric acid levels and prognostic outcomes were analysed. Results Men had higher serum uric acid levels and better neurological functional outcomes compared with women. There was a strong negative correlation between serum uric acid levels and unfavourable neurological functional outcomes. Generalized estimated equation analysis showed that a higher serum uric acid level (>237 µmol/L) was a protective factor for neurological functional outcome in male, but not female, patients. Among five trial of ORG 10172 in acute stroke treatment classification subtypes, only patients with the large-artery atherosclerosis subtype had a significant protective effect of serum uric acid levels on neurological outcome. Conclusions Our study shows that high serum uric acid levels are a significant protective factor in men and in the large-artery atherosclerosis subtype in patients with ischaemic stroke. This is helpful for determining the prognostic value of serum uric acid levels for neurological outcome of acute ischaemic stroke.

Epidemiology, pathophysiology, and treatment of hypertension in ischaemic stroke patients.

PubMed

Hisham, Nur Fatirul; Bayraktutan, Ulvi

2013-10-01

Stroke continues to be one of the leading causes of mortality and morbidity worldwide. There are 2 main types of stroke: ischaemic strokes, which are caused by obstruction of the blood vessels leading to or within the brain, and haemorrhagic strokes, which are induced by the disruption of blood vessels. Stroke is a disease of multifactorial aetiology that may develop as an end state in patients with serious vascular conditions--most notably, uncontrolled arterial hypertension--thereby necessitating the effective control of this risk factor to prevent stroke or its recurrence. This paper focuses specifically on the epidemiology and pathogenesis of ischaemic stroke mainly in chronically hypertensive patients and pays particular attention to the efficacy of a select group of routinely used major antihypertensive drugs (i.e., angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, and calcium channel blockers) in the treatment of strokes. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Ethnic disparities in incidence of stroke subtypes: Auckland Regional Community Stroke Study, 2002-2003.

PubMed

Feigin, Valery; Carter, Kristie; Hackett, Maree; Barber, P Alan; McNaughton, Harry; Dyall, Lorna; Chen, Mei-hua; Anderson, Craig

2006-02-01

Limited population-based data exist on differences in the incidence of major pathological stroke types and ischaemic stroke subtypes across ethnic groups. We aimed to provide such data within the large multi-ethnic population of Auckland, New Zealand. All first-ever cases of stroke (n=1423) in a population-based register in 940 000 residents (aged 15 years) in Auckland, New Zealand, for a 12-month period in 2002-2003, were classified into ischaemic stroke, primary intracerebral haemorrhage (PICH), subarachnoid haemorrhage, and undetermined stroke, according to standard definitions and results of neuroimaging/necropsy (in over 90% of cases). Ischaemic stroke was further classified into five subtypes. Ethnicity was self-identified and grouped as New Zealand (NZ)/European, Maori/Pacific, and Asian/other. Incidence rates were standardised to the WHO world population by the direct method, and differences in rates between ethnic groups expressed as rate ratios (RRs), with NZ/European as the reference group. In NZ/European people, ischaemic stroke comprised 73%, PICH 11%, and subarachnoid haemorrhage 6%, but PICH was higher in Maori/Pacific people (17%) and in Asian/other people (22%). Compared with NZ/European people, age-adjusted RRs for PICH were 2.7 (95% CI 1.8-4.0) and 2.3 (95% CI 1.4-3.7) among Maori/Pacific and Asian/other people, respectively. The corresponding RR for ischaemic stroke was greater for Maori/Pacific people (1.7 [95% CI 1.4-2.0]), particularly embolic stroke, and for Asian/other people (1.3 [95% CI 1.0-1.7]). The onset of stroke in Maori/Pacific and Asian/other people began at significantly younger ages (62 years and 64 years, respectively) than in NZ/Europeans (75 years; p<0.0001). There were ethnic differences in the risk factor profiles (such as age, sex, hypertension, cardiac disease, diabetes, hypercholesterolaemia, smoking status, overweight) for the stroke types and subtypes. Compared to NZ/Europeans, Maori/Pacific and Asian/other people are at higher risk of ischaemic stroke and PICH, whereas similar rates of subarachnoid haemorrhage were evident across ethnic groups. The ethnic disparities in the rates of stroke types could be due to substantial differences found in risk factor profiles between ethnic groups. This information should be considered when planning prevention and stroke-care services in multi-ethnic communities.

Suboptimal lipid management before and after ischaemic stroke and TIA-the North Dublin Population Stroke Study.

PubMed

Ní Chróinín, Danielle; Ní Chróinín, Chantelle; Akijian, Layan; Callaly, Elizabeth L; Hannon, Niamh; Kelly, Lisa; Marnane, Michael; Merwick, Áine; Sheehan, Órla; Horgan, Gillian; Duggan, Joseph; Kyne, Lorraine; Dolan, Eamon; Murphy, Seán; Williams, David; Kelly, Peter J

2018-01-24

Few population-based studies have assessed lipid adherence to international guidelines for primary and secondary prevention in stroke/transient ischaemic attack (TIA) patients. This study aims to evaluate adherence to lipid-lowering therapy (LLT) guidelines amongst patients with ischaemic stroke/TIA. Using hot and cold pursuit methods from multiple hospital/community sources, all stroke and TIA cases in North Dublin City were prospectively ascertained over a 1-year period. Adherence to National Cholesterol Education Programme (NCEP) III guidelines, before and after index ischaemic stroke/TIA, was assessed. Amongst 616 patients (428 ischaemic stroke, 188 TIA), total cholesterol was measured following the qualifying event in 76.5% (471/616) and low-density lipoprotein (LDL) in 60.1% (370/616). At initial stroke/TIA presentation, 54.1% (200/370) met NCEP III LDL goals. Compliance was associated with prior stroke (odds ratio [OR] 2.19, p = 0.02), diabetes (OR 1.91, p = 0.04), hypertension (OR 1.57, p = 0.03), atrial fibrillation (OR 1.78, p = 0.01), pre-event LLT (OR 2.85, p < 0.001) and higher individual LDL goal (p = 0.001). At stroke/TIA onset, 32.7% (195/596) was on LLT. Nonetheless, LDL exceeded individual NCEP goal in 29.2% (56/192); 21.6% (53/245) warranting LLT was not on treatment prior to stroke/TIA onset. After index stroke/TIA, 75.9% (422/556) was on LLT; 15.3% (30/196) meeting NCEP III criteria was not prescribed a statin as recommended. By 2 years, actuarial survival was 72.8% and 11.9% (59/497) experienced stroke recurrence. No association was observed between initial post-event target adherence and 2-year outcomes. In this population-based study, LLT recommended by international guidelines was under-used, before and after index stroke/TIA. Strategies to improve adherence are needed.

Co-morbid conditions in use of recombinant tissue plasminogen activator (rt-PA) for the treatment of acute ischaemic stroke.

PubMed

Nathaniel, Thomas I; Cochran, Thomas; Chaves, Jose; Fulmer, Eric; Sosa, Crystal; Yi, Sara; Fredwall, Megan; Sternberg, Shannon; Blackhurst, Dawn; Nelson, Alfred; Leacock, Rodney

2016-01-01

The objective of this study was to characterize the comorbidities in a population of patients with an acute ischaemic stroke, comparing patients that received recombinant tissue plasminogen activator (rt-PA) to those that did not receive rt-PA. In a retrospective sample of 663 patients admitted for acute ischaemic stroke, this study analysed the effects of co-morbid conditions in the use of rt-PA. It determined non-cerebrovascular risk factors (comorbidities) that differentiate patients who received rt-PA from those who did not receive rt-PA. Patients with a history of carotid stenosis, CHF and previous strokes are significantly (p < 0.05) associated with high risk of not receiving rt-PA. A significant number of patients with a history of hypertension and smoking received rt-PA (p < 0.05). The findings indicate that certain risk factors including carotid stenosis, CHF and previous stroke history impact the treatment of patients with acute ischaemic stroke, specifically the decision to administer rt-PA. Treatment with rt-PA is dependent on stroke severity and onset to treatment time, but the findings suggest that rt-PA use may also depend on patient comorbidities.

Body temperature and major neurological improvement in tPA-treated stroke patients.

PubMed

Kvistad, C E; Thomassen, L; Waje-Andreassen, U; Logallo, N; Naess, H

2014-05-01

Major neurological improvement (MNI) at 24 hours represents a marker of early recanalization in ischaemic stroke. Although low body temperature is considered neuroprotective in cerebral ischaemia, some studies have suggested that higher body temperature may promote clot lysis in the acute phase of ischaemic stroke. We hypothesized that higher body temperature was associated with MNI in severe stroke patients treated with tPA, suggesting a beneficial effect of higher body temperature on clot lysis and recanalization. Patients with ischaemic stroke or transient ischaemic attack (TIA) treated with tPA between February 2006 and August 2012 were prospectively included and retrospectively analysed. Body temperature was measured upon admission. MNI was defined by a ≥8 point improvement in NIHSS score at 24 hours as compared to NIHSS score on admission. No significant improvement (no-MNI) was defined by either an increase in NIHSS score or a decrease of ≤2 points at 24 hours in patients with an admission NIHSS score of ≥8. Of the 2351 patients admitted with ischaemic stroke or TIA, 347 patients (14.8%) were treated with tPA. A total of 32 patients (9.2%) had MNI and 56 patients (16.1%) had no-MNI. Patients with MNI had higher body temperatures compared with patients with no-MNI (36.7°C vs 36.3°C, P = 0.004). Higher body temperature was independently associated with MNI when adjusted for confounders (OR 5.16, P = 0.003). Higher body temperature was independently associated with MNI in severe ischaemic stroke patients treated with tPA. This may suggest a beneficial effect of higher body temperature on clot lysis and recanalization. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The role of atrial fibrillation on mortality and morbidity in patients with ischaemic stroke.

PubMed

Cögen, Etem Emre; Tombul, Temel; Yildirim, Gökhan; Odabas, Faruk Omer; Sayin, Refah

2013-12-01

To investigate the impact of atrial fibrillation on mortality and morbidity in ischaemic stroke patients. The retrospective study was conducted at the Neurology Clinic, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey, and comprised records of ischaemic stroke patients hospitalised between January 2006 and September 2009. SPSS 13 was used for statistical analysis. Of the 404 patients in the study, 69 (17.1%) had atrial fibrilation. The mean age of such patients was 66.78 +/- 12.23 years compared to 61.01 +/- 15.11 years for the rest. Besides 47 (68.1%) of these patients were females. According to the modified Rankin Scale scores, the degree of disability was significantly higher at the time of arrival and discharge, and mortality rates were significantly higher also (p < 0.01). Atrial fibrillation affected the prognosis of ischaemic stroke adversely in terms of mortality and morbidity.

Protein supplementation may enhance the spontaneous recovery of neurological alterations in patients with ischaemic stroke.

PubMed

Aquilani, Roberto; Scocchi, Marco; Iadarola, Paolo; Franciscone, Piero; Verri, Manuela; Boschi, Federica; Pasini, Evasio; Viglio, Simona

2008-12-01

To determine whether protein supplementation could enhance neurological recovery in subacute patients with ischaemic stroke. Alimentation-independent patients with ischaemic stroke were randomly allocated to either 21 days of protein supplementation (protein-supplemented group; n=20) or to a spontaneous diet only (control group; n=21) in order to investigate the recovery of neurological changes (measured using the National Institute of Health (NIH) Stroke Scale). Tertiary care rehabilitation in Italy. Forty-two patients (27 male and 15 female; 66.4 +/- 11 years) 16 +/-2 days after the acute event. Supplementation with a hyperproteic nutritional formula (10% protein). NIH Stroke Scale and protein intake. At admission to rehabilitation, both groups of patients were homogeneous for demographic, clinical and functional characteristics. After 21 days from the start of the protocol, the NIH Stroke Scale was found to be enhanced in the group with supplemental proteins (-4.4 +/- 1.5 score versus -3 +/- 1.4 of control group; P<0.01). When expressed as difference (triangle up) between baseline and 21 days, the NIH Stroke Scale correlated negatively with change in protein intake (g/day) (r=-0.50, P= 0.001) and positively with change in carbohydrate/protein ratio (r = +0.40, P=0.01) Protein supplementation may enhance neurological recovery in subacute patients with ischaemic stroke.

Functional magnetic resonance imaging in chronic ischaemic stroke.

PubMed

Lake, Evelyn M R; Bazzigaluppi, Paolo; Stefanovic, Bojana

2016-10-05

Ischaemic stroke is the leading cause of adult disability worldwide. Effective rehabilitation is hindered by uncertainty surrounding the underlying mechanisms that govern long-term ischaemic injury progression. Despite its potential as a sensitive non-invasive in vivo marker of brain function that may aid in the development of new treatments, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has found limited application in the clinical research on chronic stage stroke progression. Stroke affects each of the physiological parameters underlying the BOLD contrast, markedly complicating the interpretation of BOLD fMRI data. This review summarizes current progress on application of BOLD fMRI in the chronic stage of ischaemic injury progression and discusses means by which more information may be gained from such BOLD fMRI measurements. Concomitant measurements of vascular reactivity, neuronal activity and metabolism in preclinical models of stroke are reviewed along with illustrative examples of post-ischaemic evolution in neuronal, glial and vascular function. The realization of the BOLD fMRI potential to propel stroke research is predicated on the carefully designed preclinical research establishing an ischaemia-specific quantitative model of BOLD signal contrast to provide the framework for interpretation of fMRI findings in clinical populations.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Author(s).

Influence of prior transient ischaemic attack on stroke prognosis.

PubMed

Aboa-Eboulé, Corine; Béjot, Yannick; Osseby, Guy-Victor; Rouaud, Olivier; Binquet, Christine; Marie, Christine; Cottin, Yves; Giroud, Maurice; Bonithon-Kopp, Claire

2011-09-01

To evaluate potential neuroprotection afforded by prior transient ischaemic attack (TIA) on functional and survival outcomes after ischaemic stroke. All cases of first-ever ischaemic strokes, diagnosed between 1985 and 2008, were identified from the Dijon Stroke Registry. Patients were analysed in three groups according to the time interval between prior TIA and stroke (<4 weeks, ≥ 4 weeks, no TIA) or the duration of TIA (≤ 30 min, >30 min, no TIA). Outcomes were severe functional handicap (unable to walk, bedridden or death) at hospital discharge or at outpatient consultation, and 1-month and 1-year any-cause mortality. Stratified analyses were performed by stroke subtypes (non-lacunar, lacunar). Generalised linear mixed models and Cox proportional hazard models with a sandwich covariance matrix accounting for the treatment centre as a random effect were used for multivariate analyses. Among the 3015 patients with first-ever ischaemic stroke, 389 had had a prestroke TIA <4 weeks and 97 a prestroke TIA ≥ 4 weeks. Patients with TIAs had better ambulatory status (adjusted OR 0.61, 95% CI 0.45 to 0.81; p = 0.008) and better survival at 1 month (adjusted HR 0.76, 95% CI 0.65 to 0.89; p = 0.0006) and at 1 year (adjusted HR 0.72, 95% CI 0.67 to 0.76; p<0.0001) than those with no TIAs. Prestroke TIA <4 weeks and TIA duration ≤ 30 min also significantly improved the outcomes in overall, non-lacunar and lacunar strokes. Recent prestroke TIA was associated with better functional outcome and lower 1-month and 1-year mortality after stroke, suggesting a neuroprotective effect.

Young adult ischaemic stroke related acute symptomatic and late seizures: risk factors.

PubMed

Roivainen, R; Haapaniemi, E; Putaala, J; Kaste, M; Tatlisumak, T

2013-09-01

After first-ever ischaemic stroke, to assess the risk and baseline factors associated with acute symptomatic seizure (ASS) (occurring within 7 days) and late post-stroke seizure (LPS) (>7 days). All consecutive patients aged 15-49 with first-ever ischaemic stroke between 1994 and 2007 treated at the Helsinki University Central Hospital were included, using Cox proportional hazard models to identify factors associated with seizures. Adjustment was for age, gender, vascular risk factors, admission hyperglycemia (>6.1 mm) and hyponatremia (<137 mm), use of psychiatric medication, stroke severity (NIH Stroke Scale) and anatomical (Bamford criteria) and etiological (Trial of Org in Acute Stroke Treatment) stroke subtype. ASSs emerged in 35 (3.5%) patients. LPSs (n = 102) occurred at a cumulative rate of 6.1% at 1 year, 9.5% at 5 years and 11.5% at 10 years. In multivariate analysis, anxiolytic use at time of index stroke (hazard ratio 13.43, 95% confidence interval 3.91-46.14), moderate stroke severity (3.95, 1.86-8.41), cortical involvement (3.69, 1.66-8.18) and hyponatremia (3.26, 1.41-7.57) were independently associated with ASSs. Risk factors for LPSs were total anterior circulation infarct (15.94, 7.62-33.33), partial anterior circulation infarct (3.48, 1.52-7.93), history of ASS (3.94, 2.07-7.48), antidepressant use at the time of LPS (3.88, 2.46-6.11), hemorrhagic infarct (1.94, 1.19-3.15), male gender (1.79, 1.10-2.92) and hyperglycemia (1.62, 1.05-2.51). In young ischaemic stroke patients, the magnitude of seizure risk and the major risk factors were similar to older ischaemic stroke patients but risk factors for ASSs and LPSs differed. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population: Inter99 randomised trial.

PubMed

Jørgensen, Torben; Jacobsen, Rikke Kart; Toft, Ulla; Aadahl, Mette; Glümer, Charlotte; Pisinger, Charlotta

2014-06-09

To investigate the effect of systematic screening for risk factors for ischaemic heart disease followed by repeated lifestyle counselling on the 10 year development of ischaemic heart disease at a population level. Randomised controlled community based trial. Suburbs of Copenhagen, Denmark. 59,616 people aged 30-60 years randomised with different age and sex randomisation ratios to an intervention group (n = 11,629) and a control group (n = 47,987). The intervention group was invited for screening, risk assessment, and lifestyle counselling up to four times over a five year period. All participants with an unhealthy lifestyle had individually tailored lifestyle counselling at all visits (at baseline and after one and three years); those at high risk of ischaemic heart disease, according to predefined criteria, were furthermore offered six sessions of group based lifestyle counselling on smoking cessation, diet, and physical activity. After five years all were invited for a final counselling session. Participants were referred to their general practitioner for medical treatment, if relevant. The control group was not invited for screening. The primary outcome measure was incidence of ischaemic heart disease in the intervention group compared with the control group. Secondary outcome measures were stroke, combined events (ischaemic heart disease, stroke, or both), and mortality. 6091 (52.4%) people in the intervention group participated at baseline. Among 5978 people eligible at five year follow-up (59 died and 54 emigrated), 4028 (67.4%) attended. A total of 3163 people died in the 10 year follow-up period. Among 58,308 without a history of ischaemic heart disease at baseline, 2782 developed ischaemic heart disease. Among 58,940 without a history of stroke at baseline, 1726 developed stroke. No significant difference was seen between the intervention and control groups in the primary end point (hazard ratio for ischaemic heart disease 1.03, 95% confidence interval 0.94 to 1.13) or in the secondary endpoints (stroke 0.98, 0.87 to 1.11; combined endpoint 1.01, 0.93 to 1.09; total mortality 1.00, 0.91 to 1.09). A community based, individually tailored intervention programme with screening for risk of ischaemic heart disease and repeated lifestyle intervention over five years had no effect on ischaemic heart disease, stroke, or mortality at the population level after 10 years.Trial registration Clinical trials NCT00289237. © Jørgensen et al 2014.

The Christchurch earthquake stroke incidence study.

PubMed

Wu, Teddy Y; Cheung, Jeanette; Cole, David; Fink, John N

2014-03-01

We examined the impact of major earthquakes on acute stroke admissions by a retrospective review of stroke admissions in the 6 weeks following the 4 September 2010 and 22 February 2011 earthquakes. The control period was the corresponding 6 weeks in the previous year. In the 6 weeks following the September 2010 earthquake there were 97 acute stroke admissions, with 79 (81.4%) ischaemic infarctions. This was similar to the 2009 control period which had 104 acute stroke admissions, of whom 80 (76.9%) had ischaemic infarction. In the 6 weeks following the February 2011 earthquake, there were 71 stroke admissions, and 61 (79.2%) were ischaemic infarction. This was less than the 96 strokes (72 [75%] ischaemic infarction) in the corresponding control period. None of the comparisons were statistically significant. There was also no difference in the rate of cardioembolic infarction from atrial fibrillation between the study periods. Patients admitted during the February 2011 earthquake period were less likely to be discharged directly home when compared to the control period (31.2% versus 46.9%, p=0.036). There was no observable trend in the number of weekly stroke admissions between the 2 weeks leading to and 6 weeks following the earthquakes. Our results suggest that severe psychological stress from earthquakes did not influence the subsequent short term risk of acute stroke, but the severity of the earthquake in February 2011 and associated civil structural damages may have influenced the pattern of discharge for stroke patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Headache in acute ischaemic stroke: a lesion mapping study.

PubMed

Seifert, Christian L; Schönbach, Etienne M; Magon, Stefano; Gross, Elena; Zimmer, Claus; Förschler, Anette; Tölle, Thomas R; Mühlau, Mark; Sprenger, Till; Poppert, Holger

2016-01-01

Headache is a common symptom in acute ischaemic stroke, but the underlying mechanisms are incompletely understood. The aim of this lesion mapping study was to identify brain regions, which are related to the development of headache in acute ischaemic stroke. Patients with acute ischaemic stroke (n = 100) were assessed by brain MRI at 3 T including diffusion weighted imaging. We included 50 patients with stroke and headache as well as 50 patients with stroke but no headache symptoms. Infarcts were manually outlined and images were transformed into standard stereotaxic space using non-linear warping. Voxel-wise overlap and subtraction analyses of lesions as well as non-parametric statistics were conducted. The same analyses were carried out by flipping of left-sided lesions, so that all strokes were transformed to the same hemisphere. Between the headache group as well as the non-headache there was no difference in infarct volumes, in the distribution of affected vascular beds or in the clinical severity of strokes. The headache phenotype was tension-type like in most cases. Subtraction analysis revealed that in headache sufferers infarctions were more often distributed in two well-known areas of the central pain matrix: the insula and the somatosensory cortex. This result was confirmed in the flipped analysis and by non-parametric statistical testing (whole brain corrected P-value < 0.01). To the best of our knowledge, this is the first lesion mapping study investigating potential lesional patterns associated with headache in acute ischaemic stroke. Insular strokes turned out to be strongly associated with headache. As the insular cortex is a well-established region in pain processing, our results suggest that, at least in a subgroup of patients, acute stroke-related headache might be centrally driven. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Seizure development after stroke.

PubMed

Misirli, H; Ozge, A; Somay, G; Erdoğan, N; Erkal, H; Erenoğlu, N Y

2006-12-01

Although there have been many studies on seizures following stroke, there is still much we do not know about them. In this study, we evaluated the characteristics of seizures in stroke patients. There were 2267 patients with a first-ever stroke, and after excluding 387 patients, 1880 were available for analysis. Of these 1880 patients, we evaluated 200 patients with seizures and 400 patients without seizures. We investigated the seizures according to age, gender, stroke type, the aetiology of ischaemic stroke and the localisation of the lesion. The seizures were classified as early onset and late onset and the seizure type as partial, generalised or secondarily generalised. Seizures occurred in 200 (10.6%) of 1880 strokes. The number of patients with seizures were 138 (10.6%) in ischaemic stroke group and 62 (10.7%) in haemorrhagic stroke group. Patients with ischaemic strokes had 41 embolic (29.7%) and 97 thrombotic (70.3%) origin, and these were not statistically significant in comparison with controls. Cortical involvement for the development of seizures was the most important risk factor (odds ratios = 4.25, p < 0.01). It was concluded that embolic strokes, being younger than 65 years old, and cortical localisation of stroke were important risks for developing seizures.

The effectiveness of reinforced feedback in virtual environment in the first 12 months after stroke.

PubMed

Kiper, Paweł; Piron, Lamberto; Turolla, Andrea; Stożek, Joanna; Tonin, Paolo

2011-01-01

Reinforced feedback in virtual environment (RFVE) therapy is emerging as an innovative method in rehabilitation, which may be advantageous in the treatment of the affected arm after stroke. The purpose of this study was to investigate the impact of assisted motor training in a virtual environment for the treatment of the upper extremity (UE) after stroke compared to traditional neuromotor rehabilitation (TNR), studying also if differences exist related to the type of stroke (haemorrhagic or ischaemic). Eighty patients affected by a stroke (48 ischaemic and 32 haemorrhagic) that occurred at least 1 year before were enrolled. The clinical assessment comprising the Fugl-Meyer UE (F-M UE), modified Ashworth (Bohannon and Smith) and Functional Independence Measure scale (FIM) was administered before and after the treatment. A statistically significant difference between RFVE and TNR groups (Mann-Whitney U-test) was observed in the clinical outcomes of F-M UE and FIM (both p < 0.001), but not Ashworth (p = 0.053). The outcomes of F-M UE and FIM improved in the RFVE haemorrhagic group and in the TNR haemorrhagic group with a significant difference between groups (both p < 0.001), but not for Ashworth (p = 0.651). Comparing the RFVE ischaemic group to the TNR ischaemic group, statistically significant differences emerged in F-M UE (p < 0.001), FIM (p < 0.001), and Ashworth (p = 0.036). The RFVE therapy in combination with TNR showed better improvements compared to the TNR treatment only. The RFVE therapy combined with the TNR treatment was more effective than the TNR double training, in both post-ischaemic and post-haemorrhagic groups. We observed improvements in both groups of patients: post-haemorrhagic and post-ischaemic stroke after RFVE training.

Has the aetiology of ischaemic stroke changed in the past decades? Analysis and comparison of data from current and historical stroke databases.

PubMed

Sánchez-Larsen, Á; García-García, J; Ayo-Martín, O; Hernández-Fernández, F; Díaz-Maroto, I; Fernández-Díaz, E; Monteagudo, M; Segura, T

2016-09-16

We aimed to determine whether the aetiology of ischaemic stroke has changed in recent years and, if so, to ascertain the possible reasons for these changes. We analysed the epidemiological history and vascular risk factors of all patients diagnosed with ischaemic stroke at Complejo Hospitalario Universitario de Albacete (CHUA) from 2009 to 2014. Ischaemic stroke subtypes were established using the TOAST criteria. Our results were compared to data from the classic Stroke Data Bank (SDB); in addition, both series were compared to those of other hospital databases covering the period between the two. We analysed 1664 patients (58% were men) with a mean age of 74 years. Stroke aetiology in both series (CHUA, SDB) was as follows: atherosclerosis (12%, 9%), small-vessel occlusion (13%, 25%), cardioembolism (32%, 19%), stroke of other determined aetiology (3%, 4%), and stroke of undetermined aetiology (40%, 44%). Sixty-three percent of the patients from the CHUA and 42% of the patients from the SDB were older than 70 years. Cardioembolic strokes were more prevalent in patients older than 70 years in both series. Untreated hypertension was more frequent in the SDB (SDB = 31% vs CHUA = 10%). The analysis of other databases shows that the prevalence of cardioembolic stroke is increasing worldwide. Our data show that the prevalence of lacunar strokes is decreasing worldwide whereas cardioembolic strokes are increasingly more frequent in both our hospital and other series compared to the SDB. These differences may be explained by population ageing and the improvements in management of hypertension and detection of cardioembolic arrhythmias in stroke units. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with worse functional outcome of ischaemic stroke.

PubMed

Malueka, Rusdy Ghazali; Dwianingsih, Ery Kus; Sutarni, Sri; Bawono, Rheza Gandi; Bayuangga, Halwan Fuad; Gofir, Abdul; Setyopranoto, Ismail

2017-12-29

Insertion/deletion polymorphism in ACE gene (ACE I/D) is known to be associated with the occurrence of ischaemic stroke through its effect on pathogenesis of atherosclerosis and hypertension. This study was aimed to examine the association between this polymorphism with functional outcome of ischaemic stroke. This was a cross-sectional study. The subjects were patients with ischaemic stroke in a reference hospital in Yogyakarta, Indonesia. Data on demographic characteristics, stroke risk factors, comorbidities and stroke severity were assessed on admission. The functional outcome, Barthel index (BI), was assessed when the patients were discharged from the hospital. ACE I/D genotypes of the patients were identified by polymerase chain reaction (PCR). In total, 61 patients were included. Of these, 38 patients (62.3%) had II polymorphism, 22 patients (36.1%) had ID polymorphism and 1 patient (1.6%) had DD polymorphism in the ACE gene. There were significant differences in the functional outcomes between patients without D allele (II polymorphisms) and patients with D allele (ID and DD polymorphism) (mean BI on discharge: 75 ± 23.57 and 60.65 ± 27.15, respectively; p = 0.034). Multiple linear regression model showed that the availability of D allele is an independent variable negatively associated with functional outcome as assessed by BI (β = -0.232, p = 0.024). This study showed that the D allele in ACE I/D polymorphism is associated with worse functional outcomes. This highlights the possibility of further research to improve functional outcomes of ischaemic stroke by inhibiting the ACE system.

Audit report and systematic review of orolingual angioedema in post-acute stroke thrombolysis.

PubMed

Lekoubou, Alain; Philippeau, Frédéric; Derex, Laurent; Olaru, Angel; Gouttard, Michel; Vieillart, Anne; Kengne, Andre Pascal

2014-07-01

Post-intravenous recombinant tissue plasminogen activator (r-tPA) orolingual angioedema (PIROLA), including the life-threatening form, is an underappreciated complication of ischaemic stroke treatment. We present an audit report and a systematic review of published observational studies on PIROLA occurrence in acute ischaemic stroke patients. Clinical files of patients treated in the stroke unit of Bourg-en-Bresse General Hospital (France) from January 2010 to December 2012 were reviewed, and MEDLINE (inception to May 2013) were searched and bibliographies/citations of retrieved articles examined for evidence of PIROLA. Of the 129 acute ischaemic stroke patients treated at Bourg-en-Bresse between 2010 and 2012, four patients, all receiving angiotensin converting enzyme inhibitor (ACEI), developed a PIROLA (cumulative incidence rate: 32‰). The complication started within an hour of receiving r-tPA and integrally resolved within 3-24 hours, with antihistamines/steroid treatment in two patients. The systematic review identified 27 studies, totalising with ours, over 9050 acute ischaemic stroke patients from 12 countries, among whom 100 (cumulative incidence rate: 17‰; 95% confidence intervals: 8-26), developed a PIROLA within 6-240 minutes of receiving r-tPA, 0-100% of them occurring among patients on ACEI. The complication was contralateral to the stroke location in 47% cases, ipsilateral in 14%, and bilateral in 39%; and resolved within 24 hours with treatment in 90%. No related death was recorded. About 17‰ acute ischaemic stroke patients receiving r-tPA develop PIROLA, occurring essentially among those on concomitant ACEI. PIROLA occurrence should be actively monitored, particularly within the first few hours as some may require urgent lifesaving procedures.

Polygenic overlap between kidney function and large artery atherosclerotic stroke

PubMed Central

Holliday, Elizabeth G.; Traylor, Matthew; Malik, Rainer; Bevan, Stephen; Maguire, Jane; Koblar, Simon A.; Sturm, Jonathan; Hankey, Graeme J.; Oldmeadow, Christopher; McEvoy, Mark; Sudlow, Cathie; Rothwell, Peter M.; Coresh, Josef; Hamet, Pavel; Tremblay, Johanne; Turner, Stephen T.; de Andrade, Mariza; Rao, Madhumathi; Schmidt, Reinhold; Crick, Peter A.; Robino, Antonietta; Peralta, Carmen A.; Jukema, J. Wouter; Mitchell, Paul; Rosas, Sylvia E.; Wang, Jie Jin; Scott, Rodney J.; Dichgans, Martin; Mitchell, Braxton D.; Linda Kao, W. H.; Fox, Caroline S.; Levi, Christopher; Attia, John; Markus, Hugh S

2014-01-01

Background and Purpose Epidemiological studies show strong associations between kidney dysfunction and risk of ischaemic stroke, the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability due to a common polygenic basis and whether this differed for ischaemic stroke subtypes. Methods Polygenic models were derived using GWAS meta-analysis results for three kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: N=73,998), eGFR using cystatin C (eGFRcys: N=22,937) and urinary albumin to creatinine ratio (UACR: N=31,580). For each, SNPs passing ten P-value thresholds were used to form profile scores in 4,561 ischaemic stroke cases and 7,094 controls from the UK, Germany and Australia. Scores were tested for association with ischaemic stroke and its three aetiological subtypes: large artery atherosclerosis (LAA), cardioembolism (CE) and small vessel disease (SVD). Results Polygenic scores correlating with higher eGFRcrea were associated with reduced risk of LAA, with five scores reaching P<0.05 (peak P=0.004) and all showing the epidemiologically expected direction of effect. A similar pattern was observed for polygenic scores reflecting higher UACR, of which three associated with LAA (peak P=0.01) and all showed the expected directional association. One UACR-based score also associated with SVD (P=0.03). The global pattern of results was unlikely to have occurred by chance (P=0.02). Conclusions This study suggests possible polygenic correlation between renal dysfunction and ischaemic stroke. The shared genetic components may be specific to stroke subtypes, particularly large artery atherosclerotic stroke. Further study of the genetic relationships between these disorders appears merited. PMID:25352485

The Sigma-1 Receptor Antagonist, S1RA, Reduces Stroke Damage, Ameliorates Post-Stroke Neurological Deficits and Suppresses the Overexpression of MMP-9.

PubMed

Sánchez-Blázquez, Pilar; Pozo-Rodrigálvarez, Andrea; Merlos, Manuel; Garzón, Javier

2018-06-01

The glutamate N-methyl-D-aspartate receptor (NMDAR) plays an essential role in the excitotoxic neural damage that follows ischaemic stroke. Because the sigma-1 receptor (σ1R) can regulate NMDAR transmission, exogenous and putative endogenous regulators of σ1R have been investigated using animal models of ischaemic stroke. As both agonists and antagonists provide some neural protection, the selective involvement of σ1Rs in these effects has been questioned. The availability of S1RA (E-52862/MR309), a highly selective σ1R antagonist, prompted us to explore its therapeutic potential in an animal model of focal cerebral ischaemia. Mice were subjected to right middle cerebral artery occlusion (MCAO), and post-ischaemic infarct volume and neurological deficits were determined across a range of intervals after the stroke-inducing surgery. Intracerebroventricular or intravenous treatment with S1RA significantly reduced the cerebral infarct size and neurological deficits caused by permanent MCAO (pMCAO). Compared with the control/sham-operated mice, the neuroprotective effects of S1RA were observed when delivered up to 5 h prior to surgery and 3 h after ischaemic onset. Interestingly, neither mice with the genetic deletion of σ1R nor wild-type mice that were pre-treated with the σ1R agonist PRE084 showed beneficial effects after S1RA administration with regard to stroke infarction. S1RA-treated mice showed faster behavioural recovery from stroke; this finding complements the significant decreases in matrix metalloproteinase-9 (MMP-9) expression and reactive astrogliosis surrounding the infarcted cortex. Our data indicate that S1RA, via σ1R, holds promising potential for clinical application as a therapeutic agent for ischaemic stroke.

Platelet morphology, soluble P selectin and platelet P-selectin in acute ischaemic stroke. The West Birmingham Stroke Project.

PubMed

Nadar, Sunil K; Lip, Gregory Y H; Blann, Andrew D

2004-12-01

The pathophysiology of ischaemic stroke involves the platelet. In this study, we hypothesised that abnormalities in platelet morphology, as well as soluble (sPsel) and total platelet P-selectin (pPsel) levels would be present in patients presenting with an acute ischaemic stroke, and that these changes would improve at > or = 3 months' follow-up. We studied 59 hypertensive patients (34 male; mean age 68 +/- 12 years) who presented with an acute ischaemic stroke (ictus < 24 hours), and compared them with 2 groups: (i) age-, sex- and ethnic- origin matched normotensive healthy controls; and (ii) uncomplicated 'high risk' hypertensive patients as 'risk factor control' subjects. Platelet morphology (volume and mass) was quantified, and sPsel (plasma marker of platelet activation) was measured (ELISA) in citrated plasma. The mass of P-selectin in each platelet (pPsel) was determined by lysing a fixed number of platelets and then determining the levels of P-selectin in the lysate. Results show that patients who presented with a stroke had significantly higher levels of sPsel and pPsel (both p < 0.001), compared to the normal controls and the hypertensive patients. Patients with an acute stroke had lower mean platelet mass (MPM) and mean platelet volume (MPV) as compared to the uncomplicated hypertensive patients, who had significantly higher mean MPM and MPV values, as compared to normal controls. On follow-up, the levels of both sPsel (p = 0.011), pPsel (< 0.001) and MPV (p = 0.03) were significantly lower. Mean MPM levels remained unchanged. We conclude that patients presenting with an acute ischaemic stroke have activated platelets, as evident by the increased levels of soluble and platelet P-selectin. Further study of platelet activation and the role of P-selectin is warranted.

Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.

PubMed

2016-02-01

The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes. To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16 851 cases with state-of-the-art phenotyping data and 32 473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20 941 cases and 364 736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis. We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50 × 10 -8 ; joint OR 1·19, 1·12-1·26, p=1·30 × 10 -9 ). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26 × 10 -19 ; joint OR 1·37, 1·30-1·45, p=2·79 × 10 -32 ) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93 × 10 -7 ; joint OR 1·17, 1·11-1·23, p=2·29 × 10 -10 ) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50 × 10 -8 ; joint OR 1·24, 1·15-1·33, p=4·52 × 10 -9 ) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82 × 10 -8 ; joint OR 1·17, 1·11-1·23, p=2·92 × 10 -9 ). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed. Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke. US National Institute of Neurological Disorders and Stroke, National Institutes of Health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Guidelines for the preventive treatment of ischaemic stroke and TIA (I). Update on risk factors and life style.

PubMed

Fuentes, B; Gállego, J; Gil-Nuñez, A; Morales, A; Purroy, F; Roquer, J; Segura, T; Tejada, J; Lago, A; Díez-Tejedor, E; Alonso de Leciñana, M; Alvarez-Sabin, J; Arenillas, J; Calleja, S; Casado, I; Castellanos, M; Castillo, J; Dávalos, A; Díaz-Otero, F; Egido, J A; López-Fernández, J C; Freijo, M; García Pastor, A; Gilo, F; Irimia, P; Maestre, J; Masjuan, J; Martí-Fábregas, J; Martínez-Sánchez, P; Martínez-Vila, E; Molina, C; Nombela, F; Ribó, M; Rodríguez-Yañez, M; Rubio, F; Serena, J; Simal, P; Vivancos, J

2012-01-01

To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischaemic stroke (IS) and transient ischaemic attack (TIA). We reviewed available evidence on risk factors and means of modifying them to prevent ischaemic stroke and TIA. Levels of evidence and recommendation grades are based on the classification of the Centre for Evidence-Based Medicine. This first section summarises the recommendations for action on the following factors: blood pressure, diabetes, lipids, tobacco and alcohol consumption, diet and physical activity, cardio-embolic diseases, asymptomatic carotid stenosis, hormone replacement therapy and contraceptives, hyperhomocysteinemia, prothrombotic states and sleep apnea syndrome. Changes in lifestyle and pharmacological treatment for hypertension, diabetes mellitus and dyslipidemia, according to criteria of primary and secondary prevention, are recommended for preventing ischemic stroke. © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Design and rationale of the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) Trial.

PubMed

Kidwell, Chelsea S; Jahan, Reza; Alger, Jeffry R; Schaewe, Timothy J; Guzy, Judy; Starkman, Sidney; Elashoff, Robert; Gornbein, Jeffrey; Nenov, Val; Saver, Jeffrey L

2014-01-01

Multimodal imaging has the potential to identify acute ischaemic stroke patients most likely to benefit from late recanalization therapies. The general aim of the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy Trial is to investigate whether multimodal imaging can identify patients who will benefit substantially from mechanical embolectomy for the treatment of acute ischaemic stroke up to eight-hours from symptom onset. Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy is a randomized, controlled, blinded-outcome clinical trial. Acute ischaemic stroke patients with large vessel intracranial internal carotid artery or middle cerebral artery M1 or M2 occlusion enrolled within eight-hours of symptom onset are eligible. The study sample size is 120 patients. Patients are randomized to endovascular embolectomy employing the Merci Retriever (Concentric Medical, Mountain View, CA) or the Penumbra System (Penumbra, Alameda, CA) vs. standard medical care, with randomization stratified by penumbral pattern. The primary aim of the trial is to test the hypothesis that the presence of substantial ischaemic penumbral tissue visualized on multimodal imaging (magnetic resonance imaging or computed tomography) predicts patients most likely to respond to mechanical embolectomy for treatment of acute ischaemic stroke due to a large vessel, intracranial occlusion up to eight-hours from symptom onset. This hypothesis will be tested by analysing whether pretreatment imaging pattern has a significant interaction with treatment as a determinant of functional outcome based on the distribution of scores on the modified Rankin Scale measure of global disability assessed 90 days post-stroke. Nested hypotheses test for (1) treatment efficacy in patients with a penumbral pattern pretreatment, and (2) absence of treatment benefit (equivalency) in patients without a penumbral pattern pretreatment. An additional aim will only be tested if the primary hypothesis of an interaction is negative: that patients treated with mechanical embolectomy have improved functional outcome vs. standard medical management. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Vinpocetine for acute ischaemic stroke.

PubMed

Bereczki, D; Fekete, I

2008-01-23

Vasoactive and neuroprotective drugs such as vinpocetine are used to treat stroke in some countries. To assess the effect of vinpocetine in acute ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched February 2007), MEDLINE (1966 to February 2007) and Scopus (1960 to February 2007). We also searched the Internet Stroke Center Stroke Trials Registry, Google Scholar, the science-specific search engine Scirus and Wanfang Data, the leading information provider in China. We contacted researchers in the field and four pharmaceutical companies that manufacture vinpocetine. Searches were complete to February 2007. Unconfounded randomised trials of vinpocetine compared with placebo, or any other reference treatment, in people with acute ischaemic stroke. We included trials if treatment started no later than 14 days after stroke onset. Two review authors independently applied the inclusion criteria. One review author extracted the data, which was then checked by the second review author. We assessed trial quality. The primary outcome measure was death or dependency. We included two trials, involving a total of 70 participants. Data for 63 participants were reported in the two trials combined. The rate of death or dependency did not differ between the treatment and placebo groups at one and three months. The 95% confidence intervals for the outcome measures were wide and included the possibility of both significant benefit and significant harm. No adverse effects were reported. There is not enough evidence to evaluate the effect of vinpocetine on survival or dependency in patients with acute ischaemic stroke.

Sociodemographic factors are associated with utilisation of statins after ischaemic stroke/TIA.

PubMed

Geary, Lukas; Aronius, Jonas; Wettermark, Björn; Hasselström, Jan; Sjöborg, Bengt; von Euler, Mia

2017-03-01

To analyse if there are sociodemographic differences in the utilisation of statins 9-12 months after ischaemic stroke or transitory ischaemic attack. Anonymised linkage of registry data on all patients >18 years discharged from the hospitals in Stockholm, Sweden 2006-2010 with diagnosis of ischaemic stroke (ICD-10: I63.0-9) or TIA (ICD-10: G45.9) was performed. Data on hospitalisations and diagnoses were collected from the Stockholm County Council administrative databases on healthcare consumption. Dispensed prescriptions with statins and, for comparative purposes, antihypertensive agents 9-12 months after discharge were acquired from the National Swedish Prescribed Drug Register. Data about socioeconomic factors were obtained from Statistics Sweden. The dispensing of statins and antihypertensive agents, relative to sociodemographic variables were analysed. Using logistic regression odds ratios, crude, and adjusted with education, income, origin of birth, age, and sex as predictors where calculated. Of 24 312 patients with ischaemic stroke/TIA, 19 335 were alive 12 months after discharge. Statins were dispensed to 44% of all patients in the cohort, more frequently to men of all age groups, to patients with higher education, and to those with higher income. Antihypertensive agents were dispensed to 68% of all patients and there were no differences related to sex and income whilst patients with lower education were dispensed with antihypertensives more frequently. We find a low utilisation of statins one year after ischaemic stroke/TIA. Patients with low education, low income, and female sex were dispensed fewer prescriptions of statins indicating a need for improvement. © 2017 John Wiley & Sons Ltd.

Control of main risk factors after ischaemic stroke across Europe: data from the stroke-specific module of the EUROASPIRE III survey.

PubMed

Heuschmann, Peter U; Kircher, Julia; Nowe, Tim; Dittrich, Ralf; Reiner, Zeljko; Cifkova, Renata; Malojcic, Branko; Mayer, Otto; Bruthans, Jan; Wloch-Kopec, Dorota; Prugger, Christof; Heidrich, Jan; Keil, Ulrich

2015-10-01

Previous cross-sectional surveys in different European countries within the EUROASPIRE programme demonstrated a high prevalence of modifiable risk factors, unhealthy lifestyles and inadequate drug treatment in coronary heart disease patients. Comparable data for ischaemic stroke patients is lacking. A stroke-specific study module was added to the EUROASPIRE III core survey. This cross-sectional multicentre survey included consecutive patients with first-ever ischaemic stroke from four European countries. Data were obtained from medical records, patient interviews and patient examinations within 6-36 months after the stroke event. Control of modifiable risk factors after stroke was evaluated against contemporary European guidelines. A total of 881 patients was recruited. Median age was 66 years, 37.5% were female; average time from the stroke event to interview was 550 days. At the time of the interview, 17.6% of stroke patients smoked cigarettes, 35.5% had a body mass index ≥30 kg/m(2), 62.4% showed elevated blood pressure and 75.7% exhibited elevated LDL cholesterol levels. Antiplatelet drugs or oral anticoagulants were used by 87.2%, antihypertensive medication by 84.4% and statins by 56.8% of stroke patients. Among patients using antihypertensive drugs and lipid-lowering medication at the time of the interview, 34.3% and 34.4%, respectively, achieved target blood pressure and total cholesterol values according to current European guidelines. The EUROASPIRE III stroke-specific module shows that secondary prevention and risk factor control in patients after ischaemic stroke need to be improved in four European centres at the time of the study since about half of patients are not achieving risk factor targets defined in European guidelines. © The European Society of Cardiology 2014.

The Course and Outcome of Unilateral Intracranial Arteriopathy in 79 Children with Ischaemic Stroke

ERIC Educational Resources Information Center

Braun, K. P. J.; Bulder, M. M. M.; Chabrier, S.; Kirkham, F. J.; Uiterwaal, C. S. P.; Tardieu, M.; Sebire, G.

2009-01-01

Arteriopathies are the commonest cause of arterial ischaemic stroke (AIS) in children. Repeated vascular imaging in children with AIS demonstrated the existence of a "transient cerebral arteriopathy" (TCA), characterized by lenticulostriate infarction due to non-progressive unilateral arterial disease affecting the supraclinoid internal…

National use of thrombolysis with alteplase for acute ischaemic stroke via telemedicine in Denmark: a model of budgetary impact and cost effectiveness.

PubMed

Ehlers, Lars; Müskens, Wilhelmina Maria; Jensen, Lotte Groth; Kjølby, Mette; Andersen, Grethe

2008-01-01

The purpose of this analysis was to assess the budgetary impact and cost effectiveness of the national use of thrombolysis with alteplase (recombinant tissue plasminogen activator; rt-PA) for acute ischaemic stroke via telemedicine in Denmark. Computations were based on a Danish health economic model of thrombolysis treatment of acute ischaemic stroke via telemedicine. Cost data for stroke units and satellite clinics were taken from the first practical experiences in Denmark with implementing thrombolysis via telemedical linkage to the Stroke Department at Aarhus University Hospital. Effectiveness data were taken from a published pooled analysis of results from randomized controlled trials of alteplase. The calculations showed that the additional total costs to the hospitals of implementing thrombolysis with alteplase for acute ischaemic stroke via telemedicine were approximately $US3.0 (range 2.0-5.8) million per year in the case of five centres and five satellite clinics, or $US3.6 (range 2.4-7.0) million per year based on seven centres and seven satellite clinics. The incremental cost-effectiveness ratio was calculated to be approximately $US50,000 when taking a short time perspective (1 year), but thrombolysis was dominant (both cheaper and more effective) after as little as 2 years and cost effectiveness improved over longer time scales. The budgetary impact of using thrombolysis with alteplase for acute ischaemic stroke via telemedicine depends on the existing capacity and organizational conditions at the local hospitals. The health economic model computations suggest that the macroeconomic costs may balance with savings in care and rehabilitation after as little as 2 years, and that potentially large long-term savings are associated with thrombolysis with alteplase delivered by telemedicine, although the long-term calculations are uncertain.

Nox2 Knockout Delays Infarct Progression and Increases Vascular Recovery through Angiogenesis in Mice following Ischaemic Stroke with Reperfusion

PubMed Central

McCann, Sarah K.; Dusting, Gregory J.; Roulston, Carli L.

2014-01-01

Evidence suggests the NADPH oxidases contribute to ischaemic stroke injury and Nox2 is the most widely studied subtype in the context of stroke. There is still conjecture however regarding the benefits of inhibiting Nox2 to improve stroke outcome. The current study aimed to examine the temporal effects of genetic Nox2 deletion on neuronal loss after ischaemic stroke using knockout (KO) mice with 6, 24 and 72 hour recovery. Transient cerebral ischaemia was induced via intraluminal filament occlusion and resulted in reduced infarct volumes in Nox2 KO mice at 24 h post-stroke compared to wild-type controls. No protection was evident at either 6 h or 72 h post-stroke, with both genotypes exhibiting similar volumes of damage. Reactive oxygen species were detected using dihydroethidium and were co-localised with neurons and microglia in both genotypes using immunofluorescent double-labelling. The effect of Nox2 deletion on vascular damage and recovery was also examined 24 h and 72 h post-stroke using an antibody against laminin. Blood vessel density was decreased in the ischaemic core of both genotypes 24 h post-stroke and returned to pre-stroke levels only in Nox2 KO mice by 72 h. Overall, these results are the first to show that genetic Nox2 deletion merely delays the progression of neuronal loss after stroke but does not prevent it. Additionally, we show for the first time that Nox2 deletion increases re-vascularisation of the damaged brain by 72 h, which may be important in promoting endogenous brain repair mechanisms that rely on re-vascularisation. PMID:25375101

Prediabetes is associated with post-stroke cognitive impairment in ischaemic stroke patients.

PubMed

Wang, Qiongzhang; Zhao, Kai; Cai, Yan; Tu, Xinjie; Liu, Yuntao; He, Jincai

2018-05-15

Diabetes mellitus is associated with post-stroke cognitive impairment. To the best of our knowledge, no study has explored the relationship between prediabetes and post-stroke cognitive impairment. The purpose of this study is to explore the association between prediabetes and cognitive impairment in ischaemic stroke patients at 1 month. Two hundred one acute ischaemic stroke patients were consecutively recruited within the first 24 h after admission and were followed up for 1 month. Patients were divided into a diabetes mellitus group, prediabetes group and non-diabetes mellitus group by fasting glucose levels, 2-h postprandial blood glucose levels and glycosylated haemoglobin levels at admission. Cognitive function was evaluated by the Mini-Mental State Examination at 1 month after stroke. The prediabetes group had a higher risk of post-stroke cognitive impairment than the non-diabetes group (35.7% vs. 18.1%, χ 2  = 4.252, P = .039). In logistical analyses, prediabetes was associated with post-stroke cognitive impairment after adjusting for potential confounding factors (odds ratio 3.062, 95% confidence interval 1.130-8.299, P = .028). Our findings show that prediabetes is associated with post-stroke cognitive impairment and may predict its development at 1 month post-stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Antiplatelet regimens in the long-term secondary prevention of transient ischaemic attack and ischaemic stroke: an updated network meta-analysis

PubMed Central

Niu, Peng-Peng; Guo, Zhen-Ni; Jin, Hang; Xing, Ying-Qi; Yang, Yi

2016-01-01

Objective To examine the comparative efficacy and safety of different antiplatelet regimens in patients with prior non-cardioembolic ischaemic stroke or transient ischaemic attack. Design Systematic review and network meta-analysis. Data sources As on 31 March 2015, all randomised controlled trials that investigated the effects of antiplatelet agents in the long-term (≥3 months) secondary prevention of non-cardioembolic transient ischaemic attack or ischaemic stroke were searched and identified. Outcome measures The primary outcome measure of efficacy was serious vascular events (non-fatal stroke, non-fatal myocardial infarction and vascular death). The outcome measure of safety was any bleeding. Results A total of 36 randomised controlled trials (82 144 patients) were included. Network meta-analysis showed that cilostazol was significantly more effective than clopidogrel (OR 0.77, 95% credible interval 0.60–0.98) and low-dose (75–162 mg daily) aspirin (0.69, 0.55–0.86) in the prevention of serious vascular events. Aspirin (50 mg daily) plus dipyridamole (400 mg daily) and clopidogrel reduced the risk of serious vascular events compared with low-dose aspirin; however, the difference was not statistically significant. Furthermore, low-dose aspirin was as effective as higher daily doses. Cilostazol was associated with a significantly lower bleeding risk than most of the other regimens. Moreover, aspirin plus clopidogrel was associated with significantly more haemorrhagic events than other regimens. Direct comparisons showed similar results as the network meta-analysis. Conclusions Cilostazol was significantly more effective than aspirin and clopidogrel alone in the long-term prevention of serious vascular events in patients with prior non-cardioembolic ischaemic stroke or transient ischaemic attack. Cilostazol was associated with a significantly lower bleeding risk than low-dose aspirin (75–162 mg daily) and aspirin (50 mg daily) plus dipyridamole (400 mg daily). Low-dose aspirin was as effective as higher daily doses. However, further large, randomised, controlled, head-to-head trials are needed, especially in non-Asian ethnic groups. PMID:26988347

Post-ischaemic administration of the murine Canakinumab-surrogate antibody improves outcome in experimental stroke.

PubMed

Liberale, Luca; Diaz-Cañestro, Candela; Bonetti, Nicole R; Paneni, Francesco; Akhmedov, Alexander; Beer, Jürg H; Montecucco, Fabrizio; Lüscher, Thomas F; Camici, Giovanni G

2018-05-16

The CANTOS trial underscored the efficacy of selective antibody-based interleukin (IL)-1β inhibition with Canakinumab in secondary prevention of cardiovascular events. Despite the success of the trial, incidence of stroke was not reduced likely due to the low number of events and the relatively young age of patients enrolled. Given the established role of IL-1β in stroke, we tested the efficacy of the murine Canakinumab-equivalent antibody in a mouse model of ischaemic stroke. To mimic the clinical scenario of modern stroke management, IL-1β inhibition was performed post-ischaemically upon reperfusion as it would be the case in patients presenting to the emergency room and eligible for thrombolytic therapy. Transient middle cerebral artery occlusion (tMCAO) was performed in wild type mice; upon reperfusion, mice were randomly allocated to anti-IL-1β antibody or vehicle treatment. Following tMCAO, cerebral IL-1β levels, unlike tumour necrosis factor-α, were increased underscoring a role for this cytokine. Post-ischaemic treatment with IL-1β antibody reduced infarct size, cerebral oedema and improved neurological performance as assessed by 2,3,5-triphenyltetrazolium chloride staining, Bederson and RotaRod tests. Antibody-treated animals also exhibited a reduced neutrophil and matrix metalloproteinase (MMP)-2 but not MMP-9, activity in ipsilateral hemispheres as compared to vehicle-treated mice. Noteworthy, tMCAO associated vascular endothelial-cadherin reduction was blunted in IL-1β antibody-treated mice compared to vehicle-treated, likely providing the mechanistic explanation for the improved outcome. Our data for the first time demonstrate the efficacy of selective post-ischaemic IL-1β blockade in improving outcome following experimental ischaemia/reperfusion brain injury in the mouse and encourage further focused clinical studies assessing the potential of the approved IL-1β antibody Canakinumab, as an adjuvant therapy to thrombolysis in acute ischaemic stroke patients.

Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

PubMed

Mao, Leilei; Li, Peiying; Zhu, Wen; Cai, Wei; Liu, Zongjian; Wang, Yanling; Luo, Wenli; Stetler, Ruth A; Leak, Rehana K; Yu, Weifeng; Gao, Yanqin; Chen, Jun; Chen, Gang; Hu, Xiaoming

2017-07-01

Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic studies demonstrated that regulatory T cells completely abolished the tPA-induced elevation of MMP9 and CCL2 after stroke. Using MMP9 and CCL2 knockout mice, we discovered that both molecules partially contributed to the protective actions of regulatory T cells. In an in vitro endothelial cell-based model of the blood-brain barrier, we confirmed that regulatory T cells inhibited tPA-induced endothelial expression of CCL2 and preserved blood-brain barrier integrity after an ischaemic challenge. Lentivirus-mediated CCL2 knockdown in endothelial cells completely abolished the blood-brain barrier protective effect of regulatory T cells in vitro. Altogether, our studies suggest that regulatory T cell adoptive transfer may alleviate thrombolytic treatment-induced haemorrhage in stroke victims. Furthermore, regulatory T cell-afforded protection in the tPA-treated stroke model is mediated by two inhibitory mechanisms involving CCL2 and MMP9. Thus, regulatory T cell adoptive transfer may be useful as a cell-based therapy to improve the efficacy and safety of thrombolytic treatment for ischaemic stroke. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Relation between troponin T concentration and mortality in patients presenting with an acute stroke: observational study

PubMed Central

James, P; Ellis, C J; Whitlock, R M L; McNeil, A R; Henley, J; Anderson, N E

2000-01-01

Objective To assess whether a raised serum troponin T concentration would be an independent predictor of death in patients with an acute ischaemic stroke. Design Observational study. Setting Auckland Hospital, Auckland, New Zealand. Subjects All 181 patients with an acute ischaemic stroke admitted over nine months in 1997-8, from a total of 8057 patients admitted to the acute medical service. Main outcome measures Blood samples for measuring troponin T concentration were collected 12-72 hours after admission; other variables previously associated with severity of stroke were also recorded and assessed as independent predictors of inpatient mortality. Results Troponin T concentration was raised (>0.1 μg/l) in 17% (30) of patients admitted with an acute ischaemic stroke. Thirty one patients died in hospital (12/30 (40%) patients with a raised troponin T concentration v 19/151 (13%) patients with a normal concentration (relative risk 3.2 (95% confidence 1.7 to 5.8; P=0.0025)). Of 17 possible predictors of death, assessed in a multivariate stepwise model, only a raised troponin T concentration (P=0.0002), age (P=0.0008), and an altered level of consciousness at presentation (P=0.0074) independently predicted an adverse outcome. Conclusions Serum troponin T concentration at hospital admission is a powerful predictor of mortality in patients admitted with an acute ischaemic stroke. PMID:10834890

Severe ipsilateral carotid stenosis and middle cerebral artery disease in lacunar ischaemic stroke: innocent bystanders?

PubMed

Mead, G E; Lewis, S C; Wardlaw, J M; Dennis, M S; Warlow, C P

2002-03-01

Lacunar infarcts are thought to be mostly due to intracranial small vessel disease. Therefore, when a stroke patient with a relevant lacunar infarct does have severe ipsilateral internal carotid artery (ICA) or middle cerebral artery (MCA) disease, it is unclear whether the arterial disease is causative or coincidental. If causative, we would expect ICA/MCA disease to be more severe on the symptomatic side than on the asymptomatic side. Therefore, our aim was to compare the severity of ipsilateral with contralateral ICA and MCA disease in patients with lacunar ischaemic stroke. We studied 259 inpatients and outpatients with a recent lacunar ischaemic stroke and no other prior stroke. We used carotid Duplex ultrasound and transcranial Doppler (TCD) ultrasound to identify ICA and MCA disease, and compared our results with previously published data. In our study, there was no difference between the severity of ipsilateral and contralateral ICA stenosis within individuals (median difference 0%, Wilcoxon paired data p=0.24, comparing severity of ipsilateral and contralateral stenosis). The overall prevalence of severe ipsilateral stenosis was 5%, and the prevalence of severe contralateral stenosis was 4% (OR 1.6, 95% CI 0.6, 4.8). There was no difference in the prevalence of ipsilateral and contralateral MCA disease. A systematic review of the other available studies strengthened this conclusion. Carotid stenosis in patients with a lacunar ischaemic stroke may be coincidental. Further studies are required to elucidate the causes of lacunar stroke, and to evaluate the role of carotid endarterectomy.

Air pollution and the incidence of ischaemic and haemorrhagic stroke in the South London Stroke Register: a case-cross-over analysis.

PubMed

Butland, B K; Atkinson, R W; Crichton, S; Barratt, B; Beevers, S; Spiridou, A; Hoang, U; Kelly, F J; Wolfe, C D

2017-07-01

Few European studies investigating associations between short-term exposure to air pollution and incident stroke have considered stroke subtypes. Using information from the South London Stroke Register for 2005-2012, we investigated associations between daily concentrations of gaseous and particulate air pollutants and incident stroke subtypes in an ethnically diverse area of London, UK. Modelled daily pollutant concentrations based on a combination of measurements and dispersion modelling were linked at postcode level to incident stroke events stratified by haemorrhagic and ischaemic subtypes. The data were analysed using a time-stratified case-cross-over approach. Conditional logistic regression models included natural cubic splines for daily mean temperature and daily mean relative humidity, a binary term for public holidays and a sine-cosine annual cycle. Of primary interest were same day mean concentrations of particulate matter <2.5 and <10 µm in diameter (PM 2.5 , PM 10 ), ozone (O 3 ), nitrogen dioxide (NO 2 ) and NO 2 +nitrogen oxide (NO X ). Our analysis was based on 1758 incident strokes (1311 were ischaemic and 256 were haemorrhagic). We found no evidence of an association between all stroke or ischaemic stroke and same day exposure to PM 2.5 , PM 10 , O 3 , NO 2 or NO X . For haemorrhagic stroke, we found a negative association with PM 10 suggestive of a 14.6% (95% CI 0.7% to 26.5%) fall in risk per 10 µg/m 3 increase in pollutant. Using data from the South London Stroke Register, we found no evidence of a positive association between outdoor air pollution and incident stroke or its subtypes. These results, though in contrast to recent meta-analyses, are not inconsistent with the mixed findings of other UK studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Epilepsy in Hemiplegic Cerebral Palsy Due to Perinatal Arterial Ischaemic Stroke

ERIC Educational Resources Information Center

Wanigasinghe, Jithangi; Reid, Susan M.; Mackay, Mark T.; Reddihough, Dinah S.; Harvey, A. Simon; Freeman, Jeremy L.

2010-01-01

Aim: The aim of this study was to describe the frequency, risk factors, manifestations, and outcome of epilepsy in children with hemiplegic cerebral palsy (CP) due to perinatal arterial ischaemic stroke (AIS). Method: The study group comprised 63 participants (41 males, 22 females) from a population-based CP register whose brain imaging showed…

Antiepileptic drugs and the risk of ischaemic stroke and myocardial infarction: a population-based cohort study

PubMed Central

Renoux, Christel; Dell'Aniello, Sophie; Saarela, Olli; Filion, Kristian B; Boivin, Jean-François

2015-01-01

Objectives Hepatic enzyme-inducing antiepileptic drugs (AEDs) increase serum lipid levels and other atherogenic markers via the induction of cytochrome P450 and may therefore increase the risk of vascular events. We sought to assess the risk of ischaemic stroke and myocardial infarction (MI) according to AED enzymatic properties. Design Population-based cohort study with nested case–control analysis. Setting 650 general practices in the UK contributing to the Clinical Practice Research Datalink. Participants A cohort of 252 407 incident AED users aged 18 or older between January 1990 and April 2013. For each case of ischaemic stroke or MI, up to 10 controls were randomly selected among the cohort members in the risk sets defined by the case and matched on age, sex, indication for AED, calendar time and duration of follow-up. Interventions Current use of enzyme-inducing and enzyme-inhibiting AEDs compared with non-inducing AEDs. Primary outcome measures Incidence rate ratios (RRs) of ischaemic stroke and MI. Results 5069 strokes and 3636 MIs were identified during follow-up. Inducing AEDs use was associated with a small increased risk of ischaemic stroke (RR=1.16, 95% CI 1.02 to 1.33) relative to non-inducing AEDs, most likely due to residual confounding. However, current use of inducing AEDs for ≥24 months was associated with a 46% increased risk of MI (RR=1.46, 95% CI 1.15 to 1.85) compared with the same duration of non-inducing AED, corresponding to a risk difference of 1.39/1000 (95% CI 0.33 to 2.45) persons per year. Current use of inhibiting AED was associated with a decreased risk of MI (RR=0.81, 95% CI 0.66 to 1.00). Conclusions The use of enzyme-inducing AEDs was not associated with an increased risk of ischaemic stroke; a small increase of MI with prolonged use was observed. In contrast, use of inhibiting AEDs was associated with a decreased risk of MI. PMID:26270948

Prognostic indices for early mortality in ischaemic stroke - meta-analysis.

PubMed

Mattishent, K; Kwok, C S; Mahtani, A; Pelpola, K; Myint, P K; Loke, Y K

2016-01-01

Several models have been developed to predict mortality in ischaemic stroke. We aimed to evaluate systematically the performance of published stroke prognostic scores. We searched MEDLINE and EMBASE in February 2014 for prognostic models (published between 2003 and 2014) used in predicting early mortality (<6 months) after ischaemic stroke. We evaluated discriminant ability of the tools through meta-analysis of the area under the curve receiver operating characteristic curve (AUROC) or c-statistic. We evaluated the following components of study validity: collection of prognostic variables, neuroimaging, treatment pathways and missing data. We identified 18 articles (involving 163 240 patients) reporting on the performance of prognostic models for mortality in ischaemic stroke, with 15 articles providing AUC for meta-analysis. Most studies were either retrospective, or post hoc analyses of prospectively collected data; all but three reported validation data. The iSCORE had the largest number of validation cohorts (five) within our systematic review and showed good performance in four different countries, pooled AUC 0.84 (95% CI 0.82-0.87). We identified other potentially useful prognostic tools that have yet to be as extensively validated as iSCORE - these include SOAR (2 studies, pooled AUC 0.79, 95% CI 0.78-0.80), GWTG (2 studies, pooled AUC 0.72, 95% CI 0.72-0.72) and PLAN (1 study, pooled AUC 0.85, 95% CI 0.84-0.87). Our meta-analysis has identified and summarized the performance of several prognostic scores with modest to good predictive accuracy for early mortality in ischaemic stroke, with the iSCORE having the broadest evidence base. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stroke injury, cognitive impairment and vascular dementia☆

PubMed Central

Kalaria, Raj N.; Akinyemi, Rufus; Ihara, Masafumi

2016-01-01

The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26806700

[Moyamoya disease as a rare cause of ischaemic stroke--case report].

PubMed

Kułakowska, Alina; Kapica-Topczewska, Katarzyna; Borowik, Helena; Drozdowski, Wiesław

2009-10-01

Moyamoya disease is a rare, progressive disease of the vessels diagnosed according to characteristic abnormalities of brain arteries in the angiography. The incidence of moyamoya disease in Europe is lower than in Asia and its clinical course in European population is probably different from Asiatic (older age of onset and rare incidence of hemorrhagic strokes). Two young patients were diagnosed as moyamoya disease on the basis of clinical symptoms (ischaemic stroke) and results of brain vessels' angiography, which documented an occlusion of both internal carotid arteries above branching-off the ocular arteries in the first patient and stenosis of distal internal carotid arteries and proximal medial and anterior cerebral arteries in the second one. Both patients are under control of the Neurological Outpatient Department and their neurological state is stable. Despite that moyamoya disease is a rare cause of ischaemic stroke, it should be always considered as one of etiologic factors, especially in young patients.

Unprocessed red meat and processed meat consumption and risk of stroke in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).

PubMed

Amiano, P; Chamosa, S; Etxezarreta, N; Arriola, L; Sánchez, M-J; Ardanaz, E; Molina-Montes, E; Chirlaque, M-D; Moreno-Iribas, C; Huerta, J-M; Egües, N; Navarro, C; Requena, M; Quirós, J-R; Fonseca-Nunes, A; Jakszyn, P; González, C-A; Dorronsoro, M

2016-03-01

High intakes of unprocessed red or processed meat may increase the risk of stroke. We aimed to examine the association between unprocessed red meat, processed meat and total red meat consumption and risk of total stroke and ischaemic stroke. Cox proportional hazards regression analyses were conducted based on the data for 41,020 men and women aged 29-69 years at baseline. During a mean follow-up of 13.8 years, 674 incident cases of stroke (531 ischaemic strokes, 79 haemorrhagic strokes, 42 subarachnoid haemorrhages and 22 mixed or unspecified events) were identified. After multiple adjustment, unprocessed red meat, processed meat and total red meat consumption were not correlated with incidence of total stroke or ischaemic stroke in either men or women. The hazard ratios (HRs) for unprocessed red meat and processed meat and risk of total stroke comparing the highest with the lowest quintiles were, respectively, 0.81 (95% confidence interval (CI) 0.54-1.21; P-trend=0.15) and 0.92 (95% CI 0.64-1.32; P-trend=0.82) in men and 1.21 (95% CI 0.79-1.85; P-trend=0.10) and 0.81 (95% CI 0.51-1.27; P-trend=0.17) in women. The HRs for unprocessed red meat and processed meat and risk of ischaemic stroke were, respectively, 0.80 (95% CI 0.51-1.25; P-trend=0.51) and 0.86 (95% CI 0.57-1.29; P-trend=0.77) in men and 1.24 (95% CI 0.74-2.05; P-trend=0.13) and 0.82 (95% CI 0.47-1.42; P-trend=0.31) in women. In the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, unprocessed red meat and processed meat consumption were not associated with risk of stroke in men or women.

Ischaemic Strokes in Patients with Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia: Associations with Iron Deficiency and Platelets

PubMed Central

Shovlin, Claire L.; Chamali, Basel; Santhirapala, Vatshalan; Livesey, John A.; Angus, Gillian; Manning, Richard; Laffan, Michael A.; Meek, John; Tighe, Hannah C.; Jackson, James E.

2014-01-01

Background Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke. Methodology 497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies. Principal Findings Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021). Significance These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets. PMID:24586400

Modelling projections for the uptake of edoxaban in an European population to 2050: effects on stroke, thromboembolism, and health economics perspectives.

PubMed

Blann, Andrew D; Boriani, Giuseppe; Lip, Gregory Y H

2016-10-01

In the coming decades, the number of Europeans with atrial fibrillation (AF) is set to rise as the population ages, and so with it will the number of strokes. The risk of thromboembolism (principally stroke and systemic embolism) and death can be reduced by the use of the vitamin K antagonists (VKA, e.g. warfarin) and more so by non-VKA oral anticoagulants (NOACs) such as edoxaban. We modelled the effect of the increasing use of edoxaban in preference to warfarin in a European AF population from both clinical and economic perspectives. We estimate that the introduction of NOACs in 2010 eliminated over 88 000 thromboembolisms and deaths annually, of which over 17 000 were ischaemic strokes. At a 1-year cost of €30k per ischaemic stroke, this strategy saved €510 million annually. Should the use of edoxaban increase from 11% in 2013 to 75% by 2030, we expect that rate of thromboembolism and death will fall from 5.67 to 5.42 total events per million patients per year, which will further eliminate over 12 000 of these events annually. At an inflation-adjusted 1-year cost of approximately €35k per ischaemic stroke, this will save €44.5 million each year. At a conservative rate of increase in the AF population of 2.2-fold from 2005, in 2050 there will be around 180 000 AF-related ischaemic strokes that, at an inflation-adjusted cost of around €62k per stroke, sums to €11 116 million. Should the rate of AF rise 2.6-fold from 2005, then in 2050 there will be 214 500 ischaemic strokes that will cost around €13 300 million. Our data point to a substantial increase in the human and economic cost burden of AF and so emphasize the need to reduce this burden. This may be achieved by the increased use of oral anticoagulants, particularly with the NOACs such as edoxaban. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited.

PubMed

Sandercock, Peter; Lindley, Richard; Wardlaw, Joanna; Dennis, Martin; Innes, Karen; Cohen, Geoff; Whiteley, Will; Perry, David; Soosay, Vera; Buchanan, David; Venables, Graham; Czlonkowska, Anna; Kobayashi, Adam; Berge, Eivind; Slot, Karsten Bruins; Murray, Veronica; Peeters, Andre; Hankey, Graeme J; Matz, Karl; Brainin, Michael; Ricci, Stefano; Cantisani, Teresa A; Gubitz, Gordon; Phillips, Stephen J; Antonio, Arauz; Correia, Manuel; Lyrer, Phillippe; Kane, Ingrid; Lundstrom, Erik

2011-11-30

Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics. The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials. The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials. ISRCTN25765518.

Factors associated with coronary artery disease and stroke in adults with congenital heart disease.

PubMed

Bokma, Jouke P; Zegstroo, Ineke; Kuijpers, Joey M; Konings, Thelma C; van Kimmenade, Roland R J; van Melle, Joost P; Kiès, Philippine; Mulder, Barbara J M; Bouma, Berto J

2018-04-01

To determine factors associated with coronary artery disease (CAD) and ischaemic stroke in ageing adult congenital heart disease (ACHD) patients. We performed a multicentre case-control study, using data from the national CONgenital CORvitia (CONCOR) registry to identify ACHD patients within five participating centres. Patients with CAD were matched (1:2 ratio) with ACHD patients without CAD on age, CHD defect group and gender. Patients with ischaemic stroke (or transient ischaemic attack) were matched similarly. Medical charts were reviewed and a standardised questionnaire was used to determine presence of risk factors. Of 6904 ACHD patients, a total of 55 cases with CAD (80% male, mean age 55.1±12.4 years) and 56 cases with stroke (46% male, mean age 46.9±15.2) were included and matched with control patients. In multivariable logistic regression analysis, traditional atherosclerotic risk factors (hypertension (OR 2.45; 95% CI 1.15 to 5.23), hypercholesterolaemia (OR 3.99; 95% CI 1.62 to 9.83) and smoking (OR 2.25; 95% CI 1.09 to 4.66)) were associated with CAD. In contrast, these risk factors were not associated with ischaemic stroke. In multivariable analysis, stroke was associated with previous shunt operations (OR 4.20; 95% CI 1.36 to 12.9), residual/unclosed septal defects (OR 2.38; 95% CI 1.03 to 5.51) and left-sided mechanical valves (OR 2.67; 95% CI 1.09 to 6.50). Traditional atherosclerotic risk factors were associated with CAD in ACHD patients. In contrast, ischaemic stroke was related to factors (previous shunts, septal defects, mechanical valves) suggesting a cardioembolic aetiology. These findings may inform surveillance and prevention strategies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Early blood pressure lowering treatment in acute stroke. Ordinal analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial (SCAST).

PubMed

Jusufovic, Mirza; Sandset, Else Charlotte; Bath, Philip M; Berge, Eivind

2016-08-01

Early blood pressure-lowering treatment appears to be beneficial in patients with acute intracerebral haemorrhage and potentially in ischaemic stroke. We used a new method for analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial to see if the effect was dependent on the timing of treatment. Scandinavian Candesartan Acute Stroke Trial was a randomized controlled and placebo-controlled trial of candesartan within 30 h of ischaemic or haemorrhagic stroke. Of 2029 patients, 231 (11.4%) had a vascular event (vascular death, nonfatal stroke or nonfatal myocardial infarction) during the first 6 months. The modified Rankin Scale (mRS) score following a vascular event was used to categorize vascular events in order of severity: no event (n = 1798), minor (mRS 0-2, n = 59), moderately severe (mRS 3-4, n = 57) and major event (mRS 5-6, n = 115). We used ordinal logistic regression for analysis and adjusted for predefined prognostic variables. Candesartan had no overall effect on vascular events (adjusted common odds ratio 1.11, 95% confidence interval 0.84-1.47, P = 0.48), and the effects were the same in ischaemic and haemorrhagic stroke. Among the patients treated within 6 h, the adjusted common odds ratio for vascular events was 0.37, 95% confidence interval 0.16-0.84, P = 0.02, and there was no heterogeneity of effect between ischaemic and haemorrhagic strokes. Ordinal analysis of vascular events showed no overall effect of candesartan in the subacute phase of stroke. The effect of treatment given within 6 h of stroke onset appears promising, and will be addressed in ongoing trials. Ordinal analysis of vascular events is feasible and can be used in future trials.

Expression patterns of histone deacetylases in experimental stroke and potential targets for neuroprotection.

PubMed

Chen, Yan-Ting; Zang, Xue-Feng; Pan, Jie; Zhu, Xiao-Lei; Chen, Fei; Chen, Zhi-Bin; Xu, Yun

2012-09-01

1. Histone deacetylase (HDAC) inhibitors exert neuroprotection in both cellular and animal models of ischaemic stroke. However, which HDAC isoform (or isoforms) mediates this beneficial effect has not yet been determined. 2. In the present study, gene levels of the HDAC isoforms were determined in the mouse cortex using reverse transcription-polymerase chain reaction (RT-PCR), whereas changes in the expression of individual zinc-dependent HDAC family members were evaluated by western blotting, 3, 12, 24 and 48 h after cerebral ischaemia induced by transient middle cerebral artery occlusion in male Kunming mice. 3. The HDAC isoforms HDAC1-11 were all expressed in the mouse cortex and differentially affected by cerebral ischaemia. Notably, there was a substantial increase in HDAC3, HDAC6 and HDAC11 expression during the early phases of experimental stroke, indicating their contribution to stroke pathogenesis. Furthermore, induction of HDAC3 and HDAC6 in cortical neurons by ischaemic stroke was confirmed in vivo and in vitro using double-labelled immunostaining and RT-PCR, respectively. Therefore, small hairpin (sh) RNAs were used to selectively knock down HDAC3 or HDAC6. This knockdown appreciably promoted the survival of cortical neurons subjected to oxygen and glucose deprivation. 4. The findings of the present study demonstrate the expression patterns of HDAC isoforms during experimental ischaemic stroke. Furthermore, HDAC3 and HDAC6 were identified as potential mediators in the neurotoxicity of ischaemic stroke, suggesting that specific therapeutic approaches may be considered according to HDAC subtype. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.

Circulating endothelial cells in acute ischaemic stroke.

PubMed

Nadar, Sunil K; Lip, Gregory Y H; Lee, Kaeng W; Blann, Andrew D

2005-10-01

Increased numbers of CD146-bearing circulating endothelial cells (CECs) in the peripheral blood probably represent the most direct evidence of endothelial cell damage. As acute ischaemic strokes are associated with endothelial abnormalities, we hypothesised that these CECs are raised in acute stroke, and that they would correlate with the other indices of endothelial perturbation, i.e. plasma von Willebrand factor (vWf) and soluble E-selectin. We studied 29 hypertensive patients (19 male; mean age 63 years) who presented with an acute stroke and compared them with 30 high risk hypertensive patients (21 male; mean age 62 years) and 30 normotensive controls (16 male; mean age 58 years). CECs were estimated by CD146 immunobead capture, vWf and soluble E-selectin by ELISA. Patients with an acute ischaemic stroke had significantly higher numbers of CECs/ml of blood (p<0.001) plasma vWf (p=0.008) soluble E-selectin (p=0.002) and higher systolic blood pressure (SBP) as compared to the other groups. The number of CECs significantly correlated with soluble E-selectin (r=0.432, p<0.001) and vWf (r=0.349, p=0.001) but not with SBP (r=0.198, p=0.069). However, in multivariate analysis, only disease group (i.e. health, hypertension or stroke) was associated with increased CECs. Acute ischaemic stroke is associated with increased numbers of CECs. The latter correlate well with established plasma markers of endothelial dysfunction or damage, thus unequivocally confirming severe vasculopathy in this condition. However, the greatest influence on CECs numbers was clinical group.

Cerebral small vessel disease, medial temporal lobe atrophy and cognitive status in patients with ischaemic stroke and transient ischaemic attack.

PubMed

Arba, F; Quinn, T; Hankey, G J; Ali, M; Lees, K R; Inzitari, D

2017-02-01

Small vessel disease (SVD) and Alzheimer's disease (AD) are two common causes of cognitive impairment and dementia, traditionally considered as distinct processes. The relationship between radiological features suggestive of AD and SVD was explored, and the association of each of these features with cognitive status at 1 year was investigated in patients with stroke or transient ischaemic attack. Anonymized data were accessed from the Virtual International Stroke Trials Archive (VISTA). Medial temporal lobe atrophy (MTA; a marker of AD) and markers of SVD were rated using validated ordinal visual scales. Cognitive status was evaluated with the Mini Mental State Examination (MMSE) 1 year after the index stroke. Logistic regression models were used to investigate independent associations between (i) baseline SVD features and MTA and (ii) all baseline neuroimaging features and cognitive status 1 year post-stroke. In all, 234 patients were included, mean (±SD) age 65.7 ± 13.1 years, 145 (62%) male. Moderate to severe MTA was present in 104 (44%) patients. SVD features were independently associated with MTA (P < 0.001). After adjusting for age, sex, disability after stroke, hypertension and diabetes mellitus, MTA was the only radiological feature independently associated with cognitive impairment, defined using thresholds of MMSE ≤ 26 (odds ratio 1.94; 95% confidence interval 1.28-2.94) and MMSE ≤ 23 (odds ratio 2.31; 95% confidence interval 1.48-3.62). In patients with ischaemic cerebrovascular disease, SVD features are associated with MTA, which is a common finding in stroke survivors. SVD and AD type neurodegeneration coexist, but the AD marker MTA, rather than SVD markers, is associated with post-stroke cognitive impairment. © 2016 EAN.

[Effectiveness of endarterectomy for symptomatic stenosis of the internal carotid artery; more risk factors important than only the severity of the stenosis].

PubMed

Klijn, C J M; Hoefnagels, W A J; Brouwers, P J A M; Luijckx, G J; Moll, F L; Kappelle, L J

2007-12-15

Carotid endarterectomy prevents ischaemic stroke in patients who have suffered either a transient ischaemic attack (TIA) or a non-disabling ischaemic stroke and are also diagnosed with severe stenosis of the internal carotid artery (ICA). In order to prevent the occurrence ofa single stroke, 6 patients with a symptomatic 70 to 99% ICA stenosis will have to be operated upon. A meta-analysis of individual patient data from 3 randomised trials shows that the decision whether to advise endarterectomy to an individual patient should not be based solely on the degree of the ICA stenosis, but also on the time interval between symptoms and surgery, the type and severity of symptoms and the plaque morphology. In general, endarterectomy is more effective in men than in women, it is very effective in the elderly, and it is even more effective when performed within two weeks of the symptoms occurring. A decision scheme has been set up enabling one to predict the absolute risk of an ipsilateral stroke in the next 5 years in individual patients who have symptomatic ICA stenosis. This is based on 5 factors: sex, age, the most severe symptom in the last 6 months (stroke, TIA, or ischaemic retinopathy), the number of weeks since the last incident and the morphological characteristics of the plaque.

Cluster-randomized, controlled trial of computer-based decision support for selecting long-term anti-thrombotic therapy after acute ischaemic stroke.

PubMed

Weir, C J; Lees, K R; MacWalter, R S; Muir, K W; Wallesch, C-W; McLelland, E V; Hendry, A

2003-02-01

Identifying the appropriate long-term anti-thrombotic therapy following acute ischaemic stroke is a challenging area in which computer-based decision support may provide assistance. To evaluate the influence on prescribing practice of a computer-based decision support system (CDSS) that provided patient-specific estimates of the expected ischaemic and haemorrhagic vascular event rates under each potential anti-thrombotic therapy. Cluster-randomized controlled trial. We recruited patients who presented for a first investigation of ischaemic stroke or TIA symptoms, excluding those with a poor prognosis or major contraindication to anticoagulation. After observation of routine prescribing practice (6 months) in each hospital, centres were randomized for 6 months to either control (routine practice observed) or intervention (practice observed while the CDSS provided patient-specific information). We compared, between control and intervention centres, the risk reduction (estimated by the CDSS) in ischaemic and haemorrhagic vascular events achieved by long-term anti-thrombotic therapy, and the proportions of subjects prescribed the optimal therapy identified by the CDSS. Sixteen hospitals recruited 1952 subjects. When the CDSS provided information, the mean relative risk reduction attained by prescribing increased by 2.7 percentage units (95%CI -0.3 to 5.7) and the odds ratio for the optimal therapy being prescribed was 1.32 (0.83 to 1.80). Some 55% (5/9) of clinicians believed the CDSS had influenced their prescribing. Cluster-randomized trials provide excellent frameworks for evaluating novel clinical management methods. Our CDSS was feasible to implement and acceptable to clinicians, but did not substantially influence prescribing practice for anti-thrombotic drugs after acute ischaemic stroke.

Emergency medical service in the stroke chain of survival.

PubMed

Chenaitia, Hichem; Lefevre, Oriane; Ho, Vanessa; Squarcioni, Christian; Pradel, Vincent; Fournier, Marc; Toesca, Richard; Michelet, Pierre; Auffray, Jean Pierre

2013-02-01

The Emergency Medical Services (EMS) play a primordial role in the early management of adults with acute ischaemic stroke (AIS). The aim of this study was to evaluate the role and effectiveness of the EMS in the stroke chain of survival in Marseille. A retrospective observational study was conducted in patients treated for AIS or transient ischaemic attack in three emergency departments and at the Marseille stroke centre over a period of 12 months. In 2009, of 1034 patients ultimately presenting a diagnosis of AIS or transient ischaemic attack, 74% benefited from EMS activation. Dispatchers correctly diagnosed 57% of stroke patients. The symptoms most frequently reported included limb weakness, speech problems and facial paresis. Elements resulting in misdiagnosis by dispatchers were general discomfort, chest pain, dyspnoea, fall or vertigo. Stroke patients not diagnosed by emergency medical dispatchers but calling within 3 h of symptom onset accounted for 20% of cases. Our study demonstrates that public intervention programmes must stress the urgency of recognizing stroke symptoms and the importance of calling EMS through free telephone numbers. Further efforts are necessary to disseminate guidelines for healthcare providers concerning stroke recognition and the new therapeutic possibilities in order to increase the likelihood of acute stroke patients presenting to a stroke team early enough to be eligible for acute treatment. In addition, EMS dispatchers should receive further training about atypical stroke symptoms, and 'Face Arm Speech Test' tests must be included in the routine questionnaires used in emergency medical calls concerning elderly persons.

Acupuncture treatment for ischaemic stroke in young adults: protocol for a randomised, sham-controlled clinical trial

PubMed Central

Chen, Lifang; Fang, Jianqiao; Jin, Xiaoming; Keeler, Crystal Lynn; Gao, Hong; Fang, Zhen; Chen, Qin

2016-01-01

Introduction Stroke in young adults is not uncommon. Although the overall incidence of stroke has been recently declining, the incidence of stroke in young adults is increasing. Traditional vascular risk factors are the main cause of young ischaemic stroke. Acupuncture has been shown to benefit stroke rehabilitation and ameliorate the risk factors for stroke. The aims of this study were to determine whether acupuncture treatment will be effective in improving the activities of daily living (ADL), motor function and quality of life (QOL) in patients of young ischaemic stroke, and in preventing stroke recurrence by controlling blood pressure, lipids and body weight. Methods and analysis In this randomised, sham-controlled, participant-blinded and assessor-blinded clinical trial, 120 patients between 18 and 45 years of age with a recent (within 1 month) ischaemic stroke will be randomised for an 8-week acupuncture or sham acupuncture treatment. The primary outcome will be the Barthel Index for ADL. The secondary outcomes will include the Fugl-Meyer Assessment for motor function; the World Health Organization Quality of Life BREF (WHOQOL-BREF) for QOL; and risk factors that are measured by ambulatory blood pressure, the fasting serum lipid, body mass index and waist circumference. Incidence of adverse events and long-term mortality and recurrence rate during a 10-year and 30-year follow-up will also be investigated. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of The Third Affiliated Hospital of Zhejiang Chinese Medical University. Protocol V.3 was approved in June 2013. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients by telephone during follow-up calls enquiring on the patient's post-study health status. Trial registration number ChiCTR-TRC- 13003317; Pre-results. PMID:26739742

Catheter-based interventions for acute ischaemic stroke.

PubMed

Widimsky, Petr; Hopkins, L Nelson

2016-10-21

Catheter-based interventions for acute ischaemic stroke currently include clot removal (usually from the medial cerebral artery) with modern stent-retrievers and in one of five patients (who have simultaneous or stand-alone internal carotid occlusion) also extracranial carotid intervention. Several recently published randomized trials clearly demonstrated superiority of catheter-based interventions (with or without bridging thrombolysis) over best medical therapy alone. The healthcare systems should adopt the new strategies for acute stroke treatment (including fast track to interventional lab) to offer the benefits to all suitable acute stroke patients. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Chickenpox and stroke in children: case studies and literature review.

PubMed

Reis, Ana F; Pais, Patrícia; Monteiro, José P

2014-04-01

Postvaricella cerebral arteriopathy (PVCA) presents with acute haemiparesis and/or haemidistonia, caused by ischaemic lesions of internal capsule and/or basal ganglia, related to stenosis of proximal middle and/or anterior cerebral arteries. Anti-aggregant drugs are recommended to prevent thrombus expansion and recurrent stroke, but neurologic outcome is usually good regardless of the therapeutic approach. Chickenpox should be considered in differential diagnosis of ischaemic stroke in healthy children who fit the clinical and radiological typical profile of PVCA. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Left atrial function to identify patients with atrial fibrillation at high risk of stroke: new insights from a large registry.

PubMed

Leung, Melissa; van Rosendael, Philippe J; Abou, Rachid; Ajmone Marsan, Nina; Leung, Dominic Y; Delgado, Victoria; Bax, Jeroen J

2018-04-21

Atrial fibrillation (AF) is an independent risk factor for ischaemic stroke. The CHA2DS2-VASc is the most widely used risk stratification model; however, echocardiographic refinement may be useful, particularly in low risk AF patients. The present study examined the association between advanced echocardiographic parameters and ischaemic stroke, independent of CHA2DS2-VASc score. One thousand, three hundred and sixty-one patients (mean age 65±12 years, 74% males) with first diagnosis of AF and baseline transthoracic echocardiogram were followed by chart review for the occurrence of stroke over a mean of 7.9 years. Left atrial (LA) volumes, LA reservoir strain, P-wave to A' duration on tissue Doppler imaging (PA-TDI, reflecting total atrial conduction time), and left ventricular (LV) global longitudinal strain (GLS) were evaluated in patients with and without stroke. The independent association of these echocardiographic parameters with the occurrence of ischaemic stroke was evaluated with Cox proportional hazard models. One-hundred patients (7%) developed an ischaemic stroke, representing an annualized stroke rate of 0.9%. The incident stroke rate in the year following the first diagnosis of AF was 2.6% in the entire population and higher than the remainder of the follow-up period. Left atrial reservoir (14.5% vs. 18.9%, P = 0.005) and conduit strains were reduced (10.5% vs. 13.5%, P = 0.013), and PA-TDI lengthened (166 ms vs. 141 ms, P < 0.001) in the stroke compared with non-stroke group, despite similar LV dimensions, LV ejection fraction, GLS, and LA volumes. Left atrial reservoir strain and PA-TDI were independently associated with risk of stroke in a model including CHA2DS2-VASc score, age, and anticoagulant use. The assessment of LA reservoir strain and PA-TDI on echocardiography after initial CHA2DS2-VASc scoring provides additional risk stratification for stroke and may be useful to guide decisions regarding anticoagulation for patients upon first diagnosis of AF.

When the heart rules the head: ischaemic stroke and intracerebral haemorrhage complicating infective endocarditis.

PubMed

Jiad, Estabrak; Gill, Sumanjit K; Krutikov, Maria; Turner, David; Parkinson, Michael H; Curtis, Carmel; Werring, David J

2017-01-01

Sir William Osler meticulously described the clinical manifestations of infective endocarditis in 1885, concluding that: 'few diseases present greater difficulties in the way of diagnosis … which in many cases are practically insurmountable'. Even with modern investigation techniques, diagnosing infective endocarditis can be hugely challenging, yet is critically important in patients presenting with stroke (both cerebral infarction and intracranial haemorrhage), its commonest neurological complication. In ischaemic stroke, intravenous thrombolysis carries an unacceptably high risk of intracranial haemorrhage, while in intracerebral haemorrhage, mycotic aneurysms require urgent treatment to avoid rebleeding, and in all cases, prompt treatment with antibiotics and valve surgery may be life-saving. Here, we describe typical presentations of ischaemic stroke and intracerebral haemorrhage caused by infective endocarditis. We review the diagnostic challenges, the importance of rapid diagnosis, treatment options and controversies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Did the introduction of a prospective payment system for nursing home stays reduce the likelihood of pharmacological management of secondary ischaemic stroke?

PubMed

Lapane, Kate L; Hughes, Carmel M

2006-01-01

Since 1998, a prospective payment system (PPS) for Medicare services provided by nursing homes in the US has been in operation. Concerns have been expressed that the PPS may affect the quality of care delivered to residents. This study evaluates the impact of the PPS on pharmacological secondary ischaemic stroke prevention in nursing homes. The nationally mandated Minimum Data Set and Online Survey Certification and Automated Record data system from 1997 and 2000 for four states were used. We conducted a quasi-experimental study comparing the pharmacological treatment rates for secondary stroke prevention in the pre-PPS period (1997) with those in the post-PPS period (2000) in residents who experienced an ischaemic stroke within 6 months (n1997 = 5008; n2000 = 5243) of living in nursing facilities (n1997 = 1226; n2000 = 1092) in Kansas, Maine, Mississippi or Ohio. The sample was stratified according to recommendations for use of warfarin. Logistic regression models adjusting for clustering effects of residents residing in homes using generalised estimating equations provided estimates of the PPS effect on use of antiplatelets and the use of warfarin. The unadjusted proportion of use of pharmacological agents for the secondary prevention of stroke was similar for warfarin in both time periods and increased for antiplatelets in 2000. Relative to the pre-PPS era, the likelihood of use of antiplatelets increased in the post-PPS era (adjusted odds ratio 1.26; 95% CI 1.15, 1.38); there was no effect on the use of warfarin. Although the lack of a PPS effect on pharmacological management of secondary ischaemic stroke is encouraging, there is still room for improvement in overall stroke management.

Guidelines for the preventive treatment of ischaemic stroke and TIA (II). Recommendations according to aetiological sub-type.

PubMed

Fuentes, B; Gállego, J; Gil-Nuñez, A; Morales, A; Purroy, F; Roquer, J; Segura, T; Tejada, J; Lago, A; Díez-Tejedor, E; Alonso de Leciñana, M; Alvarez-Sabin, J; Arenillas, J; Calleja, S; Casado, I; Castellanos, M; Castillo, J; Dávalos, A; Díaz-Otero, F; Egido, J A; López-Fernández, J C; Freijo, M; García Pastor, A; Gilo, F; Irimia, P; Maestre, J; Masjuan, J; Martí-Fábregas, J; Martínez-Sánchez, P; Martínez-Vila, E; Molina, C; Nombela, F; Ribó, M; Rodríguez-Yañez, M; Rubio, F; Serena, J; Simal, P; Vivancos, J

2014-04-01

To update the ad hoc Committee of the Cerebrovascular Diseases Study Group of The Spanish Neurological Society guidelines on prevention of ischaemic stroke (IS) and Transient Ischaemic Attack (TIA). We reviewed the available evidence on ischaemic stroke and TIA prevention according to aetiological subtype. Levels of evidence and recommendation levels are based on the classification of the Centre for Evidence-Based Medicine. In atherothrombotic IS, antiplatelet therapy and revascularization procedures in selected cases of ipsilateral carotid stenosis (70%-90%) reduce the risk of recurrences. In cardioembolic IS (atrial fibrillation, valvular diseases, prosthetic valves and myocardial infarction with mural thrombus) prevention is based on the use of oral anticoagulants. Preventive therapies for uncommon causes of IS will depend on the aetiology. In the case of cerebral venous thrombosis oral anticoagulation is effective. We conclude with recommendations for clinical practice in prevention of IS according to the aetiological subtype presented by the patient. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Ischaemic stroke with patent foramen ovale.

PubMed

Jusufovic, Mirza; Thomassen, Lars; Skjelland, Mona

2014-01-28

There is no sound scientific documentation of current guidelines for the treatment of cerebral infarction assumed to be due to patent foramen ovale. In this article, we present a young patient with this condition. In addition, we provide a general overview of the prevalence, recommended assessment and indications for treatment of patent foramen ovale in ischaemic stroke patients. The article is based on a non-systematic search in PubMed. We emphasise three recently published randomised trials on the subject. Transoesophageal echocardiography with saline contrast is the gold standard for detecting patent foramen ovale. Just who will benefit from the diagnosis and treatment of this condition remains unclear, however. None of the three randomised studies of antithrombotic treatment versus transcatheter closure in patients who have suffered ischaemic stroke show a difference in outcomes, but subgroup analyses indicate that closure in young patients (age <50 years) with a large foramen ovale reduces the number of recurrent ischaemic events. Two other randomised studies of antithrombotic treatment alone versus closure are presently ongoing. For stroke patients with patent foramen ovale, the choice between lifelong antithrombotic therapy alone and transcatheter closure is a difficult one. Treatment with antiplatelet agents remains the first choice in most cases. Well-designed studies are needed to identify which patients will benefit most from closure.

Association between patency of the circle of Willis and diabetes mellitus in patients with cerebral ischaemic stroke

PubMed Central

Chi, Ying

2017-01-01

Objective To examine patency of the cerebral anterior and posterior communicating arteries in patients with ischaemic stroke with or without diabetes mellitus. Methods This retrospective study included patients with acute ischaemic stroke treated between July 2011 and May 2016. Cerebral infarction was evaluated by magnetic resonance imaging. Anterior and posterior communicating-artery patency was determined using magnetic resonance angiography. Vessels were defined as patent or occluded. Results Out of 1 406 patients, incidence of vertebral basilar artery brain infarction and posterior cerebral artery brain infarction were significantly higher in patients with diabetes versus those without diabetes (35.5% versus 22.3% and 11.7% versus 6.8%, respectively). Among patients with posterior cerebral artery brain infarction, anterior and posterior communicating-artery patency rates were higher in patients with diabetes versus those without diabetes (66.7 versus 23.5% and 33.3% versus 5.9% [bilateral], respectively). Among patients with vertebral basilar artery infarction and posterior cerebral artery P1 segment infarction, patency rate of the anterior communicating artery was higher in patients with diabetes versus those without diabetes (55.7% versus 45.9%). Conclusion Among patients with ischaemic stroke, patency rate of the circle of Willis may be higher in patients with diabetes than those without diabetes. PMID:28173711

Ischaemic stroke management at Al-Shifa Hospital in the Gaza Strip: a clinical audit.

PubMed

Abukaresh, Amir; Al-Abadlah, Rami; Böttcher, Bettina; El-Essi, Khamis

2018-02-21

In the 2014 Palestinian annual health report, cerebrovascular accident was ranked as the third leading cause of death in the occupied Palestinian territory. Cerebrovascular accident is also one the most common causes of disability worldwide. Good management decreases mortality and morbidity. The aim of this study was to assess the current management of patients with ischaemic stroke at the Al-Shifa Hospital and to compare this with international guidelines. For this clinical audit, we used simple random sampling to select files of patients admitted with the diagnosis of ischaemic stroke to the Al-Shifa Hospital. Data collection sheets were completed, and clinical practice was compared with the 2013 American Stroke Association guidelines. Between January and June, 2016, 254 patients were admitted with ischaemic stroke, haemorrhagic stroke, or transient ischaemic attack. We selected 55 patient files. The International Classification of Diseases coding for cerebral infarction in patient files was relatively good, with 92% of files correctly coded. However, we found a substantial weakness in the documentation of duration, progression of symptoms (documented in 20% of files only), and physiotherapy assessment. Most essential acute investigations were done on time (for all [100%] patients needing blood count, renal function tests, and CT scan and for 42 [76%] patients needing ECG). However, thrombolytic drugs were not used because they were not available. Long-term antiplatelet therapy was provided properly to 51 (92%) patients discharged from hospital. However, the initial doses of antiplatelet therapy were generally lower than the international recommendations. Findings also showed a marked inconformity of blood pressure management, especially with respect to the treatment decision and the choice of antihypertensive drug. No local guidelines exist. Furthermore, the lack of availability of thrombolysis medication and the poor deviation in blood pressure management show a lack of evidence-based practice. These findings point to the urgent need for the development of local, evidence-based guidelines. None. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fatal encephalopathy after an isolated overdose of cocaine

PubMed Central

Kondziella, D; Danielsen, E R; Arlien-Soeborg, P

2009-01-01

Cocaine induced brain damage can be divided into primary neurotoxic effects causing toxic encephalopathy, secondary effects of compromised cerebral blood flow in ischaemic and haemorrhagic stroke, cerebral vasculitis and vasospasm, and tertiary effects due to hypoxia as a result of cardiopulmonary collapse. Toxic leucoencephalopathy mainly affects white matter (WM) tracts serving higher cerebral function, thereby leading to altered personality, attention deficits and memory impairment in mild cases and to dementia, coma and brain death in severe cases. Here we describe the case of a 21-year-old man who committed suicide by injecting cocaine. The cocaine induced a toxic leucoencephalopathy, which was proven at autopsy. PMID:21731586

A pragmatic approach to sonothrombolysis in acute ischaemic stroke: the Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS).

PubMed

Nacu, Aliona; Kvistad, Christopher E; Logallo, Nicola; Naess, Halvor; Waje-Andreassen, Ulrike; Aamodt, Anne Hege; Solhoff, Ragnar; Lund, Christian; Tobro, Håkon; Rønning, Ole Morten; Salvesen, Rolf; Idicula, Titto T; Thomassen, Lars

2015-07-11

Ultrasound accelerates thrombolysis with tPA (sonothrombolysis). Ultrasound in the absence of tPA also accelerates clot break-up (sonolysis). Adding intravenous gaseous microbubbles may potentiate the effect of ultrasound in both sonothrombolysis and sonolysis. The Norwegian Sonothrombolysis in Acute Stroke Study aims in a pragmatic approach to assess the effect and safety of contrast enhanced ultrasound treatment in unselected acute ischaemic stroke patients. Acute ischaemic stroke patients ≥ 18 years, with or without visible arterial occlusion on computed tomography angiography (CTA) and treatable ≤ 4(½) hours after symptom onset, are included in NOR-SASS. NOR-SASS is superimposed on a separate trial randomising patients with acute ischemic stroke to either tenecteplase or alteplase (The Norwegian Tenecteplase Stroke Trial NOR-TEST). The NOR-SASS trial has two arms: 1) the thrombolysis-arms (NOR-SASS A and B) includes patients given intravenous thrombolysis (tenecteplase or alteplase), and 2) the no-thrombolysis-arm (NOR-SASS C) includes patients with contraindications to thrombolysis. First step randomisation of NOR-SASS A is embedded in NOR-TEST as a 1:1 randomisation to either tenecteplase or alteplase. Second step NOR-SASS randomisation is 1:1 to either contrast enhanced sonothrombolysis (CEST) or sham CEST. Randomisation in NOR-SASS B (routine alteplase group) is 1:1 to either CEST or sham CEST. Randomisation of NOR-SASS C is 1:1 to either contrast enhanced sonolysis (CES) or sham CES. Ultrasound is given for one hour using a 2-MHz pulsed-wave diagnostic ultrasound probe. Microbubble contrast (SonoVue®) is given as a continuous infusion for ~30 min. Recanalisation is assessed at 60 min after start of CEST/CES. Magnetic resonance imaging and angiography is performed after 24 h of stroke onset. Primary study endpoints are 1) major neurological improvement measured with NIHSS score at 24 h and 2) favourable functional outcome defined as mRS 0-1 at 90 days. NOR-SASS is the first randomised controlled trial designed to test the superiority of contrast enhanced ultrasound treatment given ≤ 4(½) hours after stroke onset in an unselected acute ischaemic stroke population eligible or not eligible for intravenous thrombolysis, with or without a defined arterial occlusion on CTA. If a positive effect and safety can be proven, contrast enhanced ultrasound treatment will be an option for all acute ischaemic stroke patients. EudraCT No 201200032341; www.clinicaltrials.gov NCT01949961.

Trends in stroke hospitalisation rates and in-hospital mortality in Aragon, 1998-2010.

PubMed

Giménez-Muñoz, A; Ara, J R; Abad Díez, J M; Campello Morer, I; Pérez Trullén, J M

2018-05-01

Despite the impact of cerebrovascular disease (CVD) on global health, its morbidity and time trends in Spain are not precisely known. The purpose of our study was to characterise the epidemiology and trends pertaining to stroke in Aragon over the period 1998-2010. We conducted a retrospective, descriptive study using the data of the Spanish health system's Minimum Data Set and included all stroke patients admitted to acute care hospitals in Aragon between 1 January 1998 and 31 December 2010. We present data globally and broken down by stroke subtype, sex, and age group. The number of cases increased by 13% whereas age- and sex-adjusted hospitalisation rates showed a significant decrease for all types of stroke (mean annual decrease of 1.6%). Men and women in younger age groups showed opposite trends in hospitalisation rates for ischaemic stroke. Case fatality rate at 28 days (17.9%) was higher in patients with intracerebral haemorrhage (35.8%) than in those with subarachnoid haemorrhage (26.2%) or ischaemic stroke (13%). CVD case fatality showed a mean annual decline of 2.8%, at the expense of the fatality rate of ischaemic stroke, and it was more pronounced in men than in women. Understanding stroke epidemiology and trends at the regional level will help establish an efficient monitoring system and design appropriate strategies for health planning. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The natural history of prevalent ischaemic heart disease in middle-aged men.

PubMed

Lampe, F C; Whincup, P H; Wannamethee, S G; Shaper, A G; Walker, M; Ebrahim, S

2000-07-01

To describe the long-term outcome of different forms of symptomatic and asymptomatic ischaemic heart disease in middle-aged men. 7735 men aged 40-59, randomly selected from 24 general practices in Britain were classified into one of seven ischaemic heart disease groups according to a questionnaire and electrocardiogram (ECG): I=diagnosed myocardial infarction; II=unrecognized myocardial infarction; III= diagnosed angina; IV=angina symptoms; V=possible myocardial infarction symptoms; VI=ECG ischaemia or possible myocardial infarction; VII=no evidence of ischaemic heart disease. The association of disease group with a range of fatal and non-fatal outcomes during 15 years of follow-up was assessed. At baseline 25% of men had evidence of ischaemic heart disease (groups I-VI). Risks of major ischaemic heart disease events, total and cardiovascular mortality, stroke, and major cardiovascular events tended to increase strongly from group VII to I. Diagnosed myocardial infarction was associated with a much poorer prognosis than all other groups (including unrecognized infarction) for all cardiovascular outcomes other than stroke. The relative risk associated with ischaemic heart disease at baseline declined dramatically over time. However, men with myocardial infarction who survived event-free for 10 years continued to experience a high excess risk in the subsequent 5 years, in contrast to event-free survivors of angina and other ischaemic heart disease. Adjusted to an average age of 50, the percentage of men surviving for 15 years free of a new major cardiovascular event was 44 for diagnosed myocardial infarction, 52 for unrecognized myocardial infarction, 66 for diagnosed angina, 68 for angina symptoms, 73 for possible myocardial infarction symptoms, 73 for ECG ischaemia, and 79 for no ischaemic heart disease. Comparison of outcome between prevalent and incident myocardial infarction illustrated the improved prognosis of men surviving the initial years after their event. Differing manifestations of prevalent ischaemic heart disease are associated with widely differing outcome, and the majority of middle-aged men in the community who have evidence of ischaemic heart disease short of myocardial infarction survive for 15 years without heart attack or stroke. The excess risk associated with myocardial infarction appears more persistent than that associated with angina and other ischaemic heart disease, remaining high even after 10 years of event-free survival.

Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial.

PubMed

Wachter, Rolf; Gröschel, Klaus; Gelbrich, Götz; Hamann, Gerhard F; Kermer, Pawel; Liman, Jan; Seegers, Joachim; Wasser, Katrin; Schulte, Anna; Jürries, Falko; Messerschmid, Anna; Behnke, Nico; Gröschel, Sonja; Uphaus, Timo; Grings, Anne; Ibis, Tugba; Klimpe, Sven; Wagner-Heck, Michaela; Arnold, Magdalena; Protsenko, Evgeny; Heuschmann, Peter U; Conen, David; Weber-Krüger, Mark

2017-04-01

Atrial fibrillation is a major risk factor for recurrent ischaemic stroke, but often remains undiagnosed in patients who have had an acute ischaemic stroke. Enhanced and prolonged Holter-electrocardiogram-monitoring might increase detection of atrial fibrillation. We therefore investigated whether enhanced and prolonged rhythm monitoring was better for detection of atrial fibrillation than standard care procedures in patients with acute ischaemic stroke. Find-AF randomised is an open-label randomised study done at four centres in Germany. We recruited patients with acute ischaemic stroke (symptoms for 7 days or less) aged 60 years or older presenting with sinus rhythm and without history of atrial fibrillation. Patients were included irrespective of the suspected cause of stroke, unless they had a severe ipsilateral carotid or intracranial artery stenosis, which were the exclusion criteria. We used a computer-generated allocation sequence to randomly assign patients in a 1:1 ratio with permuted block sizes of 2, 4, 6, and 8, stratified by centre, to enhanced and prolonged monitoring (ie, 10-day Holter-electrocardiogram [ECG]-monitoring at baseline, and at 3 months and 6 months of follow-up) or standard care procedures (ie, at least 24 h of rhythm monitoring). Participants and study physicians were not masked to group assignment, but the expert committees that adjudicated endpoints were. The primary endpoint was the occurrence of atrial fibrillation or atrial flutter (30 sec or longer) within 6 months after randomisation and before stroke recurrence. Because Holter ECG is a widely used procedure and not known to harm patients, we chose not to assess safety in detail. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01855035. Between May 8, 2013, and Aug 31, 2014, we recruited 398 patients. 200 patients were randomly assigned to the enhanced and prolonged monitoring group and 198 to the standard care group. After 6 months, we detected atrial fibrillation in 14% of 200 patients in the enhanced and prolonged monitoring group (27 patients) versus 5% in the control group (nine of 198 patients, absolute difference 9·0%; 95% CI 3·4-14·5, p=0·002; number needed to screen 11). Enhanced and prolonged monitoring initiated early in patients with acute ischaemic stroke aged 60 years or older was better than standard care for the detection of atrial fibrillation. These findings support the consideration of all patients aged 60 years or older with stroke for prolonged monitoring if the detection of atrial fibrillation would result in a change in medical management (eg, initiation of anticoagulation). Boehringer Ingelheim. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of proteinuria and glomerular filtration rate on risk of ischaemic and intracerebral hemorrhagic stroke: a result from the Kailuan study.

PubMed

Li, Z; Wang, A; Cai, J; Gao, X; Zhou, Y; Luo, Y; Wu, S; Zhao, X

2015-02-01

Persons with chronic kidney disease, defined by a reduced estimated glomerular filtration rate and proteinuria, have an increased risk of cardiovascular disease including stroke. However, data from developing countries are limited. Our aim was to assess the relationship between chronic kidney disease and risk of stroke and its subtypes in a community-based population in China. The study was based on 92,013 participants (18-98 years old; 73,248 men and 18,765 women) of the Kailuan study who at baseline were free from stroke and myocardial infarction and had undergone tests for serum creatinine or proteinuria. Glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration formula and proteinuria by the urine dipstick result in laboratory databases. The primary outcome was the first occurrence of stroke. Data were analyzed using Cox proportional hazards models adjusted for relevant confounders and results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs). During a follow-up of 4 years, 1575 stroke events (1128 ischaemic, 406 intracerebral hemorrhagic and 41 subarachnoid hemorrhagic strokes) occurred. After adjustment for variable confounders, patients with proteinuria were found to have increased HRs for the total and subtypes of stroke events (HR 1.61; 95% CI 1.35-1.92 for total stroke; HR 1.53; 95% CI 1.24-1.89 for ischaemic stroke; and HR 1.90; 95% CI 1.35-2.67 for hemorrhagic stroke). However, estimated glomerular filtration rate was not associated with incident stroke after adjustment for established cardiovascular risk factors. Proteinuria increased the risk of stroke in a general Chinese population. © 2014 EAN.

Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial.

PubMed

Bousser, Marie-Germaine; Amarenco, Pierre; Chamorro, Angel; Fisher, Marc; Ford, Ian; Fox, Kim M; Hennerici, Michael G; Mattle, Heinrich P; Rothwell, Peter M; de Cordoüe, Agnès; Fratacci, Marie-Dominique

2011-06-11

Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke or other cardiovascular events. We compared the selective thromboxane-prostaglandin receptor antagonist terutroban with aspirin in the prevention of cerebral and cardiovascular ischaemic events in patients with a recent non-cardioembolic cerebral ischaemic event. This randomised, double-blind, parallel-group trial was undertaken in 802 centres in 46 countries. Patients who had an ischaemic stroke in the previous 3 months or a TIA in the previous 8 days were randomly allocated with a central interactive response system to 30 mg per day terutroban or 100 mg per day aspirin. Patients and investigators were masked to treatment allocation. The primary efficacy endpoint was a composite of fatal or non-fatal ischaemic stroke, fatal or non-fatal myocardial infarction, or other vascular death (excluding haemorrhagic death). We planned a sequential statistical analysis of non-inferiority (margin 1·05) followed by analysis of superiority. Analysis was by intention to treat. The study was stopped prematurely for futility on the basis of the recommendation of the Data Monitoring Committee. This study is registered, number ISRCTN66157730. 9562 patients were assigned to terutroban (9556 analysed) and 9558 to aspirin (9544 analysed); mean follow-up was 28·3 months (SD 7·7). The primary endpoint occurred in 1091 (11%) patients receiving terutroban and 1062 (11%) receiving aspirin (hazard ratio [HR] 1·02, 95% CI 0·94-1·12). There was no evidence of a difference between terutroban and aspirin for the secondary or tertiary endpoints. We recorded some increase in minor bleedings with terutroban compared with aspirin (1147 [12%] vs 1045 [11%]; HR 1·11, 95% CI 1·02-1·21), but no significant differences in other safety endpoints. The trial did not meet the predefined criteria for non-inferiority, but showed similar rates of the primary endpoint with terutroban and aspirin, without safety advantages for terutroban. In a worldwide perspective, aspirin remains the gold standard antiplatelet drug for secondary stroke prevention in view of its efficacy, tolerance, and cost. Servier, France. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Chinese Stroke Association scientific statement: intravenous thrombolysis in acute ischaemic stroke

PubMed Central

Dong, Qiang; Dong, Yi; Liu, Liping; Xu, Anding; Zhang, Yusheng; Zheng, Huaguang; Wang, Yongjun

2017-01-01

The most effective medical treatment for acute ischaemic stroke (AIS) is to offer intravenous thrombolysis during the ultra-early period of time after the onset. Even based on the Consensus of Chinese Experts on Intravenous Thrombolysis for AIS in 2012 and 2014 Chinese Guidelines on the Diagnosis and Treatment of AIS, the rate of thrombolysis for AIS in China remained around 2.4%, and the rate of intravenous tissue plasminogen activator usage was only about 1.6% in real world. The indication of thrombolysis for AIS has been expanded, and contraindications have been reduced with recently published studies. In order to facilitate the standardisation of treating AIS, improve the rate of thrombolysis and benefit patients who had a stroke, Chinese Stroke Association has organised and developed this scientific statement. PMID:28989804

A qualitative study exploring patients' experiences of standard care or cardiac rehabilitation post minor stroke and transient ischaemic attack.

PubMed

Hillsdon, Kaye M; Kersten, Paula; Kirk, Hayden J S

2013-09-01

To explore individuals' experiences of receiving either standard care or comprehensive cardiac rehabilitation post minor stroke or transient ischaemic attack. A qualitative study using semi-structured interviews, alongside a randomized controlled trial, exploring the effectiveness of comprehensive cardiac rehabilitation compared with standard care. Interviews were transcribed verbatim and subjected to thematic analysis. Individuals' homes. People who have experienced a minor stroke or transient ischaemic attack and who were partaking in a secondary prevention randomized controlled trial (6-7 months post the event, 17 males, five females; mean age 67 years). Not relevant. Not relevant. Four themes were identified: information delivery, comparing oneself with others, psychological impact, attitudes and actions regarding risk factor reduction. Participants indicated a need for improved information delivery, specific to their own risk factors and lifestyle changes. Many experienced psychological impact as a result of their minor stroke. Participants were found to make two types of social comparison; the comparison of self to another affected by stroke, and the comparison of self to cardiac patients. Comprehensive cardiac rehabilitation was reported to have positive effects on people's motivation to exercise. Following a minor stroke, many individuals do not recall information given or risk factors specific to them. Downward comparison with individuals who have had a cardiovascular event led to some underplaying the significance of their minor stroke.

Abnormal blood pressure circadian rhythm in acute ischaemic stroke: are lacunar strokes really different?

PubMed

Castilla-Guerra, L; Espino-Montoro, A; Fernández-Moreno, M C; López-Chozas, J M

2009-08-01

A pathologically reduced or abolished circadian blood pressure variation has been described in acute stroke. However, studies on alterations of circadian blood pressure patterns after stroke and stroke subtypes are scarce. The objective of this study was to evaluate the changes in circadian blood pressure patterns in patients with acute ischaemic stroke and their relation to the stroke subtype. We studied 98 consecutive patients who were admitted within 24 h after ischaemic stroke onset. All patients had a detailed clinical examination, laboratory studies and a CT scan study of the brain on admission. To study the circadian rhythm of blood pressure, a continuous blood pressure monitor (Spacelab 90217) was used. Patients were classified according to the percentage fall in the mean systolic blood pressure or diastolic blood pressure at night compared with during the day as: dippers (fall> or =10-20%); extreme dippers (> or =20%); nondipper (<10%); and reverse dippers (<0%, that is, an increase in the mean nocturnal blood pressure compared with the mean daytime blood pressure). Data were separated and analysed in two groups: lacunar and nonlacunar infarctions. Statistical testing was conducted using the SSPS 12.0. Methods We studied 60 males and 38 females, mean age: 70.5+/-11 years. The patient population consisted of 62 (63.2%) lacunar strokes and 36 (36.8%) nonlacunar strokes. Hypertension was the most common risk factor (67 patients, 68.3%). Other risk factors included hypercholesterolaemia (44 patients, 44.8%), diabetes mellitus (38 patients, 38.7%), smoking (24 patients, 24.8%) and atrial fibrillation (19 patients, 19.3%). The patients with lacunar strokes were predominantly men (P=0.037) and had a lower frequency of atrial fibrillation (P=0.016) as compared with nonlacunar stroke patients. In the acute phase, the mean systolic blood pressure was 136+/-20 mmHg and diastolic blood pressure was 78.7+/-11.8. Comparing stroke subtypes, there were no differences in 24-h systolic blood pressure and 24-h diastolic blood pressure between patients with lacunar and nonlacunar infarction. However, patients with lacunar infarction showed a mean decline in day-night systolic blood pressure and diastolic blood pressure of approximately 4 mmHg [systolic blood pressure: 3.9 (SD 10) mmHg, P=0.003; diastolic blood pressure 3.7 (SD 7) mmHg, P=0.0001] compared with nonlacunar strokes. Nonlacunar strokes showed a lack of 24-h nocturnal systolic blood pressure and diastolic blood pressure fall. The normal diurnal variation in systolic blood pressure was abolished in 87 (88.9%) patients, and the variation in diastolic blood pressure was abolished in 76 (77.5%) patients. On comparing lacunar and nonlacunar strokes, we found that the normal diurnal variation in systolic blood pressure was abolished in 53 (85.4%) lacunar strokes and in 34 (94.4%) nonlacunar strokes (P=nonsignificant). In terms of diurnal variation in diastolic blood pressure, it was abolished in 43 (69.3%) lacunar strokes and in 33 (91.6%) nonlacunar strokes (P=0.026). Our results show clear differences in the blood pressure circadian rhythm of acute ischaemic stroke between lacunar and nonlacunar infarctions by means of 24-h blood pressure monitoring. The magnitude of nocturnal systolic and diastolic blood pressure dip was significantly higher in lacunar strokes. Besides, patients with lacunar strokes presented a higher percentage of dipping patterns in the diastolic blood pressure circadian rhythm. Therefore, one should consider the ischaemic stroke subtype when deciding on the management of blood pressure in acute stroke.

Adverse events with intravitreal injection of vascular endothelial growth factor inhibitors: nested case-control study

PubMed Central

Gill, Sudeep S; Bronskill, Susan E; Paterson, J Michael; Whitehead, Marlo

2012-01-01

Objective To assess the risk of systemic adverse events associated with intravitreal injections of vascular endothelial growth factor inhibiting drugs. Design Population based nested case-control study. Setting Ontario, Canada. Participants 91 378 older adults with a history of physician diagnosed retinal disease identified between 1 April 2006 and 31 March 2011. Cases were 1477 patients admitted to hospital for ischaemic stroke, 2229 admitted for an acute myocardial infarction, 1059 admitted or assessed in an emergency department for venous thromboembolism, and 2623 admitted for congestive heart failure. Event-free controls (at a ratio of 5:1) were matched to cases on the basis of year of birth, sex, history of the outcome in the previous 5 years, and diabetes. Main exposure measure Exposure to vascular endothelial growth factor inhibiting drugs identified within 180 days before the index date. Results After adjustment for potential confounders, participants who had ischaemic stroke, acute myocardial infarction, congestive heart failure, or venous thromboembolism were not more likely than control participants to have been exposed to either bevacizumab (adjusted odds ratios of 0.95 (95% confidence interval 0.68 to 1.34) for ischaemic stroke, 1.04 (0.77 to 1.39) for acute myocardial infarction, 0.81 (0.49 to 1.34) for venous thromboembolism, and 1.21 (0.91 to 1.62) for congestive heart failure) or ranibizumab (adjusted odds ratios 0.87 (0.68 to 1.10) for ischaemic stroke, 0.90 (0.72 to 1.11) for acute myocardial infarction, 0.88 (0.67 to 1.16) for venous thromboembolism, and 0.87 (0.70 to 1.07) for congestive heart failure). Similarly, a secondary analysis of exclusive users of bevacizumab or ranibizumab showed no differences in risk between the two drugs (adjusted odds ratios for bevacizumab relative to ranibizumab of 1.03 (0.67 to 1.60) for ischaemic stroke, 1.23 (0.85 to 1.77) for acute myocardial infarction, 0.92 (0.51 to 1.69) for venous thromboembolism, and 1.35 (0.93 to 1.95) for congestive heart failure). These findings were consistent for all but one outcome in subgroup analyses. Conclusions Intravitreal injections of bevacizumab and ranibizumab were not associated with significant risks of ischaemic stroke, acute myocardial infarction, congestive heart failure, or venous thromboembolism. PMID:22763393

Adiposity and risk of ischaemic and haemorrhagic stroke in 0·5 million Chinese men and women: a prospective cohort study.

PubMed

Chen, Zhengming; Iona, Andri; Parish, Sarah; Chen, Yiping; Guo, Yu; Bragg, Fiona; Yang, Ling; Bian, Zheng; Holmes, Michael V; Lewington, Sarah; Lacey, Ben; Gao, Ruqin; Liu, Fang; Zhang, Zengzhi; Chen, Junshi; Walters, Robin G; Collins, Rory; Clarke, Robert; Peto, Richard; Li, Liming

2018-06-01

China has high stroke rates despite the population being relatively lean. Uncertainty persists about the relevance of adiposity to risk of stroke types. We aimed to assess the associations of adiposity with incidence of stroke types and effect mediation by blood pressure in Chinese men and women. The China Kadoorie Biobank enrolled 512 891 adults aged 30-79 years from ten areas (five urban and five rural) during 2004-08. During a median 9 years (IQR 8-10) of follow-up, 32 448 strokes (about 90% confirmed by neuroimaging) were recorded among 489 301 participants without previous cardiovascular disease. Cox regression analysis was used to produce adjusted hazard ratios (HRs) for ischaemic stroke (n=25 210) and intracerebral haemorrhage (n=5380) associated with adiposity. Mean baseline body-mass index (BMI) was 23·6 kg/m 2 (SD 3·2), and 331 723 (67·8%) participants had a BMI of less than 25 kg/m 2 . Throughout the range examined (mean 17·1 kg/m 2 [SD 0·9] to 31·7 kg/m 2 [2·0]), each 5 kg/m 2 higher BMI was associated with 8·3 mm Hg (SE 0·04) higher systolic blood pressure. BMI was positively associated with ischaemic stroke, with an HR of 1·30 (95% CI 1·28-1·33 per 5 kg/m 2 higher BMI), which was generally consistent with that predicted by equivalent differences in systolic blood pressure (1·25 [1·24-1·26]). The HR for intracerebral haemorrhage (1·11 [1·07-1·16] per 5 kg/m 2 higher BMI) was less extreme, and much weaker than that predicted by the corresponding difference in systolic blood pressure (1·48 [1·46-1·50]). Other adiposity measures showed similar associations with stroke types. After adjustment for usual systolic blood pressure, the positive associations with ischaemic stroke were attenuated (1·05 [1·03-1·07] per 5 kg/m 2 higher BMI); for intracerebral haemorrhage, they were reversed (0·73 [0·70-0·77]). High adiposity (BMI >23 kg/m 2 ) accounted for 14·7% of total stroke (16·5% of ischaemic stroke and 6·7% of intracerebral haemorrhage). In Chinese adults, adiposity was strongly positively associated with ischaemic stroke, chiefly through its effect on blood pressure. For intracerebral haemorrhage, leanness, either per se or through some other factor (or factors), might increase risk, offsetting the protective effects of lower blood pressure. UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, Chinese National Natural Science Foundation. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

High urinary albumin/creatinine ratio at admission predicts poor functional outcome in patients with acute ischaemic stroke.

PubMed

Watanabe, Yoko; Suda, Satoshi; Kanamaru, Takuya; Katsumata, Toshiya; Okubo, Seiji; Kaneko, Tomohiro; Mii, Akiko; Sakai, Yukinao; Katayama, Yasuo; Kimura, Kazumi; Tsuruoka, Shuichi

2017-03-01

Albuminuria and a low estimated glomerular filtration rate (eGFR) are widely recognized indices of kidney dysfunction and have been linked to cardiovascular events, including stroke. We evaluated albuminuria, measured using the urinary albumin/creatinine ratio (UACR), and the eGFR in the acute phase of ischaemic stroke, and investigated the clinical characteristics of ischaemic stroke patients with and those without kidney dysfunction. The study included 422 consecutive patients admitted between June 2010 and May 2012. General blood and urine examinations were performed at admission. Kidney dysfunction was defined as a low eGFR (<60 mL/min per 1.73 m 2 ), high albuminuria (≥30 mg/g creatinine), or both. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and the modified Rankin scale (mRS) at discharge. A poor outcome was defined as a mRS score of 3-5 or death. The impacts of the eGFR and UACR on outcomes at discharge were evaluated using multiple logistic regression analysis. Kidney dysfunction was diagnosed in 278 of the 422 patients (65.9%). The eGFR was significantly lower and UACR was significantly higher in patients with a poor outcome than in those with a good outcome. In multivariate analyses performed after adjusting for confounding factors, UACR >31.2 mg/g creatinine (OR, 2.58; 95% CI, 1.52-4.43; P = 0.0005) was independently associated with a poor outcome, while a low eGFR was not associated. A high UACR at admission may predict a poor outcome at discharge in patients with acute ischaemic stroke. © 2016 Asian Pacific Society of Nephrology.

Functional status and use of healthcare facilities in long‐term survivors of transient ischaemic attack or minor ischaemic stroke

PubMed Central

van Wijk, I; Lindeman, E; Kappelle, L J; van Gijn, J; Koudstaal, P J; Gorter, J W; Algra, A

2006-01-01

Background Stroke may have a major effect on survivors and on the healthcare system. Aims To study the functional status and use of healthcare facilities in long‐term survivors of a transient ischaemic attack (TIA) or minor ischaemic stroke (MIS) and evaluate associations with baseline and follow‐up characteristics. Methods Follow‐up of patients who had participated in the Dutch TIA Trial or the European Atrial Fibrillation Trial was extended to a mean period of 15.6 years. Patients were interviewed through a postal questionnaire (n = 468) and a sample of this group was also interviewed at home (n = 198). Demographic data, information on comorbidity, functional status (Barthel Index, Frenchay Activities Index and modified Rankin Scale) and use of healthcare facilities were recorded. Results About one third of the survivors interviewed at home experienced any residual disability and 26% were moderately to severely handicapped. Factors associated with poor functional status were advanced age and the presence of any infarct on a baseline computed tomography scan, the recurrence of a new major stroke or the presence of comorbidity of locomotion. One third of survivors used any kind of professional care, which was predominantly related to the functional status at follow‐up. Conclusions Recurrent stroke and the presence of comorbidity of locomotion are important determinants of long‐term disability of survivors of a TIA or an MIS, which, in turn, is strongly associated with the long‐term use of professional care. The need for measuring comorbidity with regard to functional status is recommended in research on stroke outcome. PMID:16735396

Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: an individual patient data meta-analysis of randomised controlled trials

PubMed Central

Whiteley, William N; Adams, Harold P; Bath, Philip MW; Berge, Eivind; Sandset, Per Morten; Dennis, Martin; Murray, Gordon D; Wong, Ka-Sing Lawrence; Sandercock, Peter AG

2013-01-01

Summary Background Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke. Methods We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome “dead or dependent” in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis. Findings Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59–0·67) and for haemorrhagic events was 0·60 (0·55–0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events. Interpretation There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable to define a targeted approach to select the patients who would benefit from treatment with early anticoagulant therapy. We recommend that guidelines for routine or selective use of heparin in stroke should be revised. Funding MRC. PMID:23642343

Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: an individual patient data meta-analysis of randomised controlled trials.

PubMed

Whiteley, William N; Adams, Harold P; Bath, Philip M W; Berge, Eivind; Sandset, Per Morten; Dennis, Martin; Murray, Gordon D; Wong, Ka-Sing Lawrence; Sandercock, Peter A G

2013-06-01

Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke. We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome "dead or dependent" in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis. Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59-0·67) and for haemorrhagic events was 0·60 (0·55-0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events. There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable to define a targeted approach to select the patients who would benefit from treatment with early anticoagulant therapy. We recommend that guidelines for routine or selective use of heparin in stroke should be revised. MRC. Copyright © 2013 Elsevier Ltd. All rights reserved.

Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study

PubMed Central

Markus, Hugh S; King, Alice; Shipley, Martin; Topakian, Raffi; Cullinane, Marisa; Reihill, Sheila; Bornstein, Natan M; Schaafsma, Arjen

2010-01-01

Summary Background Whether surgery is beneficial for patients with asymptomatic carotid stenosis is controversial. Better methods of identifying patients who are likely to develop stroke would improve the risk–benefit ratio for carotid endarterectomy. We aimed to investigate whether detection of asymptomatic embolic signals by use of transcranial doppler (TCD) could predict stroke risk in patients with asymptomatic carotid stenosis. Methods The Asymptomatic Carotid Emboli Study (ACES) was a prospective observational study in patients with asymptomatic carotid stenosis of at least 70% from 26 centres worldwide. To detect the presence of embolic signals, patients had two 1 h TCD recordings from the ipsilateral middle cerebral artery at baseline and one 1 h recording at 6, 12, and 18 months. Patients were followed up for 2 years. The primary endpoint was ipsilateral stroke and transient ischaemic attack. All recordings were analysed centrally by investigators masked to patient identity. Findings 482 patients were recruited, of whom 467 had evaluable recordings. Embolic signals were present in 77 of 467 patients at baseline. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack from baseline to 2 years in patients with embolic signals compared with those without was 2·54 (95% CI 1·20–5·36; p=0·015). For ipsilateral stroke alone, the hazard ratio was 5·57 (1·61–19·32; p=0·007). The absolute annual risk of ipsilateral stroke or transient ischaemic attack between baseline and 2 years was 7·13% in patients with embolic signals and 3·04% in those without, and for ipsilateral stroke was 3·62% in patients with embolic signals and 0·70% in those without. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack for patients who had embolic signals on the recording preceding the next 6-month follow-up compared with those who did not was 2·63 (95% CI 1·01–6·88; p=0·049), and for ipsilateral stroke alone the hazard ratio was 6·37 (1·59–25·57; p=0·009). Controlling for antiplatelet therapy, degree of stenosis, and other risk factors did not alter the results. Interpretation Detection of asymptomatic embolisation on TCD can be used to identify patients with asymptomatic carotid stenosis who are at a higher risk of stroke and transient ischaemic attack, and also those with a low absolute stroke risk. Assessment of the presence of embolic signals on TCD might be useful in the selection of patients with asymptomatic carotid stenosis who are likely to benefit from endarterectomy. Funding British Heart Foundation. PMID:20554250

Electrolyte changes in stroke.

PubMed

Alam, M N; Uddin, M J; Rahman, K M; Ahmed, S; Akhter, M; Nahar, N; Swapan, M K; Alam, M M; Sultana, N; Hallaz, M M; Alam, M M; Uddin, M M; Bari, M S; Israil, M A

2012-10-01

The present study was carried out in the department of Neurology and Medicine, Mymensingh Medical College Hospital, Bangladesh during the period of January 2009 to December 2010 to see the electrolyte changes in stroke. The serum concentration of Na⁺, K⁺, and Cl⁻ were measured in 110 cases during acute period of stroke (55 ischemic and 55 haemorrhagic strokes). Data were analyzed by computer with SPSS programme using 't' test and chi square test. In haemorrhagic stroke, out of 55 patients 29(52.72%) had abnormal sodium level, of them 23(41.8%) had hyponatremia, 6(10.9%) had hypernatremia. In contrast in ischemic stroke 23(41.80%) out of 55 had abnormal sodium level, of them 21(38%) had hyponatremia. The result showed that hyponatremia is almost equally common in both haemorrhagic and ischaemic group without significant difference (p>0.05). The study also revealed that hyponatremia is more common than hypernatremia in both groups. Mean ± SD of age of the haemorrhagic group was 60.80 ± 15.97 while the age of ischaemic group was 59.89 ± 15.84 years. Male, female ratio in haemorrhagic and ischaemic group 1:0.62 and 1:0.89 respectively. Mean ± SD of serum Na⁺, K⁺, Cl⁻ in haemorrhagic group were 136.18 ± 10.5, 3.83 ± 0.65, 97.96 ± 16.74 mmol/L, in ischaemic group 135.08 ± 9.08, 4.00 ± 0.75, 100.27 ± 8.39 mmol/L. The result showed no significant difference in haemorrhagic and ischemic stroke. Hyponatremia, hypokalamia and hyperchloredemia were more common than hypernatremia, hyperkalamia and hyperchloredemia. In haemorrhagic stroke, out of 55 patients, 21(38.18%) had abnormal potassium level, of them 19(34.55%) had hypokalemia, 2(3.63%) had hyperkalemia. In contrasts, in ischemic stroke, 15 out of 55(27.22%) had abnormal potassium level. Of them 12(21.81%) had hypokalemia and 3(5.45%) had hyperkalemia. The finding showed that hypokalemia is almost equally common in both haemorrhagic and ischaemic group without significant difference. The study also revealed that hypokalemia is more common than hyperkalemia in both groups. In haemorrhagic stroke, out of 55 patients 33(60%) had abnormal chloride level. Of them 20(36.4%) had hypochrloridemia, 13(23%) had hyperchrloridemia, in contrast, in ischemic stroke, 40 out of 55(60%) had abnormal chloride level, of them 22(40%) had hypochrloridemia and 18(32.7%) had hyperchrloridemia. The result showed that changes in chloride level after haemorrhagic and ischemic stroke are similar. The result showed hypochrloridemia is more common than hyperchrloridemia in both groups.

Lesion patterns in patients with cryptogenic stroke with and without right-to-left-shunt.

PubMed

Feurer, R; Sadikovic, S; Esposito, L; Schwarze, J; Bockelbrink, A; Hemmer, B; Sander, D; Poppert, H

2009-10-01

Despite numerous studies, the role of patent foramen ovale (PFO) as a risk factor for stroke due to paradoxical embolism is still controversial. On the assumption that specific lesion patterns, in particular multiple acute ischaemic lesions on diffusion-weighted magnetic resonance imaging, indicate a cardioembolic origin, we compared the MRI findings in stroke patients with right-to-left shunt (RLS) and those without. The records of 486 patients with diagnosis of cerebral ischaemia were reviewed. For detection of RLS, contrast-enhanced transcranial Doppler (c-TCD) was carried out in all patients. An MRI scan of the brain was performed in all patients. Affected vascular territories were divided into anterior cerebral artery, middle cerebral artery, vertebrobasilar artery system including posterior cerebral artery, brain stem and cerebellar stroke, and strokes occurring in more than one territory. We did not find a specific difference in neuroradiological lesion patterns in patients with RLS compared with patients without RLS. In particular, 23 of 165 patients (13.9%) with RLS showed multiple ischaemic lesions on MRI in comparison with 45 of 321 patients (14.0%) without RLS (P = 0.98). These findings also applied for the subgroup of cryptogenic strokes with and without RLS. We found no association between an ischaemic lesion pattern that is considered as being typical for stroke due to cardiac embolism and the existence of PFO. Therefore, our findings do not provide any support for the common theory of paradoxical embolism as a major cause of stroke in PFO carriers.

Stroke in young adults: Incidence rate, risk factors, treatment and prognosis.

PubMed

González-Gómez, F J; Pérez-Torre, P; DeFelipe, A; Vera, R; Matute, C; Cruz-Culebras, A; Álvarez-Velasco, R; Masjuan, J

2016-10-01

To analyse the incidence, risk factors, aetiology, treatment and clinical evolution of young patients with stroke. Retrospective registry of patients aged 55 years or younger hospitalised in a stroke unit during 2014. We recorded the incidence rate for all strokes and analysed demographic data, risk factors, degree of stress, stroke type and aetiology, reperfusion treatments and clinical evolution. The study included 110 patients, the majority of whom were men (60.9%, 1.6:1 ratio). The incidence rate was 13.3% (110 of 830 strokes). Most of the patients had cardiovascular risk factors. Smoking was the most common risk factor (56.4%), followed by arterial hypertension (50%), dyslipidaemia (42.7%), obesity (33%), diabetes (18.2%) and emboligenic heart disease (12.7%). Some 64.3% of the heart disease cases and 51.1% of the dyslipidaemia cases were discovered during hospitalisation. Some 57.2% of the patients experienced psychosocial stress in the stage prior to the stroke. Some 83.6% of the stroke cases were ischaemic, 12.7% were haemorrhagic and 3.6% were venous sinus thrombosis. Of the ischaemic stroke cases, 30.4% were cryptogenic, 23.9% were lacunar, 16.3% were from uncommon causes, 15.2% were atherothrombotic and 14.1% were cardioembolic. Some 78.6% of the cerebral haemorrhage cases were hypertensive. Some 23.3% of the ischaemic stroke cases underwent reperfusion treatments in the acute phase, achieving levels of functional independence at 3 months of 62.5%. The majority of stroke events in patients 55 years of age or younger appear to be related to a high prevalence of classical cardiovascular risk factors and possibly to psychosocial stress. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

[Endovascular treatment in acute ischaemic stroke. A stroke care plan for the region of Madrid].

PubMed

Alonso de Leciñana, M; Díaz-Guzmán, J; Egido, J A; García Pastor, A; Martínez-Sánchez, P; Vivancos, J; Díez-Tejedor, E

2013-09-01

Endovascular therapies (intra-arterial thrombolysis and mechanical thrombectomy) after acute ischaemic stroke are being implemented in the clinical setting even as they are still being researched. Since we lack sufficient data to establish accurate evidence-based recommendations for use of these treatments, we must develop clinical protocols based on current knowledge and carefully monitor all procedures. After review of the literature and holding work sessions to reach a consensus among experts, we developed a clinical protocol including indications and contraindications for endovascular therapies use in acute ischaemic stroke. The protocol includes methodology recommendations for diagnosing and selecting patients, performing revascularisation procedures, and for subsequent patient management. Its objective is to increase the likelihood of efficacy and treatment benefit and minimise risk of complications and ineffective recanalisation. Based on an analysis of healthcare needs and available resources, a cooperative inter-hospital care system has been developed. This helps to ensure availability of endovascular therapies to all patients, a fast response time, and a good cost-to-efficacy ratio. It includes also a prospective register which serves to monitor procedures in order to identify any opportunities for improvement. Implementation of endovascular techniques for treating acute ischaemic stroke requires the elaboration of evidence-based clinical protocols and the establishment of appropriate cooperative healthcare networks guaranteeing both the availability and the quality of these actions. Such procedures must be monitored in order to improve methodology. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

High frequency of intracranial arterial stenosis and cannabis use in ischaemic stroke in the young.

PubMed

Wolff, Valérie; Armspach, Jean-Paul; Beaujeux, Rémy; Manisor, Monica; Rouyer, Olivier; Lauer, Valérie; Meyer, Nicolas; Marescaux, Christian; Geny, Bernard

2014-01-01

Leading aetiologies of ischaemic stroke in young adults are cervico-cerebral arterial dissections and cardio-embolism, but the causes remain undetermined in a considerable proportion of cases. In a few reports, intracranial arterial stenosis has been suggested to be a potential cause of ischaemic stroke in young adults. The aim of our work was to evaluate the frequency, characteristics and risk factors of intracranial arterial stenosis in a prospective series of young ischaemic stroke patients. The study was based on a prospective consecutive hospital-based series of 159 patients aged 18-45 years who were admitted to our unit for an acute ischaemic stroke from October 2005 to December 2010. A structured questionnaire was used in order to assess common vascular risk factors such as hypertension, diabetes, hypercholesterolemia, use of tobacco, alcohol and illicit drugs, migraine, and, in women, oral contraceptive use. A systematic screening was performed, including the following: brain magnetic resonance imaging or, if not feasible, brain computed tomography scan, carotid and vertebral Duplex scanning and trans-cranial Doppler sonography, 3D time-of-flight magnetic resonance cerebral angiography or cerebral computed tomography angiography. Long-duration electrocardiography, trans-thoracic and trans-oesophageal echocardiography were performed and laboratory blood investigations were extensive. Urine samples were screened for cannabinoids, cocaine, amphetamine and methylene-dioxy-methamphetamine. When this initial work-up was inconclusive, trans-femoral intra-arterial selective digital subtraction angiography with reconstructed 3D images was performed. In this series, 49 patients (31%) had intracranial arterial stenosis. Other defined causes were found in 91 patients (57%), including cardio-embolism in 32 (20%), cervical dissection in 23 (14%), extracranial atherosclerosis in 7 (4%), haematological disorders in 7 (4%), small vessel disease in 1, and isolated patent foramen ovale in 21 (13%); in 19 patients (12%), ischaemic stroke was related to an undetermined aetiology. Comparing risk factors between patients with intracranial arterial stenosis and those with other definite causes showed that there were only two significant differences: a lower age and a higher frequency of vasoactive substances (especially cannabis) in patients with intracranial arterial stenosis. All intracranial arterial stenosis in patients who used vasoactive substances were located in several intracranial vessels. Intracranial arterial stenosis may be an important mechanism of stroke in young patients and it should be systematically investigated using vascular imaging. Strong questioning about illicit drug consumption (including cannabis) or vasoactive medication use should also be performed. It should be emphasized for health prevention in young adults that cannabis use might be associated with critical consequences such as stroke. © 2014 S. Karger AG, Basel.

Haemodilution for acute ischaemic stroke

PubMed Central

Chang, Timothy S; Jensen, Matthew B

2014-01-01

Background Ischaemic stroke interrupts the flow of blood to part of the brain. Haemodilution is thought to improve the flow of blood to the affected areas of the brain and thus reduce infarct size. Objectives To assess the effects of haemodilution in acute ischaemic stroke. Search methods We searched the Cochrane Stroke Group Trials Register (February 2014), the Cochrane Central Register of Controlled Trials (Issue 1, 2014), MEDLINE (January 2008 to October 2013) and EMBASE (January 2008 to October 2013). We also searched trials registers, scanned reference lists and contacted authors. For the previous version of the review, the authors contacted manufacturers and investigators in the field. Selection criteria Randomised trials of haemodilution treatment in people with acute ischaemic stroke. We included only trials in which treatment was started within 72 hours of stroke onset. Data collection and analysis Two review authors assessed trial quality and one review author extracted the data. Main results We included 21 trials involving 4174 participants. Nine trials used a combination of venesection and plasma volume expander. Twelve trials used plasma volume expander alone. The plasma volume expander was plasma alone in one trial, dextran 40 in 12 trials, hydroxyethyl starch (HES) in five trials and albumin in three trials. Two trials tested haemodilution in combination with another therapy. Evaluation was blinded in 14 trials. Five trials probably included some participants with intracerebral haemorrhage. Haemodilution did not significantly reduce deaths within the first four weeks (risk ratio (RR) 1.10; 95% confidence interval (CI) 0.90 to 1.34). Similarly, haemodilution did not influence deaths within three to six months (RR 1.05; 95% CI 0.93 to 1.20), or death and dependency or institutionalisation (RR 0.96; 95% CI 0.85 to 1.07). The results were similar in confounded and unconfounded trials, and in trials of isovolaemic and hypervolaemic haemodilution. No statistically significant benefits were documented for any particular type of haemodiluting agents, but the statistical power to detect effects of HES was weak. Six trials reported venous thromboembolic events. There was a tendency towards reduction in deep venous thrombosis or pulmonary embolism or both at three to six months’ follow-up (RR 0.68; 95% CI 0.37 to 1.24). There was no statistically significant increased risk of serious cardiac events among haemodiluted participants. Authors’ conclusions The overall results of this review showed no clear evidence of benefit of haemodilution therapy for acute ischaemic stroke. These results are compatible with no persuasive beneficial evidence of haemodilution therapy for acute ischaemic stroke. This therapy has not been proven to improve survival or functional outcome. PMID:25159027

Endovascular stent thrombectomy: the new standard of care for large vessel ischaemic stroke.

PubMed

Campbell, Bruce C V; Donnan, Geoffrey A; Lees, Kennedy R; Hacke, Werner; Khatri, Pooja; Hill, Michael D; Goyal, Mayank; Mitchell, Peter J; Saver, Jeffrey L; Diener, Hans-Christoph; Davis, Stephen M

2015-08-01

Results of initial randomised trials of endovascular treatment for ischaemic stroke, published in 2013, were neutral but limited by the selection criteria used, early-generation devices with modest efficacy, non-consecutive enrollment, and treatment delays. In the past year, six positive trials of endovascular thrombectomy for ischaemic stroke have provided level 1 evidence for improved patient outcome compared with standard care. In most patients, thrombectomy was performed in addition to thrombolysis with intravenous alteplase, but benefits were also reported in patients ineligible for alteplase treatment. Despite differences in the details of eligibility requirements, all these trials required proof of major vessel occlusion on non-invasive imaging and most used some imaging technique to exclude patients with a large area of irreversibly injured brain tissue. The results indicate that modern thrombectomy devices achieve faster and more complete reperfusion than do older devices, leading to improved clinical outcomes compared with intravenous alteplase alone. The number needed to treat to achieve one additional patient with independent functional outcome was in the range of 3·2-7·1 and, in most patients, was in addition to the substantial efficacy of intravenous alteplase. No major safety concerns were noted, with low rates of procedural complications and no increase in symptomatic intracerebral haemorrhage. WHERE NEXT?: Thrombectomy benefits patients across a range of ages and levels of clinical severity. A planned meta-analysis of individual patient data might clarify effects in under-represented subgroups, such as those with mild initial stroke severity or elderly patients. Imaging-based selection, used in some of the recent trials to exclude patients with large areas of irreversible brain injury, probably contributed to the proportion of patients with favourable outcomes. The challenge is how best to implement imaging in clinical practice to maximise benefit for the entire population and to avoid exclusion of patients with smaller yet clinically important potential to benefit. Although favourable imaging identifies patients who might benefit despite long delays from symptom onset to treatment, the proportion of patients with favourable imaging decreases with time. Health systems therefore need to be reorganised to deliver treatment as quickly as possible to maximise benefits. On the basis of available trial data, intravenous alteplase remains the initial treatment for all eligible patients within 4·5 h of stroke symptom onset. Those patients with major vessel occlusion should, in parallel, proceed to endovascular thrombectomy immediately rather than waiting for an assessment of response to alteplase, because minimising time to reperfusion is the ultimate aim of treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of acupuncture therapy as a supplement to conventional medical treatments for acute ischaemic stroke patients in an academic medical centre in Korea.

PubMed

Chang, Hyejung; Kwon, Young Dae; Yoon, Sung Sang

2011-10-01

Acupuncture has served as a major complementary and alternative therapy that supplements conventional medicine and is the subject of growing public interest. This study was conducted to estimate the usage rate of acupuncture as a supplemental treatment in acute ischaemic stroke patients and to identify factors associated with the choice to use this therapy. Using the registry of stroke patients admitted to an academic medical centre in Korea, the use of acupuncture therapy was recorded and analysed, along with the patients' socio-demographic characteristics, hospital access variables, risk factors for ischaemic stroke and clinical characteristics. The data were analysed using descriptive statistics, chi-square tests and multiple logistic regression analyses. Of 2167 patients, 18% received acupuncture therapy. The choice of acupuncture therapy was significantly associated with stroke severity as well as gender, age, geographical residence and previous history of stroke. After controlling for other significant factors, there was an approximately 3.4-fold greater usage in patients with moderately severe strokes (95% confidence interval (CI)=2.5-4.6) and 4.1-fold greater usage in patients with severe strokes (95% CI=2.7-6.4). The findings provide a better understanding of patients' utilization of acupuncture therapy as a supplement to conventional medical treatments and of factors associated with the utilization of acupuncture in patients with acute ischemic stroke. Strategic implications of acupuncture therapy are suggested for both health-care providers and policy makers. Copyright © 2011 Elsevier Ltd. All rights reserved.

Blood pressure in the initial phase of acute ischaemic stroke: evolution and its role as an independent prognosis factor at discharge and after 3 months of follow-up.

PubMed

Armario, Pedro; Mártin-Baranera, Montserrat; Miguel Ceresuela, Luis; Hernández Del Rey, Raquel; Iribarnegaray, Eduardo; Pintado, Sara; Avila, Asunción; Bello, Juan; Luis Tovar, José; Alvarez-Sabin, José

2008-01-01

A prospective observational study was aimed at assessing the role of blood pressure (BP) during the first 24 h from stroke onset on the outcome of acute ischaemic stroke. Subjects admitted within the first 3 h from stroke onset were included. Stroke severity was evaluated with the Canadian Stroke Scale (CSS). Functional recovery was defined as a modified Rankin Scale score < or =2. One hundred subjects were included. In a logistic regression model, the independent predictors of poor functional recovery at discharge were: age (OR = 1.12; 95% CI 1.04-1.21; p = 0.0033), non-lacunar stroke subtype (OR = 4.31; 95% CI 1.07-17.31; p = 0.0395), diabetes mellitus (OR = 8.38; 95% CI 1.67-41.95; p = 0.0097), a CSS score at admission < or =8 (OR = 28.64; 95% CI 5.59-146.68; p<0.0001), an average systolic BP during the first 6 h > or =180 mmHg (OR = 13.34; 95% CI 1.34-133.10; p = 0.0272) and a lower diastolic BP average from 6 to 24 h (OR for 5 mmHg increase: 0.57; CI 95% 0.36-0.88; p = 0.0115). Similar results were observed after 3 months of follow-up. In ischaemic stroke patients, systolic BP over 180 mmHg in the first 6 h and a decrease of diastolic BP during the 6-24 h from stroke onset were independent predictors of a poor functional recovery.

Helicobacter pylori infection: a risk factor for ischaemic cerebrovascular disease and carotid atheroma

PubMed Central

Markus, H.; Mendall, M.

1998-01-01

OBJECTIVES—Chronic Helicobacter pylori infection has been associated with ischaemic heart disease although the mechanism by which it mediates this effect remains unclear.The objective was to determine whether it is also a risk factor for ischaemic cerebrovascular disease
METHODS—A total of 238 patients and 119 controls were studied. Patients were characterised into stroke subtypes based on pathogenic mechanisms and carotid atheroma load was estimated using duplex ultrasound. H pylori seropositivity was determined on serum samples.
RESULTS—H pylori seropositivity was more common in cases (58.8% v 44.5%, p=0.01). The odds ratio for cerebrovascular disease associated with seropositivity was 1.78 (95% confidence interval (95% CI) 1.14-2.77), and this remained significant after controlling for other risk factors including socioeconomic status (1.63 (95% CI 1.02-2.60). H pylori seropositivity was associated with large vessel disease (odds ratio 2.58 (95% CI 1.44-4.63), p=0.001) and lacunar stroke (odds ratio 2.21 (95% CI 1.12-4.38), p=0.02) but not stroke due to cardioembolism or unknown aetiology (odds ratio 1.16 (95% CI 0.66-2.02), p=0.5). Mean (SD) carotid stenosis was greater in patients seropositive for H pylori (37.3 (29.7) v 27.9(26.2)%, p=0.01). There was no difference in the prevalence of seropositivity between patients with stroke and transient ischaemic attack (59.6% v 58.6%, p=0.9)
CONCLUSION—Chronic H pylori infection is an independent risk factor for ischaemic cerebrovascular disease and may act, at least in part, by increasing atherosclerosis.

 PMID:9436737

Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial.

PubMed

Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Hill, Michael D; Jonasson, Jenny; Kasner, Scott E; Ladenvall, Per; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence; Johnston, S Claiborne

2017-04-01

Ticagrelor is an effective antiplatelet therapy for patients with coronary atherosclerotic disease and might be more effective than aspirin in preventing recurrent stroke and cardiovascular events in patients with acute cerebral ischaemia of atherosclerotic origin. Our aim was to test for a treatment-by-ipsilateral atherosclerotic stenosis interaction in a subgroup analysis of patients in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial. SOCRATES was a randomised, double-blind, controlled trial of ticagrelor versus aspirin in patients aged 40 years or older with a non-cardioembolic, non-severe acute ischaemic stroke, or high-risk transient ischaemic attack from 674 hospitals in 33 countries. We randomly allocated patients (1:1) to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90, given orally) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90, given orally) within 24 h of symptom onset. Investigators classified all patients into atherosclerotic and non-atherosclerotic groups for the prespecified, exploratory analysis reported in this study. The primary endpoint was the time to occurrence of stroke, myocardial infarction, or death within 90 days. Efficacy analysis was by intention to treat. The SOCRATES trial is registered with ClinicalTrials.gov, number NCT01994720. Between Jan 7, 2014, and Oct 29, 2015, we randomly allocated 13 199 patients (6589 [50%] to ticagrelor and 6610 [50%] to aspirin). Potentially symptomatic ipsilateral atherosclerotic stenosis was reported in 3081 (23%) of 13 199 patients. We found a treatment-by-atherosclerotic stenosis interaction (p=0·017). 103 (6·7%) of 1542 patients with ipsilateral stenosis in the ticagrelor group and 147 (9·6%) of 1539 patients with ipsilateral stenosis in the aspirin group had an occurrence of stroke, myocardial infarction, or death within 90 days (hazard ratio 0·68 [95% CI 0·53-0·88]; p=0·003). In 10 118 patients with no ipsilateral stenosis, 339 (6·7%) of 5047 patients in the ticagrelor group had an occurrence of stroke, myocardial infarction, or death within 90 days compared with 350 (6·9%) of 5071 in the aspirin group (0·97 [0·84-1·13]; p=0·72). There were no significant differences in the proportion of life-threatening bleeding or major or minor bleeding events in patients with ipsilateral stenosis in the ticagrelor group compared with the aspirin group. In this prespecified exploratory analysis, ticagrelor was superior to aspirin at preventing stroke, myocardial infarction, or death at 90 days in patients with acute ischaemic stroke or transient ischaemic attack when associated with ipsilateral atherosclerotic stenosis. An understanding of stroke mechanisms and causes is important to deliver safe and efficacious treatments for early stroke prevention. AstraZeneca. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

PubMed

McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J

2015-01-15

Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights reserved.

Genetic variants influencing elevated myeloperoxidase levels increase risk of stroke.

PubMed

Phuah, Chia-Ling; Dave, Tushar; Malik, Rainer; Raffeld, Miriam R; Ayres, Alison M; Goldstein, Joshua N; Viswanathan, Anand; Greenberg, Steven M; Jagiella, Jeremiasz M; Hansen, Björn M; Norrving, Bo; Jimenez-Conde, Jordi; Roquer, Jaume; Pichler, Alexander; Enzinger, Christian; Montaner, Joan; Fernandez-Cadenas, Israel; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Biffi, Alessandro; Rost, Natalia; Langefeld, Carl D; Markus, Hugh S; Mitchell, Braxton D; Worrall, Brad B; Kittner, Steven J; Woo, Daniel; Dichgans, Martin; Rosand, Jonathan; Anderson, Christopher D

2017-10-01

Primary intracerebral haemorrhage and lacunar ischaemic stroke are acute manifestations of progressive cerebral microvascular disease. Current paradigms suggest atherosclerosis is a chronic, dynamic, inflammatory condition precipitated in response to endothelial injury from various environmental challenges. Myeloperoxidase plays a central role in initiation and progression of vascular inflammation, but prior studies linking myeloperoxidase with stroke risk have been inconclusive. We hypothesized that genetic determinants of myeloperoxidase levels influence the development of vascular instability, leading to increased primary intracerebral haemorrhage and lacunar stroke risk. We used a discovery cohort of 1409 primary intracerebral haemorrhage cases and 1624 controls from three studies, an extension cohort of 12 577 ischaemic stroke cases and 25 643 controls from NINDS-SiGN, and a validation cohort of 10 307 ischaemic stroke cases and 29 326 controls from METASTROKE Consortium with genome-wide genotyping to test this hypothesis. A genetic risk score reflecting elevated myeloperoxidase levels was constructed from 15 common single nucleotide polymorphisms identified from prior genome-wide studies of circulating myeloperoxidase levels (P < 5 × 10-6). This genetic risk score was used as the independent variable in multivariable regression models for association with primary intracerebral haemorrhage and ischaemic stroke subtypes. We used fixed effects meta-analyses to pool estimates across studies. We also used Cox regression models in a prospective cohort of 174 primary intracerebral haemorrhage survivors for association with intracerebral haemorrhage recurrence. We present effects of myeloperoxidase elevating single nucleotide polymorphisms on stroke risk per risk allele, corresponding to a one allele increase in the myeloperoxidase increasing genetic risk score. Genetic determinants of elevated circulating myeloperoxidase levels were associated with both primary intracerebral haemorrhage risk (odds ratio, 1.07, P = 0.04) and recurrent intracerebral haemorrhage risk (hazards ratio, 1.45, P = 0.006). In analysis of ischaemic stroke subtypes, the myeloperoxidase increasing genetic risk score was strongly associated with lacunar subtype only (odds ratio, 1.05, P = 0.0012). These results, demonstrating that common genetic variants that increase myeloperoxidase levels increase risk of primary intracerebral haemorrhage and lacunar stroke, directly implicate the myeloperoxidase pathway in the pathogenesis of cerebral small vessel disease. Because genetic variants are not influenced by environmental exposures, these results provide new support for a causal rather than bystander role for myeloperoxidase in the progression of cerebrovascular disease. Furthermore, these results support a rationale for chronic inflammation as a potential modifiable stroke risk mechanism, and suggest that immune-targeted therapies could be useful for treatment and prevention of cerebrovascular disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Autologous intravenous bone marrow mononuclear cell therapy for patients with subacute ischaemic stroke: A pilot study

PubMed Central

Prasad, Kameshwar; Mohanty, Sujata; Bhatia, Rohit; Srivastava, M.V.P.; Garg, Ajay; Srivastava, Achal; Goyal, Vinay; Tripathi, Manjari; Kumar, Amit; Bal, Chandrashekar; Vij, Aarti; Mishra, Nalini Kant

2012-01-01

Background & objectives: Bone marrow mononuclear cell therapy has emerged as one of the option for the treatment of Stroke. Several preclinical studies have shown that the treatment with mononuclear cell (MNCs) can reduce the infarct size and improve the functional outcome. We evaluated the feasibility, safety and clinical outcome of administering bone marrow mononuclear cell (MNCs) intravenously to patients with subacute ischaemic stroke. Methods: In a non-randomized phase-I clinical study, 11 consecutive, eligible and consenting patients, aged 30-70 yr with ischaemic stroke involving anterior circulation within 7 to 30 days of onset of stroke were included. Bone marrow was aspirated from iliac crest and the harvested mononuclear cells were infused into antecubital vein. Outcomes measured for safety included immediate reactions after cell infusion and evidence of tumour formation at one year in whole body PET scan. Patients were followed at week 1, 4-6, 24 and 52 to determine clinical progress using National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), MRI, EEG and PET. Feasibility outcomes included target-dose feasibility. Favourable clinical outcome was defined as mRS score of 2 or less or BI score of 75 to 100 at six months after stem cell therapy. Results: Between September 2006 and April 2007, 11 patients were infused with bone-marrow mononuclear cells (mean 80 million with CD-34+ mean 0.92 million). Protocol was target-dose feasible in 9 patients (82%). FDG-PET scan at 24 and 52 wk in nine patients did not reveal evidence of tumour formation. Seven patients had favourable clinical outcome. Interpretation & conclusions: Intravenous bone marrow mononuclear cell therapy appears feasible and safe in patients with subacute ischaemic stroke. Further, a randomized controlled trial to examine its efficacy is being conducted. PMID:22960888

Management of acute ischaemic stroke at Nasser Hospital, Gaza Strip: a clinical audit.

PubMed

Alkhatib, Mohammed N; Abd-Alghafoor, Tamer; Elmassry, AlaaEldeen; Albarqouni, Loai; Böttcher, Bettina; Alfaqawi, Maha

2018-02-21

Stroke is a leading cause of morbidity and mortality worldwide. The aim of this study was to assess the standard of care for patients with acute ischaemic stroke at the internal medicine department of Nasser Hospital, Gaza Strip. For this retrospective clinical audit, we selected a random sample of 100 medical records for patients with stroke who were admitted to Nasser Hospital between January and August, 2016. Clinical practice was compared with the recommendations in the 2013 American Heart Association and American Stroke Association guidelines. Patient confidentiality was maintained, and ethical approval was obtained from the Palestinian Ministry of Health. Five patient records were not coded and therefore excluded. Of the remaining 95 patients, 51 (54%) were men with a mean age of 67 years (SD 14). 53 patients presented with dysarthria. The duration of stroke symptoms before admission was not reported in 86 (91%) records. A complete blood count and renal function tests were done for all patients, lipid profiling for 87 (92%) patients, electrocardiography for 85 (89%) patients, carotid duplex ultrasound for 32 (34%) patients, and CT scan for all patients. None of the patients had continuous cardiac monitoring or an assessment of swallowing function, and 70 (74%) patients received immediate anti-platelet therapy (325 mg aspirin). 80 (85%) patients received venous thromboembolism prophylaxis. 41 (43%) patients were given antibiotics without a recorded indication. None of the patients received thrombolytic therapy. As recommended in the guidelines, 41 (43%) patients did not receive anti-hypertensive agents on the first day of hospitalisation. 46 (48%) patients had diabetes, and glycaemic control was achieved by day 3 in 26 (57%) patients. No Palestinian guidelines exist for the management of patients with acute ischaemic stroke, and in most cases management was based on personal experience rather than evidence. The development of evidence-based guidelines is mandatory to improve management of ischaemic stroke. Furthermore, implementing staff education activities, regular clinical audit, and team feedback would encourage adherence to such guidelines. Combined with the establishment of a specialised stroke unit and development of a multidisciplinary team approach, patient outcome could be improved further. None. Copyright © 2018 Elsevier Ltd. All rights reserved.

Blood pressure as a prognostic factor after acute stroke.

PubMed

Tikhonoff, Valérie; Zhang, Haifeng; Richart, Tom; Staessen, Jan A

2009-10-01

Stroke is the second most common cause of death worldwide and is the complication of hypertension that is most directly linked to blood pressure. Hypertension affects nearly 30% of the world's population; therefore, reducing blood pressure is key for the prevention of stroke. Unlike the established role of hypertension as a risk factor for stroke, the prognostic importance of blood pressure in determining outcome after acute stroke is unclear. The acute hypertensive response occurs in more than 50% of all patients with acute stroke and is associated with poor prognosis. The relation between the outcome of acute stroke and blood pressure is U-shaped, with the best outcome at systolic blood-pressure levels ranging from about 140 to 180 mm Hg. The evidence that decreasing blood pressure in hypertensive patients with acute ischaemic or haemorrhagic stroke improves prognosis needs further confirmation. Whether raising blood pressure to improve perfusion of ischaemic brain areas is beneficial remains even more uncertain. Present guidelines for the management of blood pressure in patients with acute stroke are not evidence-based, but results from ongoing trials might provide more informed recommendations for the future.

Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study.

PubMed

Diener, Hans-Christoph; Sacco, Ralph L; Yusuf, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2008-10-01

The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT00153062. 20,332 patients (mean age 66 years) were randomised and followed-up for a median of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0.38), or with telmisartan versus placebo (p=0.61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups. Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan.

Stroke management: Informal caregivers' burdens and strians of caring for stroke survivors.

PubMed

Gbiri, Caleb Ademola; Olawale, Olajide Ayinla; Isaac, Sarah Oghenekewe

2015-04-01

Stroke survivors live with varied degrees of disabilities and cares are provided largely by the informal caregivers. This study investigated informal caregivers' burden and strains of caring for stroke patients. This study involved 157 (81 males and 76 females) informal caregivers of stroke survivors receiving care in all secondary and tertiary health institutions with physiotherapy services in Lagos State, Nigeria. Information was collected through self-administered questionnaire during clinic-hours. Data was analyzed using Spearman's Rank Correlation Coefficient. The patients' age ranged between 20 and 79 (mean=59.6 ± 14.6 years). Sixty-one had haemorrhagic stroke while 96 had ischaemic stroke. The informal caregivers' age was 39.2 ± 12.8 years (range: 17-36 years). More (60.8%) participants reported moderate objective while 79.2% had mild subjective burdens. The following factors significantly increased (P<0.05) the level of burden and strains experienced by the informal caregivers: closer intimacy with the stroke survivors, fewer number of caregivers for the stroke patient, longer duration since the onset of stroke and more hours of caregiving per day. Caregiving had negative significant influence (P<0.05) on the social, emotional, health and financial well-beings of the informal caregivers. Caring for stroke survivors put social, emotional, health and financial burdens and strains on the informal caregivers. These burdens and strains increase with duration of stroke, intimacy, smaller number of caregivers and length of daily caregiving. Therefore, informal caregivers should be involved in the rehabilitation plan for stroke patients and their well-being should also be given adequate attention. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Predictors of symptomatic intracranial haemorrhage in patients with an ischaemic stroke with neurological deterioration after intravenous thrombolysis.

PubMed

James, Brandon; Chang, Andrew D; McTaggart, Ryan A; Hemendinger, Morgan; Mac Grory, Brian; Cutting, Shawna M; Burton, Tina M; Reznik, Michael E; Thompson, Bradford; Wendell, Linda; Mahta, Ali; Siket, Matthew; Madsen, Tracy E; Sheth, Kevin N; Nouh, Amre; Furie, Karen L; Jayaraman, Mahesh V; Khatri, Pooja; Yaghi, Shadi

2018-02-27

Early neurological deterioration prompting urgent brain imaging occurs in nearly 15% of patients with ischaemic stroke receiving intravenous tissue plasminogen activator (tPA). We aim to determine risk factors associated with symptomatic intracranial haemorrhage (sICH) in patients with ischaemic stroke undergoing emergent brain imaging for early neurological deterioration after receiving tPA. We abstracted data from our prospective stroke database and included all patients receiving tPA for ischaemic stroke between 1 March 2015 and 1 March 2017. We then identified patients with neurological deterioration who underwent urgent brain imaging prior to their per-protocol surveillance imaging and divided patients into two groups: those with and without sICH. We compared baseline demographics, clinical variables, in-hospital treatments and functional outcomes at 90 days between the two groups. We identified 511 patients who received tPA, of whom 108 (21.1%) had an emergent brain CT. Of these patients, 17.5% (19/108) had sICH; 21.3% (23/108) of emergent scans occurred while tPA was infusing, though only 4.3% of these scans (1/23) revealed sICH. On multivariable analyses, the only predictor of sICH was a change in level of consciousness (OR 6.62, 95% CI 1.64 to 26.70, P=0.008). Change in level of consciousness is associated with sICH among patients undergoing emergent brain imaging after receiving tPA. In this group of patients, preparation of tPA reversal agents while awaiting brain imaging may reduce reversal times. Future studies are needed to study the cost-effectiveness of this approach. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Thrombolysis in Acute Ischaemic Stroke: An Update

PubMed Central

Robinson, Thompson; Zaheer, Zahid; Mistri, Amit K.

2011-01-01

Stroke is a major cause of mortality and morbidity, and thrombolysis has served as a catalyst for major changes in the management of acute ischaemic stroke. Intravenous alteplase (recombinant tissue plasminogen activator) is the only approved thrombolytic agent at present indicated for acute ischaemic stoke. While the licensed time window extends to 3h from symptom onset, recent data suggest that the trial window can be extended up to 4.5 h with overall benefit. Nonetheless, 'time is brain' and every effort must be made to reduce the time delay to thrombolysis. Intracranial haemorrhage is the major complication associated with thrombolysis, and key factors increasing risk of haemorrhage include increasing age, high blood pressure, diabetes and stroke severity. Currently, there is no direct evidence to support thrombolysis in patients >80 years of age, with a few case series indicating no overt harm. Identification of viable penumbra based on computed tomography/magnetic resonance imaging may allow future extension of the time window. Adjuvant transcranial Doppler ultrasound has the potential to improve reperfusion rates. While intra-arterial thrombolysis has been in vogue for a few decades, there is no clear advantage over intravenous thrombolysis. The evidence base for thrombolysis in specific situations (e.g. dissection, pregnancy) is inadequate, and individualized decisions are needed, with a clear indication to the patient/carer about the lack of direct evidence, and the risk-benefit balance. Patient-friendly information leaflets may facilitate the process of consent for thrombolysis. This article summarizes the recent advances in thrombolysis for acute ischaemic stroke. Key questions faced by clinicians during the decision-making process are answered based on the evidence available. PMID:23251746

Hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation.

PubMed

Marsh, E B; Llinas, R H; Hillis, A E; Gottesman, R F

2013-06-01

Intracerebral hemorrhage (ICH) can occur in patients following acute ischaemic stroke in the form of hemorrhagic transformation, and results in significant long-term morbidity and mortality. Anticoagulation theoretically increases risk. We evaluated stroke patients with an indication for anticoagulation to determine the factors associated with hemorrhagic transformation. Three-hundred and forty-five patients with ICD-9 codes indicating: (i) acute ischaemic stroke; and (ii) an indication for anticoagulation were screened. One-hundred and twenty-three met inclusion criteria. Data were collected retrospectively. Neuroimaging was reviewed for infarct volume and evidence of ICH. Hemorrhages were classified as: hemorrhagic conversion (petechiae) versus intracerebral hematoma (a space occupying lesion); symptomatic versus asymptomatic. Using multivariable logistic regression, we determined the hypothesized factors associated with intracerebral bleeding. Age [odds ratio (OR) = 1.50 per 10-year increment, 95% confidence interval (CI) 1.07-2.08], infarct volume (OR = 1.10 per 10 ccs, 95% CI 1.06-1.18) and worsening category of renal impairment by estimated glomerular filtration rate (eGFR; OR = 1.95, 95% CI 1.04-3.66) were predictors of hemorrhagic transformation. Ninety- nine out of 123 patients were anticoagulated. Hemorrhage rates of patients on and off anticoagulation did not differ (25.3% vs. 20.8%; P = 0.79); however, all intracerebral hematomas (n = 7) and symptomatic bleeds (n = 8) occurred in the anticoagulated group. The risk of hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation is multifactorial, and most closely associated with an individual's age, infarct volume and eGFR. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Cardiovascular risk in patients with sleep apnoea with or without continuous positive airway pressure therapy: follow-up of 4.5 million Danish adults.

PubMed

Lamberts, M; Nielsen, O W; Lip, G Y H; Ruwald, M H; Christiansen, C B; Kristensen, S L; Torp-Pedersen, C; Hansen, M L; Gislason, G H

2014-12-01

The prognostic significance of age and continuous positive airway pressure (CPAP) therapy on cardiovascular disease in patients with sleep apnoea has not been assessed previously. Using nationwide databases, the entire Danish population was followed from 2000 until 2011. First-time sleep apnoea diagnoses and use of CPAP therapy were determined. Incidence rate ratios (IRRs) of ischaemic stroke and myocardial infarction (MI) were analysed using Poisson regression models. Amongst 4.5 million individuals included in the study, 33 274 developed sleep apnoea (mean age 53, 79% men) of whom 44% received persistent CPAP therapy. Median time to initiation of CPAP therapy was 88 days (interquartile range 34-346). Patients with sleep apnoea had more comorbidities compared to the general population. Crude rates of MI and ischaemic stroke were increased for sleep apnoea patients (5.4 and 3.6 events per 1000 person-years compared to 4.0 and 3.0 in the general population, respectively). Relative to the general population, risk of MI [IRR 1.71, 95% confidence interval (CI) 1.57-1.86] and ischaemic stroke (IRR 1.50, 95% CI 1.35-1.66) was significantly increased in patients with sleep apnoea, in particular in patients younger than 50 years (IRR 2.12, 95% CI 1.64-2.74 and IRR 2.34, 95% CI 1.77-3.10, respectively). Subsequent CPAP therapy was not associated with altered prognosis. Sleep apnoea is associated with increased risk of ischaemic stroke and MI, particularly in patients younger than 50 years of age. CPAP therapy was not associated with a reduced rate of stroke or MI. © 2014 The Association for the Publication of the Journal of Internal Medicine.

Stroke.

PubMed

Hankey, Graeme J

2017-02-11

In the past decade, the definition of stroke has been revised and major advances have been made for its treatment and prevention. For acute ischaemic stroke, the addition of endovascular thrombectomy of proximal large artery occlusion to intravenous alteplase increases functional independence for a further fifth of patients. The benefits of aspirin in preventing early recurrent ischaemic stroke are greater than previously recognised. Other strategies to prevent recurrent stroke now include direct oral anticoagulants as an alternative to warfarin for atrial fibrillation, and carotid stenting as an alternative to endarterectomy for symptomatic carotid stenosis. For acute intracerebral haemorrhage, trials are ongoing to assess the effectiveness of acute blood pressure lowering, haemostatic therapy, minimally invasive surgery, anti-inflammation therapy, and neuroprotection methods. Pharmacological and stem-cell therapies promise to facilitate brain regeneration, rehabilitation, and functional recovery. Despite declining stroke mortality rates, the global burden of stroke is increasing. A more comprehensive approach to primary prevention of stroke is required that targets people at all levels of risk and is integrated with prevention strategies for other diseases that share common risk factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lack of experience of intravenous thrombolysis for acute ischaemic stroke does not influence the proportion of patients treated

PubMed Central

Kobayashi, Adam; Skowronska, Marta; Litwin, Tomasz; Czlonkowska, Anna

2007-01-01

Objectives To determine the eligibility of patients with ischaemic stroke admitted to the 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland, for intravenous thrombolysis; to identify the major exclusions and assess whether organisational changes in the in‐hospital stroke pathway and informative campaign in the local community and medical services can increase the number of patients treated; and to establish whether lack of previous experience with thrombolytic treatment or trials is predictive of the low proportion of patients treated. Methods A survey of the database of patients with stroke admitted during the first 30 months after the introduction of intravenous thrombolysis for acute ischaemic stroke was conducted to search for all eligible patients. This included patients admitted within 2 h of symptom onset (assuming a 1 h door‐to‐needle time), age <80 years, National Institute of Health Stroke Scale (NIHSS) Score of 5–22, seizures at onset, platelet count >100 000/ml, glycaemia 50–400 mg/dl and international normalised ratio (INR) <1.6. The number of eligible patients was compared with the number actually treated. Results 745 patients with acute ischaemic stroke were admitted during the study period. 18.4% were admitted within 2 h of symptom onset, 71% were aged <80 years, 55.4% had an NIHSS score between 5 and 22, 96.1% had INR <1.6, 98.9% had a platelet count >100 000/ml, 99.4% had blood glucose concentrations of 50–400 mg/dl and 97.4% had no seizures at onset. After adjusting for all inclusion criteria, 7.1% of the patients were found to be potentially eligible and 8.7% were actually treated (p = 0.25). Of the 65 treated patients, 63.1% were independent after 3 months, 16.9% died and none had a symptomatic intracranial haemorrhage. Conclusions The proportion of patients with ischaemic stroke treated with intravenous thrombolysis in a previously inexperienced centre was not lower than in other centres and in countries where this treatment has been provided for a longer period of time. The number of patients treated was higher than that estimated mainly owing to organisational changes introduced in our centre, allowing treatment of those admitted between 2 and 3 h after symptom onset. PMID:17251612

Carotid artery stenting versus no stenting assisting thrombectomy for acute ischaemic stroke: protocol for a systematic review of randomised clinical trials with meta-analyses and trial sequential analyses.

PubMed

Steglich-Arnholm, Henrik; Holtmannspötter, Markus; Gluud, Christian; Krieger, Derk Wolfgang

2016-12-01

In patients with intracranial large vessel arterial occlusion, ipsilateral extracranial carotid artery occlusions or near-occlusions pose a significant hurdle in endovascular management of acute ischaemic stroke. Stenting of the carotid lesion may be beneficial in this situation to provide a stable access for introducing catheters through the carotid lesion into the intracranial vasculature and the target occlusion. Furthermore, carotid stenting may ensure ample blood flow for wash-out of clot material and reperfusion of the ischaemic penumbral tissue. However, antiplatelet therapy administered to prevent stent thrombosis and sudden increase in blood flow after reopening of the carotid lesion may increase the risk for intracranial haemorrhagic complications. This review aims to assess the benefits and harms of carotid stenting vs. no stenting assisting thrombectomy for acute ischaemic stroke. International and regional electronic databases will be searched to identify eligible randomised clinical trials. To identify further published, unpublished, or on-going and planned trials searches of Google Scholar, Worldwide Food and Drug Administrations, Worldwide Medicines Agencies, company homepages, reference lists, conference proceedings, and the Science Citation Index cited reference search index will be conducted. Manufacturers of relevant interventional equipment, authors, colleagues, and researchers active in the field will be contacted. No language restrictions will be applied to these searches. Randomised clinical trials will be included for assessing benefits and harms and quasi-randomised studies, and observational studies will be included for assessing harms of the intervention. Meta-analyses will be performed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, and Trial Sequential Analyses will be conducted to control the risk of random errors and prevent premature statements of superiority of the experimental or control intervention or premature statement of futility. The quality of the evidence will be evaluated with the Grading of Recommendations Assessment, Development, and Evaluation. This systematic review of carotid stenting in endovascular management of acute ischaemic stroke in patients with concomitant extracranial carotid lesions and intracranial embolism will assess benefits and harms of this intervention and assesses whether carotid stenting should be encouraged or avoided in acute ischaemic stroke and identify targets for further research. PROSPERO CRD42016033346.

Perioperative management of adult patients with a history of stroke or transient ischaemic attack undergoing elective non-cardiac surgery.

PubMed

Mehdi, Zehra; Birns, Jonathan; Partridge, Judith; Bhalla, Ajay; Dhesi, Jugdeep

2016-12-01

It is increasingly common for physicians and anaesthetists to be asked for advice in the medical management of surgical patients who have an incidental history of stroke or transient ischaemic attack (TIA). Advising clinicians requires an understanding of the common predictors, outcomes and management of perioperative stroke. The most important predictor of perioperative stroke is a previous history of stroke, and outcomes associated with such an event are extremely poor. The perioperative management of this patient group needs careful consideration to minimise the thrombotic risk and a comprehensive, individualised approach is crucial. Although there is literature supporting the management of such patients undergoing cardiac surgery, evidence is lacking in the setting of non-cardiac surgical intervention. This article reviews the current evidence and provides a pragmatic interpretation to inform the perioperative management of patients with a history of stroke and/or TIA presenting for elective non-cardiac surgery. © Royal College of Physicians 2016. All rights reserved.

Non-ketotic hyperglycaemia hemichorea–hemiballismus and acute ischaemic stroke

PubMed Central

Carrion, Diego M; Carrion, Andres F

2013-01-01

Here we describe a patient with a rare movement disorder, hemichorea–hemiballismus, which is described as a complication of non-ketotic hyperglycaemia. This complication may be seen in individuals with poorly controlled long-standing diabetes mellitus. Proper diagnosis is established with CT and MRI of the brain, which typically show classic findings in the basal ganglia. Treatment focuses on improvement of glycaemic control and usually results in rapid resolution of the movement disorder. Nevertheless, recurrent episodes of hemichorea–hemiballismus, and even more ominous complications such as ischaemic stroke may occur. PMID:23470671

Is management of hyperglycaemia in acute phase stroke still a dilemma?

PubMed

Savopoulos, C; Kaiafa, G; Kanellos, I; Fountouki, A; Theofanidis, D; Hatzitolios, A I

2017-05-01

Close monitoring of blood glucose levels during the immediate post-acute stroke phase is of great clinical value, as there is evidence that the risk of neurological deterioration is associated with both hyper- and hypoglycaemia. The aim of this review paper is to summarise the evidence on post-stroke blood glucose management and its impact on clinical outcomes, during the early post-acute stage. Post-stroke hyperglycaemia has been associated with increased cerebral oedema, haemorrhagic transformation, lower likelihood of recanalisation and deteriorating neurological state. Thus, hyperglycaemia during an acute stroke may result in poorer clinical outcomes, infarct progression, poor functional recovery and increased mortality rates. Although hypoglycaemia may also lead to poorer outcomes via further brain injury, it can be readily reversed by glucose administration. In most patients, the goal of regular treatment is euglycaemia and for acute-stroke patients, a reasonable approach is to target control of glucose level at 100-150 mg/dL. Both hypoglycaemia and hyperglycaemia may lead to further brain injury and clinical deterioration; that is the reason these conditions should be avoided after stroke. Yet, when correcting hyperglycaemia, great care should be taken not to switch the patient into hypoglycaemia, and subsequently aggressive insulin administration treatment should be avoided. Early identification and prompt management of hyperglycaemia, especially in acute ischaemic stroke, is recommended. Although the appropriate level of blood glucose during acute stroke is still debated, a reasonable approach is to keep the patient in a mildly hyperglycaemic state, rather than risking hypoglycaemia, using continuous glucose monitoring.

Socioeconomic disparities in first stroke incidence, quality of care, and survival: a nationwide registry-based cohort study of 44 million adults in England.

PubMed

Bray, Benjamin D; Paley, Lizz; Hoffman, Alex; James, Martin; Gompertz, Patrick; Wolfe, Charles D A; Hemingway, Harry; Rudd, Anthony G

2018-04-01

We aimed to estimate socioeconomic disparities in the incidence of hospitalisation for first-ever stroke, quality of care, and post-stroke survival for the adult population of England. In this cohort study, we obtained data collected by a nationwide register on patients aged 18 years or older hospitalised for first-ever acute ischaemic stroke or primary intracerebral haemorrhage in England from July 1, 2013, to March 31, 2016. We classified socioeconomic status at the level of Lower Super Output Areas using the Index of Multiple Deprivation, a neighbourhood measure of deprivation. Multivariable models were fitted to estimate the incidence of hospitalisation for first stroke (negative binomial), quality of care using 12 quality metrics (multilevel logistic), and all-cause 1 year case fatality (Cox proportional hazards). Of the 43·8 million adults in England, 145 324 were admitted to hospital with their first-ever stroke: 126 640 (87%) with ischaemic stroke, 17 233 (12%) with intracerebral haemorrhage, and 1451 (1%) with undetermined stroke type. We observed a socioeconomic gradient in the incidence of hospitalisation for ischaemic stroke (adjusted incidence rate ratio 2·0, 95% CI 1·7-2·3 for the most vs least deprived deciles) and intracerebral haemorrhage (1·6, 1·3-1·9). Patients from the lowest socioeconomic groups had first stroke a median of 7 years earlier than those from the highest (p<0·0001), and had a higher prevalence of pre-stroke disability and diabetes. Patients from lower socioeconomic groups were less likely to receive five of 12 care processes but were more likely to receive early supported discharge (adjusted odds ratio 1·14, 95% CI 1·07-1·22). Low socioeconomic status was associated with a 26% higher adjusted risk of 1-year mortality (adjusted hazard ratio 1·26, 95% CI 1·20-1·33, for highest vs lowest deprivation decile), but this gradient was largely attenuated after adjustment for the presence of pre-stroke diabetes, hypertension, and atrial fibrillation (1·11, 1·05-1·17). Wide socioeconomic disparities exist in the burden of ischaemic stroke and intracerebral haemorrhage in England, most notably in stroke hospitalisation risk and case fatality and, to a lesser extent, in the quality of health care. Reducing these disparities requires interventions to improve the quality of acute stroke care and address disparities in cardiovascular risk factors present before stroke. NHS England and the Welsh Government. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia.

PubMed

Stokowska, Anna; Atkins, Alison L; Morán, Javier; Pekny, Tulen; Bulmer, Linda; Pascoe, Michaela C; Barnum, Scott R; Wetsel, Rick A; Nilsson, Jonas A; Dragunow, Mike; Pekna, Marcela

2017-02-01

Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells and extensive rewiring of the remaining neural connections, yet about 50% of stroke survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in the subacute to chronic phase after ischaemic stroke. We previously showed that complement-derived peptide C3a regulates neural progenitor cell migration and differentiation in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice. To determine the role of C3a-C3a receptor signalling in ischaemia-induced neural plasticity, we subjected C3a receptor-deficient mice, GFAP-C3a transgenic mice expressing biologically active C3a in the central nervous system, and their respective wild-type controls to photothrombotic stroke. We found that C3a overexpression increased, whereas C3a receptor deficiency decreased post-stroke expression of GAP43 (P < 0.01), a marker of axonal sprouting and plasticity, in the peri-infarct cortex. To verify the translational potential of these findings, we used a pharmacological approach. Daily intranasal treatment of wild-type mice with C3a beginning 7 days after stroke induction robustly increased synaptic density (P < 0.01) and expression of GAP43 in peri-infarct cortex (P < 0.05). Importantly, the C3a treatment led to faster and more complete recovery of forepaw motor function (P < 0.05). We conclude that C3a-C3a receptor signalling stimulates post-ischaemic neural plasticity and intranasal treatment with C3a receptor agonists is an attractive approach to improve functional recovery after ischaemic brain injury. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Evaluation of treatment outcome after nicergoline and pentoxifylline in patients with ischemic stroke].

PubMed

Brola, W

1997-01-01

The study has been taken up to compare the effect of treatment with nicergoline or pentoxifylline and typical treatment in early ischaemic stroke. The study included 121 patients aged 42-75, with the ischaemic stroke confirmed by CT scan, in early stage of stroke (within 24 hours after onset). Excluded from the study were patients with severe physical diseases. The patients were divided into three groups. Group I was treated typically, group II was given both typical treatment and nicergoline during 30 days, with a daily dose 8 mg i.v. within the first 5 days followed by an oral delivery with a dose of 30 mg per day during the following 25 days. Group III had been profited from a typical, appropriate therapy and pentoxifylline delivery during 30 days as well, with a daily dose of 1200 mg i.v. within the first 5 days followed by an oral dose of 800 mg subsequent days. The neurological state was assessed according to the European Stroke Scale (ESS), general fitness according to the Karnofsky Scale (KS) at the admission and after 30 days of the treatment. After 30 days of the treatment, no statistically essential differences between all study groups was found in: 1) mortality, 2) mean survival time, 3) neurological state, 4) patients general fitness. According to the above results the beneficial influence of nicergoline and pentoxiphylline treatment of ischaemic stroke was not confirmed.

Prospective multicentre cohort study of heparin-induced thrombocytopenia in acute ischaemic stroke patients

PubMed Central

Kawano, Hiroyuki; Yamamoto, Haruko; Miyata, Shigeki; Izumi, Manabu; Hirano, Teruyuki; Toratani, Naomi; Kakutani, Isami; Sheppard, Jo-Ann I; Warkentin, Theodore E; Kada, Akiko; Sato, Shoichiro; Okamoto, Sadahisa; Nagatsuka, Kazuyuki; Naritomi, Hiroaki; Toyoda, Kazunori; Uchino, Makoto; Minematsu, Kazuo

2011-01-01

Acute ischaemic stroke patients sometimes receive heparin for treatment and/or prophylaxis of thromboembolic complications. This study was designed to elucidate the incidence and clinical features of heparin-induced thrombocytopenia (HIT) in acute stroke patients treated with heparin. We conducted a prospective multicentre cohort study of 267 patients who were admitted to three stroke centres within 7 d after stroke onset. We examined clinical data until discharge and collected blood samples on days 1 and 14 of hospitalization to test anti-platelet factor 4/heparin antibodies (anti-PF4/H Abs) using an enzyme-linked immunosorbent assay (ELISA); platelet-activating antibodies were identified by serotonin-release assay (SRA). Patients with a 4Ts score ≥4 points, positive-ELISA, and positive-SRA were diagnosed as definite HIT. Heparin was administered to 172 patients (64·4%: heparin group). Anti-PF4/H Abs were detected by ELISA in 22 cases (12·8%) in the heparin group. Seven patients had 4Ts ≥ 4 points. Among them, three patients (1·7% overall) were also positive by both ELISA and SRA. National Institutes of Health Stroke Scale score on admission was high (range, 16–23) and in-hospital mortality was very high (66·7%) in definite HIT patients. In this study, the incidence of definite HIT in acute ischaemic stroke patients treated with heparin was 1·7% (95% confidence interval: 0·4–5·0). The clinical severity and outcome of definite HIT were unfavourable. PMID:21671895

An audit of the pharmacological management of ischaemic stroke patients in a metropolitan Australian hospital.

PubMed

Khalil, Viviane; Li, Matthew; Hua, Qiantong Amanda

2015-02-01

According to the Australian Bureau of Statistics, stroke is the second leading cause of death in Australia. The clinical Guidelines for stroke management published by the National Stroke Foundation provide a series of evidence based recommendations to assist clinicians in the management of stroke patients. Appropriate management of patients admitted to stroke units reduces death and disability by 20 %. Moreover, a multidisciplinary team approach also improves patient outcomes. To retrospectively review the pharmacological management of ischaemic stroke patients in a metropolitan Australian hospital, and to compare adherence with the guidelines for stroke management with the national stroke foundation data with and without pharmacist intervention. A retrospective audit of medical records was undertaken of all patients admitted to a large teaching hospital with the diagnosis of stroke or cerebral infarction from January 2013 to May 2013. A total of 124 patients were included in the study. Most patients were discharged on appropriate pharmacological intervention for the prevention of secondary stroke: antihypertensive agents (71 %), lipid lowering agents (67 %) and antithrombotic (85 %) medications. The majority of the cohort was discharged on the appropriate evidence based medications for the management of secondary stroke. Further improvement may be achieved by pharmacist intervening as part of a multidisciplinary team.

Trends in stroke hospitalisation rates in Extremadura between 2002 and 2014: Changing the notion of stroke as a disease of the elderly.

PubMed

Ramírez-Moreno, J M; Felix-Redondo, F J; Fernández-Bergés, D; Lozano-Mera, L

2016-10-21

The incidence of stroke in Spain has been evaluated in several studies, whose results are highly variable and not comparable. No studies of stroke have analysed epidemiological changes in younger patients. We conducted a retrospective observational study using the Spanish health system's Minimum Data Set and included all patients older than 19 hospitalised due to stroke (ICD-9-CM codes 434.01, 434.11, 434.91, 430, 431, 432.9, 436, and 435) between 2002 and 2013. The analysis was performed using joinpoint regression. A total of 39,321 patients were identified (47.25% were women); 3.73% were aged 20-44, 6.29% were 45-54, 11.49% were 55-64, 23.89% were 65-74, and 54.60% were > 74 years. The hospitalisation rate due to ischaemic stroke has increased significantly in men aged 45-54 (+6.7%; 95% CI, 3.3-10.2) and in women aged 20-44 and 45-54 (+6.1%; 95% CI, 0.8-11.7 and +5.7%; 95% CI, 3.0-8.4, respectively). We also observed a significant increase in the rate of hospitalisation due to ischaemic stroke in men aged over 74 (+4.2%; 95% CI, 1.3-7.2). The rate of hospitalisations due to transient ischaemic attack has also increased significantly whereas the rate of hospitalisations due to brain haemorrhage has stabilised over time. Our results provide indirect evidence that the epidemiological profile of stroke is changing based on the increase in hospitalisation rates in young adults. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Guidelines for the treatment of acute ischaemic stroke.

PubMed

Alonso de Leciñana, M; Egido, J A; Casado, I; Ribó, M; Dávalos, A; Masjuan, J; Caniego, J L; Martínez Vila, E; Díez Tejedor, E; Fuentes, B; Álvarez-Sabin, J; Arenillas, J; Calleja, S; Castellanos, M; Castillo, J; Díaz-Otero, F; López-Fernández, J C; Freijo, M; Gállego, J; García-Pastor, A; Gil-Núñez, A; Gilo, F; Irimia, P; Lago, A; Maestre, J; Martí-Fábregas, J; Martínez-Sánchez, P; Molina, C; Morales, A; Nombela, F; Purroy, F; Rodríguez-Yañez, M; Roquer, J; Rubio, F; Segura, T; Serena, J; Simal, P; Tejada, J; Vivancos, J

2014-03-01

Update of Acute Ischaemic Stroke Treatment Guidelines of the Spanish Neurological Society based on a critical review of the literature. Recommendations are made based on levels of evidence from published data and studies. Organized systems of care should be implemented to ensure access to the optimal management of all acute stroke patients in stroke units. Standard of care should include treatment of blood pressure (should only be treated if values are over 185/105 mmHg), treatment of hyperglycaemia over 155 mg/dl, and treatment of body temperature with antipyretic drugs if it rises above 37.5 °C. Neurological and systemic complications must be prevented and promptly treated. Decompressive hemicraniectomy should be considered in cases of malignant cerebral oedema. Intravenous thrombolysis with rtPA should be administered within 4.5 hours from symptom onset, except when there are contraindications. Intra-arterial pharmacological thrombolysis can be considered within 6 hours, and mechanical thrombectomy within 8 hours from onset, for anterior circulation strokes, while a wider window of opportunity up to 12-24 hours is feasible for posterior strokes. There is not enough evidence to recommend routine use of the so called neuroprotective drugs. Anticoagulation should be administered to patients with cerebral vein thrombosis. Rehabilitation should be started as early as possible. Treatment of acute ischaemic stroke includes management of patients in stroke units. Systemic thrombolysis should be considered within 4.5 hours from symptom onset. Intra-arterial approaches with a wider window of opportunity can be an option in certain cases. Protective and restorative therapies are being investigated. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

ICARUSS, the Integrated Care for the Reduction of Secondary Stroke trial: rationale and design of a randomized controlled trial of a multimodal intervention to prevent recurrent stroke in patients with a recent cerebrovascular event, ACTRN = 12611000264987.

PubMed

Joubert, J; Davis, S M; Hankey, G J; Levi, C; Olver, J; Gonzales, G; Donnan, G A

2015-07-01

The majority of strokes, both ischaemic and haemorrhagic, are attributable to a relatively small number of risk factors which are readily manageable in primary care setting. Implementation of best-practice recommendations for risk factor management is calculated to reduce stroke recurrence by around 80%. However, risk factor management in stroke survivors has generally been poor at primary care level. A model of care that supports long-term effective risk factor management is needed. To determine whether the model of Integrated Care for the Reduction of Recurrent Stroke (ICARUSS) will, through promotion of implementation of best-practice recommendations for risk factor management reduce the combined incidence of stroke, myocardial infarction and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. A prospective, Australian, multicentre, randomized controlled trial. Academic stroke units in Melbourne, Perth and the John Hunter Hospital, New South Wales. 1000 stroke survivors recruited as from March 2007 with a recent (<3 months) stroke (ischaemic or haemorrhagic) or a TIA (brain or eye). Randomization and data collection are performed by means of a central computer generated telephone system (IVRS). Exposure to the ICARUSS model of integrated care or usual care. The composite of stroke, MI or death from any vascular cause, whichever occurs first. Risk factor management in the community, depression, quality of life, disability and dementia. With 1000 patients followed up for a median of one-year, with a recurrence rate of 7-10% per year in patients exposed to usual care, the study will have at least 80% power to detect a significant reduction in primary end-points The ICARUSS study aims to recruit and follow up patients between 2007 and 2013 and demonstrate the effectiveness of exposure to the ICARUSS model in stroke survivors to reduce recurrent stroke or vascular events and promote the implementation of best practice risk factor management at primary care level. © 2015 World Stroke Organization.

Autoregulation after ischaemic stroke

PubMed Central

Powers, William J.; Videen, Tom O.; Diringer, Michael N.; Aiyagari, Venkatesh; Zazulia, Allyson R.

2010-01-01

Objectives Absent outcome data from randomized clinical trials, management of hypertension in acute ischaemic stroke remains controversial. Data from human participants have failed to resolve the question whether cerebral blood flow (CBF) in the peri-infarct region will decrease due to impaired autoregulation when systemic mean arterial pressure (MAP) is rapidly reduced. Methods Nine participants, 1–11 days after hemispheric ischaemic stroke, with systolic blood pressure more than 145 mmHg, underwent baseline PET measurements of regional CBF. Intravenous nicardipine infusion was then used to rapidly reduce mean arterial pressure 16 ± 7 mmHg and CBF measurement was repeated. Results Compared with the contralateral hemisphere, there were no significant differences in the percent change in CBF in the infarct (P = 0.43), peri-infarct region (P = 1.00) or remainder of the ipsilateral hemisphere (P = 0.50). Two participants showed CBF reductions of greater than 19% in both hemispheres. Conclusion In this study, selective regional impairment of CBF autoregulation in the infarcted hemisohere to reduced systemic blood pressure was not a characteristic of acute cerebral infarction. Reductions in CBF did occur in some individuals, but it was bihemispheric phenomenon that likely was due to an upward shift of the autoregulatory curve as a consequence of chronic hypertension. These results indicate individual monitoring of changes in global CBF, such as with bedside transcranial Doppler, may be useful to determine individual safe limits when MAP is lowered in the setting of acute ischaemic stroke. The benefit of such an approach can only be demonstrated by clinical trials demonstrating improved patient outcome. PMID:19644387

Nicergoline increases serum substance P levels in patients with an ischaemic stroke.

PubMed

Nishiyama, Yasuhiro; Abe, Arata; Ueda, Masayuki; Katsura, Ken-ichiro; Katayama, Yasuo

2010-01-01

Aspiration pneumonia is one of the most important complications following ischaemic stroke, and a leading cause of mortality in stroke patients. This is particularly prevalent in patients with involvement of the basal ganglia, which may be due to impaired neurotransmission through lack of production of substance P. Consecutive patients in the chronic stage, 1-3 months after cerebral ischaemic infarction, were assessed for basal ganglia involvement by magnetic resonance imaging. The patients were randomised to 4 weeks of treatment with (n = 25) or without (n = 25) nicergoline (15 mg t.i.d.). Serum concentration of substance P was measured by radioimmunoassay. At entry to the study, mean concentration of substance P was significantly (p < 0.001) lower in patients with bilateral basal ganglia lesions than in patients with no or unilateral basal ganglia involvement. Nicergoline administration caused a significant (p = 0.021) increase from baseline in mean substance P concentration. No significant change was seen in the nicergoline-untreated patients (p = 0.626). Among the patients who received nicergoline, 11 patients had bilateral basal ganglia involvement and there was no significant mean change in substance P in these patients, whereas there was a significant increase (p = 0.032) in the 14 nicergoline-treated patients with no or unilateral basal ganglia involvement. The present study suggests a possible effect of nicergoline to increase substance P level in ischaemic stroke patients with partial damage to basal ganglia, who have a decreased swallowing response and consequent risk of aspiration pneumonia. Further trials of nicergoline treatment in patients at risk for aspiration pneumonia are warranted. (c) 2009 S. Karger AG, Basel.

The current management of carotid atherosclerotic disease: who, when and how?

PubMed Central

Ritter, Jens C.; Tyrrell, Mark R.

2013-01-01

Ischaemic stroke represents a major health hazard in the western world, which has a severe impact on society and the health-care system. Roughly, 10% of all first ischaemic strokes can be attributed to significant atherosclerotic disease of the carotid arteries. Correct management of these lesions is essential in the prevention and treatment of carotid disease-related ischaemic events. The close relationship between diagnosis and medical and surgical management makes it necessary that all involved physicians and surgeons have profound knowledge of management strategies beyond their specific speciality. Continuous improvement in pharmacological therapy and operative techniques as well as frequently changing guidelines represent a constant challenge for the individual health-care professional. This review gives a thorough outline of the up-to-date evidence-based management of carotid artery disease and discusses its current controversies. PMID:23197661

Closure of patent foramen ovale: when and how?

PubMed

Lisignoli, Veronica; Lanzone, Alberto M; Zavalloni, Dennis; Pagnotta, Paolo; Presbitero, Patrizia

2007-10-01

Percutaneous closure of a patent foramen ovale (PFO) was performed in 98 consecutive patients (mean age 52.5 +/- 13 years, 61 women). Indications included recurrent transient ischaemic attack (47%), cryptogenic stroke (34%), peripheral embolism (11%), disabling migraine with aura (4%), professional scuba diving (1 pt) and severe platypnea-orthodeoxia syndrome (1 pt). Each PFO was characterized by transesophageal echocardiography (TEE) according to anatomy, degree of shunt (1-mild, 2-moderate, 3-severe), right atrial anatomical features relevant for PFO closure (such as presence of an Eustachian valve, Chiari network, lipomatosis or absence of septum secundum) with a new classification scheme. According to this classification successful device delivery was obtained in 100% of pts. Major complications included heparin-induced thrombocytopenia in 1 pt and device dislodgment in 1 pt; minor complications were mostly related to the catheter introduction site (2 pts) and mild immediate shunt (2 pts). In conclusion, percutaneous PFO closure based on strict anatomic criteria is a safe procedure with minimal periprocedural complications.

No Relation between Body Temperature and Arterial Recanalization at Three Days in Patients with Acute Ischaemic Stroke.

PubMed

Geurts, Marjolein; van der Worp, H Bart; Horsch, Alexander D; Kappelle, L Jaap; Biessels, Geert J; Velthuis, Birgitta K

2015-01-01

Recanalization of an occluded intracranial artery is influenced by temperature-dependent enzymes, including alteplase. We assessed the relation between body temperature on admission and recanalization. We included 278 patients with acute ischaemic stroke within nine hours after symptom onset, who had an intracranial arterial occlusion on admission CT angiography, in 13 participating centres. We calculated the relation per every 0.1°Celsius increase in admission body temperature and recanalization at three days. Recanalization occurred in 80% of occluded arteries. There was no relation between body temperature and recanalization at three days after adjustments for age, NIHSS score on admission and treatment with alteplase (adjusted odds ratio per 0.1°Celsius, 0.99; 95% confidence interval, 0.94-1.05; p = 0.70). Results for patients treated or not treated with alteplase were essentially the same. Our findings suggest that in patients with acute ischaemic stroke there is no relation between body temperature on admission and recanalization of an occluded intracranial artery three days later, irrespective of treatment with alteplase.

No Relation between Body Temperature and Arterial Recanalization at Three Days in Patients with Acute Ischaemic Stroke

PubMed Central

Geurts, Marjolein; van der Worp, H. Bart; Horsch, Alexander D.; Kappelle, L. Jaap; Biessels, Geert J.; Velthuis, Birgitta K.

2015-01-01

Background Recanalization of an occluded intracranial artery is influenced by temperature-dependent enzymes, including alteplase. We assessed the relation between body temperature on admission and recanalization. Methods We included 278 patients with acute ischaemic stroke within nine hours after symptom onset, who had an intracranial arterial occlusion on admission CT angiography, in 13 participating centres. We calculated the relation per every 0.1°Celsius increase in admission body temperature and recanalization at three days. Results Recanalization occurred in 80% of occluded arteries. There was no relation between body temperature and recanalization at three days after adjustments for age, NIHSS score on admission and treatment with alteplase (adjusted odds ratio per 0.1°Celsius, 0.99; 95% confidence interval, 0.94–1.05; p = 0.70). Results for patients treated or not treated with alteplase were essentially the same. Conclusions Our findings suggest that in patients with acute ischaemic stroke there is no relation between body temperature on admission and recanalization of an occluded intracranial artery three days later, irrespective of treatment with alteplase. PMID:26473959

United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results

PubMed Central

1988-01-01

From 1979 to 1985, 2435 patients thought to have had a transient ischaemic attack or minor ischaemic stroke were allocated at random to receive long term blind treatment with either aspirin 600 mg twice daily (n=815), aspirin 300 mg once daily (806), or placebo (814). Treatment continued with about 85% compliance until September 1986 (mean four years). The odds of suffering one or more of four categories of event—namely, non-fatal myocardial infarction, non-fatal major stroke, vascular death, or non-vascular death—were 18% less in the two groups allocated to receive aspirin than in the group allocated to receive placebo (2p=0·01). The more relevant but less frequent composite event of disabling stroke or vascular death was reduced by only 7%; this reduction was not significantly different from zero, but nor was it significantly different from a 25% reduction. There was no definite difference between responses to the 300 mg and 1200 mg daily doses, except that the lower dose was significantly less gastrotoxic. PMID:2894232

Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial

PubMed Central

Muir, Keith W; Ford, Gary A; Messow, Claudia-Martina; Ford, Ian; Murray, Alicia; Clifton, Andrew; Brown, Martin M; Madigan, Jeremy; Lenthall, Rob; Robertson, Fergus; Dixit, Anand; Cloud, Geoffrey C; Wardlaw, Joanna; Freeman, Janet; White, Philip

2017-01-01

Objective The Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial was a multicentre, randomised, controlled clinical trial comparing intravenous thrombolysis (IVT) alone with IVT and adjunctive intra-arterial mechanical thrombectomy (MT) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography (CTA). Design Eligible patients had IVT started within 4.5 hours of stroke symptom onset. Those randomised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device, with target interval times for IVT start to arterial puncture of <90 min. The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale (mRS) score of 0–2 at day 90. Results Ten UK centres enrolled 65 patients between April 2013 and April 2015. Median National Institutes of Health Stroke Scale score was 16 (IQR 13–21). Median stroke onset to IVT start was 120 min. In the intention-to-treat analysis, there was no significant difference in disability-free survival at day 90 with MT (absolute difference 11%, adjusted OR 2.12, 95% CI 0.65 to 6.94, p=0.20). Secondary analyses showed significantly greater likelihood of full neurological recovery (mRS 0–1) at day 90 (OR 7.6, 95% CI 1.6 to 37.2, p=0.010). In the per-protocol population (n=58), the primary and most secondary clinical outcomes significantly favoured MT (absolute difference in mRS 0–2 of 22% and adjusted OR 4.9, 95% CI 1.2 to 19.7, p=0.021). Conclusions The trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability-free survival. Trial registration number NCT01745692; Results. PMID:27756804

Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study

PubMed Central

Diener, Hans-Christoph; Sacco, Ralph L; Yusuf, Salim; Cotton, Daniel; Ôunpuu, Stephanie; Lawton, William A; Palesch, Yuko; Martin, Reneé H; Albers, Gregory W; Bath, Philip; Bornstein, Natan; Chan, Bernard P L; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; Keyser, Jacques De; Donnan, Geoffrey A; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

2009-01-01

Summary Background The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. Methods Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NTC00153062. Findings 20 332 patients (mean age 66 years) were randomised and followed-up for a median of 2·4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0·38), or with telmisartan versus placebo (p=0·61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups. Interpretation Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan. Funding Boehringer Ingelheim; Bayer-Schering Pharma (in selected countries); GlaxoSmithKline (in selected countries). PMID:18757238

Retrospective audit of the acute management of stroke in two district general hospitals in the uk.

PubMed

Faluyi, O O; Omodara, J A; Tay, K H; Muhiddin, K

2008-06-01

There is some evidence to suggest that the standard of acute medical care provided to patients with cerebrovascular disease is a major determinant of the eventual outcome. Consequently, the Royal College of Physicians (RCP) of London issues periodic guidelines to assist healthcare providers in the management of patients presenting with stroke. An audit of the acute management of stroke in two hospitals belonging to the same health care trust in the UK. Retrospective review of 98 randomly selected case-notes of patients managed for cerebrovascular disease in two acute hospitals in the UK between April and June 2004. The pertinent guidelines of RCP (London) are highlighted while audit targets were set at 70%. 84% of patients presenting with cerebrovascular disease had a stroke rather than a TIA, anterior circulation strokes were commonest. All patients with stroke were admitted while those with TIAs were discharged on the same day but most patients with TIA were not followed up by Stroke specialists. Most CT-imaging of the head was done after 24 hours delaying the commencement of anti-platelets for patients with ischaemic stroke or neurosurgical referral for haemorrhagic stroke. Furthermore, there was a low rate of referral for carotid ultrasound in patients with anterior circulation strokes. Anti-platelets and statins were commenced for most patients with ischaemic stroke while diabetes was well controlled in most of them. However, ACE-inhibitors and diuretics such as indapamide were under-utilized for secondary prevention in such patients. Warfarin anti-coagulation was underutilized in patients with ischaemic stroke who had underlying chronic atrial fibrillation. While there was significant multi-disciplinary team input, dysphagia and physiotherapy assessments were delayed. Similarly, occupational therapy input and psychological assesment were omitted from the care of most patients. Hospital service provision for the management of cerebrovascular disease needs to provide appropriate specialist follow up for patients with TIA, prompt radiological imaging and multi-disciplinary team input for patients with stroke. Furthermore, physicians need to utilize appropriate antihypertensives and anti-coagulation more frequently in the secondary prevention of stroke.

RETROSPECTIVE AUDIT OF THE ACUTE MANAGEMENT OF STROKE IN TWO DISTRICT GENERAL HOSPITALS IN THE UK.

PubMed Central

Faluyi, O.O.; Omodara, J.A.; Tay, K.H.; Muhiddin, K.

2008-01-01

Background: There is some evidence to suggest that the standard of acute medical care provided to patients with cerebrovascular disease is a major determinant of the eventual outcome. Consequently, the Royal College of Physicians (RCP) of London issues periodic guidelines to assist healthcare providers in the management of patients presenting with stroke. Objective: An audit of the acute management of stroke in two hospitals belonging to the same health care trust in the UK. Method: Retrospective review of 98 randomly selected case-notes of patients managed for cerebrovascular disease in two acute hospitals in the UK between April and June 2004. The pertinent guidelines of RCP (London) are highlighted while audit targets were set at 70%. Results: 84% of patients presenting with cerebrovascular disease had a stroke rather than a TIA, anterior circulation strokes were commonest. All patients with stroke were admitted while those with TIAs were discharged on the same day but most patients with TIA were not followed up by Stroke specialists. Most CT-imaging of the head was done after 24 hours delaying the commencement of anti-platelets for patients with ischaemic stroke or neurosurgical referral for haemorrhagic stroke. Furthermore, there was a low rate of referral for carotid ultrasound in patients with anterior circulation strokes. Anti-platelets and statins were commenced for most patients with ischaemic stroke while diabetes was well controlled in most of them. However, ACE-inhibitors and diuretics such as indapamide were under-utilized for secondary prevention in such patients. Warfarin anti-coagulation was underutilized in patients with ischaemic stroke who had underlying chronic atrial fibrillation. While there was significant multi-disciplinary team input, dysphagia and physiotherapy assessments were delayed. Similarly, occupational therapy input and psychological assesment were omitted from the care of most patients. Conclusion: Hospital service provision for the management of cerebrovascular disease needs to provide appropriate specialist follow up for patients with TIA, prompt radiological imaging and multi-disciplinary team input for patients with stroke. Furthermore, physicians need to utilize appropriate antihypertensives and anti-coagulation more frequently in the secondary prevention of stroke. PMID:25161444

Genetics of ischaemic stroke; single gene disorders.

PubMed

Flossmann, Enrico

2006-08-01

Examples of single gene disorders have been described for all major subtypes of ischaemic stroke: accelerated atherosclerosis and subsequent thrombo-embolism (e.g. homocysteinuria), weakening of connective tissue resulting in arterial dissections (e.g. Ehler-Danlos type IV), disorders of cerebral small vessels (e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and the collagen COL4A1 mutation), disorders increasing the thrombogenic potential of the heart through affecting the myocardium or the heart valves or through disturbance of the heart rhythm (e.g. hypertrophic cardiomyopathy), mitochondrial cytopathies increasing cerebral tissue susceptibility to insults (e.g. mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), and finally disorders of coagulation that can either directly cause stroke or act synergistically with the aforementioned abnormalities (e.g. sickle cell disease). Most of these disorders are rare but they are important to consider particularly in young patients with stroke, those with a family history or those who have other characteristics of a particular syndrome.

Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: a Canadian payer perspective.

PubMed

Sorensen, S V; Kansal, A R; Connolly, S; Peng, S; Linnehan, J; Bradley-Kennedy, C; Plumb, J M

2011-05-01

Oral dabigatran etexilate is indicated for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF) in whom anticoagulation is appropriate. Based on the RE-LY study we investigated the cost-effectiveness of Health Canada approved dabigatran etexilate dosing (150 mg bid for patients <80 years, 110 mg bid for patients ≥80 years) versus warfarin and "real-world" prescribing (i.e. warfarin, aspirin, or no treatment in a cohort of warfarin-eligible patients) from a Canadian payer perspective. A Markov model simulated AF patients at moderate to high risk of stroke while tracking clinical events [primary and recurrent ischaemic strokes, systemic embolism, transient ischaemic attack, haemorrhage (intracranial, extracranial, and minor), acute myocardial infarction and death] and resulting functional disability. Acute event costs and resulting long-term follow-up costs incurred by disabled stroke survivors were based on a Canadian prospective study, published literature, and national statistics. Clinical events, summarized as events per 100 patient-years, quality-adjusted life years (QALYs), total costs, and incremental cost effectiveness ratios (ICER) were calculated. Over a lifetime, dabigatran etexilate treated patients experienced fewer intracranial haemorrhages (0.49 dabigatran etexilate vs. 1.13 warfarin vs. 1.05 "real-world" prescribing) and fewer ischaemic strokes (4.40 dabigatran etexilate vs. 4.66 warfarin vs. 5.16 "real-world" prescribing) per 100 patient-years. The ICER of dabigatran etexilate was $10,440/QALY versus warfarin and $3,962/QALY versus "real-world" prescribing. This study demonstrates that dabigatran etexilate is a highly cost-effective alternative to current care for the prevention of stroke and systemic embolism among Canadian AF patients.

Vegetable and fruit intake and mortality from chronic disease in New Zealand.

PubMed

Tobias, Martin; Turley, Maria; Stefanogiannis, Niki; Vander Hoorn, Stephen; Lawes, Carlene; Mhurchu, Cliona Ni; Rodgers, Anthony

2006-02-01

To estimate mortality attributable to inadequate vegetable and fruit intake in New Zealand in 1997, and the burden of disease that could be avoided in 2011 if modest increases in vegetable and fruit intake were to occur. Comparative risk assessment methodology was used to estimate both attributable and avoidable mortality due to inadequate vegetable and fruit consumption (< 600 g/day). Vegetables and fruit were defined as all fresh, frozen, canned, dried or juiced vegetables and fruit, except potatoes, nuts, seeds and pulses. Disease outcomes assessed were mortality from ischaemic heart disease, ischaemic stroke, and lung, oesophageal, stomach and colorectal cancers. In 1997, mean vegetable and fruit intake was 420 g/day in males and 404 g/day in females. Inadequate vegetable and fruit intake is estimated to have contributed to 1,559 deaths (6% of all deaths) in that year, including 1,171 from ischaemic heart disease, 179 from ischaemic stroke and 209 from cancer. Modest increases in vegetable and fruit intake (40 g/day above the historic trend) could prevent 334 deaths each year from 2011, mostly from ischaemic heart disease. Inadequate vegetable and fruit intake is an important cause of mortality in New Zealand. Small increases in vegetable and fruit intake could have a major impact on population health within a decade.

Migraine and risk of cardiovascular diseases: Danish population based matched cohort study

PubMed Central

Szépligeti, Szimonetta Komjáthiné; Holland-Bill, Louise; Ehrenstein, Vera; Horváth-Puhó, Erzsébet; Henderson, Victor W; Sørensen, Henrik Toft

2018-01-01

Abstract Objective To examine the risks of myocardial infarction, stroke (ischaemic and haemorrhagic), peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter, and heart failure in patients with migraine and in a general population comparison cohort. Design Nationwide, population based cohort study. Setting All Danish hospitals and hospital outpatient clinics from 1995 to 2013. Participants 51 032 patients with migraine and 510 320 people from the general population matched on age, sex, and calendar year. Main outcome measures Comorbidity adjusted hazard ratios of cardiovascular outcomes based on Cox regression analysis. Results Higher absolute risks were observed among patients with incident migraine than in the general population across most outcomes and follow-up periods. After 19 years of follow-up, the cumulative incidences per 1000 people for the migraine cohort compared with the general population were 25 v 17 for myocardial infarction, 45 v 25 for ischaemic stroke, 11 v 6 for haemorrhagic stroke, 13 v 11 for peripheral artery disease, 27 v 18 for venous thromboembolism, 47 v 34 for atrial fibrillation or atrial flutter, and 19 v 18 for heart failure. Correspondingly, migraine was positively associated with myocardial infarction (adjusted hazard ratio 1.49, 95% confidence interval 1.36 to 1.64), ischaemic stroke (2.26, 2.11 to 2.41), and haemorrhagic stroke (1.94, 1.68 to 2.23), as well as venous thromboembolism (1.59, 1.45 to 1.74) and atrial fibrillation or atrial flutter (1.25, 1.16 to 1.36). No meaningful association was found with peripheral artery disease (adjusted hazard ratio 1.12, 0.96 to 1.30) or heart failure (1.04, 0.93 to 1.16). The associations, particularly for stroke outcomes, were stronger during the short term (0-1 years) after diagnosis than the long term (up to 19 years), in patients with aura than in those without aura, and in women than in men. In a subcohort of patients, the associations persisted after additional multivariable adjustment for body mass index and smoking. Conclusions Migraine was associated with increased risks of myocardial infarction, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter. Migraine may be an important risk factor for most cardiovascular diseases. PMID:29386181

Migraine and risk of cardiovascular diseases: Danish population based matched cohort study.

PubMed

Adelborg, Kasper; Szépligeti, Szimonetta Komjáthiné; Holland-Bill, Louise; Ehrenstein, Vera; Horváth-Puhó, Erzsébet; Henderson, Victor W; Sørensen, Henrik Toft

2018-01-31

To examine the risks of myocardial infarction, stroke (ischaemic and haemorrhagic), peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter, and heart failure in patients with migraine and in a general population comparison cohort. Nationwide, population based cohort study. All Danish hospitals and hospital outpatient clinics from 1995 to 2013. 51 032 patients with migraine and 510 320 people from the general population matched on age, sex, and calendar year. Comorbidity adjusted hazard ratios of cardiovascular outcomes based on Cox regression analysis. Higher absolute risks were observed among patients with incident migraine than in the general population across most outcomes and follow-up periods. After 19 years of follow-up, the cumulative incidences per 1000 people for the migraine cohort compared with the general population were 25 v 17 for myocardial infarction, 45 v 25 for ischaemic stroke, 11 v 6 for haemorrhagic stroke, 13 v 11 for peripheral artery disease, 27 v 18 for venous thromboembolism, 47 v 34 for atrial fibrillation or atrial flutter, and 19 v 18 for heart failure. Correspondingly, migraine was positively associated with myocardial infarction (adjusted hazard ratio 1.49, 95% confidence interval 1.36 to 1.64), ischaemic stroke (2.26, 2.11 to 2.41), and haemorrhagic stroke (1.94, 1.68 to 2.23), as well as venous thromboembolism (1.59, 1.45 to 1.74) and atrial fibrillation or atrial flutter (1.25, 1.16 to 1.36). No meaningful association was found with peripheral artery disease (adjusted hazard ratio 1.12, 0.96 to 1.30) or heart failure (1.04, 0.93 to 1.16). The associations, particularly for stroke outcomes, were stronger during the short term (0-1 years) after diagnosis than the long term (up to 19 years), in patients with aura than in those without aura, and in women than in men. In a subcohort of patients, the associations persisted after additional multivariable adjustment for body mass index and smoking. Migraine was associated with increased risks of myocardial infarction, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter. Migraine may be an important risk factor for most cardiovascular diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Knowledge of Stroke Risk Factors and Warning Signs in Patients with Recurrent Stroke or Recurrent Transient Ischaemic Attack in Thailand.

PubMed

Saengsuwan, Jittima; Suangpho, Pathitta; Tiamkao, Somsak

2017-01-01

Stroke is a global burden. It is not known whether patients who are most at risk of stroke (recurrent stroke or recurrent transient ischaemic attack) have enough knowledge of stroke risk factors and warning signs. The aim of this study was to assess the knowledge of stroke risk factors and warning signs in this high-risk population. We performed a cross-sectional questionnaire-based study of patients with recurrent stroke or recurrent TIA admitted to Srinagarind Hospital and Khon Kaen Hospital, Thailand. A total of 140 patients were included in the study (age 65.6 ± 11.3 years [mean ± SD], 62 females). Using an open-ended questionnaire, nearly one-third of patients (31.4%) could not name any risk factors for stroke. The most commonly recognized risk factors were hypertension (35%), dyslipidemia (28.6%), and diabetes (22.9%). Regarding stroke warning signs, the most commonly recognized warning signs were sudden unilateral weakness (61.4%), sudden trouble with speaking (25.7%), and sudden trouble with walking, loss of balance, or dizziness (21.4%). Nineteen patients (13.6%) could not identify any warning signs. The results showed that knowledge of stroke obtained from open-ended questionnaires is still unsatisfactory. The healthcare provider should provide structured interventions to increase knowledge and awareness of stroke in these patients.

Educational inequality in cardiovascular diseases: a sibling approach.

PubMed

Søndergaard, Grethe; Dalton, Susanne Oksbjerg; Mortensen, Laust Hvas; Osler, Merete

2018-02-01

Educational inequality in diseases in the circulatory system (here termed cardiovascular disease) is well documented but may be confounded by early life factors. The aim of this observational study was to examine whether the associations between education and all cardiovascular diseases, ischaemic heart disease and stroke, respectively, were explained by family factors shared by siblings. The study population included all individuals born in Denmark between 1950 and 1979 who had at least one full sibling born in the same period. Using Cox regression, data were analysed in conventional cohort and within-sibship analyses in which the association was examined within siblings discordant on education. Assuming that attenuation of associations in the within-sibship as compared with the cohort analyses would indicate confounding from factors shared within families. A lower educational status was associated with a higher risk of cardiovascular disease, ischaemic heart disease and stroke. All associations attenuated in the within-sibship analyses, in particular in the analyses on ischaemic heart disease before age 45 years. For instance, in the cohort analyses, the hazard rate of ischaemic heart disease among women less than 45 years who had a primary school education was 94% (hazard ratio 1.94 (1.78-2.12) higher than among those with a vocational education, while it attenuated to 51% (hazard ratio 1.51 (1.34-1.71)) in the within-sibship analysis. Confounding from factors shared by siblings explained the associations between education and the cardiovascular disease outcomes but to varying degrees. This should be taken into account when planning interventions aimed at reducing educational inequalities in the development of cardiovascular disease, ischaemic heart disease and stroke.

Factors determining case fatality in myocardial infarction "who dies in a heart attack"?

PubMed

Wannamethee, G; Whincup, P H; Shaper, A G; Walker, M; MacFarlane, P W

1995-09-01

To examine the determinants of case fatality in the first major ischaemic heart disease event (heart attack) after screening. Prospective study of 7735 middle aged men drawn from general practices in 24 British towns. During 11.5 years follow up there were 743 major ischaemic heart disease events of which 302 (40.6%) were fatal within 28 days of onset. Previous definite myocardial infarction or stroke and age at time of event were most strongly associated with case fatality. In men with no previous myocardial infarction or stroke, after adjustment for a range of risk factors, antihypertensive treatment (odds ratio (OR) = 1.97, P < 0.05), arrhythmia (OR = 1.93, P = 0.06), increased heart rate (OR = 2.03, P = 0.06), and diabetes (OR = 2.61, P = 0.07) were associated with increased case fatality. High levels of physical activity (OR = 0.53, P < 0.05) and moderate drinking (16-42 units/week) (OR = 0.61, P < 0.05) were associated with lower case fatality, although moderate drinking was not associated with a lower incidence of major ischaemic heart disease events. Current smoking, serum total cholesterol, and systolic blood pressure were not significantly associated with case fatality. In men with previous myocardial infarction or stroke, arrhythmia and to a lesser degree antihypertensive treatment, moderate or heavy drinking, and diabetes were associated with higher case fatality. These findings suggest that physical activity may be an important modifiable factor influencing the incidence of ischaemic heart disease and the chance of survival in men without a previous heart attack or stroke. Arrhythmia, increased heart rate, diabetes, and treatment for hypertension are also areas of concern.

Safety and Efficacy of Mechanical Thrombectomy Using Stent Retrievers in the Endovascular Treatment of Acute Ischaemic Stroke: A Systematic Review

PubMed Central

Puñal-Riobóo, Janet; Atienza, Gerardo; Blanco, Miguel

2015-01-01

Background The treatment of choice for acute ischaemic stroke is the intravenous administration of recombinant tissue plasminogen activator within 3-4.5 h of symptom onset. However, the use of a thrombolytic would be limited by its narrow therapeutic window and contraindications. As a result, in recent years, techniques such as mechanical thrombectomy have emerged, which employ thrombus retrieval devices, such as stent retrievers (Solitaire™, Trevo® or Revive™), whose safety and efficacy in the endovascular treatment of acute ischaemic stroke is analysed in this article. Methods A systematic literature search was undertaken until March 2015. The quality of evidence was assessed according to the GRADE methodology. A meta-analysis of the results of randomised controlled trials (RCTs) was performed, and the weighted average for the case series' sample size was calculated (Review Manager v5.2 and SPSS v19). Results Seventeen primary studies (2 RCTs, Solitaire™ and Trevo® vs. Merci®, and 15 case series) were selected. The RCT results show that stent retrievers have a safety profile similar to the Merci® device. However, both Solitaire™ and Trevo® achieved a higher recanalisation success rate (OR, 4.56; 95% CI, 2.63-7.90; p < 0.00001) and appropriate clinical outcome at 90 days (OR, 2.54; 95% CI, 1.52-4.25; p < 0.0004), although the 90-day mortality rate was similar in both groups (OR, 0.75; 95% CI, 0.17-3.37; p = 0.70). Conclusions Stent retrievers appear to be safe and effective devices, achieving high recanalisation rates and good clinical outcomes in the endovascular treatment of patients with acute ischaemic stroke due to the occlusion of intracranial arteries in comparison with the clot retriever Merci®. PMID:26279662

Uric acid predicts mortality and ischaemic stroke in subjects with diastolic dysfunction: the Tromsø Study 1994-2013.

PubMed

Norvik, Jon V; Schirmer, Henrik; Ytrehus, Kirsti; Storhaug, Hilde M; Jenssen, Trond G; Eriksen, Bjørn O; Mathiesen, Ellisiv B; Løchen, Maja-Lisa; Wilsgaard, Tom; Solbu, Marit D

2017-05-01

To investigate whether serum uric acid predicts adverse outcomes in persons with indices of diastolic dysfunction in a general population. We performed a prospective cohort study among 1460 women and 1480 men from 1994 to 2013. Endpoints were all-cause mortality, incident myocardial infarction, and incident ischaemic stroke. We stratified the analyses by echocardiographic markers of diastolic dysfunction, and uric acid was the independent variable of interest. Hazard ratios (HR) were estimated per 59 μmol/L increase in baseline uric acid. Multivariable adjusted Cox proportional hazards models showed that uric acid predicted all-cause mortality in subjects with E/A ratio <0.75 (HR 1.12, 95% confidence interval [CI] 1.00-1.25) or E/A ratio >1.5 (HR 1.51, 95% CI 1.09-2.09, P for interaction between E/A ratio category and uric acid = 0.02). Elevated uric acid increased mortality risk in persons with E-wave deceleration time <140 ms or >220 ms (HR 1.46, 95% CI 1.01-2.12 and HR 1.13, 95% CI 1.02-1.26, respectively; P for interaction = 0.04). Furthermore, in participants with isovolumetric relaxation time ≤60 ms, mortality risk was higher with increasing uric acid (HR 4.98, 95% CI 2.02-12.26, P for interaction = 0.004). Finally, elevated uric acid predicted ischaemic stroke in subjects with severely enlarged left atria (HR 1.62, 95% CI 1.03-2.53, P for interaction = 0.047). Increased uric acid was associated with higher all-cause mortality risk in subjects with echocardiographic indices of diastolic dysfunction, and with higher ischaemic stroke risk in persons with severely enlarged left atria.

B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial.

PubMed

2010-09-01

Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye. In this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0.5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratified by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT00097669, and Current Controlled Trials, ISRCTN74743444. Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3.4 years (IQR 2.0-5.5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0.91, 95% CI 0.82 to 1.00, p=0.05; absolute risk reduction 1.56%, -0.01 to 3.16). There were no unexpected serious adverse reactions and no significant differences in common adverse effects between the treatment groups. Daily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins. Australia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, Singapore National Medical Research Council, Australia National Heart Foundation, Royal Perth Hospital Medical Research Foundation, and Health Department of Western Australia. Copyright 2010 Elsevier Ltd. All rights reserved.

Profile of von Willebrand factor antigen and von Willebrand factor propeptide in an overall TIA and ischaemic stroke population and amongst subtypes.

PubMed

Tobin, W O; Kinsella, J A; Kavanagh, G F; O'Donnell, J S; McGrath, R T; Tierney, S; Egan, B; Feeley, T M; Coughlan, T; Collins, D R; O'Neill, D; Murphy, Sjx; Lim, S J; Murphy, R P; McCabe, Djh

2017-04-15

Von Willebrand factor propeptide (VWF:Ag II) is proposed to be a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). Simultaneous data on VWF:Ag and VWF:Ag II profiles are very limited following TIA and ischaemic stroke. In this prospective, observational, case-control study, plasma VWF:Ag and VWF:Ag II levels were quantified in 164 patients≤4weeks of TIA or ischaemic stroke (baseline), and then ≥14days (14d) and ≥90days (90d) later, and compared with those from 27 healthy controls. TIA and stroke subtyping was performed according to the TOAST classification. The relationship between VWF:Ag and VWF:Ag II levels and platelet activation status was assessed. 'Unadjusted' VWF:Ag and VWF:Ag II levels were higher in patients at baseline, 14d and 90d than in controls (p≤0.03). VWF:Ag levels remained higher in patients than controls at baseline (p≤0.03), but not at 14d or 90d after controlling for differences in age or hypertension, and were higher in patients at baseline and 90d after controlling for smoking status (p≤0.04). 'Adjusted' VWF:Ag II levels were not higher in patients than controls after controlling for age, hypertension or smoking (p≥0.1). Patients with symptomatic carotid stenosis (N=46) had higher VWF:Ag and VWF:Ag II levels than controls at all time-points (p≤0.002). There was no significant correlation between platelet activation status and VWF:Ag or VWF:Ag II levels. VWF:Ag and VWF:Ag II levels are increased in an overall TIA and ischaemic stroke population, especially in patients with recently symptomatic carotid stenosis. VWF:Ag II was not superior to VWF:Ag at detecting acute endothelial activation in this cohort and might reflect timing of blood sampling in our study. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical outcomes and a high prevalence of abnormalities on comprehensive arterial and venous thrombophilia screening in TIA or ischaemic stroke patients with a patent foramen ovale, an inter-atrial septal aneurysm or both.

PubMed

Lim, Soon Tjin; Murphy, Stephen J X; Smith, Deirdre R; Williams, Jennifer; Navarro, Silvia Gil; McCabe, John; Moore, David P; McHugh, Johnny; McCabe, Dominick J H

2017-06-15

Data are limited on the optimal management of cryptogenic TIA/stroke patients with a patent foramen ovale (PFO)±inter-atrial septal aneurysm (IASA), especially with an inherited thrombophilia. Prospectively-collected data on TIA/ischaemic stroke patients with PFO, IASA or both who received 'goal-directed secondary-prevention medical treatment' were analysed. All patients had trans-oesophageal echocardiography, anti-nuclear, anti-cardiolipin, anti-beta 2 glycoprotein I antibodies, rheumatoid factor, lupus anticoagulant, protein C&S, anti-thrombin, factor VIII activity, activated protein C resistance, Factor V Leiden, prothrombin gene and MTHFR-c.677C>T mutation screening. ENA and homocysteine were assessed in the latter study period. Eighty-three patients were recruited. Mean follow-up: 48.1months. Forty-seven patients (56.6%) had an isolated PFO, 32 (38.6%) a PFO and an IASA, and 4 (4.8%) an IASA alone. Eighteen (21.7%) had ≥1 abnormality on thrombophilia screening. The most important abnormalities which lead to treatment changes in 11 patients (13.3%) were primary anti-phospholipid syndrome (N=3; 3.6%), protein S deficiency (N=2; 2.4%) hyper-homocysteinaemia (N=6/72 screened, 8.3%). Four patients (4.8%) opted for PFO closure: two with protein S deficiency, and two with no identified thrombophilia. Seven (8.4%) had recurrent TIA/ischaemic stroke during follow-up (overall annualised incidence: 2.1%), of whom five had a PFO alone and two a PFO and IASA. Comprehensive arterial and venous thrombophilia screening is warranted in TIA/ischaemic stroke patients with a PFO±IASA, is conclusively abnormal in over a fifth, and informed important decision-making regarding individualised therapy in 13.3% of patients. The incidence of recurrent vascular events in this population is low on optimal, personalised secondary-prevention treatment, even with an underlying thrombophilia. Copyright © 2017 Elsevier B.V. All rights reserved.

Is anti-platelet therapy needed in continuous flow left ventricular assist device patients? A single-centre experience.

PubMed

Litzler, Pierre-Yves; Smail, Hassiba; Barbay, Virginie; Nafeh-Bizet, Catherine; Bouchart, François; Baste, Jean-Marc; Abriou, Caroline; Bessou, Jean-Paul

2014-01-01

We report our 5-year experience of continuous flow left ventricular assist device (LVAD) implantation without the use of anti-platelet therapy. Between February 2006 and September 2011, 27 patients (26 men; 1 woman) were implanted with a continuous flow LVAD (HeartMate II, Thoratec Corporation, Pleasanton, CA, USA). The mean age was 55.7 ± 9.9 years. The mean duration of support was 479 ± 436 (1-1555) days with 35.4 patient-years on support. Twenty-one patients were implanted as a bridge to transplantation and 6 for destination therapy. The anticoagulation regimen was fluindione for all patients, with aspirin for only 4 patients. At the beginning of our experience, aspirin was administered to 4 patients for 6, 15, 60 and 460 days. Due to gastrointestinal (GI) bleeding and epistaxis, aspirin was discontinued, and since August 2006, no patients have received anti-platelet therapy. At 3 years, the survival rate during support was 76%. The most common postoperative adverse event was GI bleeding (19%) and epistaxis (30%) (median time: 26 days) for patients receiving fluindione and aspirin. The mean International Normalized Ratio (INR) was 2.58 ± 0.74 during support. Fifteen patients have been tested for acquired Von Willebrand disease. A diminished ratio of collagen-binding capacity and ristocetin cofactor activity to Von Willebrand factor antigen was observed in 7 patients. In the postoperative period, 2 patients presented with ischaemic stroke at 1 and 8 months. One of these 2 patients had a previous history of carotid stenosis with ischaemic stroke. There were no patients with haemorrhagic stroke, transient ischaemic attack or pump thrombosis. The event rate of stroke (ischaemic and haemorrhagic) per patient-year was 0.059 among the patients without aspirin with fluindione regimen only. A fluindione regimen without aspirin in long-duration LVAD support appears to not increase thromboembolic events and could lead to a diminished risk of haemorrhagic stroke.

A randomised controlled trial of aerobic exercise after transient ischaemic attack or minor stroke to prevent cognitive decline: the MoveIT study protocol.

PubMed

Boss, H M; Van Schaik, S M; Deijle, I A; de Melker, E C; van den Berg, B T J; Scherder, E J A; Bosboom, W M J; Weinstein, H C; Van den Berg-Vos, R M

2014-12-31

Patients with transient ischaemic attack (TIA) or stroke are at risk for cognitive impairment and dementia. Currently, there is no known effective strategy to prevent this cognitive decline. Increasing evidence exists that physical exercise is beneficial for cognitive function. However, in patients with TIA or stroke who are at risk of cognitive impairment and dementia, only a few trials have been conducted. In this study, we aim to investigate whether a physical exercise programme (MoveIT) can prevent cognitive decline in patients in the acute phase after a TIA or minor ischaemic stroke. A single-blinded randomised controlled trial will be conducted to investigate the effect of an aerobic exercise programme on cognition compared with usual care. 120 adult patients with a TIA or minor ischaemic stroke less than 1 month ago will be randomly allocated to an exercise programme consisting of a 12-week aerobic exercise programme and regular follow-up visits to a specialised physiotherapist during the period of 1 year or to usual care. Outcome measures will be assessed at the baseline, and at the 1-year and 2-year follow-up. The primary outcome is cognitive functioning measured with the Montreal Cognitive Assessment (MoCA) test and with additional neuropsychological tests. Secondary outcomes include maximal exercise capacity, self-reported physical activity and measures of secondary prevention. The study received ethical approval from the VU University Amsterdam Ethics committee (2011/383). The results of this study will be published in peer-reviewed journals and presented at international conferences. We will also disseminate the main results to our participants in a letter. The Nederlands Trial Register NTR3884. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Identification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies.

PubMed

2016-06-01

Genetic determinants of stroke, the leading neurological cause of death and disability, are poorly understood and have seldom been explored in the general population. Our aim was to identify additional loci for stroke by doing a meta-analysis of genome-wide association studies. For the discovery sample, we did a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts comprising 84 961 participants, of whom 4348 had stroke. Stroke diagnosis was ascertained and validated by the study investigators. Mean age at stroke ranged from 45·8 years to 76·4 years, and data collection in the studies took place between 1948 and 2013. We did validation analyses for variants yielding a significant association (at p<5 × 10(-6)) with all-stroke, ischaemic stroke, cardioembolic ischaemic stroke, or non-cardioembolic ischaemic stroke in the largest available cross-sectional studies (70 804 participants, of whom 19 816 had stroke). Summary-level results of discovery and follow-up stages were combined using inverse-variance weighted fixed-effects meta-analysis, and in-silico lookups were done in stroke subtypes. For genome-wide significant findings (at p<5 × 10(-8)), we explored associations with additional cerebrovascular phenotypes and did functional experiments using conditional (inducible) deletion of the probable causal gene in mice. We also studied the expression of orthologs of this probable causal gene and its effects on cerebral vasculature in zebrafish mutants. We replicated seven of eight known loci associated with risk for ischaemic stroke, and identified a novel locus at chromosome 6p25 (rs12204590, near FOXF2) associated with risk of all-stroke (odds ratio [OR] 1·08, 95% CI 1·05-1·12, p=1·48 × 10(-8); minor allele frequency 21%). The rs12204590 stroke risk allele was also associated with increased MRI-defined burden of white matter hyperintensity-a marker of cerebral small vessel disease-in stroke-free adults (n=21 079; p=0·0025). Consistently, young patients (aged 2-32 years) with segmental deletions of FOXF2 showed an extensive burden of white matter hyperintensity. Deletion of Foxf2 in adult mice resulted in cerebral infarction, reactive gliosis, and microhaemorrhage. The orthologs of FOXF2 in zebrafish (foxf2b and foxf2a) are expressed in brain pericytes and mutant foxf2b(-/-) cerebral vessels show decreased smooth muscle cell and pericyte coverage. We identified common variants near FOXF2 that are associated with increased stroke susceptibility. Epidemiological and experimental data suggest that FOXF2 mediates this association, potentially via differentiation defects of cerebral vascular mural cells. Further expression studies in appropriate human tissues, and further functional experiments with long follow-up periods are needed to fully understand the underlying mechanisms. NIH, NINDS, NHMRC, CIHR, European national research institutions, Fondation Leducq. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sexual intercourse and risk of ischaemic stroke and coronary heart disease: the Caerphilly study

PubMed Central

Ebrahim, S; May, M; Ben, S; McCarron, P; Frankel, S; Yarnell, J; Davey, S

2002-01-01

Objective: To examine the relation between frequency of sexual intercourse and risk of ischaemic stroke and coronary heart disease. Design: Cohort study with 20 year follow up. Setting: The town of Caerphilly, South Wales and five adjacent villages. Subjects: 914 men aged 45–59 years at time of recruitment in 1979 to 1983. Main outcome measures: Ischaemic stroke and coronary heart disease, all first events and fatal events. Results: Of the 914 men studied, 197 (21.5%) reported sexual intercourse less often than once a month, 231 (25.3%) reported sexual intercourse twice or more a week, and the remaining 486 (53.2%) men fell into the intermediate category. Frequency of sexual intercourse was not associated with all first ischaemic stroke events: age adjusted odds ratios (95% CI) for intermediate and low frequency of sexual intercourse of 0.61 (0.32 to 1.16) and 0.71 (0.34 to 1.49) respectively compared with the reference category of high frequency. A graded relation with fatal coronary heart disease events was observed in events recorded up to 10 years. The age adjusted relative risk (95% CI) of fatal coronary heart disease contrasting low frequency of sexual intercourse (that is, less than monthly) with the highest group (at least twice a week) was 2.80 (1.13 to 6.96, test for trend, p=0.04) which was not attenuated by adjustment for a wide range of potential confounders. Longer follow up to 20 years showed attenuation of this risk with odds of 1.69 (95% CI 0.90 to 3.20), contrasting low frequency of sexual intercourse with the highest group. Conclusions: The differential relation between frequency of sexual intercourse, stroke and coronary heart disease suggests that confounding is an unlikely explanation for the observed association with fatal coronary heart disease events. Middle aged men should be heartened to know that frequent sexual intercourse is not likely to result in a substantial increase in risk of strokes, and that some protection from fatal coronary events may be an added bonus. PMID:11812807

Post-stroke Movement Disorders: Clinical Manifestations and Pharmacological Management

PubMed Central

Siniscalchi, Antonio; Gallelli, Luca; Labate, Angelo; Malferrari, Giovanni; Palleria, Caterina; Sarro, Giovambattista De

2012-01-01

Involuntary abnormal movements have been reported after ischaemic and haemorrhagic stroke. Post stroke movement disorders can appear as acute or delayed sequel. At the moment, for many of these disorders the knowledge of pharmacological treatment is still inadequate. Dopaminergic and GABAergic systems may be mainly involved in post-stroke movement disorders. This article provides a review on drugs commonly used in post-stroke movement disorders, given that some post-stroke movement disorders have shown a partial benefit with pharmacological approach. PMID:23449883

Post-stroke Movement Disorders: Clinical Manifestations and Pharmacological Management.

PubMed

Siniscalchi, Antonio; Gallelli, Luca; Labate, Angelo; Malferrari, Giovanni; Palleria, Caterina; Sarro, Giovambattista De

2012-09-01

Involuntary abnormal movements have been reported after ischaemic and haemorrhagic stroke. Post stroke movement disorders can appear as acute or delayed sequel. At the moment, for many of these disorders the knowledge of pharmacological treatment is still inadequate. Dopaminergic and GABAergic systems may be mainly involved in post-stroke movement disorders. This article provides a review on drugs commonly used in post-stroke movement disorders, given that some post-stroke movement disorders have shown a partial benefit with pharmacological approach.

A Cognitive and Affective Pattern in Posterior Fossa Strokes in Children: A Case Series

ERIC Educational Resources Information Center

Kossorotoff, Manoelle; Gonin-Flambois, Coralie; Gitiaux, Cyril; Quijano, Susana; Boddaert, Nathalie; Bahi-Buisson, Nadia; Barnerias, Christine; Dulac, Olivier; Brunelle, Francis; Desguerre, Isabelle

2010-01-01

Aim: Posterior fossa strokes account for about 10% of ischaemic strokes in children. Although motor and dysautonomic symptoms are common, to our knowledge cognitive and affective deficits have not been described in the paediatric literature. Our aim, therefore, was to describe these symptoms and deficits. Method: In a retrospective study, we…

l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease: A systematic review.

PubMed

Karlsson, William K; Sørensen, Caspar G; Kruuse, Christina

2017-01-01

Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and N G -monomethyl-l-arginine (l-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most studies applied transcranial Doppler to quantify cerebral ED. Endothelium-dependent vasodilatation (EDV) induced by l-arginine was impaired in elderly and subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l-arginine. Responses to l-NMMA deviated between subjects with type 2 DM and the elderly. We found only few studies investigating cerebral endothelial responses to l-arginine and l-NMMA in subjects with vascular risk factors or ischaemic cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease. © 2016 John Wiley & Sons Australia, Ltd.

Amelioration of cerebral infarction and improvement of neurological deficit by a Korean herbal medicine, modified Bo-Yang-Hwan-O-Tang.

PubMed

Choi, Yookeum; Kim, Seul-Ki; Choi, In-Young; Ju, Chung; Nam, Kung-Woo; Hwang, Sunyoung; Kim, Byung-Woo; Yoon, Min Ji; Won, Moo-Ho; Park, Yong-Ki; Kim, Won-Ki

2011-05-01

Modified Bo-Yang-Hwan-O-Tang (mBHT) is an improved herbal formula of BHT, which has been widely used to treat ischaemic stroke in East Asia, by the addition of five herbs having anti-ischaemic properties. In this study, we investigated whether mBHT would reduce cerebral ischaemic injury in rats. Sprague-Dawley rats were subjected to a 90-min middle cerebral artery occlusion (MCAO) and subsequent 22-h reperfusion. mBHT was administered either intraperitoneally twice 15 min before and 15 min after, or orally once 30 min or 120 min after the onset of MCAO (50 or 200 mg/kg each). Intraperitoneal administration of mBHT markedly reduced the cerebral infarct size and neurological deficit caused by MCAO/reperfusion. mBHT treatment also significantly improved long-term survival rate after cerebral ischaemic injury. Oral administration of mBHT 30 min after ischaemia also markedly reduced the infarct size after cerebral ischaemia. The anti-ischaemic effect of mBHT was significantly, but not fully, reduced when mBHT-induced hypothermia was abolished. In cultured cortical neurons, we further found that mBHT decreased oxygen-glucose deprivation/re-oxygenation-evoked neuronal injury by inhibiting production of reactive oxygen species, decrease in mitochondrial transmembrane potential, and activation of caspase-3. However, mBHT did not inhibit N-Methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. Taken together, our data suggest that mBHT has multiple anti-ischaemic properties and would be a good therapeutic herbal prescription for the treatment of cerebral ischaemic stroke. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Oxidative Stress and the Use of Antioxidants in Stroke

PubMed Central

Shirley, Rachel; Ord, Emily N. J.; Work, Lorraine M.

2014-01-01

Transient or permanent interruption of cerebral blood flow by occlusion of a cerebral artery gives rise to an ischaemic stroke leading to irreversible damage or dysfunction to the cells within the affected tissue along with permanent or reversible neurological deficit. Extensive research has identified excitotoxicity, oxidative stress, inflammation and cell death as key contributory pathways underlying lesion progression. The cornerstone of treatment for acute ischaemic stroke remains reperfusion therapy with recombinant tissue plasminogen activator (rt-PA). The downstream sequelae of events resulting from spontaneous or pharmacological reperfusion lead to an imbalance in the production of harmful reactive oxygen species (ROS) over endogenous anti-oxidant protection strategies. As such, anti-oxidant therapy has long been investigated as a means to reduce the extent of injury resulting from ischaemic stroke with varying degrees of success. Here we discuss the production and source of these ROS and the various strategies employed to modulate levels. These strategies broadly attempt to inhibit ROS production or increase scavenging or degradation of ROS. While early clinical studies have failed to translate success from bench to bedside, the combination of anti-oxidants with existing thrombolytics or novel neuroprotectants may represent an avenue worthy of clinical investigation. Clearly, there is a pressing need to identify new therapeutic alternatives for the vast majority of patients who are not eligible to receive rt-PA for this debilitating and devastating disease. PMID:26785066

Atrial fibrillation.

PubMed

Medi, Caroline; Hankey, Graeme J; Freedman, Saul B

2007-02-19

The incidence and prevalence of atrial fibrillation are increasing because of both population ageing and an age-adjusted increase in incidence of atrial fibrillation. Deciding between a rate control or rhythm control approach depends on patient age and comorbidities, symptoms and haemodynamic consequences of the arrhythmia, but either approach is acceptable. Digoxin is no longer a first-line drug for rate control: beta-blockers and verapamil and diltiazem control heart rate better during exercise. Anti-arrhythmic drugs have only a 40%-60% success rate of maintaining sinus rhythm at 1 year, and have significant side effects. The selection of optimal antithrombotic prophylaxis depends on the patient's risk of ischaemic stroke and the benefits and risks of long-term warfarin versus aspirin, but is independent of rate or rhythm control strategy. Ischaemic stroke risk is best estimated with the CHADS2 score (Congestive heart failure, Hypertension, Age > or = 75 years, Diabetes, 1 point each; prior Stroke or transient ischaemic attack, 2 points). For patients with valvular atrial fibrillation or a CHADS(2) score > or = 2, anticoagulation with warfarin is recommended (INR 2-3, higher for mechanical valves) unless contraindicated or annual major bleeding risk > 3%. Aspirin or warfarin may be used when the CHADS(2) score = 1. Aspirin, 81-325 mg daily, is recommended in patients with a CHADS(2) score of 0 or if warfarin is contraindicated. Stroke rate is similar for paroxysmal, persistent, and permanent atrial fibrillation, and probably for atrial flutter.

The Lectin Pathway in Thrombotic Conditions-A Systematic Review.

PubMed

Larsen, Julie Brogaard; Hvas, Christine Lodberg; Hvas, Anne-Mette

2018-06-04

The lectin pathway of the complement system can activate the coagulation system in vitro, but the role of the lectin pathway in haemostatic activation and thrombosis in vivo is not clear. We performed a systematic review of the existing literature on associations between the lectin pathway and arterial and venous thrombosis, in accordance with the Assessing the Methodological Quality of Systematic Reviews guidelines. PubMed and Embase were searched from January 1990 to March 2017. We included original studies on human study populations investigating associations between the lectin pathway (protein serum levels, genotype or gene expression) and thrombotic conditions or laboratory coagulation markers. Exclusion criteria were case studies including fewer than five cases, conference abstracts or any other language than English. In total, 43 studies were included which investigated associations between the lectin pathway and cardiovascular thrombotic events (CVEs) ( n  = 22), ischaemic stroke ( n  = 9), CVE and stroke ( n  = 1) and other conditions (systemic lupus erythematosus [ n  = 6], sepsis-related coagulopathy [ n  = 3], pulmonary embolism [ n  = 1], asparaginase treatment [ n  = 1]). Studies on the lectin pathway and CVE risk reported discrepant results, as both high and low mannose-binding lectin (MBL) serum levels were found to correlate with increased CVE risk. In ischaemic stroke patients, occurrence of stroke as well as increased stroke severity and poor outcome were consistently associated with high serum MBL. For other thromboembolic conditions, only few studies were identified. In conclusion, lectin pathway activation may negatively influence outcome after ischaemic stroke and possibly contribute to CVE risk. Further research is warranted to elucidate the role of the lectin pathway in other thrombotic conditions. Schattauer GmbH Stuttgart.

Body mass index and cardiovascular disease in the Asia-Pacific Region: an overview of 33 cohorts involving 310 000 participants.

PubMed

Ni Mhurchu, C; Rodgers, A; Pan, W H; Gu, D F; Woodward, M

2004-08-01

Few prospective data from the Asia-Pacific region are available relating body mass index (BMI) to the risks of stroke and ischaemic heart disease (IHD). Our objective was to assess the age-, sex-, and region-specific associations of BMI with cardiovascular disease using individual participant data from prospective studies in the Asia-Pacific region. Studies were identified from literature searches, proceedings of meetings, and personal communication. All studies had at least 5000 person-years of follow-up. Hazard ratios were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk and smoking. The first 3 years of follow-up were excluded in order to reduce confounding due to disease at baseline. A total of 33 cohort studies, including 310 283 participants, contributed 2 148 354 person-years of follow-up, during which 3332 stroke and 2073 IHD events were observed. There were continuous positive associations between baseline BMI and the risks of ischaemic stroke, haemorrhagic stroke, and IHD, with each 2 kg/m(2) lower BMI associated a 12% (95% CI: 9, 15%) lower risk of ischaemic stroke, 8% (95% CI: 4, 12%) lower risk in haemorrhagic stroke, and 11% (95% CI: 9, 13%) lower risk of IHD. The strengths of all associations were strongly age dependent, and there was no significant difference between Asian and Australasian cohorts. This overview provides the most reliable estimates to date of the associations between BMI and cardiovascular disease in the Asia-Pacific region, and the first direct comparisons within the region. Continuous relationships of approximately equal strength are evident in both Asian and Australasian populations. These results indicate considerable potential for cardiovascular disease reduction with population-wide lowering of BMI.

Simple prediction scores predict good and devastating outcomes after stroke more accurately than physicians.

PubMed

Reid, John Michael; Dai, Dingwei; Delmonte, Susanna; Counsell, Carl; Phillips, Stephen J; MacLeod, Mary Joan

2017-05-01

physicians are often asked to prognosticate soon after a patient presents with stroke. This study aimed to compare two outcome prediction scores (Five Simple Variables [FSV] score and the PLAN [Preadmission comorbidities, Level of consciousness, Age, and focal Neurologic deficit]) with informal prediction by physicians. demographic and clinical variables were prospectively collected from consecutive patients hospitalised with acute ischaemic or haemorrhagic stroke (2012-13). In-person or telephone follow-up at 6 months established vital and functional status (modified Rankin score [mRS]). Area under the receiver operating curves (AUC) was used to establish prediction score performance. five hundred and seventy-five patients were included; 46% female, median age 76 years, 88% ischaemic stroke. Six months after stroke, 47% of patients had a good outcome (alive and independent, mRS 0-2) and 26% a devastating outcome (dead or severely dependent, mRS 5-6). The FSV and PLAN scores were superior to physician prediction (AUCs of 0.823-0.863 versus 0.773-0.805, P < 0.0001) for good and devastating outcomes. The FSV score was superior to the PLAN score for predicting good outcomes and vice versa for devastating outcomes (P < 0.001). Outcome prediction was more accurate for those with later presentations (>24 hours from onset). the FSV and PLAN scores are validated in this population for outcome prediction after both ischaemic and haemorrhagic stroke. The FSV score is the least complex of all developed scores and can assist outcome prediction by physicians. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

Evolution of Endovascular Therapy in Acute Stroke: Implications of Device Development

PubMed Central

Balasubramaian, Adithya; Mitchell, Peter; Dowling, Richard

2015-01-01

Intravenous thrombolysis is an effective treatment for acute ischaemic stroke. However, vascular recanalization rates remain poor especially in the setting of large artery occlusion. On the other hand, endovascular intra-arterial therapy addresses this issue with superior recanalization rates compared with intravenous thrombolysis. Although previous randomized controlled studies of intra-arterial therapy failed to demonstrate superiority, the failings may be attributed to a combination of inferior intra-arterial devices and suboptimal selection criteria. The recent results of several randomized controlled trials have demonstrated significantly improved outcomes, underpinning the advantage of newer intra-arterial devices and superior recanalization rates, leading to renewed interest in establishing intra-arterial therapy as the gold standard for acute ischaemic stroke. The aim of this review is to outline the history and development of different intra-arterial devices and future directions in research. PMID:26060800

A higher body temperature is associated with haemorrhagic transformation in patients with acute stroke untreated with recombinant tissue-type plasminogen activator (rtPA).

PubMed

Leira, Rogelio; Sobrino, Tomás; Blanco, Miguel; Campos, Francisco; Rodríguez-Yáñez, Manuel; Castellanos, Mar; Moldes, Octavio; Millán, Mónica; Dávalos, Antoni; Castillo, José

2012-02-01

Higher body temperature is a prognostic factor of poor outcome in acute stroke. Our aim was to study the relationship between body temperature, HT (haemorrhagic transformation) and biomarkers of BBB (blood-brain barrier) damage in patients with acute ischaemic stroke untreated with rtPA (recombinant tissue-type plasminogen activator). We studied 229 patients with ischaemic stroke <12 h from symptom onset. Body temperature was determined at admission and every 6 h during the first 3 days. HT was evaluated according to ECASS II (second European Co-operative Acute Stroke Study) criteria in a multimodal MRI (magnetic resonance imaging) at 72 h. We found that 55 patients (34.1%) showed HT. HT was associated with cardioembolic stroke (64.2% against 23.0%; P<0.0001), higher body temperature during the first 24 h (36.9°C compared with 36.5°C; P<0.0001), more severe stroke [NIHSS (National Institutes of Health Stroke Scale) score, 14 (9-20) against 10 (7-15); P=0.002], and greater DWI (diffusion-weighted imaging) lesion volume at admission (23.2 cc compared with 13.2 cc; P<0.0001). Plasma MMP-9 (matrix metalloproteinase 9) (187.3 ng/ml compared with 44.2 ng/ml; P<0.0001) and cFn (cellular fibronectin) levels (16.3 μg/ml compared with 7.1 μg/ml; P=0.001) were higher in patients with HT. Body temperature within the first 24 h was independently associated with HT {OR (odds ratio), 7.3 [95% CI (confidence interval), 2.4-22.6]; P<0.0001} after adjustment for cardioembolic stroke subtype, baseline NIHSS score and DWI lesion volume. This effect remained unchanged after controlling for MMP-9 and cFn. In conclusion, high body temperature within the first 24 h after ischaemic stroke is a risk factor for HT in patients untreated with rtPA. This effect is independent of some biological signatures of BBB damage.

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study.

PubMed

Wilson, Duncan; Ambler, Gareth; Shakeshaft, Clare; Brown, Martin M; Charidimou, Andreas; Al-Shahi Salman, Rustam; Lip, Gregory Y H; Cohen, Hannah; Banerjee, Gargi; Houlden, Henry; White, Mark J; Yousry, Tarek A; Harkness, Kirsty; Flossmann, Enrico; Smyth, Nigel; Shaw, Louise J; Warburton, Elizabeth; Muir, Keith W; Jäger, Hans Rolf; Werring, David J

2018-06-01

Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0-20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1-5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27-10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29-0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53-0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60-0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07-0·43, p=0·0065; and 0·33, 0·14-0·51, p=0·00059, respectively). In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. The Stroke Association and the British Heart Foundation. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Machine learning for outcome prediction of acute ischemic stroke post intra-arterial therapy.

PubMed

Asadi, Hamed; Dowling, Richard; Yan, Bernard; Mitchell, Peter

2014-01-01

Stroke is a major cause of death and disability. Accurately predicting stroke outcome from a set of predictive variables may identify high-risk patients and guide treatment approaches, leading to decreased morbidity. Logistic regression models allow for the identification and validation of predictive variables. However, advanced machine learning algorithms offer an alternative, in particular, for large-scale multi-institutional data, with the advantage of easily incorporating newly available data to improve prediction performance. Our aim was to design and compare different machine learning methods, capable of predicting the outcome of endovascular intervention in acute anterior circulation ischaemic stroke. We conducted a retrospective study of a prospectively collected database of acute ischaemic stroke treated by endovascular intervention. Using SPSS®, MATLAB®, and Rapidminer®, classical statistics as well as artificial neural network and support vector algorithms were applied to design a supervised machine capable of classifying these predictors into potential good and poor outcomes. These algorithms were trained, validated and tested using randomly divided data. We included 107 consecutive acute anterior circulation ischaemic stroke patients treated by endovascular technique. Sixty-six were male and the mean age of 65.3. All the available demographic, procedural and clinical factors were included into the models. The final confusion matrix of the neural network, demonstrated an overall congruency of ∼ 80% between the target and output classes, with favourable receiving operative characteristics. However, after optimisation, the support vector machine had a relatively better performance, with a root mean squared error of 2.064 (SD: ± 0.408). We showed promising accuracy of outcome prediction, using supervised machine learning algorithms, with potential for incorporation of larger multicenter datasets, likely further improving prediction. Finally, we propose that a robust machine learning system can potentially optimise the selection process for endovascular versus medical treatment in the management of acute stroke.

Pathophysiological consequences of VEGF-induced vascular permeability

NASA Astrophysics Data System (ADS)

Weis, Sara M.; Cheresh, David A.

2005-09-01

Although vascular endothelial growth factor (VEGF) induces angiogenesis, it also disrupts vascular barrier function in diseased tissues. Accordingly, VEGF expression in cancer and ischaemic disease has unexpected pathophysiological consequences. By uncoupling endothelial cell-cell junctions VEGF causes vascular permeability and oedema, resulting in extensive injury to ischaemic tissues after stroke or myocardial infarction. In cancer, VEGF-mediated disruption of the vascular barrier may potentiate tumour cell extravasation, leading to widespread metastatic disease. Therefore, by blocking the vascular permeability promoting effects of VEGF it may be feasible to reduce tissue injury after ischaemic disease and minimize the invasive properties of circulating tumour cells.

Aerobic exercise interventions reduce blood pressure in patients after stroke or transient ischaemic attack: a systematic review and meta-analysis.

PubMed

Wang, Cheng; Redgrave, Jessica; Shafizadeh, Mohsen; Majid, Arshad; Kilner, Karen; Ali, Ali N

2018-05-09

Secondary vascular risk reduction is critical to preventing recurrent stroke. We aimed to evaluate the effect of exercise interventions on vascular risk factors and recurrent ischaemic events after stroke or transient ischaemic attack (TIA). Intervention systematic review and meta-analysis. OVID MEDLINE, PubMed, The Cochrane Library, Web of Science, The National Institute for Health and Care Excellence, TRIP Database, CINAHL, PsycINFO, SCOPUS, UK Clinical Trials Gateway and the China National Knowledge Infrastructure were searched from 1966 to October 2017. Randomised controlled trials evaluating aerobic or resistance exercise interventions on vascular risk factors and recurrent ischaemic events among patients with stroke or TIA, compared with control. Twenty studies (n=1031) were included. Exercise interventions resulted in significant reductions in systolic blood pressure (SBP) -4.30 mm Hg (95% CI -6.77 to -1.83) and diastolic blood pressure -2.58 mm Hg (95% CI -4.7 to -0.46) compared with control. Reduction in SBP was most pronounced among studies initiating exercise within 6 months of stroke or TIA (-8.46 mm Hg, 95% CI -12.18 to -4.75 vs -2.33 mm Hg, 95% CI -3.94 to -0.72), and in those incorporating an educational component (-7.81 mm Hg, 95% CI -14.34 to -1.28 vs -2.78 mm Hg, 95% CI -4.33 to -1.23). Exercise was also associated with reductions in total cholesterol (-0.27 mmol/L, 95% CI -0.54 to 0.00), but not fasting glucose or body mass index. One trial reported reductions in secondary vascular events with exercise, but was insufficiently powered. Exercise interventions can result in clinically meaningful blood pressure reductions, particularly if initiated early and alongside education. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Targeting von Willebrand Factor in Ischaemic Stroke: Focus on Clinical Evidence.

PubMed

Buchtele, Nina; Schwameis, Michael; Gilbert, James C; Schörgenhofer, Christian; Jilma, Bernd

2018-06-01

Despite great efforts in stroke research, disability and recurrence rates in ischaemic stroke remain unacceptably high. To address this issue, one potential target for novel therapeutics is the glycoprotein von Willebrand factor (vWF), which increases in thrombogenicity especially under high shear rates as it bridges between vascular sub-endothelial collagen and platelets. The rationale for vWF as a potential target in stroke comes from four bodies of evidence. (1) Animal models which recapitulate the pathogenesis of stroke and validate the concept of targeting vWF for stroke prevention and the use of the vWF cleavage enzyme ADAMTS13 in acute stroke treatment. (2) Extensive epidemiologic data establishing the prognostic role of vWF in the clinical setting showing that high vWF levels are associated with an increased risk of first stroke, stroke recurrence or stroke-associated mortality. As such, vWF levels may be a suitable marker for further risk stratification to potentially fine-tune current risk prediction models which are mainly based on clinical and imaging data. (3) Genetic studies showing an association between vWF levels and stroke risk on genomic levels. Finally, (4) studies of patients with primary disorders of excess or deficiency of function in the vWF axis (e.g. thrombotic thrombocytopenic purpura and von Willebrand disease, respectively) which demonstrate the crucial role of vWF in atherothrombosis. Therapeutic inhibition of VWF by novel agents appears particularly promising for secondary prevention of stroke recurrence in specific sub-groups of patients such as those suffering from large artery atherosclerosis, as designated according to the TOAST classification. Schattauer GmbH Stuttgart.

A porcine model for acute ischaemic right ventricular dysfunction.

PubMed

Haraldsen, Pernille; Lindstedt, Sandra; Metzsch, Carsten; Algotsson, Lars; Ingemansson, Richard

2014-01-01

To establish an experimental model for acute ischaemic isolated right ventricular dysfunction and the subsequent haemodynamic changes. An open-chest porcine model with ischaemic dysfunction of the right ventricle induced by ligation of the three main branches supporting the right ventricular free wall. Invasive monitoring of mean arterial blood pressure (MAP), central venous pressure (CVP), left atrial pressure (LAP) and right ventricular pressure (RVP); ultrasonic measurement of cardiac output (CO) and calculation of haemodynamic parameters such as stroke volume (SV), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and right ventricular stroke work (RVSW) using standard formulae. The ischaemic challenge to the right ventricle resulted in a significant (≥30%) reduction in RVSW associated with an increase (6-25%) in CVP and reduction (8-18%) in pulmonary artery pressure (PAP) despite unchanged PVR, all reflecting the failing right ventricle. There was also a significant drop in CO (14-22%) despite unchanged LAP indicating lessened transpulmonary delivery of left ventricular preload due to the failing right ventricle causing the haemodynamic compromise rather than left ventricular failure. Supraventricular and ventricular arrhythmias occurred in three and two out of seven pigs, respectively-all of which except one were successfully resuscitated with cardioversion and/or defibrillation. This novel open-chest porcine model of induced ischaemia of the right ventricular free wall resulted in significant haemodynamic compromise confirmed using standard haemodynamic measurements making it useful for further research on acute, ischaemic isolated right ventricular failure.

Shift work and vascular events: systematic review and meta-analysis.

PubMed

Vyas, Manav V; Garg, Amit X; Iansavichus, Arthur V; Costella, John; Donner, Allan; Laugsand, Lars E; Janszky, Imre; Mrkobrada, Marko; Parraga, Grace; Hackam, Daniel G

2012-07-26

To synthesise the association of shift work with major vascular events as reported in the literature. Systematic searches of major bibliographic databases, contact with experts in the field, and review of reference lists of primary articles, review papers, and guidelines. Observational studies that reported risk ratios for vascular morbidity, vascular mortality, or all cause mortality in relation to shift work were included; control groups could be non-shift ("day") workers or the general population. Study quality was assessed with the Downs and Black scale for observational studies. The three primary outcomes were myocardial infarction, ischaemic stroke, and any coronary event. Heterogeneity was measured with the I(2) statistic and computed random effects models. 34 studies in 2,011,935 people were identified. Shift work was associated with myocardial infarction (risk ratio 1.23, 95% confidence interval 1.15 to 1.31; I(2)=0) and ischaemic stroke (1.05, 1.01 to 1.09; I(2)=0). Coronary events were also increased (risk ratio 1.24, 1.10 to 1.39), albeit with significant heterogeneity across studies (I(2)=85%). Pooled risk ratios were significant for both unadjusted analyses and analyses adjusted for risk factors. All shift work schedules with the exception of evening shifts were associated with a statistically higher risk of coronary events. Shift work was not associated with increased rates of mortality (whether vascular cause specific or overall). Presence or absence of adjustment for smoking and socioeconomic status was not a source of heterogeneity in the primary studies. 6598 myocardial infarctions, 17,359 coronary events, and 1854 ischaemic strokes occurred. On the basis of the Canadian prevalence of shift work of 32.8%, the population attributable risks related to shift work were 7.0% for myocardial infarction, 7.3% for all coronary events, and 1.6% for ischaemic stroke. Shift work is associated with vascular events, which may have implications for public policy and occupational medicine.

Impact of collaterals on the efficacy and safety of endovascular treatment in acute ischaemic stroke: a systematic review and meta-analysis.

PubMed

Leng, Xinyi; Fang, Hui; Leung, Thomas W H; Mao, Chen; Miao, Zhongrong; Liu, Liping; Wong, Ka Sing; Liebeskind, David S

2016-05-01

We aimed to investigate the role of pretreatment collateral status in predicting the efficacy and safety of endovascular treatment (EVT) in acute ischaemic stroke due to cervical and/or cerebral arterial occlusions. Relevant full-text articles published since 1 January 2000, investigating correlations between collateral status and any efficacy or safety outcome in patients undergoing EVT in cohort or case-control studies, or randomised clinical trials, were retrieved by PubMed and manual search. Two authors extracted data from eligible studies and assessed study quality. Risk ratios (RR) were pooled for good versus poor collaterals for outcomes based on a random-effects model. Sensitivity and subgroup analyses were conducted. In total, 35 (3542 participants) and 23 (2652 participants) studies were included in qualitative review and quantitative meta-analysis, respectively. Overall, good pretreatment collaterals increased the rate of favourable functional outcome at 3 months (RR=1.98, 95% CI 1.64 to 2.38; p<0.001), and reduced the risks of periprocedural symptomatic intracranial haemorrhage (RR=0.59, 95% CI 0.43 to 0.81; p=0.001) and 3-month mortality (RR=0.49, 95% CI 0.38 to 0.63; p<0.001), as compared with poor collaterals, in patients with acute ischaemic stroke under EVT. No individual study could alter the estimate of overall effect of collateral status, but there were moderate to significant heterogeneities between subgroups of studies with different modes of EVT, different arterial occlusions and different collateral grading methods. Good pretreatment collateral status is associated with higher rates of favourable functional outcome, and lower rates of symptomatic intracranial haemorrhage and mortality, in patients with acute ischaemic stroke receiving endovascular therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

ASTRAL-R score predicts non-recanalisation after intravenous thrombolysis in acute ischaemic stroke.

PubMed

Vanacker, Peter; Heldner, Mirjam R; Seiffge, David; Mueller, Hubertus; Eskandari, Ashraf; Traenka, Christopher; Ntaios, George; Mosimann, Pascal J; Sztajzel, Roman; Mendes Pereira, Vitor; Cras, Patrick; Engelter, Stefan; Lyrer, Philippe; Fischer, Urs; Lambrou, Dimitris; Arnold, Marcel; Michel, Patrik

2015-05-01

Intravenous thrombolysis (IVT) as treatment in acute ischaemic strokes may be insufficient to achieve recanalisation in certain patients. Predicting probability of non-recanalisation after IVT may have the potential to influence patient selection to more aggressive management strategies. We aimed at deriving and internally validating a predictive score for post-thrombolytic non-recanalisation, using clinical and radiological variables. In thrombolysis registries from four Swiss academic stroke centres (Lausanne, Bern, Basel and Geneva), patients were selected with large arterial occlusion on acute imaging and with repeated arterial assessment at 24 hours. Based on a logistic regression analysis, an integer-based score for each covariate of the fitted multivariate model was generated. Performance of integer-based predictive model was assessed by bootstrapping available data and cross validation (delete-d method). In 599 thrombolysed strokes, five variables were identified as independent predictors of absence of recanalisation: Acute glucose > 7 mmol/l (A), significant extracranial vessel STenosis (ST), decreased Range of visual fields (R), large Arterial occlusion (A) and decreased Level of consciousness (L). All variables were weighted 1, except for (L) which obtained 2 points based on β-coefficients on the logistic scale. ASTRAL-R scores 0, 3 and 6 corresponded to non-recanalisation probabilities of 18, 44 and 74 % respectively. Predictive ability showed AUC of 0.66 (95 %CI, 0.61-0.70) when using bootstrap and 0.66 (0.63-0.68) when using delete-d cross validation. In conclusion, the 5-item ASTRAL-R score moderately predicts non-recanalisation at 24 hours in thrombolysed ischaemic strokes. If its performance can be confirmed by external validation and its clinical usefulness can be proven, the score may influence patient selection for more aggressive revascularisation strategies in routine clinical practice.

Neuroprotective effects of AT1 receptor antagonists after experimental ischemic stroke: what is important?

PubMed

Culman, Juraj; Jacob, Toni; Schuster, Sven O; Brolund-Spaether, Kjell; Brolund, Leonie; Cascorbi, Ingolf; Zhao, Yi; Gohlke, Peter

2017-09-01

The present study conducted in rats defines the requirements for neuroprotective effects of systemically administered AT1 receptor blockers (ARBs) in acute ischaemic stroke. The inhibition of central effects to angiotensin II (ANG II) after intravenous (i.v.) treatment with candesartan (0.3 and 3 mg/kg) or irbesartan and losartan (3 and 30 mg/kg) was employed to study the penetration of these ARBs across the blood-brain barrier. Verapamil and probenecid were used to assess the role of the transporters, P-glycoprotein and the multidrug resistance-related protein 2, in the entry of losartan and irbesartan into the brain. Neuroprotective effects of i.v. treatment with the ARBs were investigated after transient middle cerebral artery occlusion (MCAO) for 90 min. The treatment with the ARBs was initiated 3 h after the onset of MCAO and continued for two consecutive days. Blood pressure was continuously recorded before and during MCAO until 5.5 h after the onset of reperfusion. The higher dose of candesartan completely abolished, and the lower dose of candesartan and higher doses of irbesartan and losartan partially inhibited the drinking response to intracerebroventricular ANG II. Only 0.3 mg/kg candesartan improved the recovery from ischaemic stroke, and 3 mg/kg candesartan did not exert neuroprotective effects due to marked blood pressure reduction during reperfusion. Both doses of irbesartan and losartan had not any effect on the stroke outcome. An effective, long-lasting blockade of brain AT1 receptors after systemic treatment with ARBs without extensive blood pressure reductions is the prerequisite for neuroprotective effects in ischaemic stroke.

A cost-effectiveness analysis of screening for silent atrial fibrillation after ischaemic stroke.

PubMed

Levin, Lars-Åke; Husberg, Magnus; Sobocinski, Piotr Doliwa; Kull, Viveka Frykman; Friberg, Leif; Rosenqvist, Mårten; Davidson, Thomas

2015-02-01

The purpose of this study was to estimate the cost-effectiveness of two screening methods for detection of silent AF, intermittent electrocardiogram (ECG) recordings using a handheld recording device, at regular time intervals for 30 days, and short-term 24 h continuous Holter ECG, in comparison with a no-screening alternative in 75-year-old patients with a recent ischaemic stroke. The long-term (20-year) costs and effects of all alternatives were estimated with a decision analytic model combining the result of a clinical study and epidemiological data from Sweden. The structure of a cost-effectiveness analysis was used in this study. The short-term decision tree model analysed the screening procedure until the onset of anticoagulant treatment. The second part of the decision model followed a Markov design, simulating the patients' health states for 20 years. Continuous 24 h ECG recording was inferior to intermittent ECG in terms of cost-effectiveness, due to both lower sensitivity and higher costs. The base-case analysis compared intermittent ECG screening with no screening of patients with recent stroke. The implementation of the screening programme on 1000 patients resulted over a 20-year period in 11 avoided strokes and the gain of 29 life-years, or 23 quality-adjusted life years, and cost savings of €55 400. Screening of silent AF by intermittent ECG recordings in patients with a recent ischaemic stroke is a cost-effective use of health care resources saving costs and lives and improving the quality of life. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

NDT-Bobath method in normalization of muscle tone in post-stroke patients.

PubMed

Mikołajewska, Emilia

2012-01-01

Ischaemic stroke is responsible for 80-85% of strokes. There is great interest in finding effective methods of rehabilitation for post-stroke patients. The aim of this study was to assess the results of rehabilitation carried out in the normalization of upper limb muscle tonus in patients, estimated on the Ashworth Scale for Grading Spasticity. The examined group consisted of 60 patients after ischaemic stroke. 10 sessions of NDT-Bobath therapy were provided within 2 weeks (ten days of therapy). Patient examinations using the Ashworth Scale for Grading Spasticity were done twice: the first time on admission and the second after the last session of the therapy to assess rehabilitation effects. Among the patients involved in the study, the results measured on the Ashworth Scale (where possible) were as follows: recovery in 16 cases (26.67%), relapse in 1 case (1.67%), no measurable changes (or change within the same grade of the scale) in 8 cases (13.33%). Statistically significant changes were observed in the health status of the patients. These changes, in the area of muscle tone, were favorable and reflected in the outcomes of the assessment using the Ashworth Scale for Grading Spasticity.

Short- and Long-Term Stroke Risk after Urgent Management of Transient Ischaemic Attack: The Bologna TIA Clinical Pathway.

PubMed

Guarino, Maria; Rondelli, Francesca; Favaretto, Elisabetta; Stracciari, Andrea; Filippini, Massimo; Rinaldi, Rita; Zele, Ivana; Sartori, Michelangelo; Faggioli, Gianluca; Mondini, Susanna; Donti, Andrea; Strocchi, Enrico; Degli Esposti, Daniela; Muscari, Antonio; Veronesi, Maddalena; D'Addato, Sergio; Spinardi, Luca; Faccioli, Luca; Pastore Trossello, Marco; Cirignotta, Fabio

2015-01-01

Rapid management can reduce the short stroke risk after transient ischaemic attack (TIA), but the long-term effect is still little known. We evaluated 3-year vascular outcomes in patients with TIA after urgent care. We prospectively enrolled all consecutive patients with TIA diagnosed by a vascular neurologist and referred to our emergency department (ED). Expedited assessment and best secondary prevention was within 24 h. Endpoints were stroke within 90 days, and stroke, myocardial infarction, and vascular death at 12, 24 and 36 months. Between August 2010 and July 2013, we evaluated 686 patients with suspected TIA; 433 (63%) patients had confirmed TIA. Stroke at 90 days was 2.07% (95% confidence interval (CI), 1.1-3.9) compared with the ABCD2-predicted risk of 9.1%. The long-term stroke risk was 2.6% (95% CI, 1.1-4.2), 3.7% (95% CI, 1.6-5.9) and 4.4% (95% CI, 1.9-6.8) at 12, 24 and 36 months, respectively. The composite outcome of stroke, myocardial infarction, and vascular death was 3.5% (95% CI, 1.7-5.1), 4.9% (95% CI, 2.5-7.4), and 5.6% (95% CI, 2.8-8.3) at 12, 24, and 36 months, respectively. TIA expedited management driven by vascular neurologists was associated with a marked reduction in the expected early stroke risk and low long-term risk of stroke and other vascular events. © 2015 S. Karger AG, Basel.

The Role of Alcohol Consumption in the Aetiology of Different Cardiovascular Disease Phenotypes: a CALIBER Study

ClinicalTrials.gov

2013-05-28

Chronic Stable Angina; Unstable Angina; Coronary Heart Disease Not Otherwise Specified; Acute Myocardial Infarction; Heart Failure; Ventricular Arrhythmias; Cardiac Arrest; Abdominal Aortic Aneurysm; Peripheral Arterial Disease; Ischaemic Stroke; Subarachnoid Haemorrhagic Stroke; Intracerebral Haemorrhagic Stroke; Stroke Not Otherwise Specified; Sudden Cardiac Death; Unheralded Coronary Death; Mortality; Coronary Heart Disease (CHD); Cardiovascular Disease (CVD); Fatal Cardiovascular Disease (Fatal CVD); ST Elevation Myocardial Infarction (STEMI); Non-ST Elevation Myocardial Infarction (nSTEMI); Myocardial Infarction Not Otherwise Specified (MI NOS)

Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.

PubMed

Goyal, Mayank; Menon, Bijoy K; van Zwam, Wim H; Dippel, Diederik W J; Mitchell, Peter J; Demchuk, Andrew M; Dávalos, Antoni; Majoie, Charles B L M; van der Lugt, Aad; de Miquel, Maria A; Donnan, Geoffrey A; Roos, Yvo B W E M; Bonafe, Alain; Jahan, Reza; Diener, Hans-Christoph; van den Berg, Lucie A; Levy, Elad I; Berkhemer, Olvert A; Pereira, Vitor M; Rempel, Jeremy; Millán, Mònica; Davis, Stephen M; Roy, Daniel; Thornton, John; Román, Luis San; Ribó, Marc; Beumer, Debbie; Stouch, Bruce; Brown, Scott; Campbell, Bruce C V; van Oostenbrugge, Robert J; Saver, Jeffrey L; Hill, Michael D; Jovin, Tudor G

2016-04-23

In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included. We formed the HERMES collaboration to pool patient-level data from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) done between December, 2010, and December, 2014. In these trials, patients with acute ischaemic stroke caused by occlusion of the proximal anterior artery circulation were randomly assigned to receive either endovascular thrombectomy within 12 h of symptom onset or standard care (control), with a primary outcome of reduced disability on the modified Rankin Scale (mRS) at 90 days. By direct access to the study databases, we extracted individual patient data that we used to assess the primary outcome of reduced disability on mRS at 90 days in the pooled population and examine heterogeneity of this treatment effect across prespecified subgroups. To account for between-trial variance we used mixed-effects modelling with random effects for parameters of interest. We then used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in subgroups after adjustment for age, sex, baseline stroke severity (National Institutes of Health Stroke Scale score), site of occlusion (internal carotid artery vs M1 segment of middle cerebral artery vs M2 segment of middle cerebral artery), intravenous alteplase (yes vs no), baseline Alberta Stroke Program Early CT score, and time from stroke onset to randomisation. We analysed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control). Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control (adjusted cOR 2.49, 95% CI 1.76-3.53; p<0.0001). The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2.6. Subgroup analysis of the primary endpoint showed no heterogeneity of treatment effect across prespecified subgroups for reduced disability (pinteraction=0.43). Effect sizes favouring endovascular thrombectomy over control were present in several strata of special interest, including in patients aged 80 years or older (cOR 3.68, 95% CI 1.95-6.92), those randomised more than 300 min after symptom onset (1.76, 1.05-2.97), and those not eligible for intravenous alteplase (2.43, 1.30-4.55). Mortality at 90 days and risk of parenchymal haematoma and symptomatic intracranial haemorrhage did not differ between populations. Endovascular thrombectomy is of benefit to most patients with acute ischaemic stroke caused by occlusion of the proximal anterior circulation, irrespective of patient characteristics or geographical location. These findings will have global implications on structuring systems of care to provide timely treatment to patients with acute ischaemic stroke due to large vessel occlusion. Medtronic. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intravenous thrombolysis guided by a telemedicine consultation system for acute ischaemic stroke patients in China: the protocol of a multicentre historically controlled study

PubMed Central

Yuan, Ziwen; Wang, Bo; Li, Feijiang; Wang, Jing; Zhi, Jin; Luo, Erping; Liu, Zhirong; Zhao, Gang

2015-01-01

Introduction The rate of intravenous thrombolysis with tissue-type plasminogen activator or urokinase for stroke patients is extremely low in China. It has been demonstrated that a telestroke service may help to increase the rate of intravenous thrombolysis and improve stroke care quality in local hospitals. The aim of this study, also called the Acute Stroke Advancing Program, is to evaluate the effectiveness and safety of decision-making concerning intravenous thrombolysis via a telemedicine consultation system for acute ischaemic stroke patients in China. Methods and analysis This is a multicentre historically controlled study with a planned enrolment of 300 participants in each of two groups. The telestroke network consists of one hub hospital and 14 spoke hospitals in underserved regions of China. The usual stroke care quality in the spoke hospitals without guidance from the hub hospital will be used as the historical control. The telemedicine consultation system is an interactive, two-way, wireless, audiovisual system accessed on portable devices. The primary outcome is the percentage of patients treated with intravenous thrombolysis within 4.5 h of stroke onset. Ethics and dissemination The project has been approved by the Institutional Review Board of Xijing Hospital. The results will be published in scientific journals and presented to local government and relevant institutes. Trial registration number NCT02088346 (12 March 2014). PMID:25979867

C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis.

PubMed

Kaptoge, Stephen; Di Angelantonio, Emanuele; Lowe, Gordon; Pepys, Mark B; Thompson, Simon G; Collins, Rory; Danesh, John

2010-01-09

Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances. We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels. Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality. CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation. British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline. Copyright 2010 Elsevier Ltd. All rights reserved.

[Aetiological classification of ischaemic strokes: comparison of the new A-S-C-O classification and the classification by the Spanish Society of Neurology's Cerebrovascular Disease Study Group].

PubMed

Sobrino García, P; García Pastor, A; García Arratibel, A; Vicente Peracho, G; Rodriguez Cruz, P M; Pérez Sánchez, J R; Díaz Otero, F; Vázquez Alén, P; Villanueva Osorio, J A; Gil Núñez, A

2013-09-01

The A-S-C-O classification may be better than other methods for classifying ischaemic stroke by aetiology. Our aims are to describe A-S-C-O phenotype distribution (A: atherosclerosis, S: small vessel disease, C: cardiac source, O: other causes; 1: potential cause, 2: causality uncertain, 3: unlikely to be a direct cause although disease is present) and compare them to the Spanish Society of Neurology's Cerebrovascular Disease Study Group (GEECV/SEN) classification. We will also find the degree of concordance between these classification methods and determine whether using the A-S-C-O classification delivers a smaller percentage of strokes of undetermined cause. We analysed those patients with ischaemic stroke admitted to our stroke unit in 2010 with strokes that were classified according to GEECV/SEN and A-S-C-O criteria. The study included 496 patients. The percentages of strokes caused by atherosclerosis and small vessel disease according to GEECV/SEN criteria were higher than the percentages for potential atherosclerotic stroke (A1) (14.1 vs. 11.9%; P=.16) and potential small vessel stroke (S1) (14.3 vs. 3%; P<.001). Cardioembolic stroke (C1) was more frequent (22.2 vs. 31%; P<.001). No differences between unusual cause of stroke and other potential causes (O1) were observed. Some degree of atherosclerosis was present in 53.5% of patients (A1, A2, or A3); 65.5% showed markers of small vessel disease (S1, S2, or S3), and 74.9% showed signs of cardioembolism (C1, C2, or C3). Fewer patients in the group without scores of 1 or 2 for any of the A-S-C-O phenotypes were identified as having a stroke of undetermined cause (46.6 vs. 29.2%; P<.001). The agreement between the 2 classifications ranged from κ<0.2 (small vessel and S1) to κ>0.8 (unusual causes and O1). Our results show that GEECV/SEN and A-S-C-O classifications are neither fully comparable nor consistent. Using the A-S-C-O classification provided additional information on co-morbidities and delivered a smaller percentage of strokes classified as having an undetermined cause. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Neuroprotection by post-stroke administration of an oral formulation of angiotensin-(1-7) in ischaemic stroke.

PubMed

Bennion, Douglas M; Jones, Chad H; Donnangelo, Lauren L; Graham, Justin T; Isenberg, Jacob D; Dang, Alex N; Rodriguez, Vermali; Sinisterra, Ruben D M; Sousa, Frederico B; Santos, Robson A S; Sumners, Colin

2018-06-01

What is the central question of this study? Angiotensin-(1-7) decreases cerebral infarct volume and improves neurological function when delivered centrally before and during ischaemic stroke. Here, we assessed the neuroprotective effects of angiotensin-(1-7) when delivered orally post-stroke. What is the main finding and its importance? We show that oral delivery of angiotensin-(1-7) attenuates cerebral damage induced by middle cerebral artery occlusion in rats, without affecting blood pressure or cerebral blood flow. Importantly, these treatments begin post-stroke at times coincident with the treatment window for tissue plasminogen activator, providing supporting evidence for clinical translation of this new therapeutic strategy. As a target for stroke therapies, the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas [ACE2/Ang-(1-7)/Mas] axis of the renin-angiotensin system can be activated chronically to induce neuroprotective effects, in opposition to the deleterious effects of angiotensin II via its type 1 receptor. However, more clinically relevant treatment protocols with Ang-(1-7) that involve its systemic administration beginning after the onset of ischaemia have not been tested. In this study, we tested systemic post-stroke treatments using a molecule where Ang-(1-7) is included within hydroxypropyl-β-cyclodextrin [HPβCD-Ang-(1-7)] as an orally bioavailable treatment. In three separate protocols, HPβCD-Ang-(1-7) was administered orally to Sprague-Dawley rats after induction of ischaemic stroke by endothelin-1-induced middle cerebral artery occlusion: (i) to assess its effects on cerebral damage and behavioural deficits; (ii) to determine its effects on cardiovascular parameters; and (iii) to determine whether it altered cerebral blood flow. The results indicate that post-stroke oral administration of HPβCD-Ang-(1-7) resulted in 25% reductions in cerebral infarct volumes and improvement in neurological functions (P < 0.05), without inducing any alterations in blood pressure, heart rate or cerebral blood flow. In conclusion, Ang-(1-7) treatment using an oral formulation after the onset of ischaemia induces significant neuroprotection in stroke and might represent a viable approach for taking advantage of the protective ACE2/Ang-(1-7)/Mas axis in this disease. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

SOLITAIRE™ with the intention for thrombectomy (SWIFT) trial: design of a randomized, controlled, multicenter study comparing the SOLITAIRE™ Flow Restoration device and the MERCI Retriever in acute ischaemic stroke.

PubMed

Saver, J L; Jahan, R; Levy, E I; Jovin, T G; Baxter, B; Nogueira, R; Clark, W; Budzik, R; Zaidat, O O

2014-07-01

Self-expanding stent retrievers are a promising new device class designed for rapid flow restoration in acute cerebral ischaemia. The SOLITAIRE™ Flow Restoration device (SOLITAIRE) has shown high rates of recanalization in preclinical models and in uncontrolled clinical series. (1) To demonstrate non-inferiority of SOLITAIRE compared with a legally marketed device, the MERCI Retrieval System®; (2) To demonstrate safety, feasibility, and efficacy of SOLITAIRE in subjects requiring mechanical thrombectomy diagnosed with acute ischaemic stroke. DESIGN : Multicenter, randomized, prospective, controlled trial with blinded primary end-point ascertainment. Key entry criteria include: age 22-85; National Institute of Health Stroke Scale (NIHSS) ≥8 and <30; clinical and imaging findings consistent with acute ischaemic stroke; patient ineligible or failed intravenous tissue plasminogen activator; accessible occlusion in M1 or M2 middle cerebral artery, internal carotid artery, basilar artery, or vertebral artery; and patient able to be treated within 8 h of onset. Sites first participate in a roll-in phase, treating two patients with the SOLITAIRE device, before proceeding to the randomized phase. In patients unresponsive to the initially assigned therapy, after the angiographic component of the primary end-point is ascertained (reperfusion with the initial assigned device), rescue therapy with other reperfusion techniques is permitted. The primary efficacy end-point is successful recanalization with the assigned study device (no use of rescue therapy) and with no symptomatic intracranial haemorrhage. Successful recanalization is defined as achieving Thrombolysis In Myocardial Ischemia 2 or 3 flow in all treatable vessels. The primary safety end-point is the incidence of device-related and procedure-related serious adverse events. A major secondary efficacy end-point is time to achieve initial recanalization. Additional secondary end-points include clinical outcomes at 90 days and radiologic haemorrhagic transformation. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

A three-item scale for the early prediction of stroke recovery.

PubMed

Baird, A E; Dambrosia, J; Janket, S; Eichbaum, Q; Chaves, C; Silver, B; Barber, P A; Parsons, M; Darby, D; Davis, S; Caplan, L R; Edelman, R E; Warach, S

2001-06-30

Accurate assessment of prognosis in the first hours of stroke is desirable for best patient management. We aimed to assess whether the extent of ischaemic brain injury on magnetic reasonance diffusion-weighted imaging (MR DWI) could provide additional prognostic information to clinical factors. In a three-phase study we studied 66 patients from a North American teaching hospital who had: MR DWI within 36 h of stroke onset; the National Institutes of Health Stroke Scale (NIHSS) score measured at the time of scanning; and the Barthel Index measured no later than 3 months after stroke. We used logistic regression to derive a predictive model for good recovery. This logistic regression model was applied to an independent series of 63 patients from an Australian teaching hospital, and we then developed a three-item scale for the early prediction of stroke recovery. Combined measurements of the NIHSS score (p=0.01), time in hours from stroke onset to MR DWI (p=0.02), and the volume of ischaemic brain tissue on MR DWI (p=0.04) gave the best prediction of stroke recovery. The model was externally validated on the Australian sample with 0.77 sensitivity and 0.88 specificity. Three likelihood levels for stroke recovery-low (0-2), medium (3-4), and high (5-7)-were identified on the three-item scale. The combination of clinical and MR DWI factors provided better prediction of stroke recovery than any factor alone, shortly after admission to hospital. This information was incorporated into a three-item scale for clinical use.

[Stroke in paediatric patients with sickle-cell anaemia].

PubMed

Díaz-Díaz, Judit; Camacho-Salas, Ana; Núñez-Enamorado, Noemí; Carro-Rodríguez, Miguel A; Sánchez-Galán, Victoria; Martínez de Aragón, Ana; Simón-De Las Heras, Rogelio

2014-08-16

Sickle-cell anaemia is the severe homozygotic form of drepanocytosis, a genetic disorder that often occurs among black people and which is characterised by the production of haemoglobin S, chronic hemolytic anaemia and tissue ischaemia due to alterations in blood flow. A quarter of the patients presented neurological manifestations; 8-10% of children will have a stroke. AIM. To analyse the cases of stroke in children with sickle-cell anaemia in our centre. We conducted a retrospective descriptive study of children with sickle-cell anaemia and stroke. Five patients (two Dominicans and three Guineans) with sickle-cell anaemia and stroke; one patient suffered two episodes of stroke. The mean age was 27 months. Five of the episodes were ischaemic infarctions. Stroke was the initial form of presentation of drepanocytosis on three occasions. Two of the strokes occurred within a context of pneumococcal meningitis. Four of the patients had previously reported fever. The initial clinical picture was hemiparesis in four cases. Mean haemoglobin on diagnosing the stroke was 6.5 g/dL. Transcranial ultrasound imaging revealed alterations in three patients and, in all the patients, magnetic resonance imaging revealed lesions, which were bilateral in half the cases. Following the stroke, a hypertransfusion regimen protocol was established and only one patient presented a new stroke. This same patient went on to develop moya-moya disease and was submitted to an indirect revascularisation; the patient progressed well, without presenting any new ischaemic events. Drepanocytosis is a disease that is emerging in our setting as a result of immigration. It should be suspected in cases of paediatric strokes associated to anaemia, above all in black children under the age of five who were not submitted to neonatal screening.

Plasma D-dimer levels and ischaemic lesions in multiple vascular regions can predict occult cancer in patients with cryptogenic stroke.

PubMed

Gon, Y; Sakaguchi, M; Takasugi, J; Kawano, T; Kanki, H; Watanabe, A; Oyama, N; Terasaki, Y; Sasaki, T; Mochizuki, H

2017-03-01

Cancer patients with cryptogenic stroke often have high plasma D-dimer levels and lesions in multiple vascular regions. Hence, if patients with cryptogenic stroke display such characteristics, occult cancer could be predicted. This study aimed to investigate the clinical characteristics of cryptogenic stroke as the first manifestation of occult cancer and to determine whether plasma D-dimer levels and lesions in multiple vascular regions can predict occult cancer in patients with cryptogenic stroke. Between January 2006 and October 2015, data on 1225 patients with acute ischaemic stroke were extracted from the stroke database of Osaka University Hospital. Among them, 184 patients were classified as having cryptogenic stroke, and 120 patients without a diagnosis of cancer at stroke onset were identified. Clinical variables were analyzed between cryptogenic stroke patients with and without occult cancer. Among 120 cryptogenic stroke patients without a diagnosis of cancer, 12 patients had occult cancer. The body mass index, hemoglobin levels and albumin levels were lower; plasma D-dimer and high-sensitivity C-reactive protein levels were higher; and lesions in multiple vascular regions were more common in patients with than in those without occult cancer. Multiple logistic regression analysis revealed that plasma D-dimer levels (odds ratio, 3.48; 95% confidence interval, 1.68-8.33; P = 0.002) and lesions in multiple vascular regions (odds ratio, 7.40; 95% confidence interval, 1.70-39.45; P = 0.01) independently predicted occult cancer. High plasma D-dimer levels and lesions in multiple vascular regions can be used to predict occult cancer in patients with cryptogenic stroke. © 2016 EAN.

Evaluation of the Recognition of Stroke in the Emergency Room (ROSIER) Scale in Chinese Patients in Hong Kong

PubMed Central

Jiang, Hui-lin; Chan, Cangel Pui-yee; Leung, Yuk-ki; Li, Yun-mei; Graham, Colin A.; Rainer, Timothy H.

2014-01-01

Background and Purpose The objective of this study was to determine the performance of the Recognition Of Stroke In the Emergency Room (ROSIER) scale in risk-stratifying Chinese patients with suspected stroke in Hong Kong. Methods This was a prospective cohort study in an urban academic emergency department (ED) over a 7-month period. Patients over 18 years of age with suspected stroke were recruited between June 2011 and December 2011. ROSIER scale assessment was performed in the ED triage area. Logistic regression analysis was used to estimate the impacts of diagnostic variables, including ROSIER scale, past history and ED characteristics. Findings 715 suspected stroke patients were recruited for assessment, of whom 371 (52%) had acute cerebrovascular disease (302 ischaemic strokes, 24 transient ischaemic attacks (TIA), 45 intracerebral haemorrhages), and 344 (48%) had other illnesses i.e. stroke mimics. Common stroke mimics were spinal neuropathy, dementia, labyrinthitis and sepsis. The suggested cut-off score of>0 for the ROSIER scale for stroke diagnosis gave a sensitivity of 87% (95%CI 83–90), a specificity of 41% (95%CI 36–47), a positive predictive value of 62% (95%CI 57–66), and a negative predictive value of 75% (95%CI 68–81), and the AUC was 0.723. The overall accuracy at cut off>0 was 65% i.e. (323+141)/715. Interpretation The ROSIER scale was not as effective at differentiating acute stroke from stroke mimics in Chinese patients in Hong Kong as it was in the original studies, primarily due to a much lower specificity. If the ROSIER scale is to be clinically useful in Chinese suspected stroke patients, it requires further refinement. PMID:25343496

Multivitamin use and risk of stroke incidence and mortality amongst women.

PubMed

Adebamowo, S N; Feskanich, D; Stampfer, M; Rexrode, K; Willett, W C

2017-10-01

Few studies have examined the association between multivitamin use and the risk of stroke incidence and mortality, and the results remain inconclusive as to whether multivitamins are beneficial. The associations between multivitamin use and the risk of incident stroke and stroke mortality were prospectively examined in 86 142 women in the Nurses' Health Study, aged 34-59 years and free of diagnosed cardiovascular disease at baseline. Multivitamin use and covariates were updated every 2 years and strokes were documented by review of medical records. Hazard ratios of total, ischaemic and hemorrhagic strokes were calculated across categories of multivitamin use (non-user, past, current user) and duration (years), using Cox proportional hazards models. During 32 years of follow-up from 1980 to 2012, 3615 incident strokes were documented, including 758 deaths from stroke. In multivariate analyses, women who were current multivitamin users did not have a lower risk of incident total stroke compared to non-users [relative risk (RR) 1.02, 95% confidence interval (CI) 0.93-1.11], even those with longer durations of 15 or more years of use (RR 1.08, 95% CI 0.97-1.20) or those with a lower quality diet (RR 0.96, 95% CI 0.80-1.15). There was also no indication of benefit from multivitamin use for incident ischaemic or hemorrhagic strokes or for total stroke mortality. Long-term multivitamin use was not associated with reduced risk of stroke incidence or mortality amongst women in the study population, even amongst those with a lower diet quality. An effect in a less well-nourished population cannot be ruled out. © 2017 EAN.

Population-based study of blood biomarkers in prediction of sub-acute recurrent stroke

PubMed Central

Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Silver, Louise E; Rothwell, Peter M

2017-01-01

Background and purpose Risk of recurrent stroke is high in the first few weeks after TIA or stroke and clinic risk prediction tools have only limited accuracy, particularly after the hyper-acute phase. Previous studies of the predictive value of biomarkers have been small, been done in selected populations and have not concentrated on the acute phase or on intensively treated populations. We aimed to determine the predictive value of a panel of blood biomarkers in intensively treated patients early after TIA and stroke. Methods We studied 14 blood biomarkers related to inflammation, thrombosis, atherogenesis and cardiac or neuronal cell damage in early TIA or ischaemic stroke in a population-based study (Oxford Vascular Study). Biomarker levels were related to 90-day risk of recurrent stroke as Hazard Ratio (95%CI) per decile increase, adjusted for age and sex. Results Among 1292 eligible patients there were 53 recurrent ischaemic strokes within 90 days. There were moderate correlations (r>0.40; p<0001) between the inflammatory biomarkers and between the cell damage and thrombotic subsets. However, associations with risk of early recurrent stroke were weak, with significant associations limited to Interleukin-6 (HR=1.12, 1.01-1.24; p=0.035) and C-reactive protein (1.16, 1.02-1.30; p=0.019). When stratified by type of presenting event, P-selectin predicted stroke after TIA (1.31, 1.03-1.66; p=0.028) and C-reactive protein predicted stroke after stroke (1.16, 1.01-1.34; p=0.042). These associations remained after fully adjusting for other vascular risk factors. Conclusion In the largest study to date, we found very limited predictive utility for early recurrent stroke for a panel of inflammatory, thrombotic and cell damage biomarkers. PMID:25158774

Reduction of the neuroprotective transcription factor Npas4 results in increased neuronal necrosis, inflammation and brain lesion size following ischaemia

PubMed Central

Choy, Fong Chan; Klarić, Thomas S; Leong, Wai Khay; Koblar, Simon A

2015-01-01

Stroke is the second leading cause of death and the most frequent cause of adult disability. Neuronal Per-Arnt-Sim domain protein 4 (Npas4) is an activity-dependent transcription factor whose expression is induced in various brain insults, including cerebral ischaemia. Although previous studies have demonstrated that Npas4 plays a critical role in protecting neurons against neurodegenerative insults, the neuroprotective effect of Npas4 in response to ischaemic brain injury remains unknown. In this study, we used a loss-of-function approach to examine the neuroprotective potential of Npas4 in the context of ischaemic damage. Using oxygen and glucose deprivation, we demonstrated that the knockdown of Npas4 in mouse cortical neurons resulted in increased susceptibility to cell death. The protective effect of Npas4 was further investigated in vivo using a photochemically-induced stroke model in mice. We found a significantly larger lesion size and increased neurodegeneration in Npas4 knockout mice as compared to wild-type mice. Moreover, we also showed that ablation of Npas4 caused an increase in activated astrocytes and microglia, pro-inflammatory cytokines interleukin-6 and tumour necrosis factor alpha levels and a switch from apoptotic to necrotic cell death. Taken together, these data suggest that Npas4 plays a neuroprotective role in ischaemic stroke by limiting progressive neurodegeneration and neuroinflammation. PMID:26661154

Cognitive Outcome following Unilateral Arterial Ischaemic Stroke in Childhood: Effects of Age at Stroke and Lesion Location

ERIC Educational Resources Information Center

Westmacott, Robyn; Askalan, Rand; MacGregor, Daune; Anderson, Peter; deVeber, Gabrielle

2010-01-01

Aim: Plasticity in the developing brain is a controversial issue. Although language and motor function often recover remarkably well following early brain injury, recent evidence suggests that damage to the developing brain results in significant long-term neuropsychological impairment. Our aim was to investigate the relationship among age at…

Socioeconomic status and transient ischaemic attack/stroke: a prospective observational study.

PubMed

Kerr, Gillian D; Higgins, Peter; Walters, Matthew; Ghosh, Sandip K; Wright, Fiona; Langhorne, Peter; Stott, David J

2011-01-01

Lower socioeconomic status (SES) is associated with an increased risk of stroke but the mechanisms are unclear. We aimed to determine whether low-SES stroke/transient ischaemic attack (TIA) patients have a greater burden of vascular risk factors/co-morbidity and reduced health care access. We prospectively studied 467 consecutive stroke and TIA patients from 3 Scottish hospitals (outpatients and inpatients) during 2007/2008. We recorded vascular risk factors, stroke severity, co-morbidity measures, investigations and health service utilisation. SES was derived from postcodes using Scottish Neighbourhood Statistics and analysed in quartiles. TIA/stroke patients in the lowest SES quartile were younger (64 years, SD 14.1) than those in the highest quartile (72 years, SD 12.9; p < 0.0001). They were more likely to be current smokers (42 vs. 22%; p = 0.001) but there was no association with other vascular risk factors/co-morbidity. There was a trend for those with lower SES to have a more severe stroke [modified National Institutes of Health Stroke Scale score and interquartile range: 4 (2-6) vs. 3 (1-5); multivariate p = 0.05]. Lower SES groups were less likely to have neuro-imaging (82 vs. 90%; p = 0.036) or an electrocardiogram (72 vs. 87%; p = 0.003), but differences were no longer significant on multivariate analysis. However, there was equal access to stroke unit care. Low-SES TIA and stroke patients are younger and have a more severe deficit; an increased prevalence of smoking is likely to be a major contributor. We found equal access to stroke unit care for low-SES patients. Copyright © 2010 S. Karger AG, Basel.

Recurrent transient ischaemic attack and early risk of stroke: data from the PROMAPA study.

PubMed

Purroy, Francisco; Jiménez Caballero, Pedro Enrique; Gorospe, Arantza; Torres, María José; Alvarez-Sabin, José; Santamarina, Estevo; Martínez-Sánchez, Patricia; Cánovas, David; Freijo, María José; Egido, Jose Antonio; Ramírez-Moreno, Jose M; Alonso-Arias, Arantza; Rodríguez-Campello, Ana; Casado, Ignacio; Delgado-Mederos, Raquel; Martí-Fàbregas, Joan; Fuentes, Blanca; Silva, Yolanda; Quesada, Helena; Cardona, Pere; Morales, Ana; de la Ossa, Natalia Pérez; García-Pastor, Antonio; Arenillas, Juan F; Segura, Tomas; Jiménez, Carmen; Masjuán, Jaime

2013-06-01

Many guidelines recommend urgent intervention for patients with two or more transient ischaemic attacks (TIAs) within 7 days (multiple TIAs) to reduce the early risk of stroke. To determine whether all patients with multiple TIAs have the same high early risk of stroke. Between April 2008 and December 2009, we included 1255 consecutive patients with a TIA from 30 Spanish stroke centres (PROMAPA study). We prospectively recorded clinical characteristics. We also determined the short-term risk of stroke (at 7 and 90 days). Aetiology was categorised using the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Clinical variables and extracranial vascular imaging were available and assessed in 1137/1255 (90.6%) patients. 7-Day and 90-day stroke risk were 2.6% and 3.8%, respectively. Large-artery atherosclerosis (LAA) was confirmed in 190 (16.7%) patients. Multiple TIAs were seen in 274 (24.1%) patients. Duration <1 h (OR=2.97, 95% CI 2.20 to 4.01, p<0.001), LAA (OR=1.92, 95% CI 1.35 to 2.72, p<0.001) and motor weakness (OR=1.37, 95% CI 1.03 to 1.81, p=0.031) were independent predictors of multiple TIAs. The subsequent risk of stroke in these patients at 7 and 90 days was significantly higher than the risk after a single TIA (5.9% vs 1.5%, p<0.001 and 6.8% vs 3.0%, respectively). In the logistic regression model, among patients with multiple TIAs, no variables remained as independent predictors of stroke recurrence. According to our results, multiple TIAs within 7 days are associated with a greater subsequent risk of stroke than after a single TIA. Nevertheless, we found no independent predictor of stroke recurrence among these patients.

Use of medications for secondary prevention in stroke patients at hospital discharge in Australia.

PubMed

Eissa, Ashraf; Krass, Ines; Bajorek, Beata V

2014-04-01

Stroke is one of the leading causes of death and disability. Significant proportions (33 %) of stroke presentations are by patients with a previous stroke or transient ischaemic attack. Consequently, the stroke management guidelines recommend that all ischaemic stroke patients should receive three key evidence-based preventive drug therapies: antihypertensive drug therapy, a statin and an antithrombotic drug therapy (anticoagulant and/or antiplatelet). To determine the rates of utilization of the three key evidence-based drug therapies for the secondary prevention of stroke and to identify factors associated with use of treatment at discharge. Five metropolitan hospitals in New South Wales, comprising two tertiary referral centres and three district hospitals. A retrospective clinical audit was conducted in the study hospitals. Patients discharged with a principal diagnosis of ischaemic stroke during a 12-month time period (July 2009-2010) were identified for review. The rate of utilization of each of the three key evidence-based drug therapies and the factors associated with use of treatment at discharge. A total of 521 medical records were reviewed. Of these, 469 patients were discharged alive with a mean age of 73.6 ± 14.4 years. Overall, 75.4 % were prescribed an antihypertensive agent at discharge versus only 65.7 % on admission (P < 0.05). Three hundred-sixty patients (77.6 % of the eligible patients) were prescribed a statin at discharge (compared to only 43.9 % on admission, P < 0.05), of whom 74.0 % received monotherapy. Almost all (97.6 %) eligible patients were prescribed an antithrombotic drug therapy at discharge, of whom 68.5 % were prescribed monotherapy and 28.2 % were prescribed dual therapy. Only 60.0 % of eligible patients were discharged on all three key guideline recommended secondary preventive drug therapies. Multivariate logistic regression analyses showed that hypertension (OR 6.67; 95 % CI 4.35-11.11), hypercholesterolemia (OR 2.04; 95 % CI 1.32-3.23), and discharge destination (OR 0.22; 95 % CI 0.10-0.48) were associated with the utilization of all three guideline recommended therapies. There is a scope for improvement in implementing the stroke management guidelines when it comes to prescribing secondary preventive drug therapies using antihypertensives, antithrombotics and statins. Appropriate risk/benefit assessment is indispensable for optimal prescribing and maximizing patient outcomes, particularly in older people.

Anabolic steroids abuse-induced cardiomyopathy and ischaemic stroke in a young male patient.

PubMed

Shamloul, Reham Mohammed; Aborayah, Ahmed Fathy; Hashad, Assem; Abd-Allah, Foad

2014-02-26

We report a case of a 37-year-old man presented with acute stroke and hepatorenal impairment which were associated with anabolic-androgenic steroids (AAS) abuse over 2 years. Despite the absence of apparent symptoms and signs of congestive heart failure at presentation, an AAS-induced dilated cardiomyopathy with multiple thrombi in the left ventricle was attributed to be the underlying cause of his condition. Awareness of the complications of AAS led to the prompt treatment of the initially unrecognised dilated cardiomyopathy, and improved the liver and kidney functions. However, the patient was exposed to a second severe ischaemic event, which led to his death. This unique and complex presentation of AAS complications opens for better recognition and treatment of their potentially fatal effects.

[Surgical prevention of ischaemic strokes by means of an extraintracranial microanastomosis (EICMA) in the carotid basin].

PubMed

Krylov, V V; Luk'yanchikov, V A; Tokarev, A S; Nakhabin, O Yu; Polunina, N A; Sen'ko, I V; Dalibaldyan, V A; Grigor'eva, E V; Kudryashova, N E; Guseinova, G K; Udodov, E V; Fedulova, T A

Not less than 50% of all ischaemic strokes appear to occur resulting from pathology of extracranial arteries. Occlusions and stenoses are more commonly encountered in carotid arteries, with the incidence of occlusion of the internal carotid artery (ICA) ranging from 5 to 10% within the structure of all lesions of brachiocephalic arteries (BCA). The study was aimed at assessing the results of a surgical procedure of extra-intracranial microanastomosis (EICMA) performed in patients presenting with occlusive and stenotic lesions of BCA at the Neurosurgical Department. During the period between January 1st 2009 to September 30th 2015, specialists of the Neurosurgery Department of the Research Institute of Emergency Medical Care named after N.V. Sklifosovsky treated a total of 1,101 patients presenting with atherosclerotic lesions of BCA, with a total of 1,038 surgical interventions performed. Of these, there were 837 operations of carotid endarterectomy and 180 operations of EICMA in the carotid basin. The indications for performing EICMA in patients from the group with occlusive-stenosing lesions of the major arteries of the head and neck were as follows: the presence of occlusion of the internal carotid artery or M1 segment of the middle cerebral artery, verified by the findings of angiographic examinations; previously endured ischaemic-type cerebral circulation impairment in the basin on the side of occlusion; a decrease in the perfusion reserve of the brain on the side of occlusion by the findings of positron emission tomography (PET), single-photon emission computed tomography (SPECT) or CT-perfusion with loading tests. After performing EICMA, the neurological status in patients averagely improved by 1.2 points according to the NIH Stroke Scale; by 0.5 point according to the Rankin scale, and by 3.5 points according to the Rivermead Mobility Index (Table 1). The dynamics of functional outcomes of EICMA turned out to depend on the terms of the operation (R=2143, p<0.05) and the degree of neurological deficit prior to surgery (R=3422, p<0.05): the deeper the neurological deficiency was and the sooner after acute cerebral ischaemia (ACI) the operation was performed, the more significant restoration of the functions was at the moment of discharge from hospital. Major complications of EICMA in patients operated on at various terms of ischaemic stroke were as follows: recurrent cerebral circulatory impairments - in 6 (3.3%) patients, subdural and intracranial haemorrhage - in 2 (1.1%), temporal deepening of the neurological deficit on the background of reperfusion, confirmed by the findings of SPECT - in 2 (1.1%), pneumonia with a lethal outcome - in 1 (0.6%), fatal ischaemic stroke of the opposite hemisphere - in 1 (0.6%) subject. The lethality rate amounted to 1.1% (2 cases). The risk for the development of complications was higher in elderly and aged patients (75 years and over), in patients with pronounced neurological deficit and significant somatic disorders. The indications for surgical prevention of recurrent ischaemic stroke by means of EICMA should be based on the following factors: the presence of confirmed occlusion of the ICA, a history of endured acute cerebral ischaemia, and decreased cerebrovascular reserve. Performing a surgical intervention is not appropriate for patients presenting with pronounced neurological deficit and significant somatic pathology. Careful selection of patients, the use of modern methods of neuroimaging, and intraoperative control make it possible to achieve favourable functional outcomes and to decrease the postoperative complications rate.

Protocol and pilot data for establishing the Australian Stroke Clinical Registry.

PubMed

Cadilhac, Dominique A; Lannin, Natasha A; Anderson, Craig S; Levi, Christopher R; Faux, Steven; Price, Chris; Middleton, Sandy; Lim, Joyce; Thrift, Amanda G; Donnan, Geoffrey A

2010-06-01

Disease registries assist with clinical practice improvement. The Australian Stroke Clinical Registry aims to provide national, prospective, systematic data on processes and outcomes for stroke. We describe the methods of establishment and initial experience of operation. Australian Stroke Clinical Registry conforms to new national operating principles and technical standards for clinical quality registers. Features include: online data capture from acute public and private hospital sites; opt-out consent; expert consensus agreed core minimum dataset with standard definitions; outcomes assessed at 3 months poststroke; formal governance oversight; and formative evaluations for improvements. Qualitative feedback from sites indicates that the web-tool is simple to use and the user manuals, data dictionary, and training are appropriate. However, sites desire automated data-entry methods for routine demography variables and the opt-out consent protocol has sometimes been problematic. Data from 204 patients (median age 71 years, 54% males, 60% Australian) were collected from four pilot hospitals from June to October 2009 (mean, 50 cases per month) including ischaemic stroke (in 72%), intracerebral haemorrhage (16%), transient ischaemic attack (9%), and undetermined (3%), with only one case opting out. Australian Stroke Clinical Registry has been well established, but further refinements and broad roll-out are required before realising its potential of improving patient care through clinician feedback and allowance of local, national, and international comparative data.

Long working hours and stroke among employees in the general workforce of Denmark.

PubMed

Hannerz, Harald; Albertsen, Karen; Burr, Hermann; Nielsen, Martin Lindhardt; Garde, Anne Helene; Larsen, Ann Dyreborg; Pejtersen, Jan Hyld

2018-05-01

A systematic review and meta-analysis have found that long working hours were prospectively associated with an increased risk of overall stroke. The primary aim of the present study was to test if this finding could be reproduced in a sample that has been randomly selected from the general workforce of Denmark. A secondary aim was to estimate the association for haemorrhagic and ischaemic stroke separately. Individual participant data on 20- to 64-year-old employees were drawn from the Danish Labour Force Survey, 1999-2013, and linked to data on socio-economic status (SES), migrations, hospitalisations and deaths from national registers. The participants were followed from the time of the interview until the end of 2014. Poisson regression was used to estimate age-, sex- and SES-adjusted rate ratios for stroke as a function of weekly working hours. With 35-40 working hours per week as reference, the estimated rate ratios for overall stroke were 0.97 (95% confidence interval (CI) 0.83-1.13) for 41-48 working hours, 1.10 (95% CI 0.86-1.39) for 49-54 working hours and 0.89 (95% CI 0.69-1.16) for ≥55 working hours. The estimated rate ratios per one category increase in working hours were 0.99 (95% CI 0.93-1.06) for overall stroke, 0.96 (95% CI 0.88-1.05) for ischaemic stroke and 1.15 (95% CI 1.02-1.31) for haemorrhagic stroke. Our analysis does not support the hypothesis that long working hours are associated with increased rates of overall stroke. It suggests, however, that long working hours might be associated with increased rates of haemorrhagic stroke.

Plasticity in the Developing Brain: Intellectual, Language and Academic Functions in Children with Ischaemic Perinatal Stroke

ERIC Educational Resources Information Center

Ballantyne, Angela O.; Spilkin, Amy M.; Hesselink, John; Trauner, Doris A.

2008-01-01

The developing brain has the capacity for a great deal of plasticity. A number of investigators have demonstrated that intellectual and language skills may be in the normal range in children following unilateral perinatal stroke. Questions have been raised, however, about whether these skills can be maintained at the same level as the brain…

Tractography of white matter based on diffusion tensor imaging in ischaemic stroke involving the corticospinal tract: a preliminary study

NASA Astrophysics Data System (ADS)

Zhong, Chongguang; Bai, Lijun; Cui, Fangyuan; Dai, Ruwei; Xue, Ting; Wang, Hu; Wei, Wenjuan; Liu, Zhenyu; You, Youbo; Zou, Yihuai; Tian, Jie

2012-03-01

Diffusion tensor MR imaging (DTI) provides information on diffusion anisotropy in vivo, which can be exhibited three-dimensional white matter tractography. Five healthy volunteers and five right-hand affected patients with early subacute ischaemic infarction involving the posterior limb of the internal capsule or corona radiate were recruited in this study. We used 3D white matter tractography to show the corticospinal tract in both volunteer group and stroke group. Then we compared parameters of the corticospinal tract in patients with that in normal subjects and assessed the relationships between the fiber number of the corticospinal tract in ipsilesional hemisphere and indicators of the patients' rehabilitation using Pearson correlation analysis. The fractional anisotropy (FA) values and apparent diffusion coefficient (ADC) values in the ipsilesional corticospinal tract may significantly reduce comparing with the volunteer group. In addition, the stroke patient with less fiber number of the ipsilesional corticospinal tract may bear more possibilities of better motor rehabilitation. The FA values, ADC values and fiber number of the corticospinal tract in the ipsilesional hemisphere might be helpful to the prognosis and prediction of clinical treatment in stroke patients.

Visualising neuroinflammation in post-stroke patients: a comparative PET study with the TSPO molecular imaging biomarkers [11C]PK11195 and [11C]vinpocetine.

PubMed

Gulyas, Balazs; Toth, Miklos; Vas, Adam; Shchukin, Evgeni; Kostulas, Konstantinos; Hillert, Jan; Halldin, Christer

2012-01-01

With the main objective of comparing the prospective diagnostic power of two 11C-labelled molecular imaging biomarkers with affinity for TSPO and used for the visualisation of activated microglia after a stroke, we measured with positron emission tomography (PET) in four post-stroke patients the regional brain uptake and binding potential of [11C]vinpocetine and [11C]PK11195. Percentage standard uptake values (%SUV) and binding potential (BPND) were used as outcome measures. The total peak brain uptake value and average global brain uptake value were higher for [11C]vinpocetine than for [11C]PK11195. The regional %SUV values were significantly higher for [11C]vinpocetine than for [11C]PK11195 in the hemispheres as well as in almost all standard brain regions. The %SUV values of [11C]vinpocetine were higher in the peri-infarct zone than in the ischaemic core, however, the difference did not prove to be significant. There was basically no difference in %SUV values between the ischaemic core and the peri-infarct zone for [11C]PK11195. The BPND values for [11C]vinpocetine were higher in all standard regions than those for [11C]PK11195, but the difference was not significant between them. The BPND values of [11C]vinpocetine were higher in the peri-infarct zone than in the ischaemic core, however, the difference did not prove to be significant. A comparative analysis of the two ligands indicates that [11C]vinpocetine shows a number of favourable characteristics over [11C]PK11195, but to demonstrate that it may serve as a prospective molecular imaging biomarker of microglia activation in post-stroke patients, further studies are required.

Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery.

PubMed

Rothwell, P M; Eliasziw, M; Gutnikov, S A; Warlow, C P; Barnett, H J M

2004-03-20

Carotid endarterectomy reduces the risk of stroke in patients with recently symptomatic stenosis. Benefit depends on the degree of stenosis, and we aimed to see whether it might also depend on other clinical and angiographic characteristics, and on the timing of surgery. We analysed pooled data from the European Carotid Surgery Trial and North American Symptomatic Carotid Endarterectomy Trial. The risk of ipsilateral ischaemic stroke for patients on medical treatment, the perioperative risk of stroke and death, and the overall benefit from surgery were determined in relation to seven predefined and seven post hoc subgroups. 5893 patients with 33000 patient-years of follow-up were analysed. Sex (p=0.003), age (p=0.03), and time from the last symptomatic event to randomisation (p=0.009) modified the effectiveness of surgery. Benefit from surgery was greatest in men, patients aged 75 years or older, and those randomised within 2 weeks after their last ischaemic event, and fell rapidly with increasing delay. For patients with 50% or higher stenosis, the number of patients needed to undergo surgery (ie, number needed to treat) to prevent one ipsilateral stroke in 5 years was nine for men versus 36 for women, five for age 75 years or older versus 18 for younger than 65 years, and five for those randomised within 2 weeks after their last ischaemic event, versus 125 for patients randomised after more than 12 weeks. These results were consistent across the individual trials. Benefit from endarterectomy depends not only on the degree of carotid stenosis, but also on several other clinical characteristics such as delay to surgery after the presenting event. Ideally, the procedure should be done within 2 weeks of the patient's last symptoms.

30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial.

PubMed

Ringleb, P A; Allenberg, J; Brückmann, H; Eckstein, H-H; Fraedrich, G; Hartmann, M; Hennerici, M; Jansen, O; Klein, G; Kunze, A; Marx, P; Niederkorn, K; Schmiedt, W; Solymosi, L; Stingele, R; Zeumer, H; Hacke, W

2006-10-07

Carotid endarterectomy is effective in stroke prevention for patients with severe symptomatic carotid-artery stenosis, and carotid-artery stenting has been widely used as alternative treatment. Since equivalence or superiority has not been convincingly shown for either treatment, we aimed to compare the two. 1200 patients with symptomatic carotid-artery stenosis were randomly assigned within 180 days of transient ischaemic attack or moderate stroke (modified Rankin scale score of < or =3) carotid-artery stenting (n=605) or carotid endarterectomy (n=595). The primary endpoint of this hospital-based study was ipsilateral ischaemic stroke or death from time of randomisation to 30 days after the procedure. The non-inferiority margin was defined as less than 2.5% on the basis of an expected event rate of 5%. Analyses were on an intention-to-treat basis. This trial is registered at Current Controlled Trials with the international standard randomised controlled trial number ISRCTN57874028. 1183 patients were included in the analysis. The rate of death or ipsilateral ischaemic stroke from randomisation to 30 days after the procedure was 6.84% with carotid-artery stenting and 6.34% with carotid endarterectomy (absolute difference 0.51%, 90% CI -1.89% to 2.91%). The one-sided p value for non-inferiority is 0.09. SPACE failed to prove non-inferiority of carotid-artery stenting compared with carotid endarterectomy for the periprocedural complication rate. The results of this trial do not justify the widespread use in the short-term of carotid-artery stenting for treatment of carotid-artery stenoses. Results at 6-24 months are awaited.

Use of Proton-Pump Inhibitors Predicts Heart Failure and Death in Patients with Coronary Artery Disease

PubMed Central

Pello Lázaro, Ana María; Cristóbal, Carmen; Franco-Peláez, Juan Antonio; Tarín, Nieves; Aceña, Álvaro; Carda, Rocío; Huelmos, Ana; Martín-Mariscal, María Luisa; Fuentes-Antras, Jesús; Martínez-Millá, Juan; Alonso, Joaquín; Lorenzo, Óscar; Egido, Jesús; López-Bescós, Lorenzo; Tuñón, José

2017-01-01

Objectives Proton-pump inhibitors (PPIs) seem to increase the incidence of cardiovascular events in patients with coronary artery disease (CAD), mainly in those using clopidogrel. We analysed the impact of PPIs on the prognosis of patients with stable CAD. Methods We followed 706 patients with CAD. Primary outcome was the combination of secondary outcomes. Secondary outcomes were 1) acute ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and 2) heart failure (HF) or death. Results Patients on PPIs were older [62.0 (53.0–73.0) vs. 58.0 (50.0–70.0) years; p = 0.003] and had a more frequent history of stroke (4.9% vs. 1.1%; p = 0.004) than those from the non-PPI group, and presented no differences in any other clinical variable, including cardiovascular risk factors, ejection fraction, and therapy with aspirin and clopidogrel. Follow-up was 2.2±0.99 years. Seventy-eight patients met the primary outcome, 53 developed acute ischaemic events, and 33 HF or death. PPI use was an independent predictor of the primary outcome [hazard ratio (HR) = 2.281 (1.244–4.183); p = 0.008], along with hypertension, body-mass index, glomerular filtration rate, atrial fibrillation, and nitrate use. PPI use was also an independent predictor of HF/death [HR = 5.713 (1.628–20.043); p = 0.007], but not of acute ischaemic events. A propensity score showed similar results. Conclusions In patients with CAD, PPI use is independently associated with an increased incidence of HF and death but not with a high rate of acute ischaemic events. Further studies are needed to confirm these findings. PMID:28103324

Use of Proton-Pump Inhibitors Predicts Heart Failure and Death in Patients with Coronary Artery Disease.

PubMed

Pello Lázaro, Ana María; Cristóbal, Carmen; Franco-Peláez, Juan Antonio; Tarín, Nieves; Aceña, Álvaro; Carda, Rocío; Huelmos, Ana; Martín-Mariscal, María Luisa; Fuentes-Antras, Jesús; Martínez-Millá, Juan; Alonso, Joaquín; Lorenzo, Óscar; Egido, Jesús; López-Bescós, Lorenzo; Tuñón, José

2017-01-01

Proton-pump inhibitors (PPIs) seem to increase the incidence of cardiovascular events in patients with coronary artery disease (CAD), mainly in those using clopidogrel. We analysed the impact of PPIs on the prognosis of patients with stable CAD. We followed 706 patients with CAD. Primary outcome was the combination of secondary outcomes. Secondary outcomes were 1) acute ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and 2) heart failure (HF) or death. Patients on PPIs were older [62.0 (53.0-73.0) vs. 58.0 (50.0-70.0) years; p = 0.003] and had a more frequent history of stroke (4.9% vs. 1.1%; p = 0.004) than those from the non-PPI group, and presented no differences in any other clinical variable, including cardiovascular risk factors, ejection fraction, and therapy with aspirin and clopidogrel. Follow-up was 2.2±0.99 years. Seventy-eight patients met the primary outcome, 53 developed acute ischaemic events, and 33 HF or death. PPI use was an independent predictor of the primary outcome [hazard ratio (HR) = 2.281 (1.244-4.183); p = 0.008], along with hypertension, body-mass index, glomerular filtration rate, atrial fibrillation, and nitrate use. PPI use was also an independent predictor of HF/death [HR = 5.713 (1.628-20.043); p = 0.007], but not of acute ischaemic events. A propensity score showed similar results. In patients with CAD, PPI use is independently associated with an increased incidence of HF and death but not with a high rate of acute ischaemic events. Further studies are needed to confirm these findings.

Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS

PubMed Central

Gaude, Edoardo; Aksentijević, Dunja; Sundier, Stephanie Y.; Robb, Ellen L.; Logan, Angela; Nadtochiy, Sergiy M.; Ord, Emily N. J.; Smith, Anthony C.; Eyassu, Filmon; Shirley, Rachel; Hu, Chou-Hui; Dare, Anna J.; James, Andrew M.; Rogatti, Sebastian; Hartley, Richard C.; Eaton, Simon; Costa, Ana S.H.; Brookes, Paul S.; Davidson, Sean M.; Duchen, Michael R.; Saeb-Parsy, Kourosh; Shattock, Michael J.; Robinson, Alan J.; Work, Lorraine M.; Frezza, Christian; Krieg, Thomas; Murphy, Michael P.

2014-01-01

Ischaemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death, and aberrant immune responses through generation of mitochondrial reactive oxygen species (ROS)1-5. Although mitochondrial ROS production in IR is established, it has generally been considered a non-specific response to reperfusion1,3. Here, we developed a comparative in vivo metabolomic analysis and unexpectedly identified widely conserved metabolic pathways responsible for mitochondrial ROS production during IR. We showed that selective accumulation of the citric acid cycle (CAC) intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase (SDH), which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. Upon reperfusion, the accumulated succinate is rapidly re-oxidised by SDH, driving extensive ROS generation by reverse electron transport (RET) at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo IR injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of IR injury. Furthermore, these findings reveal a novel pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation upon subsequent reperfusion is a potential therapeutic target to decrease IR injury in a range of pathologies. PMID:25383517

Ischaemic stroke at a young age is a serious event--final results of a population-based long-term follow-up in Western Norway.

PubMed

Waje-Andreassen, U; Thomassen, L; Jusufovic, M; Power, K N; Eide, G E; Vedeler, C A; Naess, H

2013-05-01

Our population-based long-term follow-up of young ischaemic stroke patients and controls showed 10-fold increased mortality and fivefold increased arterial event rate nearly 12 years after study inclusion. We now assess memory, anxiety, depression and sleep in relation to employment and functional outcome, treatment goals and results from a last alive-dead survey. Patients (n = 232) ≤ 49 years with an index-stroke between 1988 and 1997 were retrospectively selected and compared with age- and sex-matched controls (n = 453). At follow-up from 2004 to 2005, 144 (77%) of 187 patients were clinically examined. Self-assessment information about memory problems, anxiety, depression, sleeping problems, education and employment was compared with answers from standardized questionnaires from 167 controls. Functional outcome was measured by the modified Rankin Scale (mRS). Patients compared with controls had more memory problems (41.0% vs. 5.4%, P < 0.001), anxiety (19.4% vs. 9%, P = 0.009), depression (29.2% vs. 13.2%, P = 0.001) and sleeping problems (36.1% vs. 19.2%, P = 0.001). In the multiple regression analysis male gender (OR 9.3, 95%CI 0.10-0.61, P = 0.002), normal memory (OR 12.7, 95%CI 0.07-0.47, P < 0.001) and mRS 0-1 (OR 15.7, 95%CI 0.002-0.12, P < 0.001) were factors for full-time employment. Blood pressure was < 140/90 mmHg in 39% of patients, 49% stopped smoking and 38.2% used statins. After a mean observation time of 18.3 years, 63 (27.2%) of 232 patients were dead. Our data show a heterogeneous prognosis and high mortality even for long-time survivors of ischaemic stroke at a young age. Prospective studies of young stroke patients and controls are necessary for direct comparison. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Associations of egg consumption with cardiovascular disease in a cohort study of 0.5 million Chinese adults.

PubMed

Qin, Chenxi; Lv, Jun; Guo, Yu; Bian, Zheng; Si, Jiahui; Yang, Ling; Chen, Yiping; Zhou, Yonglin; Zhang, Hao; Liu, Jianjun; Chen, Junshi; Chen, Zhengming; Yu, Canqing; Li, Liming

2018-05-21

To examine the associations between egg consumption and cardiovascular disease (CVD), ischaemic heart disease (IHD), major coronary events (MCE), haemorrhagic stroke as well as ischaemic stroke. During 2004-2008, over 0.5 million adults aged 30-79 years were recruited from 10 diverse survey sites in China. Participants were asked about the frequency of egg consumption and were followed up via linkages to multiple registries and active investigation. Among 461 213 participants free of prior cancer, CVD and diabetes, a total of 83 977 CVD incident cases and 9985 CVD deaths were documented, as well as 5103 MCE. Stratified Cox regression was performed to yield adjusted hazard ratios for CVD endpoints associated with egg consumption. At baseline, 13.1% of participants reported daily consumption (usual amount 0.76 egg/day) and 9.1% reported never or very rare consumption (usual amount 0.29 egg/day). Compared with non-consumers, daily egg consumption was associated with lower risk of CVD (HR 0.89, 95% CI 0.87 to 0.92). Corresponding multivariate-adjusted HRs (95% CI) for IHD, MCE, haemorrhagic stroke and ischaemic stroke were 0.88 (0.84 to 0.93), 0.86 (0.76 to 0.97), 0.74 (0.67 to 0.82) and 0.90 (0.85 to 0.95), respectively. There were significant dose-response relationships of egg consumption with morbidity of all CVD endpoints (P for linear trend <0.05). Daily consumers also had an 18% lower risk of CVD death and a 28% lower risk of haemorrhagic stroke death compared to non-consumers. Among Chinese adults, a moderate level of egg consumption (up to <1 egg/day) was significantly associated with lower risk of CVD, largely independent of other risk factors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Understanding clinicians’ decisions to offer intravenous thrombolytic treatment to patients with acute ischaemic stroke: a protocol for a discrete choice experiment

PubMed Central

De Brún,, Aoife; Flynn, Darren; Joyce, Kerry; Ternent, Laura; Price, Christopher; Rodgers, Helen; Ford, Gary A; Lancsar, Emily; Rudd, Matthew; Thomson, Richard G

2014-01-01

Background Intravenous thrombolysis is an effective emergency treatment for acute ischaemic stroke for patients meeting specific criteria. Approximately 12% of eligible patients in England, Wales and Northern Ireland received thrombolysis in the first quarter of 2013, yet as many as 15% are eligible to receive treatment. Suboptimal use of thrombolysis may have been largely attributable to structural factors; however, with the widespread implementation of 24/7 hyper acute stroke services, continuing variation is likely to reflect differences in clinical decision-making, in particular the influence of ambiguous areas within the guidelines, licensing criteria and research evidence. Clinicians’ perceptions about thrombolysis may now exert a greater influence on treatment rates than structural/service factors. This research seeks to elucidate factors influencing thrombolysis decision-making by using patient vignettes to identify (1) patient-related and clinician-related factors that may help to explain variation in treatment and (2) associated trade-offs in decision-making based on the interplay of critical factors. Methods/analysis A discrete choice experiment (DCE) will be conducted to better understand how clinicians make decisions about whether or not to offer thrombolysis to patients with acute ischaemic stroke. To inform the design, exploratory work will be undertaken to ensure that (1) all potentially influential factors are considered for inclusion; and (2) to gain insights into the ‘grey areas’ of patient factors. A fractional factorial design will be used to combine levels of patient factors in vignettes, which will be presented to clinicians to allow estimation of the variable effects on decisions to offer thrombolysis. Ethics and dissemination Ethical approval for this study was obtained from the Newcastle University Research Ethics Committee. The results will be disseminated in peer review publications and at national conferences. Findings will be translated into continuing professional development activities and will support implementation of a computerised decision aid for thrombolysis (COMPASS) in acute stroke care. PMID:25009137

Stroke in Arab countries: a systematic literature review.

PubMed

Benamer, Hani T S; Grosset, Donald

2009-09-15

Stroke is second only to ischaemic heart disease as a cause of death, and over a third of stroke deaths occur in developing countries. Arab countries constitute populations with a similar lifestyle and diet that may influence stroke risk, type and survival after stroke, as well as other characteristics in comparison to Western and Oriental populations. Therefore, a review of published reports of stroke in Arab countries was undertaken to provide a background for designing future stroke studies in Arab populations. Thirty-one articles related to incidence, prevalence, types, risk factors and outcome of stroke in Arab countries were identified by keyword searching of Medline and Embase, and review of references in all relevant papers. Studies were available for Saudi Arabia (n=16), Qatar (n=4), Libya (n=3), Kuwait (n=2), Jordan (n=1), United Arab Emirates (n=1), Bahrain (n=1), Tunisia (n=1), Iraq (n=1), and Sudan (n=1). The publication dates ranged from 1983-2008. The annual stroke incidence ranged from 27.5 to 63 per 100,000 population and prevalence was between 42 and 68 per 100,000 population. Ischaemic stroke was the commonest subtype in all series. However, one series from Sudan had a 41% rate of intracerebral haemorrhage, which is more similar to East Asian countries. Non-lacunar infarction occurred more frequently than lacunar infarcts in all but two series. Hypertension, diabetes mellitus, hyperlipidaemia, and cardiac disease were the commonest risk factors. The case-fatality rate at 30 days was between 10 and 17.5%. Therefore, the incidence and prevalence of stroke in Arab countries are lower than the Western world but within the range reported in Chinese populations. Stroke types and risk factors are similar, but an apparently higher rate of lacunar infarction in some settings needs further investigation. There is therefore a significant opportunity for further evaluation of stroke in Arab countries, especially in unstudied areas such as the populous countries of Egypt, Algeria, Syria, and Morocco.

Under-prescribing of Prevention Drugs and Primary Prevention of Stroke and Transient Ischaemic Attack in UK General Practice: A Retrospective Analysis.

PubMed

Turner, Grace M; Calvert, Melanie; Feltham, Max G; Ryan, Ronan; Fitzmaurice, David; Cheng, K K; Marshall, Tom

2016-11-01

Stroke is a leading cause of death and disability; worldwide it is estimated that 16.9 million people have a first stroke each year. Lipid-lowering, anticoagulant, and antihypertensive drugs can prevent strokes, but may be underused. We analysed anonymised electronic primary care records from a United Kingdom (UK) primary care database that covers approximately 6% of the UK population. Patients with first-ever stroke/transient ischaemic attack (TIA), ≥18 y, with diagnosis between 1 January 2009 and 31 December 2013, were included. Drugs were considered under-prescribed when lipid-lowering, anticoagulant, or antihypertensive drugs were clinically indicated but were not prescribed prior to the time of stroke or TIA. The proportions of strokes or TIAs with prevention drugs under-prescribed, when clinically indicated, were calculated. In all, 29,043 stroke/TIA patients met the inclusion criteria; 17,680 had ≥1 prevention drug clinically indicated: 16,028 had lipid-lowering drugs indicated, 3,194 anticoagulant drugs, and 7,008 antihypertensive drugs. At least one prevention drug was not prescribed when clinically indicated in 54% (9,579/17,680) of stroke/TIA patients: 49% (7,836/16,028) were not prescribed lipid-lowering drugs, 52% (1,647/3,194) were not prescribed anticoagulant drugs, and 25% (1,740/7,008) were not prescribed antihypertensive drugs. The limitations of our study are that our definition of under-prescribing of drugs for stroke/TIA prevention did not address patients' adherence to medication or medication targets, such as blood pressure levels. In our study, over half of people eligible for lipid-lowering, anticoagulant, or antihypertensive drugs were not prescribed them prior to first stroke/TIA. We estimate that approximately 12,000 first strokes could potentially be prevented annually in the UK through optimal prescribing of these drugs. Improving prescription of lipid-lowering, anticoagulant, and antihypertensive drugs is important to reduce the incidence and burden of stroke and TIA.

Feasibility, safety and cost of outpatient management of acute minor ischaemic stroke: a population-based study.

PubMed

Paul, Nicola L M; Koton, Silvia; Simoni, Michela; Geraghty, Olivia C; Luengo-Fernandez, Ramon; Rothwell, Peter M

2013-03-01

Outpatient management safely and effectively prevents early recurrent stroke after transient ischaemic attack (TIA), but this approach may not be safe in patients with acute minor stroke. To study outcomes of clinic and hospital-referred patients with TIA or minor stroke (National Institute of Health Stroke Scale score ≤3) in a prospective, population-based study (Oxford Vascular Study). Of 845 patients with TIA/stroke, 587 (69%) were referred directly to outpatient clinics and 258 (31%) directly to inpatient services. Of the 250 clinic-referred minor strokes (mean age 72.7 years), 237 (95%) were investigated, treated and discharged on the same day, of whom 16 (6.8%) were subsequently admitted to hospital within 30 days for recurrent stroke (n=6), sepsis (n=3), falls (n=3), bleeding (n=2), angina (n=1) and nursing care (n=1). The 150 patients (mean age 74.8 years) with minor stroke referred directly to hospital (median length-of-stay 9 days) had a similar 30-day readmission rate (9/150; 6.3%; p=0.83) after initial discharge and a similar 30-day risk of recurrent stroke (9/237 in clinic patients vs 8/150, OR=0.70, 0.27-1.80, p=0.61). Rates of prescription of secondary prevention medication after initial clinic/hospital discharge were higher in clinic-referred than in hospital-referred patients for antiplatelets/anticoagulants (p<0.05) and lipid-lowering agents (p<0.001) and were maintained at 1-year follow-up. The mean (SD) secondary care cost was £8323 (13 133) for hospital-referred minor stroke versus £743 (1794) for clinic-referred cases. Outpatient management of clinic-referred minor stroke is feasible and may be as safe as inpatient care. Rates of early hospital admission and recurrent stroke were low and uptake and maintenance of secondary prevention was high.

Reflection on stroke deaths and end-of-life stroke care.

PubMed

Quadri, Syed Z; Huynh, Thang; Cappelen-Smith, Cecilia; Wijesuriya, Nirupama; Mamun, Abul; Beran, Roy G; McDougall, Alan J; Cordato, Dennis

2018-03-01

The benefit of palliative care referral for severe stroke patients on end-of-life care pathway (EOLCP) is increasingly recognised. Palliative care provides assistance with symptom management and transition to end-of-life care. Advance care planning (ACP) may help accommodate patient/family expectations and guide management. This is a retrospective study of all stroke deaths (2014-2015) at Liverpool Hospital, Sydney, Australia. Data examined included age, comorbidities, living arrangements, pre-existing ACP, palliative care referral rates and 'survival time'. In total, 123 patient (mean age ± SD = 76 ± 13 years) deaths were identified from 1067 stroke admissions (11.5% mortality); 64 (52%) patients had ischaemic stroke and 59 (48%) intracerebral haemorrhage (ICH), and 40% suffered a prior stroke, and 43% required a carer at home or were in an aged care facility. Survival time from admission was significantly longer in patients with ischaemic stroke compared to intracerebral haemorrhage (median, interquartile range [IQR]: 9.5 [18] vs 2 [4] days, P < 0.001). Only two patients had pre-existing ACP; 44% of patients were referred to palliative care and 41% were commenced on dedicated EOLCP. Palliative care referral was less likely in patients who died under neurosurgery. EOLCP were significantly less likely to be commenced in patients who underwent acute intervention or were not referred to palliative care. In this cohort, palliative care referral and EOLCP were commenced in less than 50% of patients, highlighting significant variations in clinical care. These data support the need to promote awareness of ACP, particularly in patients with prior stroke or significant comorbidities. This may help reduce potentially futile invasive investigations and treatment. © 2017 Royal Australasian College of Physicians.

Development of a decision analytic model to support decision making and risk communication about thrombolytic treatment.

PubMed

McMeekin, Peter; Flynn, Darren; Ford, Gary A; Rodgers, Helen; Gray, Jo; Thomson, Richard G

2015-11-11

Individualised prediction of outcomes can support clinical and shared decision making. This paper describes the building of such a model to predict outcomes with and without intravenous thrombolysis treatment following ischaemic stroke. A decision analytic model (DAM) was constructed to establish the likely balance of benefits and risks of treating acute ischaemic stroke with thrombolysis. Probability of independence, (modified Rankin score mRS ≤ 2), dependence (mRS 3 to 5) and death at three months post-stroke was based on a calibrated version of the Stroke-Thrombolytic Predictive Instrument using data from routinely treated stroke patients in the Safe Implementation of Treatments in Stroke (SITS-UK) registry. Predictions in untreated patients were validated using data from the Virtual International Stroke Trials Archive (VISTA). The probability of symptomatic intracerebral haemorrhage in treated patients was incorporated using a scoring model from Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) data. The model predicts probabilities of haemorrhage, death, independence and dependence at 3-months, with and without thrombolysis, as a function of 13 patient characteristics. Calibration (and inclusion of additional predictors) of the Stroke-Thrombolytic Predictive Instrument (S-TPI) addressed issues of under and over prediction. Validation with VISTA data confirmed that assumptions about treatment effect were just. The C-statistics for independence and death in treated patients in the DAM were 0.793 and 0.771 respectively, and 0.776 for independence in untreated patients from VISTA. We have produced a DAM that provides an estimation of the likely benefits and risks of thrombolysis for individual patients, which has subsequently been embedded in a computerised decision aid to support better decision-making and informed consent.

Undertreatment of Vascular Risk Factors in Patients with Monocular Ischaemic Visual Loss.

PubMed

Zarkali, Angeliki; Cheng, Suk Fun; Dados, Agnes; Simister, Robert; Chandratheva, Arvind

2018-05-17

Ischaemic visual loss is often considered a lower risk factor than other transient ischaemic attacks (TIA). We aimed to determine the recurrence risk, prevalence and management of vascular risk factors in these patients. The study took place in the University College Hospital London daily TIA clinic, main referral centre for North-Central London and Moorfields Eye Hospital. Consecutive records for patients with transient (< 24 h) or permanent (> 24 h) ischaemic visual loss were reviewed during the period January 2014-October 2016. Patients diagnosed with temporal arteritis were excluded. Of 400 patients, 224 (56%) were male with mean age 64.5 years (SD 15.1); 263 patients (65.8%) presented with transient and 137 patients (34.2%) with permanent ischaemic visual loss; 51.3% had hypertension (HTN), 35.3% hypercholesterolaemia, 14.5% diabetes, 11.8% ischaemic ocular events, 10.0% ischaemic heart disease, 7.3% atrial fibrillation (AF), 6.3% TIA, 5.3% stroke, and 12.3% were smokers. Median vascular risk factors were 2 (range 1-6), but 122 (30.5%) had ≥3. Those with diabetes (p < 0.001), HTN (p = 0.008), previous myocardial infarction (p = 0.005), or ≥3 vascular risk factors (p = 0.012) were more likely to present with permanent visual loss, while patients with history of transient events, TIA (p = 0.002), or ocular (p = 0.002) presented with transient visual loss. Ninety-day recurrence was 10.5%; this was higher in patients with ≥3 risk factors (hazard ratio 1.42, 95% CI 0.95-2.11, p = 0.111). Patients with past TIA were more likely to be on secondary prevention than those with ocular ischaemia; 60.0 vs. 34.1% received antiplatelets and 76.0 vs. 43.9% statins. At presentation, only 55.2% (16 patients) with known AF were anticoagulated, despite all of them having CHADSVASC ≥1. Approximately one-third of patients with ocular ischaemia had ≥3 vascular risk factors with recurrences higher in these patients. Yet only half of those with previous ischaemic ocular events were on antiplatelets or statins. These patients should be investigated and treated as aggressively as other forms of TIA or stroke. © 2018 S. Karger AG, Basel.

Haemoglobin sickle D disease: A presentation with ischaemic stroke.

PubMed

Afzal, Hasnain; Umair, Syed Farrukh

2016-03-01

Haemoglobin-D, Los Angeles or Haemoglobin D-Punjab is not a rare variant of haemoglobin worldwide especially in Punjab, North western India, and South Asian continent. It can be inherited rarely as homozygous causing no symptoms or heterozygous with Haemoglobin A, commonly not related to clinical symptomatology. However, these variants can co-exist rarely with other haemoglobinopathies such as thalassemia or haemoglobin-S. We describe the case of doubly heterozygous Hb-SD Punjab in a 8 year old girl who presented with ischaemic stroke. Before this case, only one case has been reported but it was with reversible hyperbilirubinaemia in Hb-SD from Rawalpindi, Pakistan. This case images the propensity for occurrence of rare phenotype within our population and underlines the importance of genotyping to avoid erroneous management and poor counseling hence preventing life altering complications which our case developed.

An assessment of the cost-effectiveness of magnetic resonance, including diffusion-weighted imaging, in patients with transient ischaemic attack and minor stroke: a systematic review, meta-analysis and economic evaluation.

PubMed

Wardlaw, Joanna; Brazzelli, Miriam; Miranda, Hector; Chappell, Francesca; McNamee, Paul; Scotland, Graham; Quayyum, Zahid; Martin, Duncan; Shuler, Kirsten; Sandercock, Peter; Dennis, Martin

2014-04-01

Patients with transient ischaemic attack (TIA) or minor stroke need rapid treatment of risk factors to prevent recurrent stroke. ABCD2 score or magnetic resonance diffusion-weighted brain imaging (MR DWI) may help assessment and treatment. Is MR with DWI cost-effective in stroke prevention compared with computed tomography (CT) brain scanning in all patients, in specific subgroups or as 'one-stop' brain-carotid imaging? What is the current UK availability of services for stroke prevention? Published literature; stroke registries, audit and randomised clinical trials; national databases; survey of UK clinical and imaging services for stroke; expert opinion. Systematic reviews and meta-analyses of published/unpublished data. Decision-analytic model of stroke prevention including on a 20-year time horizon including nine representative imaging scenarios. The pooled recurrent stroke rate after TIA (53 studies, 30,558 patients) is 5.2% [95% confidence interval (CI) 3.9% to 5.9%] by 7 days, and 6.7% (5.2% to 8.7%) at 90 days. ABCD2 score does not identify patients with key stroke causes or identify mimics: 66% of specialist-diagnosed true TIAs and 35-41% of mimics had an ABCD2 score of ≥ 4; 20% of true TIAs with ABCD2 score of < 4 had key risk factors. MR DWI (45 studies, 9078 patients) showed an acute ischaemic lesion in 34.3% (95% CI 30.5% to 38.4%) of TIA, 69% of minor stroke patients, i.e. two-thirds of TIA patients are DWI negative. TIA mimics (16 studies, 14,542 patients) make up 40-45% of patients attending clinics. UK survey (45% response) showed most secondary prevention started prior to clinic, 85% of primary brain imaging was same-day CT; 51-54% of patients had MR, mostly additional to CT, on average 1 week later; 55% omitted blood-sensitive MR sequences. Compared with 'CT scan all patients' MR was more expensive and no more cost-effective, except for patients presenting at > 1 week after symptoms to diagnose haemorrhage; strategies that triaged patients with low ABCD2 scores for slow investigation or treated DWI-negative patients as non-TIA/minor stroke prevented fewer strokes and increased costs. 'One-stop' CT/MR angiographic-plus-brain imaging was not cost-effective. Data on sensitivity/specificity of MR in TIA/minor stroke, stroke costs, prognosis of TIA mimics and accuracy of ABCD2 score by non-specialists are sparse or absent; all analysis had substantial heterogeneity. Magnetic resonance with DWI is not cost-effective for secondary stroke prevention. MR was most helpful in patients presenting at > 1 week after symptoms if blood-sensitive sequences were used. ABCD2 score is unlikely to facilitate patient triage by non-stroke specialists. Rapid specialist assessment, CT brain scanning and identification of serious underlying stroke causes is the most cost-effective stroke prevention strategy. The National Institute for Health Research Health Technology Assessment programme.

Flavocoxid, dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, exhibits neuroprotection in rat model of ischaemic stroke.

PubMed

Singh, Dhirendra Pratap; Chopra, Kanwaljit

2014-05-01

The efficacy of flavocoxid, a prescription medical food used in osteoarthritis in the USA, containing natural flavonoids, baicalin and catechin in experimentally induced cerebral ischaemia in rats was evaluated. Rationale behind the study was that the transient acute ischaemic attack triggers neuroinflammatory cascade. Global cerebral ischaemia was induced transiently by occluding both common carotid arteries for 15 min followed by restoration of perfusion. Flavocoxid (50, 100, 200mg/kg; p.o.) pre-treatment was instituted 6 days prior to surgery and fluoxetine (10mg/kg, p.o.) and rivastigmine (2mg/kg, p.o.) as a standard treatment for depression and cognition impairment was implied from day 1 after the surgery. Different behavioural, biochemical, neurochemical tests, molecular markers of inflammation e.g. tumour necrosis factor-α, interleukin-1 beta, and nuclear factor-kappa B levels and infarct volume were determined. Flavocoxid's strong antioxidant properties figured out from the decreased level of lipid peroxidation and protection of endogenous antioxidants like reduced glutathione and superoxide dismutase. It also reduced TNF-α, IL-1β, and NF-κB levels, and infarct volume as well as protected the loss of biogenic amines in brain tissue of ischaemic rats. This dual inhibitor of cyclooxygenase-1 and 2 with additional 5-lipoxygenase inhibition activity might be useful as a potential neuroprotectant medical food in ischaemic stroke prone patient population. Copyright © 2014. Published by Elsevier Inc.

Burden of stroke in Bangladesh.

PubMed

Islam, Md Nazmul; Moniruzzaman, Mohammed; Khalil, Md Ibrahim; Basri, Rehana; Alam, Mohammad Khursheed; Loo, Keat Wei; Gan, Siew Hua

2013-04-01

Stroke is the third leading cause of death in Bangladesh. The World Health Organization ranks Bangladesh's mortality rate due to stroke as number 84 in the world. The reported prevalence of stroke in Bangladesh is 0.3%, although no data on stroke incidence have been recorded. Hospital-based studies conducted in past decades have indicated that hypertension is the main cause of ischaemic and haemorrhagic stroke in Bangladesh. The high number of disability-adjusted life-years lost due to stroke (485 per 10,000 people) show that stroke severely impacts Bangladesh's economy. Although two non-governmental organizations, BRAC and the Centre for the Rehabilitation of the Paralysed, are actively involved in primary stroke prevention strategies, the Bangladeshi government needs to emphasize healthcare development to cope with the increasing population density and to reduce stroke occurrence. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

A collaborative system for endovascular treatment of acute ischaemic stroke: the Madrid Stroke Network experience.

PubMed

Alonso de Leciñana, M; Fuentes, B; Ximénez-Carrillo, Á; Vivancos, J; Masjuan, J; Gil-Nuñez, A; Martínez-Sánchez, P; Zapata-Wainberg, G; Cruz-Culebras, A; García-Pastor, A; Díaz-Otero, F; Fandiño, E; Frutos, R; Caniego, J-L; Méndez, J-C; Fernández-Prieto, A; Bárcena-Ruiz, E; Díez-Tejedor, E

2016-02-01

The complexity and expense of endovascular treatment (EVT) for acute ischaemic stroke (AIS) can present difficulties in bringing this approach closer to the patients. A collaborative node was implemented involving three stroke centres (SCs) within the Madrid Stroke Network to provide round-the-clock access to EVT for AIS. A weekly schedule was established to ensure that at least one SC was 'on-call' to provide EVT for all those with moderate to severe AIS due to large vessel occlusion, >4.5 h from symptom onset, or within this time-window but with contraindication to, or failure of, systemic thrombolysis. The time-window for treatment was 8 h for anterior circulation stroke and <24 h in posterior stroke. Outcomes measured were re-canalization rates, modified Rankin Scale (mRS) score at 3 months, mortality and symptomatic intra-cranial haemorrhage (SICH). Over a 2-year period (2012-2013), 303 candidate patients with AIS were considered for EVT as per protocol, and 196 (65%) received treatment. Reasons for non-treatment were significant improvement (14%), spontaneous re-canalization (26%), clinical worsening (9%) or radiological criteria of established infarction (31%). Re-canalization rate amongst treated patients was 80%. Median delay from symptom onset to re-canalization was 323 min (p25; p75 percentiles 255; 430). Mortality was 11%; independence (mRS 0-2) was 58%; SICH was 3%. Implementation of a collaborative network to provide EVT for AIS is feasible and effective. Results are good in terms of re-canalization rates and clinical outcomes. © 2015 EAN.

Safety and efficacy of uric acid in patients with acute stroke (URICO-ICTUS): a randomised, double-blind phase 2b/3 trial.

PubMed

Chamorro, Angel; Amaro, Sergio; Castellanos, Mar; Segura, Tomás; Arenillas, Juan; Martí-Fábregas, Joan; Gállego, Jaime; Krupinski, Jurek; Gomis, Meritxell; Cánovas, David; Carné, Xavier; Deulofeu, Ramón; Román, Luis San; Oleaga, Laura; Torres, Ferran; Planas, Anna M

2014-05-01

Uric acid is an antioxidant with neuroprotective effects in experimental models of stroke. We assessed whether uric acid therapy would improve functional outcomes at 90 days in patients with acute ischaemic stroke. URICO-ICTUS was a randomised, double-blind, placebo-controlled, phase 2b/3 trial that recruited patients with acute ischaemic stroke admitted to ten Spanish stroke centres. Patients were included if they were aged 18 years or older, had received alteplase within 4·5 h of symptom onset, and had an eligible National Institutes of Health Stroke Scale (NIHSS) score (>6 and ≤25) and premorbid (assessed by anamnesis) modified Rankin Scale (mRS) score (≤2). Patients were randomly allocated (1:1) to receive uric acid 1000 mg or placebo (both infused intravenously in 90 min during the infusion of alteplase), stratified by centre and baseline stroke severity. The primary outcome was the proportion of patients with excellent outcome (ie, an mRS score of 0-1, or 2 if premorbid score was 2) at 90 days, analysed in the target population (all randomly assigned patients who had been correctly diagnosed with ischaemic stroke and had begun study medication). The study is registered with ClinicalTrials.gov, number NCT00860366. Between July 1, 2011, and April 30, 2013, we randomly assigned 421 patients, of whom 411 (98%) were included in the target population (211 received uric acid and 200 received placebo). 83 (39%) patients who received uric acid and 66 (33%) patients who received placebo had an excellent outcome (adjusted risk ratio 1·23 [95% CI 0·96-1·56]; p=0·099). No clinically relevant or statistically significant differences were reported between groups with respect to death (28 [13%] patients who received uric acid vs 31 [16%] who received placebo), symptomatic intracerebral haemorrhage (nine [4%] vs six [3%]), and gouty arthritis (one [<1%] vs four [2%]). 516 adverse events occurred in the uric acid group and 532 in the placebo group, of which 61 (12%) and 67 (13%), respectively, were serious adverse events (p=0·703). The addition of uric acid to thrombolytic therapy did not increase the proportion of patients who achieved excellent outcome after stroke compared with placebo, but it did not lead to any safety concerns. Institute of Health Carlos III of the Spanish Ministry of Health and Fundación Doctor Melchor Colet. Copyright © 2014 Elsevier Ltd. All rights reserved.

Beyond Stroke Prevention in Atrial Fibrillation: Exploring Further Unmet Needs with Rivaroxaban.

PubMed

Gibson, C M; Hankey, G J; Nafee, T; Welsh, R C

2018-03-22

With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke. Schattauer.

Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial.

PubMed

Held, Claes; Hylek, Elaine M; Alexander, John H; Hanna, Michael; Lopes, Renato D; Wojdyla, Daniel M; Thomas, Laine; Al-Khalidi, Hussein; Alings, Marco; Xavier, Dennis; Ansell, Jack; Goto, Shinya; Ruzyllo, Witold; Rosenqvist, Mårten; Verheugt, Freek W A; Zhu, Jun; Granger, Christopher B; Wallentin, Lars

2015-05-21

In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban. Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI. Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. ClinicalTrials.gov Identifier: NCT00412984. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Therapeutic hypothermia in the prevention of hypoxic-ischaemic encephalopathy: new categories to be enrolled.

PubMed

Gancia, Paolo; Pomero, Giulia

2012-10-01

Therapeutic hypothermia is now the standard of care for brain injury control in term infants with perinatal hypoxic ischemic encephalopathy (HIE). Accumulated evidence shows a reduction in mortality and long-term neurodevelopmental disability at 12-24 months of age, with more favourable effects in the less severe forms of HIE. Only few trials recruited newborns <36 weeks gestational age, or mild-to-moderate encephalopathy with base deficit (BD) <16. The new categories of patients to be enrolled should include (late) preterm infants, neonates with unexpected postnatal collapse, and newborns with stroke. Preterm HIE: Therapeutic hypothermia shows a good safety profile in clinical studies, and no adverse effects were noted in the preterm fetal animal model. Recently, it has been shown that mild hypothermia in preterm newborns with necrotizing enterocolitis (NEC) and multiple organ dysfunction syndrome (MODS) does not increase mortality, bleeding, infection, or need for inotropes in cooled newborns. A pilot study (NCT00620711) is currently recruiting newborns of > 32 but < 36 weeks gestation with standard criteria for HIE. Postnatal Collapse: The postnatal collapse (PNC) is a rare (0.03-0.5/1000 live births) but life-threatening hypoxic-ischemic event. No clinical trials of therapeutic hypothermia have specifically addressed to PNC. Nevertheless, a beneficial effect of brain cooling is expectable, and it has been proposed to include in brain hypothermia trials the infants with PNC fulfilling the entry criteria for HIE. Stroke: Perinatal arterial ischemic stroke is the most common cause of cerebral palsy (CP) in term and near-term newborn. In a systematic review and meta-analysis of animal studies of focal cerebral ischemia, hypothermia reduced the infarct size by 44%. No specific neuroprotective interventions are available for the management of acute perinatal stroke. Hypothermia may decrease seizures in newborns with encephalopathy and a focal infarct, potentially improving the long-term outcome for these infants. Future studies of therapeutic hypothermia should include the categories of newborns excluded from the published clinical trials, that is infants <36 weeks gestation, PNC or stroke, or admitted outside of the established 6-hour window, and with encephalopathy not imputable to HIE. New entry criteria will allow significant number of newborns to benefit from the treatment.

Dramatic response to levetiracetam in post-ischaemic Holmes’ tremor

PubMed Central

Striano, P; Elefante, Andrea; Coppola, Antonietta; Tortora, Fabio; Zara, Federico; Minetti, Carlo

2009-01-01

Holmes’ tremor refers to an unusual combination of rest, postural and kinetic tremor of extremities. Common causes of Holmes’ tremor include stroke, trauma, vascular malformations and multiple sclerosis, with lesions involving the thalamus, brain stem or cerebellum. Although some drugs (eg, levodopa and dopaminergic drugs, clonazepam and propranolol) have been occasionally reported to give some benefit, medical treatment of Holmes’ tremor is unsatisfactory, and many patients require thalamic surgery to achieve satisfactory control. We report a patient in whom post-ischaemic Holmes’ tremor dramatically responded to levetiracetam treatment. PMID:21686707

Clinical and Economic Implications of AF Related Stroke.

PubMed

Ali, Ali N; Abdelhafiz, Ahmed

2016-01-01

A major cause of morbidity and mortality among patients with atrial fibrillation (AF) relates to the increased risk of stroke. The burden of illness that AF imparts on stroke is likely to increase with our aging populations and increasingly sophisticated cardiac monitoring techniques. Understanding the clinical and economic differences between AF related ischaemic stroke and non-AF related stroke is important if we are to improve future cost effectiveness analyses of potential preventative treatments, but also to help educate clinical and policy decision makers on use or availability of treatments to prevent AF related stroke. In this article we review the existing evidence that highlights differences in the clinical characteristics and outcomes between AF and non-AF stroke, as well as differences in their economic impact and discuss ways to improve future economic analyses.

A novel treatment for embolising carotid dissection

PubMed Central

Jaipersad, A.S.; Tiivas, C.; Walton, G.; Imray, C.H.E.

2011-01-01

INTRODUCTION A rare but significant cause for stroke is sub-intimal carotid dissection and this mechanism accounts for approximately 2.5% of all strokes.1 Dissection of the carotid artery is often caused by trauma to the face or neck.2 Under 45 years old, it is the second leading cause of stroke.3 Neurological symptoms can be lacking or subtle, therefore the condition may be overlooked but the pathological processed is believed to be attributed to thromboembolism.4 Microemboli in the middle cerebral artery, are known as a risk factor for ischaemic stroke following a transient ischaemic attack (TIA) and can be detected by transcranial Doppler examination (TCD).5 The established treatment regime is antiplatelet therapy, anticoagulation or both along with supportive therapy.6 Current evidence suggests managing microemboli in both crescendo TIA's and post carotid endarterectomy improves outcome.7 We have found the use of Tirofiban, a potent intravenous antiplatelet agent currently licensed for use in acute coronary syndrome, effective in the treatment of microemboli in this manner.7 CASE PRESENTATION We report a case of symptomatic carotid artery dissection post radical neck dissection, causing TCD detected microemboli and successfully treated with Tirofiban. CONCLUSION We believe further study into the use of Tirofiban in the treatment of microemboli after carotid dissection is indicated. PMID:22288033

Serum Uric Acid Levels and Onset of Cardiovascular Diseases: a CALIBER Study

ClinicalTrials.gov

2018-02-06

Stable Angina; Unstable Angina; Myocardial Infarction; Unheralded Coronary Heart Disease Death; Heart Failure; Cardiac Arrest; Transient Ischaemic Attack; Ischemic Stroke; Subarachnoid Hemorrhage; Intracerebral Hemorrhage; Peripheral Arterial Disease; Abdominal Aortic Aneurysm; Atrial Fibrillation

Cerebral arterial gas embolism from attempted mechanical thrombectomy: recovery following hyperbaric oxygen therapy.

PubMed

Segan, Louise; Permezel, Fiona; Ch'ng, Wei; Millar, Ian; Brooks, Mark; Lee-Archer, Matt; Cloud, Geoffrey

2018-04-01

Cerebral arterial gas embolism is a recognised complication of endovascular intervention with an estimated incidence of 0.08%. Its diagnosis is predominantly clinical, supported by neuroimaging. The treatment relies on alleviating mechanical obstruction and reversing the proinflammatory processes that contribute to tissue ischaemia. Hyperbaric oxygen therapy is an effective treatment and has multiple mechanisms to reverse the pathological processes involved in cerebral arterial gas embolism. Symptomatic cerebral arterial gas embolism is a rare complication of endovascular intervention for acute ischaemic stroke. Although there are no previous descriptions of its successful treatment with hyperbaric oxygen therapy following mechanical thrombectomy, this is likely to become more common as mechanical thrombectomy is increasingly used worldwide to treat acute ischaemic stroke. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Correction of electrode modelling errors in multi-frequency EIT imaging.

PubMed

Jehl, Markus; Holder, David

2016-06-01

The differentiation of haemorrhagic from ischaemic stroke using electrical impedance tomography (EIT) requires measurements at multiple frequencies, since the general lack of healthy measurements on the same patient excludes time-difference imaging methods. It has previously been shown that the inaccurate modelling of electrodes constitutes one of the largest sources of image artefacts in non-linear multi-frequency EIT applications. To address this issue, we augmented the conductivity Jacobian matrix with a Jacobian matrix with respect to electrode movement. Using this new algorithm, simulated ischaemic and haemorrhagic strokes in a realistic head model were reconstructed for varying degrees of electrode position errors. The simultaneous recovery of conductivity spectra and electrode positions removed most artefacts caused by inaccurately modelled electrodes. Reconstructions were stable for electrode position errors of up to 1.5 mm standard deviation along both surface dimensions. We conclude that this method can be used for electrode model correction in multi-frequency EIT.

Derivation and validation of in-hospital mortality prediction models in ischaemic stroke patients using administrative data.

PubMed

Lee, Jason; Morishima, Toshitaka; Kunisawa, Susumu; Sasaki, Noriko; Otsubo, Tetsuya; Ikai, Hiroshi; Imanaka, Yuichi

2013-01-01

Stroke and other cerebrovascular diseases are a major cause of death and disability. Predicting in-hospital mortality in ischaemic stroke patients can help to identify high-risk patients and guide treatment approaches. Chart reviews provide important clinical information for mortality prediction, but are laborious and limiting in sample sizes. Administrative data allow for large-scale multi-institutional analyses but lack the necessary clinical information for outcome research. However, administrative claims data in Japan has seen the recent inclusion of patient consciousness and disability information, which may allow more accurate mortality prediction using administrative data alone. The aim of this study was to derive and validate models to predict in-hospital mortality in patients admitted for ischaemic stroke using administrative data. The sample consisted of 21,445 patients from 176 Japanese hospitals, who were randomly divided into derivation and validation subgroups. Multivariable logistic regression models were developed using 7- and 30-day and overall in-hospital mortality as dependent variables. Independent variables included patient age, sex, comorbidities upon admission, Japan Coma Scale (JCS) score, Barthel Index score, modified Rankin Scale (mRS) score, and admissions after hours and on weekends/public holidays. Models were developed in the derivation subgroup, and coefficients from these models were applied to the validation subgroup. Predictive ability was analysed using C-statistics; calibration was evaluated with Hosmer-Lemeshow χ(2) tests. All three models showed predictive abilities similar or surpassing that of chart review-based models. The C-statistics were highest in the 7-day in-hospital mortality prediction model, at 0.906 and 0.901 in the derivation and validation subgroups, respectively. For the 30-day in-hospital mortality prediction models, the C-statistics for the derivation and validation subgroups were 0.893 and 0.872, respectively; in overall in-hospital mortality prediction these values were 0.883 and 0.876. In this study, we have derived and validated in-hospital mortality prediction models for three different time spans using a large population of ischaemic stroke patients in a multi-institutional analysis. The recent inclusion of JCS, Barthel Index, and mRS scores in Japanese administrative data has allowed the prediction of in-hospital mortality with accuracy comparable to that of chart review analyses. The models developed using administrative data had consistently high predictive abilities for all models in both the derivation and validation subgroups. These results have implications in the role of administrative data in future mortality prediction analyses. Copyright © 2013 S. Karger AG, Basel.

[Comparison of efficacy of different neurometabolic and vasoactive medicines in ischemic stroke patients's rehabilitation].

PubMed

Galkin, A S; Koval'chuk, V V; Gusev, A O

2011-01-01

The aim of present investigation is research of influence of vasoactive and neurometabolic medicines in stroke patients's rehabilitation. We had analysed 280 stroke patients. The degree of rehabilitation had been defined with the help of Barthel and Lindmark scales. The degree of cognitive functions's rehabilitation had been defined with the help of MMSE scale. For every medicine coefficients of efficiency were calculated. As the result of the present investigation the medicine's efficiency was found out. The most efficient medicines in ischaemic stroke patients's rehabilitation among the investigated ones are the medicines which activate the neuronal metabolism, first of all,--ceraxon (citicoline).

Progesterone in experimental permanent stroke: a dose-response and therapeutic time-window study

PubMed Central

Wali, Bushra; Ishrat, Tauheed; Won, Soonmi; Stein, Donald G.

2014-01-01

Currently, the only approved treatment for ischaemic stroke is tissue plasminogen activator, a clot-buster. This treatment can have dangerous consequences if not given within the first 4 h after stroke. Our group and others have shown progesterone to be beneficial in preclinical studies of stroke, but a progesterone dose-response and time-window study is lacking. We tested male Sprague-Dawley rats (12 months old) with permanent middle cerebral artery occlusion or sham operations on multiple measures of sensory, motor and cognitive performance. For the dose-response study, animals received intraperitoneal injections of progesterone (8, 16 or 32 mg/kg) at 1 h post-occlusion, and subcutaneous injections at 6 h and then once every 24 h for 7 days. For the time-window study, the optimal dose of progesterone was given starting at 3, 6 or 24 h post-stroke. Behavioural recovery was evaluated at repeated intervals. Rats were killed at 22 days post-stroke and brains extracted for evaluation of infarct volume. Both 8 and 16 mg/kg doses of progesterone produced attenuation of infarct volume compared with the placebo, and improved functional outcomes up to 3 weeks after stroke on locomotor activity, grip strength, sensory neglect, gait impairment, motor coordination and spatial navigation tests. In the time-window study, the progesterone group exhibited substantial neuroprotection as late as 6 h after stroke onset. Compared with placebo, progesterone showed a significant reduction in infarct size with 3- and 6-h delays. Moderate doses (8 and 16 mg/kg) of progesterone reduced infarct size and improved functional deficits in our clinically relevant model of stroke. The 8 mg/kg dose was optimal in improving motor, sensory and memory function, and this effect was observed over a large therapeutic time window. Progesterone shows promise as a potential therapeutic agent and should be examined for safety and efficacy in a clinical trial for ischaemic stroke. PMID:24374329

Baseline characteristics, analysis plan and report on feasibility for the Prevention Of Decline in Cognition After Stroke Trial (PODCAST).

PubMed

Scutt, Polly; Blackburn, Dan; Krishnan, Kailash; Ballard, Clive; Burns, Alistair; Ford, Gary A; Mant, Jonathan; Passmore, Peter; Pocock, Stuart; Reckless, John; Sprigg, Nikola; Stewart, Rob; Wardlaw, Joanna M; Bath, Philip M

2015-11-07

A common complication after stroke is development of cognitive impairment and dementia. However, effective strategies for reducing the risk of developing these problems remain undefined. Potential strategies include intensive lowering of blood pressure (BP) and/or lipids. This paper summarises the baseline characteristics, statistical analysis plan and feasibility of a randomised control trial of blood pressure and lipid lowering in patients post-stroke with the primary objective of reducing cognitive impairment and dementia. The Prevention Of Decline in Cognition After Stroke Trial (PODCAST) was a multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial internal pilot trial running in secondary and primary care. Participants without dementia were enrolled 3-7 months post ischaemic stroke or spontaneous intracerebral haemorrhage, and randomised to intensive versus guideline BP lowering (target systolic BP <125 mmHg versus <140 mmHg); patients with ischaemic stroke were also randomised to intensive or guideline lipid lowering (target LDL cholesterol <1.4 mmol/L versus <3 mmol/L). The primary outcome was the Addenbrooke's Cognitive Examination-Revised; a key secondary outcome was to assess feasibility of performing a large trial of one or both interventions. Data are number (%) or mean (standard deviation). The trial was planned to last for 8 years with follow-up between 1 and 8 years. The plan for reporting the main results is included as Additional file 2. 83 patients (of a planned 600) were recruited from 19 UK sites between 7 October 2010 and 31 January 2014. Delays, due to difficulties in the provision of excess treatment costs and to complexity of follow-up, led to few centres taking part and a much lower recruitment rate than planned. Patient characteristics at baseline were: age 74 (SD 7) years, male 64 (77 %), index stroke ischaemic 77 (93 %), stroke onset to randomisation 4.5 [SD 1.3] months, Addenbrooke's Cognitive Examination-Revised 86 (of 100, SD 8), Montreal Cognitive Assessment 24 (of 30, SD 3), BP 147/82 (SD 19/11) mmHg, total cholesterol 4.0 (SD 0.8) mmol/L and LDL cholesterol 2.0 (SD 0.7) mmol/L, modified Rankin Scale 1.1 (SD 0.8). Limited recruitment suggests that a large trial is not feasible using the current protocol. The effects of the interventions on BP, lipids, and cognition will be reported in the main publication. ISRCTN85562386 registered on 23 September 2009.

Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia

NASA Astrophysics Data System (ADS)

Ferreira, R.; Fonseca, M. C.; Santos, T.; Sargento-Freitas, J.; Tjeng, R.; Paiva, F.; Castelo-Branco, M.; Ferreira, L. S.; Bernardino, L.

2016-04-01

Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature.

Childhood hospitalisation with infection and cardiovascular disease in early-mid adulthood: a longitudinal population-based study.

PubMed

Burgner, David P; Cooper, Matthew N; Moore, Hannah C; Stanley, Fiona J; Thompson, Peter L; de Klerk, Nicholas H; Carter, Kim W

2015-01-01

Pathogen-specific and overall infection burden may contribute to atherosclerosis and cardiovascular disease (CVD), but the effect of infection severity and timing is unknown. We investigated whether childhood infection-related hospitalisation (IRH, a marker of severity) was associated with subsequent adult CVD hospitalisation. Using longitudinal population-based statutorily-collected administrative health data from Western Australia (1970-2009), we identified adults hospitalised with CVD (ischaemic heart disease, ischaemic stroke, and peripheral vascular disease) and matched them (10:1) to population controls. We used Cox regression to assess relationships between number and type of childhood IRH and adulthood CVD hospitalisation, adjusting for sex, age, Indigenous status, socioeconomic status, and birth weight. 631 subjects with CVD-related hospitalisation in adulthood (≥ 18 years) were matched with 6310 controls. One or more childhood (< 18 years) IRH was predictive of adult CVD-related hospitalisation (adjusted hazard ratio, 1.3; 95% CI 1.1-1.6; P < 0.001). The association showed a dose-response; ≥ 3 childhood IRH was associated with a 2.2 times increased risk of CVD-related hospitalisation in adulthood (adjusted hazard ratio, 2.2; 95% CI 1.7-2.9; P < 0.001). The association was observed across all clinical diagnostic groups of infection (upper respiratory tract infection, lower respiratory tract infection, infectious gastroenteritis, urinary tract infection, skin and soft tissue infection, and other viral infection), and individually with CVD diagnostic categories (ischaemic heart disease, ischaemic stroke and peripheral vascular disease). Severe childhood infection is associated with CVD hospitalisations in adulthood in a dose-dependent manner, independent of population-level risk factors.

Fish consumption and risk of stroke, coronary heart disease, and cardiovascular mortality in a Dutch population with low fish intake.

PubMed

Hengeveld, L M; Praagman, J; Beulens, J W J; Brouwer, I A; van der Schouw, Y T; Sluijs, I

2018-05-22

Fish consumption of at least 1 portion/week is related to lower cardiovascular disease (CVD) risk. It is uncertain whether a less frequent intake is also beneficial and whether the type of fish matters. We investigated associations of very low intakes of total, fatty, and lean fish, compared with no fish intake, with 18-year incidences of stroke, coronary heart disease (CHD), and CVD mortality. Data were used from 34,033 participants, aged 20-70 years, of the EPIC-Netherlands cohort. Baseline (1993-1997) fish consumption was estimated using a food frequency questionnaire. We compared any fish consumption, <1 portion/week (<100 g) and ≥1 portion/week to non-fish consumption. During 18 follow-up years, 753 stroke events, 2134 CHD events, and 540 CVD deaths occurred. Among the fish consumers (~92%) median intakes of total, lean, and fatty fish were 57.9, 32.9, and 10.7 g/week, respectively. Any fish consumption compared with non-consumption was not associated with incidences of stroke, CHD, MI, and CVD mortality. Furthermore, consumption of <1 portion/week of total, fatty, or lean fish was not associated with any CVD outcome, as compared with non-consumption. Consumption of ≥1 portion/week of lean fish (HR: 0.70, 95% CI: 0.57-0.86) and of fatty fish (HR: 0.63, 95% CI: 0.39-1.02) were associated with lower incidence of ischaemic stroke. Baseline fish consumption of <1 portion/week, regardless of the type of fish, was unrelated to incidences of stroke, CHD, and CVD mortality in this Dutch cohort. Consumption of ≥1 portion/week of fatty or of lean fish reduced the incidence of ischaemic stroke.

Piracetam for acute ischaemic stroke.

PubMed

Ricci, Stefano; Celani, Maria Grazia; Cantisani, Teresa Anna; Righetti, Enrico

2012-09-12

Piracetam has neuroprotective and antithrombotic effects that may help to reduce death and disability in people with acute stroke. This is an update of a Cochrane Review first published in 1999, and previously updated in 2006 and 2009. To assess the effects of piracetam in acute, presumed ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched 15 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1966 to May 2011), EMBASE (1980 to May 2011), and ISI Science Citation Index (1981 to May 2011). We also contacted the manufacturer of piracetam to identify further published and unpublished studies. Randomised trials comparing piracetam with control, with at least mortality reported and entry to the trial within three days of stroke onset. Two review authors extracted data and assessed trial quality and this was checked by the other two review authors. We contacted study authors for missing information. We included three trials involving 1002 patients, with one trial contributing 93% of the data. Participants' ages ranged from 40 to 85 years, and both sexes were equally represented. Piracetam was associated with a statistically non-significant increase in death at one month (approximately 31% increase, 95% confidence interval 81% increase to 5% reduction). This trend was no longer apparent in the large trial after correction for imbalance in stroke severity. Limited data showed no difference between the treatment and control groups for functional outcome, dependence or proportion of patients dead or dependent. Adverse effects were not reported. There is some suggestion (but no statistically significant result) of an unfavourable effect of piracetam on early death, but this may have been caused by baseline differences in stroke severity in the trials. There is not enough evidence to assess the effect of piracetam on dependence.

In-Depth Proteomic Analysis of the Hippocampus in a Rat Model after Cerebral Ischaemic Injury and Repair by Danhong Injection (DHI)

PubMed Central

Cui, Yiran; Liu, Xin; Li, Xianyu; Yang, Hongjun

2017-01-01

Stroke is the second most common cause of death worldwide. A systematic description and characterization of the strokes and the effects induced in the hippocampus have not been performed so far. Here, we analysed the protein expression in the hippocampus 24 h after cerebral ischaemic injury and repair. Drug intervention using Danhong injection (DHI), which has been reported to have good therapeutic effects in a clinical setting, was selected for our study of cerebral ischaemia repair in rat models. A larger proteome dataset and total 4091 unique proteins were confidently identified in three biological replicates by combining tissue extraction for rat hippocampus and LC-MS/MS analysis. A label-free approach was then used to quantify the differences among the four experimental groups (Naive, Sham, middle cerebral artery occlusion (MCAO) and MCAO + DHI groups) and showed that about 2500 proteins on average were quantified in each of the experiment group. Bioinformatics analysis revealed that in total 280 unique proteins identified above were differentially expressed (P < 0.05). By combining the subcellular localization, hierarchical clustering and pathway information with the results from injury and repair phase, 12 significant expressed proteins were chosen and verified with respect to their potential as candidates for cerebral ischaemic injury by Western blot. The primary three signalling pathways of the candidates related may be involved in molecular mechanisms related to cerebral ischaemic injury. In addition, a glycogen synthase kinase-3β (Gsk-3β) inhibitor of the candidates with the best corresponding expression trends between western blotting (WB) and label-free quantitative results were chosen for further validation. The results of Western blot analysis of protein expression and 2,3,5- chloride three phenyl tetrazole (TTC) staining of rat brains showed that DHI treatment and Gsk-3β inhibitor are both able to confer protection against ischaemic injury in rat MCAO model. The observations of the present study provide a novel understanding regarding the regulatory mechanism of cerebral ischaemic injury. PMID:28672812

Rare platelet GPCR variants: what can we learn?

PubMed

Nisar, S P; Jones, M L; Cunningham, M R; Mumford, A D; Mundell, S J

2015-07-01

Platelet-expressed GPCRs are critical regulators of platelet function. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis associated with coronary atherosclerosis and ischaemic stroke. However, anti-thrombotic drug therapy is associated with high inter-patient variability in therapeutic response and adverse bleeding side effects. In order to optimize the use of existing anti-platelet drugs and to develop new therapies, more detailed knowledge is required relating to the molecular mechanisms that regulate GPCR and therefore platelet function. One approach has been to identify rare, function-disrupting mutations within key platelet proteins in patients with bleeding disorders. In this review, we describe how an integrated functional genomics strategy has contributed important structure-function information about platelet GPCRs with specific emphasis upon purinergic and thromboxane A2 receptors. We also discuss the potential implications these findings have for pharmacotherapy and for understanding the molecular basis of mild bleeding disorders. © 2014 The British Pharmacological Society.

Under-prescribing of Prevention Drugs and Primary Prevention of Stroke and Transient Ischaemic Attack in UK General Practice: A Retrospective Analysis

PubMed Central

Fitzmaurice, David; Cheng, K. K.; Marshall, Tom

2016-01-01

Background Stroke is a leading cause of death and disability; worldwide it is estimated that 16.9 million people have a first stroke each year. Lipid-lowering, anticoagulant, and antihypertensive drugs can prevent strokes, but may be underused. Methods and Findings We analysed anonymised electronic primary care records from a United Kingdom (UK) primary care database that covers approximately 6% of the UK population. Patients with first-ever stroke/transient ischaemic attack (TIA), ≥18 y, with diagnosis between 1 January 2009 and 31 December 2013, were included. Drugs were considered under-prescribed when lipid-lowering, anticoagulant, or antihypertensive drugs were clinically indicated but were not prescribed prior to the time of stroke or TIA. The proportions of strokes or TIAs with prevention drugs under-prescribed, when clinically indicated, were calculated. In all, 29,043 stroke/TIA patients met the inclusion criteria; 17,680 had ≥1 prevention drug clinically indicated: 16,028 had lipid-lowering drugs indicated, 3,194 anticoagulant drugs, and 7,008 antihypertensive drugs. At least one prevention drug was not prescribed when clinically indicated in 54% (9,579/17,680) of stroke/TIA patients: 49% (7,836/16,028) were not prescribed lipid-lowering drugs, 52% (1,647/3,194) were not prescribed anticoagulant drugs, and 25% (1,740/7,008) were not prescribed antihypertensive drugs. The limitations of our study are that our definition of under-prescribing of drugs for stroke/TIA prevention did not address patients’ adherence to medication or medication targets, such as blood pressure levels. Conclusions In our study, over half of people eligible for lipid-lowering, anticoagulant, or antihypertensive drugs were not prescribed them prior to first stroke/TIA. We estimate that approximately 12,000 first strokes could potentially be prevented annually in the UK through optimal prescribing of these drugs. Improving prescription of lipid-lowering, anticoagulant, and antihypertensive drugs is important to reduce the incidence and burden of stroke and TIA. PMID:27846215

Factors associated with timing of early neurological improvement after thrombolysis for ischaemic stroke.

PubMed

Guettier, S; Cogez, J; Bonnet, A-L; Dean, P; Apoil, M; Tchoumi, T; Dubuc, L; Arzur, J; de la Sayette, V; Kouassi, L-K; Viader, F; Touzé, E

2016-03-01

Early neurological improvement (ENI) after fibrinolysis for ischaemic stroke is strongly associated with recanalization and favourable outcome. However, it remains unknown why some patients recover within the first hour after treatment (very ENI, VENI) whereas others recover later within 24 h. The factors associated with the timing of ENI were assessed. Consecutive stroke patients treated with intravenous recombinant tissue plasminogen activator (rt-PA) within 4.5 h after onset in four stroke centres of our geographical area were retrospectively studied. VENI assessed at 1 h and ENI assessed at 24 h post-treatment were defined by National Institutes of Health Stroke Scale (NIHSS) improvement by 40% from baseline. Of 421 patients, 65 (15%) had VENI and 110 (26%) had ENI. Patients with VENI had significantly lower serum creatinine level than patients with ENI (79 ± 19 vs. 91 ± 35 μmol/l; P = 0.01). After adjustment for age, sex, baseline NIHSS, hypertension and blood glucose level, patients with low serum creatinine level were more likely to have VENI (lowest tertile, odds ratio 3.8, 95% confidence interval 1.5-9.7; intermediate tertile, odds ratio 1.8, 95% confidence interval 0.8-4.3; P for trend <0.01). VENI patients were as likely as ENI patients to have a modified Rankin scale score ≤2 at 3 months. Low serum creatinine levels are associated with VENI, suggesting that swiftness of the efficacy of rt-PA or of neurological recovery may depend on renal function. © 2016 EAN.

UPDATE ON THE GLOBAL BURDEN OF ISCHAEMIC AND HAEMORRHAGIC STROKE IN 1990–2013: THE GBD 2013 STUDY

PubMed Central

Feigin, Valery L.; Krishnamurthi, Rita; Parmar, Priya; Norrving, Bo; Mensah, George A.; Bennett, Derrick A.; Barker-Collo, Suzanne; Moran, Andrew; Sacco, Ralph L.; Truelsen, Thomas; Davis, Stephen; Pandian, Jeyaraj Durai; Naghavi, Mohsen; Forouzanfar, Mohammad H.; Nguyen, Grant; Johnson, Catherine O.; Vos, Theo; Meretoja, Atte; Murray, Christopher; Roth, Gregory A.; Thrift, Amanda; Banerjee, Amitava; Kengne, Andre Pascal; Misganaw, Awoke; Kissela, Brett M.; Wolfe, Charles; Yu, Chuanhua; Anderson, Craig; Kim, Daniel; Rojas-Rueda, David; Tanne, David; Tirschwell, David Lawrence; Nand, Devina; Kazi, Dhruv S.; Pourmalek, Farshad; Catalá-López, Ferrán; Abd-Allah, Foad; Gankpé, Fortuné; deVeber, Gabrielle; Donnan, Geoffrey; Hankey, Graeme J.; Christensen, Hanne K.; Campos-Nonato, Ismael; Shiue, Ivy; Fernandes, Jefferson G.; Jonas, Jost B.; Sheth, Kevin; Kim, Yunjin; Dokova, Klara; Stroumpoulis, Konstantinos; Sposato, Luciano A.; Bahit, Maria Cecilia; Geleijnse, Johanna M.; Mackay, Mark T.; Mehndiratta, Man Mohan; Endres, Matthias; Giroud, Maurice; Brainin, Michael; Kravchenko, Michael; Piradov, Michael; Soljak, Michael; Liu, Ming; Connor, Myles; Venketasubramanian, Narayanaswamy; Bornstein, Natan; Shamalov, Nikolay; Roy, Nobhojit; Cabral, Norberto; Beauchamp, Norman J.; Lavados, Pablo M.; Jeemon, Panniyammakal; Lotufo, Paulo A.; Chowdhury, Rajiv; Sahathevan, Ramesh; Hamadeh, Randah R.; Malekzadeh, Reza; Gillium, Richard; Westerman, Ronny; Akinyemi, Rufus Olusola; Salman, Rustam Al-Shahi; Dharmaratne, Samath D.; Basu, Sanjay; Abera, Semaw Ferede; Kosen, Soewarta; Sampson, Uchechukwu K. A.; Caso, Valeria; Vlassov, Vasiliy; Melaku, Yohannes Adama; Kokubo, Yoshiohiro; Shinohara, Yukito; Varakin, Yuri; Wang, Wenzhi

2015-01-01

Background Global stroke epidemiology is changing rapidly. Although age-standardised rates of stroke mortality have decreased worldwide in the past two decades, the absolute numbers of people who have a stroke every year, live with the consequences of stroke, and die from their stroke are increasing. Regular updates on the current level of stroke burden are important for advancing our knowledge on stroke epidemiology and facilitate organization and planning of evidence-based stroke care. Objectives To estimate incidence, prevalence, mortality, disability-adjusted life-years (DALYs) and years lived with disability (YLDs), and their trends for ischaemic stroke (IS) and haemorrhagic stroke (HS) for 188 countries from 1990–2013. Methodology Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated using all available data on mortality and stroke incidence, prevalence and excess mortality. Statistical models and country-level covariate data were employed and all rates were age-standardised to a global population. All estimated were produced with 95% uncertainty intervals (UI). Results In 2013, there were globally almost 25.7 million stroke survivors (71% with IS), 6.5 million deaths from stroke (51% died from IS), 113 million DALYs due to stroke (58% due to IS), and 10.3 million new strokes (67% IS). Over the 1990–2013 period, there was a significant increase in the absolute number of DALYs due to IS, and of deaths from IS and HS, survivors and incident events for both IS and HS. The preponderance of the burden of stroke continued to reside in developing countries, comprising 75.2% of deaths from stroke and 81.0% of stroke-related DALYs. Globally, the proportional contribution of stroke-related DALYs and deaths due to stroke compared to all diseases increased from 1990 (3.54% [95% UI 3.11–4.00%] and 9.66% [95% UI 8.47–10.70%]) to 2013 (4.62% [95% UI 4.01–5.30%] and 11.75% [95% UI 10.45–13.31%], respectively), but there was a diverging trend in developed and developing countries with a significant increase in DALYs and deaths in developing countries, and no measurable change in the proportional contribution of DALYs and deaths from stroke in developed countries. Conclusion Global stroke burden continues to increase globally. More efficient stroke prevention and management strategies are urgently needed to halt and eventually reverse the stroke pandemic, while universal access to organized stroke services should be a priority. PMID:26505981

Understanding clinicians' decisions to offer intravenous thrombolytic treatment to patients with acute ischaemic stroke: a protocol for a discrete choice experiment.

PubMed

De Brún, Aoife; Flynn, Darren; Joyce, Kerry; Ternent, Laura; Price, Christopher; Rodgers, Helen; Ford, Gary A; Lancsar, Emily; Rudd, Matthew; Thomson, Richard G

2014-07-09

Intravenous thrombolysis is an effective emergency treatment for acute ischaemic stroke for patients meeting specific criteria. Approximately 12% of eligible patients in England, Wales and Northern Ireland received thrombolysis in the first quarter of 2013, yet as many as 15% are eligible to receive treatment. Suboptimal use of thrombolysis may have been largely attributable to structural factors; however, with the widespread implementation of 24/7 hyper acute stroke services, continuing variation is likely to reflect differences in clinical decision-making, in particular the influence of ambiguous areas within the guidelines, licensing criteria and research evidence. Clinicians' perceptions about thrombolysis may now exert a greater influence on treatment rates than structural/service factors. This research seeks to elucidate factors influencing thrombolysis decision-making by using patient vignettes to identify (1) patient-related and clinician-related factors that may help to explain variation in treatment and (2) associated trade-offs in decision-making based on the interplay of critical factors. A discrete choice experiment (DCE) will be conducted to better understand how clinicians make decisions about whether or not to offer thrombolysis to patients with acute ischaemic stroke. To inform the design, exploratory work will be undertaken to ensure that (1) all potentially influential factors are considered for inclusion; and (2) to gain insights into the 'grey areas' of patient factors. A fractional factorial design will be used to combine levels of patient factors in vignettes, which will be presented to clinicians to allow estimation of the variable effects on decisions to offer thrombolysis. Ethical approval for this study was obtained from the Newcastle University Research Ethics Committee. The results will be disseminated in peer review publications and at national conferences. Findings will be translated into continuing professional development activities and will support implementation of a computerised decision aid for thrombolysis (COMPASS) in acute stroke care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[The importance of heart disease in the various types of cerebral vascular disease. A prospective study].

PubMed

Soares Franco, A; Monteiro, J; Ferreira, D; Fonseca, T P; Melo, T P; Ferro, J; Freitas, A; Nogueira, J M; Mota, E; da Costa, J N

1990-05-01

A prospective study was performed in 106 patients with acute stroke. The main purpose was the cardiac evaluation in the different types of cerebrovascular disease: Intracerebral hemorrhage (H), Cortical ischaemic events (C) and Subcortical ischaemic events (SC) and also to evaluate the interest of echocardiography in detecting occult cardiac sources of emboli. The study population included 54 men and 52 women with a mean age of 66.8 +/- 10.3 years. A thorough neurologic and cardiologic study with a computed tomography of the brain (TAC) and an echocardiogram (ECO) were performed in all patients. It was found 24 (23%) of H, 40 (38%) of C and 32 (30%) of SC. In the past history, heart diseases were more prevalent in C (p less than 0.04); previous stroke and systemic hypertension (HTA) were less prevalent in H (p less than 0.008) and in C (p less than 0.004), respectively. Atrial fibrillation (FA) was more frequent in ischaemic stroke (p less than 0.02) and within these in C (p less than 0.005). No more clinical and functional cardiac features or echocardiographic aspects had any difference in their prevalence in different types of stroke. Without clinical heart disease there were 19 (18%) cases but only in 10 were found in their echocardiograms a potentially embolic heart disease (PEHD) but 8 of them had questionable pathologic significance. C had more heart disease in their past history; FA is more frequent in C; it is difficult to diagnose a cerebral embolism with only a coexistent C and CPE, but if there is FA or a past history of heart disease in a C, the diagnosis of cerebral embolism is more probable; finally, echocardiography is of limited value to diagnose a PEHD in the elderly, however it makes possible to better evaluate most cardiac situations.

Collateral circulation on perfusion-computed tomography-source images predicts the response to stroke intravenous thrombolysis.

PubMed

Calleja, A I; Cortijo, E; García-Bermejo, P; Gómez, R D; Pérez-Fernández, S; Del Monte, J M; Muñoz, M F; Fernández-Herranz, R; Arenillas, J F

2013-05-01

Perfusion-computed tomography-source images (PCT-SI) may allow a dynamic assessment of leptomeningeal collateral arteries (LMC) filling and emptying in middle cerebral artery (MCA) ischaemic stroke. We described a regional LMC scale on PCT-SI and hypothesized that a higher collateral score would predict a better response to intravenous (iv) thrombolysis. We studied consecutive ischaemic stroke patients with an acute MCA occlusion documented by transcranial Doppler/transcranial color-coded duplex, treated with iv thrombolysis who underwent PCT prior to treatment. Readers evaluated PCT-SI in a blinded fashion to assess LMC within the hypoperfused MCA territory. LMC scored as follows: 0, absence of vessels; 1, collateral supply filling ≤ 50%; 2, between> 50% and < 100%; 3, equal or more prominent when compared with the unaffected hemisphere. The scale was divided into good (scores 2-3) vs. poor (scores 0-1) collaterals. The predetermined primary end-point was a good 3-month functional outcome, while early neurological recovery, transcranial duplex-assessed 24-h MCA recanalization, 24-h hypodensity volume and hemorrhagic transformation were considered secondary end-points. Fifty-four patients were included (55.5% women, median NIHSS 10), and 4-13-23-14 patients had LMC score (LMCs) of 0-1-2-3, respectively. The probability of a good long-term outcome augmented gradually with increasing LMCs: (0) 0%; (1) 15.4%; (2) 65.2%; (3) 64.3%, P = 0.004. Good-LMCs was independently associated with a good outcome [OR 21.02 (95% CI 2.23-197.75), P = 0.008]. Patients with good LMCs had better early neurological recovery (P = 0.001), smaller hypodensity volumes (P < 0.001) and a clear trend towards a higher recanalization rate. A higher degree of LMC assessed by PCT-SI predicts good response to iv thrombolysis in MCA ischaemic stroke patients. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Mixed methods feasibility study for a trial of blood pressure telemonitoring for people who have had stroke/transient ischaemic attack (TIA).

PubMed

Hanley, Janet; Fairbrother, Peter; Krishan, Ashma; McCloughan, Lucy; Padfield, Paul; Paterson, Mary; Pinnock, Hilary; Sheikh, Aziz; Sudlow, Cathie; Todd, Allison; McKinstry, Brian

2015-03-25

Good blood pressure (BP) control reduces the risk of recurrence of stroke/transient ischaemic attack (TIA). Although there is strong evidence that BP telemonitoring helps achieve good control, none of the major trials have considered the effectiveness in stroke/TIA survivors. We therefore conducted a feasibility study for a trial of BP telemonitoring for stroke/TIA survivors with uncontrolled BP in primary care. Phase 1 was a pilot trial involving 55 patients stratified by stroke/TIA randomised 3:1 to BP telemonitoring for 6 months or usual care. Phase 2 was a qualitative evaluation and comprised semi-structured interviews with 16 trial participants who received telemonitoring and 3 focus groups with 23 members of stroke support groups and 7 carers. Overall, 125 patients (60 stroke patients, 65 TIA patients) were approached and 55 (44%) patients were randomised including 27 stroke patients and 28 TIA patients. Fifty-two participants (95%) attended the 6-month follow-up appointment, but one declined the second daytime ambulatory blood pressure monitoring (ABPM) measurement resulting in a 93% completion rate for ABPM - the proposed primary outcome measure for a full trial. Adherence to telemonitoring was good; of the 40 participants who were telemonitoring, 38 continued to provide readings throughout the 6 months. There was a mean reduction of 10.1 mmHg in systolic ABPM in the telemonitoring group compared with 3.8 mmHg in the control group, which suggested the potential for a substantial effect from telemonitoring. Our qualitative analysis found that many stroke patients were concerned about their BP and telemonitoring increased their engagement, was easy, convenient and reassuring. A full-scale trial is feasible, likely to recruit well and have good rates of compliance and follow-up. ISRCTN61528726 15/12/2011.

Exploratory Network Meta Regression Analysis of Stroke Prevention in Atrial Fibrillation Fails to Identify Any Interactions with Treatment Effect.

PubMed

Batson, Sarah; Sutton, Alex; Abrams, Keith

2016-01-01

Patients with atrial fibrillation are at a greater risk of stroke and therefore the main goal for treatment of patients with atrial fibrillation is to prevent stroke from occurring. There are a number of different stroke prevention treatments available to include warfarin and novel oral anticoagulants. Previous network meta-analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation acknowledge the limitation of heterogeneity across the included trials but have not explored the impact of potentially important treatment modifying covariates. To explore potentially important treatment modifying covariates using network meta-regression analyses for stroke prevention in atrial fibrillation. We performed a network meta-analysis for the outcome of ischaemic stroke and conducted an exploratory regression analysis considering potentially important treatment modifying covariates. These covariates included the proportion of patients with a previous stroke, proportion of males, mean age, the duration of study follow-up and the patients underlying risk of ischaemic stroke. None of the covariates explored impacted relative treatment effects relative to placebo. Notably, the exploration of 'study follow-up' as a covariate supported the assumption that difference in trial durations is unimportant in this indication despite the variation across trials in the network. This study is limited by the quantity of data available. Further investigation is warranted, and, as justifying further trials may be difficult, it would be desirable to obtain individual patient level data (IPD) to facilitate an effort to relate treatment effects to IPD covariates in order to investigate heterogeneity. Observational data could also be examined to establish if there are potential trends elsewhere. The approach and methods presented have potentially wide applications within any indication as to highlight the potential benefit of extending decision problems to include additional comparators outside of those of primary interest to allow for the exploration of heterogeneity.

Health Impact Assessment for Second-Hand Smoke Exposure in Germany--Quantifying Estimates for Ischaemic Heart Diseases, COPD, and Stroke.

PubMed

Fischer, Florian; Kraemer, Alexander

2016-02-05

Evidence of the adverse health effects attributable to second-hand smoke (SHS) exposure is available. This study aims to quantify the impact of SHS exposure on ischaemic heart diseases (IHD), chronic obstructive pulmonary diseases (COPD), and stroke in Germany. Therefore, this study estimated and forecasted the morbidity for the three outcomes in the German population. Furthermore, a health impact assessment was performed using DYNAMO-HIA, which is a generic software tool applying a Markov model. Overall 687,254 IHD cases, 231,973 COPD cases, and 288,015 stroke cases were estimated to be attributable to SHS exposure in Germany for 2014. Under the assumption that the population prevalence of these diseases and the prevalence of SHS exposure remain constant, the total number of cases will increase due to demographic aging. Assuming a total eradication of SHS exposure beginning in 2014 leads to an estimated reduction of 50% in cases, compared to the reference scenario in 2040 for all three diseases. The results highlight the relevance of SHS exposure because it affects several chronic disease conditions and has a major impact on the population's health. Therefore, public health campaigns to protect non-smokers are urgently needed.

Subjective experiences of transient ischaemic attack: a repertory grid approach.

PubMed

Spurgeon, Laura; James, Gill; Sackley, Cath

2013-01-01

Research on the psychosocial reactions to stroke has been used to inform rehabilitation programmes. Yet much less research has been conducted into experiences of, and reactions to, transient ischaemic attack (TIA), despite its link with secondary stroke. This study aimed to investigate the subjective psychological experiences of TIA. Repertory grid technique was used because of its capacity to make individual implicit experiences explicit. Using the standard repertory grid protocol, 12 post-TIA patients were asked to consider how five everyday activities had been affected by TIA. Each participant generated six constructs or personal perspectives, which were analysed using proprietary (RepGrid IV) software. Despite the individualised nature of the responses, six themes emerged from the constructs. These included deep-seated anxiety about future uncertainties/disruption to normality, loss of confidence, frustration, TIA as a wake-up call, a sense of loss and sadness, and embarrassment. Research has shown that the patient's subjective experience and perspective are important to the rehabilitation process post-stroke. Relatively little research has been conducted into the subjective experiences of TIA patients. This study has revealed a range of subjective reactions to TIA, which could be used to inform individualised post-TIA management, adaptation and rehabilitation.

What is the value of conducting a trial of r-tPA for the treatment of mild stroke patients?

PubMed

Guzauskas, Gregory F; Chen, Er; Lalla, Deepa; Yu, Elaine; Tayama, Darren; Veenstra, David L

2017-02-01

Background The Phase IIIb, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS) trial will assess r-tPA in ischemic stroke patients who present with mild deficits (i.e. mild stroke). Aims To assess PRISMS's societal value in clarifying the optimal care for patients with mild ischemic stroke. Methods A value of information (VOI) decision model was developed to compare the outcomes of mild stroke patients treated vs. not treated with r-tPA. Model inputs were derived from a subset of Third International Stroke Trial patients, a recent meta-analysis of r-tPA trials, expert opinion, and other published sources. VOI analyses were also used to assess the expected US societal value of the PRISMS trial and the expected value of reducing uncertainty in key trial estimates. Results The expected net societal value of the PRISMS trial was approximately $210 million ($160 m-$260 m), representing a six-fold return on investment. The value of reducing uncertainty in r-tPA efficacy was approximately $150 million ($100 m-$200 m), while reducing uncertainty in r-tPA safety (increased risk for symptomatic intracranial hemorrhage) did not add additional value in comparison. Conclusions Developing a better understanding of the outcomes of r-tPA treatment in patients with mild ischemic stroke will provide tremendous societal value by clarifying current uncertainty around treatment effectiveness. Enrollment in the PRISMS trial for patients presenting with mild ischemic stroke within 0-3 h of symptom onset should be highly encouraged.

Socioeconomic disparities in work performance following mild stroke.

PubMed

Brey, Joseph K; Wolf, Timothy J

2015-01-01

The purpose of this study was to investigate the relationships among the factors that influence return to work for young individuals with mild stroke from different socioeconomic backgrounds. Prospective cohort study of working adults with mild stroke (N = 21). Participants completed an assessment battery of cognitive, work environment and work performance measures at approximately 3 weeks and 7 months post mild stroke. Individuals were placed in "skilled" and "unskilled" worker categories based on the Hollingshead Index. Unskilled workers had significantly poorer scores on the majority of the cognitive assessments. Unskilled workers also perceived less social support (p = 0.017) and autonomy (p = 0.049) in work responsibilities than individuals in the skilled worker group and also reported significantly poorer work productivity due to stroke than those in the skilled group (p = 0.015). Individuals from low socioeconomic backgrounds have more difficulty returning to work following mild stroke than individuals from higher socioeconomic backgrounds. Future work is needed to identify factors that can increase long-term work success and quality of work performance following a mild stroke that specifically targets the needs of individuals who have a lower socioeconomic status.

Validity of Diagnostic Codes for Acute Stroke in Administrative Databases: A Systematic Review

PubMed Central

McCormick, Natalie; Bhole, Vidula; Lacaille, Diane; Avina-Zubieta, J. Antonio

2015-01-01

Objective To conduct a systematic review of studies reporting on the validity of International Classification of Diseases (ICD) codes for identifying stroke in administrative data. Methods MEDLINE and EMBASE were searched (inception to February 2015) for studies: (a) Using administrative data to identify stroke; or (b) Evaluating the validity of stroke codes in administrative data; and (c) Reporting validation statistics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), or Kappa scores) for stroke, or data sufficient for their calculation. Additional articles were located by hand search (up to February 2015) of original papers. Studies solely evaluating codes for transient ischaemic attack were excluded. Data were extracted by two independent reviewers; article quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Results Seventy-seven studies published from 1976–2015 were included. The sensitivity of ICD-9 430-438/ICD-10 I60-I69 for any cerebrovascular disease was ≥ 82% in most [≥ 50%] studies, and specificity and NPV were both ≥ 95%. The PPV of these codes for any cerebrovascular disease was ≥ 81% in most studies, while the PPV specifically for acute stroke was ≤ 68%. In at least 50% of studies, PPVs were ≥ 93% for subarachnoid haemorrhage (ICD-9 430/ICD-10 I60), 89% for intracerebral haemorrhage (ICD-9 431/ICD-10 I61), and 82% for ischaemic stroke (ICD-9 434/ICD-10 I63 or ICD-9 434&436). For in-hospital deaths, sensitivity was 55%. For cerebrovascular disease or acute stroke as a cause-of-death on death certificates, sensitivity was ≤ 71% in most studies while PPV was ≥ 87%. Conclusions While most cases of prevalent cerebrovascular disease can be detected using 430-438/I60-I69 collectively, acute stroke must be defined using more specific codes. Most in-hospital deaths and death certificates with stroke as a cause-of-death correspond to true stroke deaths. Linking vital statistics and hospitalization data may improve the ascertainment of fatal stroke. PMID:26292280

Corticotropin-releasing factor: effect on cerebral blood flow in physiologic and ischaemic conditions.

PubMed

De Michele, Manuela; Touzani, Omar; Foster, Alan C; Fieschi, Cesare; Sette, Giuliano; McCulloch, James

2005-09-01

The expression of corticotrophin-releasing factor (CRF) receptors in cerebral arteries and arterioles suggests that CRF may modulate cerebral blood flow (CBF). In the present study, the effects of CRF, CRF-like peptides and the CRF broad spectrum antagonist DPhe-CRF on CBF have been investigated under normal physiologic conditions and in the margins of focal ischaemic insult. The experiments were carried out in anaesthetised and ventilated rats. Changes in CBF after subarachnoid microapplication of CRF and related peptides were assessed with a laser-Doppler flowmetry (LDF) probe. In the ischaemic animals, agents were injected approximately 60 minutes after permanent middle cerebral artery occlusion (MCAo). Microapplication of CRF and related peptides in normal rats into the subarachnoid space produced sustained concentration-dependent increases in CBF. This effect was attenuated by co-application with DPhe-CRF, which did not alter CBF itself. A second microapplication of CRF 30 min after the first failed to produce increases in CBF in normal animals. Microapplication of CRF in the subarachnoid space overlying the ischaemic cortex effected minor increases in CBF whereas D-Phe-CRF had no significant effect on CBF. Activation of the CRF peptidergic system increases CBF in the rat. Repeated activation of CRF receptors results in tachyphylaxis of the vasodilator response. CRF vasodilator response is still present after MCAo in the ischaemic penumbra, suggesting that the CRF peptidergic system may modulate CBF in ischaemic stroke.

How good is the management of vascular risk after stroke, transient ischaemic attack or carotid endarterectomy?

PubMed

Johnson, Paul; Rosewell, Mary; James, Martin A

2007-01-01

Patients remain at high risk of vascular events after stroke, transient ischaemic attack or carotid endarterectomy. We studied how well this risk is addressed by the effective treatment of modifiable risk factors. A total of 198 consecutive attenders at a rapid access stroke clinic and 98 consecutive patients undergoing carotid endarterectomy were studied. Treatment of hypertension and hyperlipidaemia, smoking status and the use of antithrombotic therapy were assessed at baseline and 6 months later. The findings were compared with targets from the UK National Clinical Guidelines for Stroke. Baseline and follow-up data were available on 284 patients. The rates of control of vascular risk factors improved only slightly during follow-up. Blood pressure was below target levels in only 69 (24%) at baseline and 79 (28%) at 6 months, and serum cholesterol was below target levels in only 55 (19%) at baseline and 63 (22%) at 6 months. At baseline, 55 (19%) were smokers, of whom 12 (22%) had quit at 6 months. Anticoagulant therapy was prescribed in 19 of 37 patients (51%) in atrial fibrillation at 6 months. Antiplatelet therapy was prescribed in 90% of patients in sinus rhythm. Despite the identification of vascular risk factors at the time of clinic or surgery, 6 months later these risk factors remain poorly addressed. More effective methods of managing vascular risk in these patients are needed.

Long-term functional outcomes of patients with very mild stroke: does a NIHSS score of 0 mean no disability? An interim analysis of the KOSCO study.

PubMed

Chang, Won Hyuk; Sohn, Min Kyun; Lee, Jongmin; Kim, Deog Young; Lee, Sam-Gyu; Shin, Yong-Il; Oh, Gyung-Jae; Lee, Yang-Soo; Joo, Min Cheol; Han, Eun Young; Kim, Min Su; Jang, Shin Yi; Kim, Jeong Hyun; Kim, Yun-Hee

2017-05-01

To explore the long-term functional outcomes of stroke patients with very mild severity at 6 months after stroke. This study presents the interim results of the Korean Stroke Cohort for Functioning and Rehabilitation. On day 7, stroke evaluation was performed using the functional assessment battery including the National Institute of Health Stroke Scale (NIHSS). At 6 months after stroke, functional outcomes using the face-to-face functional assessment battery including Functional Independence Measure (FIM) were analyzed in the patients who had a score of 0 on the NIHSS at 7 days after stroke onset. In the very mild stroke group, 455 patients were followed up at 6 months. Out of these patients, 11.0% had impairments in cognitive function, 14.1% had motor impairment, and 2.1% had impairments in their mobility measured by the functional assessment battery. At 6 months after onset, 3.3% of stroke survivors without recurrence showed dependency according to the FIM. Many acute stroke patients with mild stroke severity as assessed by the NIHSS had impairments in various functional domains, and could have been easily overlooked for intensive rehabilitation therapy. Candidates for comprehensive rehabilitation therapy might be better identified by the functional assessment battery. Implications for rehabilitation Many acute stroke patients with mild stroke severity assessed by NIHSS could be easily overlooked for intensive rehabilitation therapy. Candidates for comprehensive rehabilitation therapy should be evaluated using a functional assessment battery rather than the NIHSS.

Educational inequality in cardiovascular disease depends on diagnosis: A nationwide register based study from Denmark.

PubMed

Christensen, Anne V; Koch, Mette B; Davidsen, Michael; Jensen, Gorm B; Andersen, Lisbeth V; Juel, Knud

2016-05-01

Social inequality is present in the morbidity as well as the mortality of cardiovascular diseases. This paper aims to quantify and compare the level of educational inequality across different cardiovascular diagnoses. Register based study. Comparison of the extent of inequality across different cardiovascular diagnoses requires a measure of inequality which is comparable across subgroups with different educational distributions. The slope index of inequality and the relative index of inequality were applied for measuring inequalities in incidence of six cardiovascular diagnoses: ischaemic heart disease, acute myocardial infarction, valvular heart disease, congestive heart failure, atrial fibrillation and stroke in the period 2005-2009. All individuals in the general Danish population aged 35-84 years were followed in national registers regarding hospitalisation, death and education from 1985 to 2009 (annual average of 2.9 million people) to define incident cases. Marked educational inequality was found in the incidence of ischaemic heart disease, acute myocardial infarction, heart failure and stroke (relative index of inequality: 0.37 (95% confidence interval 0.34; 0.40) to 0.60 (0.57; 0.63), absolute index of inequality: -241 (-254.4; -227.4) to -37 (-42.7; -31.1)) while inequality in atrial fibrillation and, in particular, in valvular heart disease was small and insignificant (relative index of inequality: 0.57 (0.49; 0.65) to 0.97 (0.88; 1.08), absolute index of inequality: -29 (-35.1; -21.9) to -1 (-4.8; -3.8)). The degree of educational inequality in cardiovascular diseases depends on the diagnosis, with the highest inequality in ischaemic heart disease, acute myocardial infarction, heart failure and stroke. Small differences were found between men and women. © The European Society of Cardiology 2015.

Acute neurovascular events in cancer patients receiving anti-vascular endothelial growth factor agents: Clinical experience in Paris University Hospitals.

PubMed

Tlemsani, Camille; Mir, Olivier; Psimaras, Dimitri; Vano, Yann-Alexandre; Ducreux, Michel; Escudier, Bernard; Rousseau, Benoit; Loirat, Delphine; Ceccaldi, Bernard; André, Thierry; Goldwasser, François; Ricard, Damien

2016-10-01

Despite the increasing and broadening use of agents targeting the vascular endothelial growth factor (VEGF) pathway, little is known on their acute neurovascular toxicities. This retrospective, multi-centre study examined the characteristics of patients with solid tumours who experienced an ischaemic or haemorrhagic stroke, a transient ischaemic accident (TIA) or a posterior reversible encephalopathy syndrome (PRES) while under anti-VEGF and until 8 weeks after termination of treatment and evaluated their management in our institutions from 2004 to 2014. Patients with newly diagnosed or progressive cerebral metastases at the time of the acute neurovascular event were excluded. Thirty-four patients (55.9% men) were identified, and experienced either ischaemic stroke (n = 18), PRES (n = 9), TIA (n = 6) or haemorrhagic stroke (n = 1). At initiation of anti-VEGF agents, 64.7% of patients had previous cardiovascular risk factors, and 52.9% had hypertension. Eight patients (23.5%) had received cerebral radiotherapy, five of which concomitantly to anti-VEGF treatment. Six (17%) patients died in the 8 weeks following the acute neurovascular event, and only 55.9% recovered their initial neurological status. Overall, 1-year and 2-year survival rates after the acute neurovascular event were 67.9% and 50%, respectively. When anti-VEGF agents were reintroduced (n = 6), severe vascular toxicity recurred in two patients. Neurovascular events under VEGF treatments are potentially severe, and the management of comorbid conditions has to be improved. A prospective collection of data and standardised management of such events is therefore being structured in our institutions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-lasting neuroprotection and neurological improvement in stroke models with new, potent and brain permeable inhibitors of poly(ADP-ribose) polymerase

PubMed Central

Moroni, F; Cozzi, A; Chiarugi, A; Formentini, L; Camaioni, E; Pellegrini-Giampietro, DE; Chen, Y; Liang, S; Zaleska, MM; Gonzales, C; Wood, A; Pellicciari, R

2012-01-01

BACKGROUND AND PURPOSES Thienyl-isoquinolone (TIQ-A) is a relatively potent PARP inhibitor able to reduce post-ischaemic neuronal death in vitro. Here we have studied, in different stroke models in vivo, the neuroprotective properties of DAMTIQ and HYDAMTIQ, two TIQ-A derivatives able to reach the brain and to inhibit PARP-1 and PARP-2. EXPERIMENTAL APPROACH Studies were carried out in (i) transient (2 h) middle cerebral artery occlusion (tMCAO), (ii) permanent MCAO (pMCAO) and (iii) electrocoagulation of the distal portion of MCA in conjunction with transient (90 min) bilateral carotid occlusion (focal cortical ischaemia). KEY RESULTS In male rats with tMCAO, HYDAMTIQ (0.1–10 mg·kg−1) injected i.p. three times, starting 4 h after MCAO, reduced infarct volumes by up to 70%, reduced the loss of body weight by up to 60% and attenuated the neurological impairment by up to 40%. In age-matched female rats, HYDAMTIQ also reduced brain damage. Protection, however, was less pronounced than in the male rats. In animals with pMCAO, HYDAMTIQ administered 30 min after MCAO reduced infarct volumes by approximately 40%. In animals with focal cortical ischaemia, HYDAMTIQ treatment decreased post-ischaemic accumulation of PAR (the product of PARP activity) and the presence of OX42-positive inflammatory cells in the ischaemic cortex. It also reduced sensorimotor deficits for up to 90 days after MCAO. CONCLUSION AND IMPLICATIONS Our results show that HYDAMTIQ is a potent PARP inhibitor that conferred robust neuroprotection and long-lasting improvement of post-stroke neurological deficits. PMID:21913897

TDAG8 activation attenuates cerebral ischaemia-reperfusion injury via Akt signalling in rats.

PubMed

Ma, X D; Hang, L H; Shao, D H; Shu, W W; Hu, X L; Luo, H

2017-07-01

T-cell death-associated gene 8 (TDAG8), a member of the proton-sensitive G-protein-coupled receptor (GPCR) class with an immune-specific expression profile, was recently shown to be expressed in the rat brain; however, its role in ischaemic stroke remains unknown. We initially confirmed the time-dependent expression of TDAG8 in rat brain tissue after ischaemic stroke and reperfusion. Further evaluations were performed to increase TDAG8 expression 6h prior to middle cerebral artery occlusion (MCAO) by injecting a specific agonist, BTB09089, into the lateral ventricle to increase TDAG8 expression. Twenty-four hours before MCAO, a specific small interfering RNA (siRNA) was introduced. The infarction volume, neurological deficit score and cleaved caspase-3 and Bcl-2 expression were used to assess the effects of TDAG8 on ischaemic stroke. Finally, the effects of TDAG8 on the development of primary cortical neurons exposed to oxygen-glucose deprivation (OGD) were investigated. TDAG8 expression increased both in vivo and in vitro. Pretreatment with BTB09089 up-regulated TDAG8 and Bcl-2 expression and down-regulated cleaved caspase-3 expression, while the infarction volume was reduced, and neurological deficits were ameliorated 24 and 72h after MCAO. However, the protective effects of TDAG8 were reversed when its level was reduced in TDAG8-deficient rats. More importantly, these findings are consistent with data from neurons subjected to OGD. TDAG8 plays an important neuroprotective role through inhibition of neuronal apoptosis and alleviation of neurological deficits by activating the Akt signalling pathway in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

The frequency, characteristics and aetiology of stroke mimic presentations: a narrative review.

PubMed

McClelland, Graham; Rodgers, Helen; Flynn, Darren; Price, Christopher I

2018-05-01

A significant proportion of patients with acute stroke symptoms have an alternative 'mimic' diagnosis. A narrative review was carried out to explore the frequency, characteristics and aetiology of stroke mimics. Prehospital and thrombolysis-treated patients were described separately. Overall, 9972 studies were identified from the initial search and 79 studies were included with a median stroke mimic rate of 19% (range: 1-64%). The prehospital median was 27% (range: 4-43%) and the thrombolysis median 10% (range: 1-25%). Seizures, migraines and psychiatric disorders are the most frequently reported causes of stroke mimics. Several characteristics are consistently associated with stroke mimics; however, they do not fully exclude the possibility of stroke. Nineteen per cent of suspected stroke patients had a mimic condition. Stroke mimics were more common with younger age and female sex. The range of mimic diagnoses, a lack of clear differentiating characteristics and the short treatment window for ischaemic stroke create challenges for early identification.

Stroke epidemiology, prevention, and management strategies at a regional level: Latin America and the Caribbean.

PubMed

Lavados, Pablo M; Hennis, Anselm J M; Fernandes, Jefferson G; Medina, Marco T; Legetic, Branca; Hoppe, Arnold; Sacks, Claudio; Jadue, Liliana; Salinas, Rodrigo

2007-04-01

Stroke is a major health problem in Latin American and Caribbean countries. In this paper, we review the epidemiology, aetiology, and management of stroke in the region based on a systematic search of articles published in Spanish, Portuguese, and English. Stroke mortality is higher than in developed countries but rates are declining. Population-based studies show variations in incidence of strokes: lower rates of ischaemic stroke and similar rates of intracranial haemorrhages, compared with other regions. A significant proportion of strokes in these populations can be attributed to a few preventable risk factors. Some countries have published national clinical guidelines, although much needs to be done in the organisation of care and rehabilitation. Even though the burden of stroke is high, there is a paucity of information for implementing evidence-based management. The Global Stroke Initiative, the WHO STEPS Stroke surveillance, and WHO-PREMISE projects provide opportunities for surveillance at institutional and community levels.

Comparative Effectiveness and Safety of Apixaban and Vitamin K Antagonist Therapy in Patients With Nonvalvular Atrial Fibrillation Treated in Routine German Practice.

PubMed

Coleman, Craig I; Peacock, W Frank; Antz, Matthias

2018-03-01

Scarce data comparing real-world outcomes between apixaban and vitamin K antagonist (VKA) users with nonvalvular atrial fibrillation (NVAF) are available. We sought to assess the effectiveness and safety of newly-initiated apixaban vs. VKA in German NVAF patients. We performed a retrospective analysis in German outpatients using IMS Disease Analyzer data. Adults newly-initiated on apixaban or a VKA from January 2013 to March 2015 with a diagnosis of NVAF on the day of the first qualifying oral anticoagulant (OAC) prescription (index date) or any time during 1 year prior, and at least 1 year of follow-up were included. Patients experiencing a prior event in the composite endpoint, receiving an OAC before the index date, >1 OAC on the index date or switched to another OAC during follow-up were excluded. Apixaban and VKA users were 1:1 propensity-score matched. We evaluated the composite of ischaemic stroke, transient ischaemic attack (TIA), myocardial infarction (MI) or intracranial haemorrhage (ICH) in the year after OAC initiation. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). In total, 835 apixaban and 835 VKA users were matched. Forty-one composite events were identified. Hazard of the composite endpoint did not differ between apixaban and VKA users (HR=0.87, 95%CI=0.47-1.60). Ischaemic stroke and MI occurred at dissimilar (albeit not statistically significant) rates between apixaban and VKA therapy (HR=1.51, 95%CI=0.54-4.24) and (HR=0.33, 95%CI=0.11-1.03). Only two patients (both in the apixaban cohort) experienced an ICH. Apixaban and VKA therapy were associated with a similar impact on the composite endpoint in real-world German practice. Additional investigation is needed to evaluate the numeric trends of ischaemic stroke and decreased number of MIs observed with apixaban, as well as the high rate of reduced dose apixaban use found in this analysis. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Challenges of stroke prevention in patients with atrial fibrillation in clinical practice.

PubMed

Hobbs, F D Richard; Leach, I

2011-09-01

Strokes and transient ischaemic attacks in patients with atrial fibrillation (AF) can be largely prevented. Risk stratification and appropriate prophylactic regimens help to alleviate the burden of AF-related thromboembolism. Guidelines recommend routine anticoagulation with oral vitamin K antagonists (VKAs) for patients at moderate-to-high risk of stroke, and acetylsalicylic acid (ASA) for those at low risk of stroke. ASA is less effective at reducing the risk of stroke than VKAs; however, ASA does not require monitoring or dose adjustment. Trials of anticoagulants show consistent benefits of oral VKAs for primary and secondary stroke prevention in patients with AF. Nevertheless, VKAs do require frequent coagulation monitoring and dose adjustment because of their variable dose-response profile, narrow therapeutic window, increased risk for bleeding complications and numerous food and drug interactions. This review aims to provide an overview of the clinical challenges of anticoagulant therapy for the prevention of stroke in patients with AF.

Permanent work disability before and after ischaemic heart disease or stroke event: a nationwide population-based cohort study in Sweden.

PubMed

Ervasti, Jenni; Virtanen, Marianna; Lallukka, Tea; Friberg, Emilie; Mittendorfer-Rutz, Ellenor; Lundström, Erik; Alexanderson, Kristina

2017-09-29

We examined the risk of disability pension before and after ischaemic heart disease (IHD) or stroke event, the burden of stroke compared with IHD and which factors predicted disability pension after either event. A population-based cohort study with follow-up 5 years before and after the event. Register data were analysed with general linear modelling with binary and Poisson distributions including interaction tests for event type (IHD/stroke). All people living in Sweden, aged 25‒60 years at the first event year, who had been living in Sweden for 5 years before the event and had no indication of IHD or stroke prior to the index event in 2006‒2008 were included, except for cases in which death occurred within 30 days of the event. People with both IHD and stroke were excluded, resulting in 18 480 cases of IHD (65%) and 9750 stroke cases (35%). Disability pension. Of those going to suffer IHD or stroke event, 25% were already on disability pension a year before the event. The adjusted OR for disability pension at first postevent year was 2.64-fold (95% CI 2.25 to 3.11) for people with stroke compared with IHD. Economic inactivity predicted disability pension regardless of event type (OR=3.40; 95% CI 2.85 to 4.04). Comorbid mental disorder was associated with the greatest risk (OR=3.60; 95% CI 2.69 to 4.83) after an IHD event. Regarding stroke, medical procedure, a proxy for event severity, was the largest contributor (OR=2.27, 95% CI 1.43 to 3.60). While IHD event was more common, stroke involved more permanent work disability. Demographic, socioeconomic and comorbidity-related factors were associated with disability pension both before and after the event. The results help occupational and other healthcare professionals to identify vulnerable groups at risk for permanent labour market exclusion after such an event. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Quality of life after ischemic stroke varies in western countries: data from the tinzaparin in Acute Ischaemic Stroke Trial (TAIST).

PubMed

Sprigg, Nikola; Gray, Laura J; Bath, Philip M W; Christensen, Hanne; De Deyn, Peter Paul; Leys, Didier; O'Neill, Desmond; Ringelstein, E Bernd

2012-10-01

Functional outcome after stroke varies significantly between countries. However, whether health-related quality of life (QoL) after stroke also differs between countries is unknown. TAIST was a randomised controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1484 patients with acute ischaemic stroke across 11 countries. Countries were grouped into 5 geographic regions: British Isles (Ireland and UK), Franco (Belgium and France), North America (Canada), northwest Europe (Germany and The Netherlands), and Scandinavia (Denmark, Finland, Norway, and Sweden). QoL was measured at 6 months using the Short-Form 36 (SF-36) health survey. The relationship between region and QoL was assessed relative to the British Isles using linear regression adjusted for case mix, service quality variables, and treatment assignment. A total of 1220 survivors were included in this analysis. Significant differences in QoL were identified between countries and regions; northwest Europe rated their QoL highest in terms of physical functioning (20.3; 95% confidence interval [CI] 10.8-29.8), bodily pain (12.3; 95% CI, 2.7-22.0), and vitality (9.0; 95% CI, 1.1-16.9). Franco countries reported the lowest QoL for emotional role (-17.9; 95% CI, -32.6 to -3.3) and mental health (-11.2; 95% CI, -18.2 to -4.3). The British Isles rated QoL lowest for physical and social functioning. Our data indicate that QoL varies considerably among countries and regions, even when adjusted for prognostic case mix and care quality variables. How different case mixes and healthcare systems might contribute to these findings merits further investigation. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Estimating the burden of disease attributable to physical inactivity in South Africa in 2000.

PubMed

Joubert, Jané; Norman, Rosana; Lambert, Estelle V; Groenewald, Pam; Schneider, Michelle; Bull, Fiona; Bradshaw, Debbie

2007-08-01

To quantify the burden of disease attributable to physical inactivity in persons 15 years or older, by age group and sex, in South Africa for 2000. The global comparative risk assessment (CRA) methodology of the World Health Organization was followed to estimate the disease burden attributable to physical inactivity. Levels of physical activity for South Africa were obtained from the World Health Survey 2003. A theoretical minimum risk exposure of zero, associated outcomes, relative risks, and revised burden of disease estimates were used to calculate population-attributable fractions and the burden attributed to physical inactivity. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. South Africa. Adults >or= 15 years. Deaths and disability-adjusted life years (DALYs) from ischaemic heart disease, ischaemic stroke, breast cancer, colon cancer, and type 2 diabetes mellitus. Overall in adults >or= 15 years in 2000, 30% of ischaemic heart disease, 27% of colon cancer, 22% of ischaemic stroke, 20% of type 2 diabetes, and 17% of breast cancer were attributable to physical inactivity. Physical inactivity was estimated to have caused 17,037 (95% uncertainty interval 11,394 - 20,407), or 3.3% (95% uncertainty interval 2.2 - 3.9%) of all deaths in 2000, and 176,252 (95% uncertainty interval 133,733 - 203,628) DALYs, or 1.1% (95% uncertainty interval 0.8 - 1.3%) of all DALYs in 2000. Compared with other regions and the global average, South African adults have a particularly high prevalence of physical inactivity. In terms of attributable deaths, physical inactivity ranked 9th compared with other risk factors, and 12th in terms of DALYs. There is a clear need to assess why South Africans are particularly inactive, and to ensure that physical activity/inactivity is addressed as a national health priority.

Leucocyte count in young adults with first-ever ischaemic stroke: associated factors and association on prognosis.

PubMed

Heikinheimo, Terttu; Putaala, Jukka; Haapaniemi, Elena; Kaste, Markku; Tatlisumak, Turgut

2015-02-01

Limited data exist on the associated factors and correlation of leucocyte count to outcome in young adults with first-ever ischaemic stroke. Our objectives were to investigate factors associated with elevated leucocyte count and whether there is correlation between leucocyte count and short- and long-term outcomes. Of our database of 1008 consecutive patients aged 15 to 49, we included those with leucocyte count measured within the first two days from stroke onset. Outcomes were three-month and long-term disability, death, and vascular events. Linear regression was used to explore baseline variables associated with leucocyte count. Logistic regression and Cox proportional models studied the association between leucocyte count and clinical outcomes. In our study cohort of 781 patients (61.7% males; mean age 41.4 years), mean leucocyte count was high: 8.8 ± 3.1 × 10(9) cells/L (Reference range: 3.4-8.2 × 10(9) cells/L). Higher leucocyte levels were associated with dyslipidaemia, smoking, peripheral arterial disease, stroke severity, and lesion size. After adjustment for age, gender, relevant risk factors, both continuous leucocyte count and the highest quartile of leucocyte count were independently associated with unfavourable three-month outcome. Regarding events in the long-term (follow-up 8.1 ± 4.2 years in survivors), no association between leucocyte count and the event risks appeared. Among young stroke patients, high leucocyte count was a common finding. It was associated with vascular disease and its risk factors as well as severity of stroke, but it was also independently associated with unfavourable three-month outcome in these patients. There was no association with the long-term outcome. [Correction added on 31 October 2013 after first online publication: In the Results section of the Abstract, the cohort of 797 patients in this study was corrected to 781 patients.]. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

[Ingestion of anabolic steroids and ischaemic stroke. A clinical case report and review of the literature].

PubMed

García-Esperón, Carlos; Hervás-García, José Vicente; Jiménez-González, Marta; Pérez de la Ossa-Herrero, Natalia; Gomis-Cortina, Meritxell; Dorado-Bouix, Laura; López-Cancio Martinez, Elena; Castaño-Duque, Carlos H; Millán-Torné, Mónica; Dávalos, Antonio

2013-03-16

INTRODUCTION. Anabolic-androgenic steroids are synthetic substances derived from testosterone that are employed for their trophic effect on muscle tissue, among other uses. Their consumption can give trigger a series of adverse side effects on the body, including the suppression of the hypothalamus-pituitary-gonadal axis as well as liver, psychiatric and cardiovascular disorders. The most common effects are altered fat profiles and blood pressure values, cardiac remodelling, arrhythmias or myocardial infarcts. CASE REPORT. We report the case of a young male, with a background of anabolic-androgenic steroids abuse, who visited because of an acute neurological focus in the right hemisphere related with an ischaemic stroke. The aetiological study, including cardiac monitoring, echocardiograph and imaging studies (magnetic resonance and arteriography) and lab findings (thrombophilia, serology, autoimmunity, tumour markers) showed no alterations. CONCLUSIONS. The association between consumption of anabolic-androgenic steroids and cardiovascular pathologies is known, but its relation with cerebrovascular disease has not received so much attention from researchers.

Annual incidence and standardized incidence ratio of cerebrovascular accidents in patients with systemic lupus erythematosus.

PubMed

Mok, C C; Ho, L Y; To, C H

2009-01-01

To study the annual incidence and standardized incidence ratio (SIR) of cerebrovascular accident (CVA) in patients with systemic lupus erythematosus (SLE). The annual incidence of CVA from 1999 to 2007 in a longitudinal cohort of SLE patients was calculated each year and compared with that of the regional population within the same study period. Age-specific SIRs and outcome of CVA in SLE patients were also studied. In 2007, there were 490 SLE patients in our cohort. The mean annual incidence of CVA between 1999 and 2007 was 6.45/1000 patients and no obvious trend over time was observed. Of the 20 CVAs in patients with SLE, 18 (90%) were ischaemic stroke whereas two (10%) were haemorrhagic stroke. The mean SIR of all types of CVA in SLE patients was 2.02 [95% confidence interval (CI) 1.30-3.81; p = 0.002]. The SIR of ischaemic stroke decreased with age and the stroke incidence was no longer significantly higher than that of the population in patients aged >or= 60 years. Haemorrhagic stroke occurred mainly in younger SLE patients. The duration of hospitalization and the mortality rate for CVA was non-significantly higher in SLE than in non-SLE patients. The incidence of CVA in SLE remained constant over the 8 years between 1999 and 2007. Younger SLE patients are at substantially increased risk of CVA compared to age-matched population. The duration of hospitalization and the mortality rate for CVA are similar in SLE and non-SLE patients.

Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials.

PubMed

Lees, Kennedy R; Bluhmki, Erich; von Kummer, Rüdiger; Brott, Thomas G; Toni, Danilo; Grotta, James C; Albers, Gregory W; Kaste, Markku; Marler, John R; Hamilton, Scott A; Tilley, Barbara C; Davis, Stephen M; Donnan, Geoffrey A; Hacke, Werner; Allen, Kathryn; Mau, Jochen; Meier, Dieter; del Zoppo, Gregory; De Silva, D A; Butcher, K S; Parsons, M W; Barber, P A; Levi, C; Bladin, C; Byrnes, G

2010-05-15

Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min. Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit. None. Copyright 2010 Elsevier Ltd. All rights reserved.

Executive function is independently associated with performances of balance and mobility in community-dwelling older adults after mild stroke: implications for falls prevention

PubMed Central

Liu-Ambrose, Teresa; Pang, Marco; Eng, Janice J

2015-01-01

Background Stroke survivors have a high incidence of falls. Impaired executive-controlled processes are frequent in stroke survivors and are associated with falls in this population. Better understanding of the independent association between executive-controlled processes and physiological fall risk (i.e. performances of balance and mobility) could enhance future interventions that aim to prevent falls and to promote an independent lifestyle among stroke survivors. Methods Cross-sectional analysis of 63 adults who suffered a mild stroke >1 year prior to the study, aged > or =50 years. Results Cognitive flexibility was independently associated with performances of balance and mobility in community-dwelling older adults after mild stroke, after accounting for age, quadriceps strength of the paretic side and current physical activity level. Conclusions Clinicians may need to consider cognitive function when assessing and treating impaired balance and mobility in community-dwelling older adults after mild stroke. PMID:17143004

How does age affect the care dependency risk one year after stroke? A study based on claims data from a German health insurance fund.

PubMed

Schnitzer, Susanne; von dem Knesebeck, Olaf; Kohler, Martin; Peschke, Dirk; Kuhlmey, Adelheid; Schenk, Liane

2015-10-23

The objective of this study is to investigate the effect of age on care dependency risk 1 year after stroke. Two research questions are addressed: (1) How strong is the association between age and care dependency risk 1 year after stroke and (2) can this association be explained by burden of disease? The study is based on claims data from a German statutory health insurance fund. The study population was drawn from all continuously insured members with principal diagnoses of ischaemic stroke, hemorrhagic stroke, or transient ischaemic attack in 2007 who survived for 1 year after stroke and who were not dependent on care before their first stroke (n = 2864). Data were collected over a 1-year period. People are considered to be dependent on care if they, due to a physical, mental or psychological illness or disability, require substantial assistance in carrying out activities of daily living for a period of at least 6 months. Burden of disease was assessed by stroke subtype, history of stroke, comorbidities as well as geriatric multimorbidity. Regression models were used for data analysis. 21.6 % of patients became care dependent during the observation period. Post-stroke care dependency risk was significantly associated with age. Relative to the reference group (0-65 years), the odds ratio of care dependency was 11.30 (95 % CI: 7.82-16.34) in patients aged 86+ years and 5.10 (95 % CI: 3.88-6.71) in patients aged 76-85 years. These associations were not explained by burden of disease. On the contrary, age effects became stronger when burden of disease was included in the regression model (by between 1.1 and 28 %). Our results show that age has an effect on care dependency risk that cannot be explained by burden of disease. Thus, there must be other underlying age-dependent factors that account for the remaining age effects (e.g., social conditions). Further studies are needed to explore the causes of the strong age effects observed.

A protocol for a prospective observational study using chest and thumb ECG: transient ECG assessment in stroke evaluation (TEASE) in Sweden.

PubMed

Magnusson, Peter; Koyi, Hirsh; Mattsson, Gustav

2018-04-03

Atrial fibrillation (AF) causes ischaemic stroke and based on risk factor evaluation warrants anticoagulation therapy. In stroke survivors, AF is typically detected with short-term ECG monitoring in the stroke unit. Prolonged continuous ECG monitoring requires substantial resources while insertable cardiac monitors are invasive and costly. Chest and thumb ECG could provide an alternative for AF detection poststroke.The primary objective of our study is to assess the incidence of newly diagnosed AF during 28 days of chest and thumb ECG monitoring in cryptogenic stroke. Secondary objectives are to assess health-related quality of life (HRQoL) using short-form health survey (SF-36) and the feasibility of the Coala Heart Monitor in patients who had a stroke. Stroke survivors in Region Gävleborg, Sweden, will be eligible for the study from October 2017. Patients with a history of ischaemic stroke without documented AF before or during ECG evaluation in the stroke unit will be evaluated by the chest and thumb ECG system Coala Heart Monitor. The monitoring system is connected to a smartphone application which allows for remote monitoring and prompt advice on clinical management. Over a period of 28 days, patients will be monitored two times a day and may activate the ECG recording at symptoms. On completion, the system is returned by mail. This system offers a possibility to evaluate the presence of AF poststroke, but the feasibility of this system in patients who recently suffered from a stroke is unknown. In addition, HRQoL using SF-36 in comparison to Swedish population norms will be assessed. The feasibility of the Coala Heart Monitor will be assessed by a self-developed questionnaire. The study was approved by The Regional Ethical Committee in Uppsala (2017/321). The database will be closed after the last follow-up, followed by statistical analyses, interpretation of results and dissemination to a scientific journal. NCT03301662; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

External validation of the A2SD2 and ISAN scales for predicting infectious respiratory complications of ischaemic stroke.

PubMed

Ramírez-Moreno, J M; Martínez-Acevedo, M; Cordova, R; Roa, A M; Constantino, A B; Ceberino, D; Muñoz, P

2016-10-21

Pneumonia as a complication of stroke is associated with poor outcomes. The A2DS2 and ISAN scales were developed by German and English researchers, respectively, to predict in-hospital stroke-associated pneumonia. We conducted an external validation study of these scales in a series of consecutive patients admitted to our hospital due to ischaemic stroke. These predictive models were applied to a sample of 340 consecutive patients admitted to hospital in 2015 due to stroke. Discrimination was assessed by calculating the area under the ROC curve for diagnostic efficacy. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test and graphing the corresponding curve. Logistic regression analysis was performed to determine the independent predictors of respiratory infection secondary to stroke. We included 285 patients, of whom 45 (15.8%) had respiratory infection after stroke according to the study criteria. Mean age was 71.01±12.62 years; men accounted for 177 of the patients (62.1%). Seventy-two patients (25.3%) had signs or symptoms of dysphagia, 42 (14.7%) had atrial fibrillation, and 14 (4.9%) were functionally dependent before stroke; the median NIHSS score was 4 points. Mean scores on A2DS2 and ISAN were 3.25±2.54 and 6.49±3.64, respectively. Our analysis showed that higher A2DS2 scores were associated with an increased risk of infection (OR=1.576; 95% CI: 1.363-1.821); the same was true for ISAN scores (OR=1.350; 95% CI: 1.214-1.501). High scores on A2DS2 and ISAN were found to be a strong predictor of respiratory infection associated with acute stroke in a cohort of consecutive patients with stroke. These easy-to-use scales are promising tools for predicting this complication in routine clinical practice. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial.

PubMed

Zinkstok, Sanne M; Roos, Yvo B

2012-08-25

Thrombolysis with intravenous alteplase is the only approved treatment for acute ischaemic stroke. After alteplase-induced recanalisation, reocclusion occurs in 14-34% of patients, probably because of platelet activation. Early administration of antiplatelet therapy after alteplase could reduce the risk of reocclusion and improve outcome. We compared the effects of early addition of intravenous aspirin to alteplase with standard alteplase without aspirin. In this multicentre, randomised, open-label trial with blind-endpoint assessment, patients with acute ischaemic stroke treated with alteplase were randomly assigned to 300 mg intravenous aspirin within 90 min after start of alteplase treatment or to no additional treatment. In both groups, oral antiplatelet therapy was started 24 h after alteplase treatment. The primary endpoint was favourable outcome, defined as a score of 0-2 on the modified Rankin scale at 3 months. This trial is registered with the Netherlands Trial Register (NTR822). Between July 29, 2008, and April 20, 2011, 642 patients (322 patients aspirin, 320 patients standard treatment) of the targeted 800 patients were enrolled. At that time, the trial was terminated prematurely because of an excess of symptomatic intracranial haemorrhage (SICH) and no evidence of benefit in the aspirin group. At 3 months, 174 (54·0%) patients in the aspirin group versus 183 (57·2%) patients in the standard treatment group had a favourable outcome (absolute difference -3·2%, 95% CI -10·8 to 4·2; crude relative risk 0·94, 0·82 to 1·09, p=0·42). Adjusted odds ratio was 0·91 (95% CI 0·66-1·26, p=0·58). SICH occurred more often in the aspirin group (14 [4·3%] patients) than in the standard treatment group (five [1·6%]; absolute difference 2·8%, 95% CI 0·2-5·4; p=0·04). SICH was more often the cause of poor outcome in the aspirin group compared with the standard treatment group (11 vs 1, p=0·006). Early administration of intravenous aspirin in patients with acute ischaemic stroke treated with alteplase does not improve outcome at 3 months and increases the risk of SICH. The results of this trial do not support a change of the current guidelines, which advise to start antiplatelet therapy 24 h after alteplase. The Dutch Heart Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Obesity and stroke: Can we translate from rodents to patients?

PubMed Central

Haley, Michael J

2016-01-01

Obesity is a risk factor for stroke and is consequently one of the most common co-morbidities found in patients. There is therefore an identified need to model co-morbidities preclinically to allow better translation from bench to bedside. In preclinical studies, both diet-induced and genetically obese rodents have worse stroke outcome, characterised by increased ischaemic damage and an altered inflammatory response. However, clinical studies have reported an ‘obesity paradox’ in stroke, characterised by reduced mortality and morbidity in obese patients. We discuss the potential reasons why the preclinical and clinical studies may not agree, and review the mechanisms identified in preclinical studies through which obesity may affects stroke outcome. We suggest inflammation plays a central role in this relationship, as obesity features increases in inflammatory mediators such as C-reactive protein and interleukin-6, and chronic inflammation has been linked to worse stroke risk and outcome. PMID:27655337

Systolic blood pressure, diabetes and the risk of cardiovascular diseases in the Asia-Pacific region.

PubMed

Kengne, A P; Patel, A; Barzi, F; Jamrozik, K; Lam, T H; Ueshima, H; Gu, D F; Suh, I; Woodward, M

2007-06-01

To assess the association between systolic blood pressure (SBP) and cardiovascular diseases (CVD) among participants with and without diabetes from cohorts in the Asia-Pacific region. Hazards ratios and 95% confidence intervals (CI) for CVD were calculated from Cox models, stratified by sex and region and adjusted for age using individual participant data from 36 cohort studies. Repeat measurements of SBP were used to adjust for regression dilution bias. During follow-up, 7387 fatal or non-fatal cardiovascular endpoints were recorded among 368 307 participants (6.4% with diabetes). SBP was associated with coronary heart disease (CHD), ischaemic stroke and haemorrhagic stroke in a continuous log-linear fashion among individuals with diabetes, as well as those without diabetes. Overall, each 10 mmHg higher usual SBP was associated with 18% (95% CI: 9-27%) and 23% (19-26%) greater risk for CHD among those with and without diabetes, respectively. The corresponding values for ischaemic stroke were 29% (14-45%) and 43% (37-50%), and for haemorrhagic stroke, 56% (32-83%) and 74% (66-82%). The test for heterogeneity by diabetes status in each of these associations was not significant (P >or= 0.10). Systolic blood pressure is an important marker of risk of CVD in people with and without diabetes. A given reduction in systolic blood pressure is likely to have a similar relative effect on reducing the risk of a cardiovascular event, regardless of diabetes status.

Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke: a randomised controlled trial

PubMed Central

Li, Shanshan; Zhang, Xinjiang; Fang, Qi; Zhou, Junshan; Zhang, Meijuan; Wang, Hui; Chen, Yan; Xu, Biyun; Wu, Yanfeng; Qian, Lai

2017-01-01

Purpose To evaluate the efficacy and safety of Ginkgo biloba extract (GBE) in acute ischaemic stroke and its impact on the recurrence of vascular events. Methods We conducted a multicentre, prospective, randomised, open label, blinded, controlled clinical trial enrollingpatients with an onset of acute stroke within 7 days from five hospitals in China Jiangsu Province. Participants were assigned to the GBE group (450 mg GBE with 100 mg aspirin daily) or the control group (100 mg aspirin daily) for 6 months. The primary outcome was the decline in the Montreal Cognitive Assessment score at 6 months. Secondary outcomes were other neuropsychological tests of cognitive and neurological function, the the incidence of adverse events and vascular events. Results 348 patients were enrolled: 179 in the GBE group and 169 in the control group. With 18 patients lost to follow-up, the dropout rate was 5.17%. Admission data between two groups were similar, but in the GBE group there was a marked slow down in the decline in the Montreal Cognitive Assessment scores (−2.77±0.21 vs −1.99±0.23, P=0.0116 (30 days); −3.34±0.24 vs −2.48±0.26, P=0.0165 (90 days); −4.00±0.26 vs −2.71±0.26, P=0.0004 (180 days)) compared with controls. The National Institutes of Health Stroke Scale scores at 12 and 30 days, the modified Rankin Scale scores for independent rate at 30, 90 and 180 days, and the Barthel Index scores at 30, 90 and 180 days in the GBE group were significantly improved compared with controls. Improvements were also observedin GBE groups for Mini-Metal State Examination scores of 30, 90 and 180 days, Webster’s digit symbol test scores at 30 days and Executive Dysfunction Index scores at 30 and 180 days. No significant differences were seen in the incidence of adverse events or vascular events. Conclusions We conclude that GBE in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischaemic stroke without increasing the incidence of vascular events. Trial registration number ChiCTR-TRC-12002688. PMID:29507779

Relationships between selective neuronal loss and microglial activation after ischaemic stroke in man.

PubMed

Morris, Rhiannon S; Simon Jones, P; Alawneh, Josef A; Hong, Young T; Fryer, Tim D; Aigbirhio, Franklin I; Warburton, Elizabeth A; Baron, Jean-Claude

2018-05-09

Modern ischaemic stroke management involves intravenous thrombolysis followed by mechanical thrombectomy, which allows markedly higher rates of recanalization and penumbral salvage than thrombolysis alone. However, <50% of treated patients eventually enjoy independent life. It is therefore important to identify complementary therapeutic targets. In rodent models, the salvaged penumbra is consistently affected by selective neuronal loss, which may hinder recovery by interfering with plastic processes, as well as by microglial activation, which may exacerbate neuronal death. However, whether the salvaged penumbra in man is similarly affected is still unclear. Here we determined whether these two processes affect the non-infarcted penumbra in man and, if so, whether they are inter-related. We prospectively recruited patients with (i) acute middle-cerebral artery stroke; (ii) penumbra present on CT perfusion obtained <4.5 h of stroke onset; and (iii) early neurological recovery as a marker of penumbral salvage. PET with 11C-flumazenil and 11C-PK11195, as well as MRI to map the final infarct, were obtained at predefined follow-up times. The presence of selective neuronal loss and microglial activation was determined voxel-wise within the MRI normal-appearing ipsilateral non-infarcted zone and surviving penumbra masks, and their inter-relationship was assessed both across and within patients. Dilated infarct contours were consistently excluded to control for partial volume effects. Across the 16 recruited patients, there was reduced 11C-flumazenil and increased 11C-PK11195 binding in the whole ipsilateral non-infarcted zone (P = 0.04 and 0.02, respectively). Within the non-infarcted penumbra, 11C-flumazenil was also reduced (P = 0.001), but without clear increase in 11C-PK11195 (P = 0.18). There was no significant correlation between 11C-flumazenil and 11C-PK11195 in either compartment. This mechanistic study provides direct evidence for the presence of both neuronal loss and microglial activation in the ipsilateral non-infarcted zone. Further, we demonstrate the presence of neuronal loss affecting the surviving penumbra, with no or only mild microglial activation, and no significant relationship between these two processes. Thus, microglial activation may not contribute to penumbral neuronal loss in man, and its presence in the ipsilateral hemisphere may merely reflect secondary remote degeneration. Selective neuronal loss in the surviving penumbra may represent a novel therapeutic target as an adjunct to penumbral salvage to further improve functional outcome. However, microglial activation may not stand as the primary therapeutic approach. Protecting the penumbra by acutely improving perfusion and oxygenation in conjunction with thrombectomy for example, may be a better approach. 11C-flumazenil PET would be useful to monitor the effects of such therapies.

Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial.

PubMed

Kim, Bum Joon; Lee, Eun-Jae; Kwon, Sun U; Park, Jong-Ho; Kim, Yong-Jae; Hong, Keun-Sik; Wong, Lawrence K S; Yu, Sungwook; Hwang, Yang-Ha; Lee, Ji Sung; Lee, Juneyoung; Rha, Joung-Ho; Heo, Sung Hyuk; Ahn, Sung Hwan; Seo, Woo-Keun; Park, Jong-Moo; Lee, Ju-Hun; Kwon, Jee-Hyun; Sohn, Sung-Il; Jung, Jin-Man; Navarro, Jose C; Kang, Dong-Wha

2018-06-01

The optimal treatment for patients with ischaemic stroke with a high risk of cerebral haemorrhage is unclear. We assessed the efficacy and safety of cilostazol versus aspirin, with and without probucol, in these patients. In this randomised, controlled, 2 × 2 factorial trial, we enrolled patients with ischaemic stroke with a history of or imaging findings of intracerebral haemorrhage or two or more microbleeds from 67 centres in three Asian countries. Patients were randomly assigned (1:1:1:1) to receive oral cilostazol (100 mg twice a day), aspirin (100 mg once a day), cilostazol plus probucol (250 mg twice a day), or aspirin plus probucol with centralised blocks stratified by centre. Cilostazol versus aspirin was investigated double-blinded; probucol treatment was open-label, but the outcome assessor was masked to assignment. The co-primary outcomes were incidence of the composite of stroke, myocardial infarction, or vascular death (efficacy) and incidence of haemorrhagic stroke (safety), which were assessed in intention-to-treat and modified intention-to-treat populations. Efficacy was analysed with a non-inferiority test and a superiority test if non-inferiority was satisfied. Safety was assessed with a superiority test only. This trial is registered with ClinicalTrials.gov, NCT01013532. Between Aug 1, 2009, and Aug 31, 2015, we randomly assigned 1534 patients to one of the four study groups, of whom 1512 were assessed for the co-primary endpoints. During a median follow-up of 1·9 years (IQR 1·0-3·0), the incidence of composite vascular events was 4·27 per 100 person-years in patients who received cilostazol and 5·33 per 100 person-years in patients who received aspirin (HR 0·80, 95% CI 0·57-1·11; non-inferiority p=0·0077; superiority p=0·18). Incidence of cerebral haemorrhage was 0·61 per 100 person-years in patients who received cilostazol and 1·20 per 100 person-years in those who received aspirin (HR 0·51, 97·5% CI 0·20-1·27; superiority p=0·18). The incidence of vascular events was 3·91 per 100 person-years in the probucol group compared with 5·75 per 100 person-years in the non-probucol group (HR 0·69, 95% CI 0·50-0·97; superiority p=0·0316). The incidence of cerebral haemorrhage was 0·72 per 100 person-years in the probucol group and 1·11 per 100 person-years in the non-probucol group (HR 0·65, 97·5% CI 0·27-1·57; p=0·55). Adverse events were similar across the four study groups; the most common events were dizziness, headache, diarrhoea, and constipation. In patients with ischaemic stroke at high risk of cerebral haemorrhage, cilostazol was non-inferior to aspirin for the prevention of cardiovascular events, but did not reduce the risk of haemorrhagic stroke. Addition of probucol to aspirin or cilostazol could be beneficial for reducing the incidence of cardiovascular events. Korea Otsuka Pharmaceutical. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Stroke in young adults: incidence and clinical picture in 280 patients according to their aetiological subtype].

PubMed

Arboix, Adrià; Massons, Joan; García-Eroles, Luís; Oliveres, Montserrat

2016-03-04

To assess the clinical features and incidence rate of stroke in young adults (less than 55 years of age). Hospital-based descriptive study of 280 young inpatients consecutively admitted for stroke over a period of 24 years. We conducted a comparison with the remaining 4,312 patients admitted for stroke. Stroke in young adults represented 6.1% of all strokes, 5.7% of transient ischaemic attacks, 5.8% of cerebral infarctions and 8.4% of brain haemorrhages. However, reported minimal frequency of cardioembolic (2.1%) and atherothrombotic (3.4%) infarctions, accounted for 5.9% of lacunar and for 10.7% of essential infarctions and showed a maximum frequency in those infarctions of unusual aetiology (36%). Factors independently associated with stroke in young adults were cigarette smoking (OR 4.23; 95% CI 3.02-5.93; P=.000), unusual aetiology (OR 4.97; 95% CI 3.15-7.84; P=.000), headache (OR 4.57; 95% CI 2.59-8.07; P=.000), alcohol abuse (OR 3.93; 95% CI 2.46-6.29; P=.000), oral contraceptives (OR 14.07; 95% CI 2.37-83.40; P=.004), atrial fibrillation (OR 0.15; 95% CI 0.08-0.28; P=.000), arterial hypertension (OR 0.43; 95% CI 0.33-0.57; P=.000), COPD (OR 0.20; 95% CI 0.09-0.44; P=.000), atherothrombotic infarction (OR 0.51; 95% CI 0.34-0.77; P=.001), female sex (OR 0.71; 95% CI 0.52-0.97; P=.029), diabetes mellitus (OR 0.66; 95% CI 0.46-0.98; P=.030), ischaemic heart disease (OR 0.56; 95% CI 0.33-0.95; P=.032) and intermittent claudication (OR 0.48; 95% CI 0.24-0.94; P=.033). Stroke in young adults is infrequent (6.1% of the total), but represents the highest frequency of cerebral infarcts of unusual aetiology (36%). We conclude that stroke in younger patients presents its own and differentiated clinical profile. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Deep subcortical infarct burden in relation to apolipoprotein B/AI ratio in patients with intracranial atherosclerotic stenosis.

PubMed

Park, J-H; Hong, K-S; Lee, J; Kim, Y-J; Song, P

2013-04-01

Pre-existing brain infarct (PBI), frequently seen on magnetic resonance imaging and usually silent, is recognized as a risk factor for future stroke. Increased apolipoprotein B (apoB)/apoAI ratio is known to be a risk predictor of ischaemic stroke and is associated with intracranial atherosclerotic stenosis (ICAS). However, little is known about the association of apoB/apoAI ratio with PBI. A total of 522 statin-/fibrate-naïve Korean patients, who experienced acute ischaemic stroke, were categorized into three groups: ICAS (n=254), extracranial (n=51), and no cerebral atherosclerotic stenosis (n=217). We explored the association between apoB/apoAI ratio and PBI lesions according to atherosclerosis type (ICAS, ECAS, and NCAS), PBI location (deep subcortical [ds-PBI] versus hemispheric [h-PBI]), and symptomatic PBI (s-PBI) which was relevant to a prior clinical stroke event. Pre-existing brain infarct(+) patients showed a higher apoB/apoAI ratio than PBI(-) patients (0.81 ± 0.28 vs. 0.72 ± 0.23, P<0.001). In ICAS group, patients with higher apoB/apoAI ratio quartiles had more PBIs, ds-PBIs, and s-PBIs (P=0.020, P=0.025, and P=0.001, respectively). With multivariable analyses, the highest apoB/apoAI ratio quartile was associated with PBI (OR, 2.56; 95% CI, 1.39-4.73), ds-PBI (2.48; 1.33-4.62), and advanced (≥ 3) ds-PBIs (2.68; 1.27-5.63) in ICAS group, but not with h-PBI. s-PBI had a dose-response relationship with apoB/apoAI ratio quartiles (6.18; 1.31-29.13 for the second; 5.34; 1.06-26.83 for the third; and 12.17; 2.50-59.19 for the fourth quartile), when referenced to the first quartile. ApoB/apoAI ratio is associated with asymptomatic deep subcortical ischaemic burden as well as with symptomatic lesion in patients with ICAS. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Rehabilitation and education are underutilized for mild stroke and TIA sufferers.

PubMed

Faux, Steven G; Arora, Pooja; Shiner, Christine T; Thompson-Butel, Angelica G; Klein, Linda A

2018-06-01

Transient ischemic attack (TIA) and mild stroke represent a large proportion of cerebrovascular events, at high risk of being followed by recurrent, serious events. The importance of early education addressing risk management, secondary prevention and lifestyle modifications is the centerpiece of further stroke prevention. However, delivering education and rehabilitation to this population can be complex and challenging. Via synthesis of a narrative review and clinical experience, we explore the unique and inherent complexities of rehabilitation management and education provision for patients following mild stroke and TIA. A considerable proportion of TIA/mild stroke survivors have ongoing rehabilitation needs that are poorly addressed. The need for rehabilitation in these patients is often overlooked, and available assessment tools lack the sensitivity to identify common subtle impairments in cognition, mood, language and fatigue. Active and accessible education interventions need to be initiated early after the event, and integrated with ongoing rehabilitation management. Priority areas in need of future development in this field are highlighted and discussed. Implications for rehabilitation Survivors of mild stroke and TIA have ongoing unmet rehabilitation needs and require a unique approach to rehabilitation and education. Rehabilitation needs are difficult to assess and poorly addressed in this cohort, where available assessment tools lack the sensitivity required to identify subtle impairments. Education needs to be initiated early after the event and involve active engagement of the patient in order to improve stroke knowledge, mood and motivate adherence to lifestyle modifications and secondary prevention. Rehabilitation physicians are currently an underutilized resource, who should be more involved in the management of all patients following TIA or mild stroke.

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.

PubMed

O'Donnell, Martin J; Chin, Siu Lim; Rangarajan, Sumathy; Xavier, Denis; Liu, Lisheng; Zhang, Hongye; Rao-Melacini, Purnima; Zhang, Xiaohe; Pais, Prem; Agapay, Steven; Lopez-Jaramillo, Patricio; Damasceno, Albertino; Langhorne, Peter; McQueen, Matthew J; Rosengren, Annika; Dehghan, Mahshid; Hankey, Graeme J; Dans, Antonio L; Elsayed, Ahmed; Avezum, Alvaro; Mondo, Charles; Diener, Hans-Christoph; Ryglewicz, Danuta; Czlonkowska, Anna; Pogosova, Nana; Weimar, Christian; Iqbal, Romaina; Diaz, Rafael; Yusoff, Khalid; Yusufali, Afzalhussein; Oguz, Aytekin; Wang, Xingyu; Penaherrera, Ernesto; Lanas, Fernando; Ogah, Okechukwu S; Ogunniyi, Adesola; Iversen, Helle K; Malaga, German; Rumboldt, Zvonko; Oveisgharan, Shahram; Al Hussain, Fawaz; Magazi, Daliwonga; Nilanont, Yongchai; Ferguson, John; Pare, Guillaume; Yusuf, Salim

2016-08-20

Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke. We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals. Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001). Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. Copyright © 2016 Elsevier Ltd. All rights reserved.

Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review.

PubMed

Feigin, Valery L; Lawes, Carlene M M; Bennett, Derrick A; Barker-Collo, Suzanne L; Parag, Varsha

2009-04-01

This systematic review of population-based studies of the incidence and early (21 days to 1 month) case fatality of stroke is based on studies published from 1970 to 2008. Stroke incidence (incident strokes only) and case fatality from 21 days to 1 month post-stroke were analysed by four decades of study, two country income groups (high-income countries and low to middle income countries, in accordance with the World Bank's country classification) and, when possible, by stroke pathological type: ischaemic stroke, primary intracerebral haemorrhage, and subarachnoid haemorrhage. This Review shows a divergent, statistically significant trend in stroke incidence rates over the past four decades, with a 42% decrease in stroke incidence in high-income countries and a greater than 100% increase in stroke incidence in low to middle income countries. In 2000-08, the overall stroke incidence rates in low to middle income countries have, for the first time, exceeded the level of stroke incidence seen in high-income countries, by 20%. The time to decide whether or not stroke is an issue that should be on the governmental agenda in low to middle income countries has now passed. Now is the time for action.

Association between self-perceived psychological stress and transitory ischaemic attack and minor stroke: A case-control study.

PubMed

Ramírez-Moreno, J M; Muñoz Vega, P; Espada, S; Bartolomé Alberca, S; Aguirre, J; Peral, D

2017-12-22

Stroke has a complex aetiopathogenesis influenced by numerous risk factors. There is growing interest in the study of the pathophysiological changes associated with stress and their potential relationship with cerebrovascular disease. The purpose of this paper is to assess the strength of association between exposure to stress and stroke. We conducted a case-control study (1:1) to compare exposure to stress in a group of patients with a history of a first transient ischaemic attack (TIA) or minor stroke and in a control group. Participants were asked a subjective question about their perception of stress in the previous months and completed the standardised Effort-Reward Imbalance (ERI) questionnaire. Logistic regression models were used for data analysis. The study included data on 50 cases and 50 controls. There were no significant differences in demographic variables and economic, social, and employment status between cases and controls. Fifty percent of the cases reported moderate to severe stress, compared to 30% of controls (OR: 2.33; 95% CI: 1.02-5.30; P=.041). ERI questionnaire results found that greater effort at work (OR: 1.48; 95% CI: 1.19-1.83) and greater commitment is associated with stroke (OR: 1.34; 95% CI: 1.17-1.54), while higher reward constitutes a protective factor against the disease (OR: 0.71; 95% CI: 0.61-0.82). There is a strong association between self-perceived psychological stress and TIA. The imbalance between effort and reward at work is also clearly related to TIA. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Machine-learning approach identifies a pattern of gene expression in peripheral blood that can accurately detect ischaemic stroke

PubMed Central

O’Connell, Grant C; Petrone, Ashley B; Treadway, Madison B; Tennant, Connie S; Lucke-Wold, Noelle; Chantler, Paul D; Barr, Taura L

2016-01-01

Early and accurate diagnosis of stroke improves the probability of positive outcome. The objective of this study was to identify a pattern of gene expression in peripheral blood that could potentially be optimised to expedite the diagnosis of acute ischaemic stroke (AIS). A discovery cohort was recruited consisting of 39 AIS patients and 24 neurologically asymptomatic controls. Peripheral blood was sampled at emergency department admission, and genome-wide expression profiling was performed via microarray. A machine-learning technique known as genetic algorithm k-nearest neighbours (GA/kNN) was then used to identify a pattern of gene expression that could optimally discriminate between groups. This pattern of expression was then assessed via qRT-PCR in an independent validation cohort, where it was evaluated for its ability to discriminate between an additional 39 AIS patients and 30 neurologically asymptomatic controls, as well as 20 acute stroke mimics. GA/kNN identified 10 genes (ANTXR2, STK3, PDK4, CD163, MAL, GRAP, ID3, CTSZ, KIF1B and PLXDC2) whose coordinate pattern of expression was able to identify 98.4% of discovery cohort subjects correctly (97.4% sensitive, 100% specific). In the validation cohort, the expression levels of the same 10 genes were able to identify 95.6% of subjects correctly when comparing AIS patients to asymptomatic controls (92.3% sensitive, 100% specific), and 94.9% of subjects correctly when comparing AIS patients with stroke mimics (97.4% sensitive, 90.0% specific). The transcriptional pattern identified in this study shows strong diagnostic potential, and warrants further evaluation to determine its true clinical efficacy. PMID:29263821

Impact of first-ever mild stroke on participation at 3 and 6 month post-event: the TABASCO study.

PubMed

Adamit, Tal; Maeir, Adina; Ben Assayag, Einor; Bornstein, Natan M; Korczyn, Amos D; Katz, Noomi

2015-01-01

This study focused on the relationships between cognition, participation and quality of life (QoL) among first-ever mild ischemic stroke patients 3 months post-event. We hypothesized that significant correlations exist between cognition, executive functions (EF), QoL and participation; and that EF and QoL will significantly contribute to participation beyond demographics and stroke severity at 3 and from 3 to 6 months post-stroke. A prospective cohort study, recruiting consecutive first-ever stroke patients from a large tertiary hospital. The inclusion criteria were first event, mild stroke (NIHSS ≤ 5), and no previous significant neurological or cognitive impairment. In addition to assessment every 6 month at the hospital, an assessment battery was administered at home 3 months post-stroke. Participants showed mild to moderate difficulties in cognition and participation (n = 249). Low to moderate correlations were found between cognition and EF with participation (-0.380, p < 0.05; r = 0.460, p < 0.001, respectively); and cognition with QoL (r = 0.421, p < 0.001). EF and QoL contributed significantly to participation at 3 months (R(2) = 0.961) and in addition education at 6 months (R(2) = 0.701). Participants after mild ischemic stroke experienced cognitive and EF difficulties that affect their participation and QoL. Further studies are needed of mild stroke survivors to enhance our understanding of the variables that affect participation. The findings of the current study have significant implications for the participation of people after mild stroke in the community. Health care systems in general and rehabilitation programs, in particular, do not consider that these clients need rehabilitation as most of them perform basic daily functions independently. Thus, although cognitive and EF deficits are found in people following even mild stroke, but are not externally apparent, these impairments are mostly neglected by the health care system. Mild stroke has long-term effects in most cases and effect family members as well. The implications of the study's results, as well as those of other studies, emphasize the necessity of follow-up and rehabilitation efforts at home and in the community. These efforts should focus on re-enabling the individual to participate in previous activities as much as possible and on providing support for family members. The strength of this study lies in the large number of participants who were evaluated at home in their natural environments. Studies of this kind are rarely performed in the participants' real-life settings, thus the current study provides an important perspective on the participation of this population in the community.

Thrombolysis for acute ischaemic stroke with alteplase in an Asian population: results of the multicenter, multinational Safe Implementation of Thrombolysis in Stroke-Non-European Union World (SITS-NEW).

PubMed

Rha, Joung-Ho; Shrivastava, Vasantha Padma; Wang, Yongjun; Lee, Kim En; Ahmed, Niaz; Bluhmki, Erich; Hermansson, Karin; Wahlgren, Nils

2014-10-01

Safe Implementation of Thrombolysis in Stroke-Non-European Union World was a multinational, prospective, open, monitored, observational study of intravenous alteplase as thrombolytic therapy in clinical practice. Safe Implementation of Thrombolysis in Stroke-Non-European Union World was required to assess the safety of alteplase in an Asian population by comparison with results from the European Safe Implementation of Thrombolysis in Stroke-Monitoring Study and pooled results from randomized controlled trials. To evaluate the efficacy and safety of intravenous alteplase (0·9 mg/kg) as thrombolytic therapy within three-hours of onset of acute ischaemic stroke in an Asian population. The 591 patients included were treated at 48 centers in four countries (South Korea, China, India, and Singapore) between 2006 and 2008. Primary outcomes were symptomatic (deterioration in National Institutes of Health Stroke Scale score ≥4 or death within the first 24 h) intracerebral haemorrhage type 2 22-36 h after the thrombolysis and mortality at three-month follow-up. The secondary outcome was functional independence (modified Rankin Scale score 0-2) at three-months. Results were compared with those from Safe Implementation of Thrombolysis in Stroke-Monitoring Study (n = 6483) and pooled results of patients (n = 415) who received intravenous alteplase (0·9 mg/kg) zero- to three-hours from onset of stroke symptoms in four randomized controlled trials (National Institute of Neurological Disorders and Stroke A and B, Altephase Thrombolysis for Acute Noninterventional Therapy in Ischaemic Stroke, and European Cooperative Acute Stroke Study II). Results are presented as Safe Implementation of Thrombolysis in Stroke-Non-European Union World vs. Safe Implementation of Thrombolysis in Stroke-Monitoring Study vs. pooled randomized controlled trials. Median age was 64 vs. 68 vs. 70 years, National Institutes of Health Stroke Scale score at baseline was 12 vs. 12 vs. 13, time from stroke onset to treatment was 130 vs. 140 vs. 135 mins, and females were 36·4% vs. 39·8% vs. 41·2%. Main outcomes (proportion of patients and 95% confidence intervals) were symptomatic intracerebral haemorrhage: 1·9% (1·1-3·3) vs. 1·7% (1·4-2·0) vs. 3·1% (1·8-5·3); mortality: 10·2% (8·0-12·9) vs. 11·3% (10·5-12·1) vs. 16·4% (13·1-20·3); and functional independence: 62·5% (58·5-66·4) vs. 54·8% (53·5-56·0) vs. 50·1% (45·3-54·9) at three-months. Adjusted odds ratio (95% confidence intervals) between Safe Implementation of Thrombolysis in Stroke-Non-European Union World and Safe Implementation of Thrombolysis in Stroke-Monitoring Study, and between Safe Implementation of Thrombolysis in Stroke-Non-European Union World and the pooled trials were 1·83 (0·89-3·77; P = 0·1156) and 0·63 (0·19-2·07; P = 0·4470) for symptomatic intracerebral haemorrhage, 0·90 (0·64-1·25; P = 0·5092) and 0·93 (0·52-1·64; P = 0·7915) for mortality at three-months, and 1·57 (1·25-1·96; P < 0·0001) and 1·35 (0·91-2·00; P = 0·1325) for functional independence. These data demonstrate the safety and efficacy of the standard dose of intravenous alteplase (0·9 mg/kg) in an Asian population, as previously observed in the European population studied in Safe Implementation of Thrombolysis in Stroke-Monitoring Study and the populations in pooled randomized controlled trials, when used in routine clinical practice within three-hours of stroke onset. The findings should encourage wider use of thrombolytic therapy in Asian countries for suitable patients treated in stroke centers. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Hypoxic Adaptation during Development: Relation to Pattern of Neurological Presentation and Cognitive Disability

ERIC Educational Resources Information Center

Kirkham, Fenella J.; Datta, Avijit K.

2006-01-01

Children with acute hypoxic-ischaemic events (e.g. stroke) and chronic neurological conditions associated with hypoxia frequently present to paediatric neurologists. Failure to adapt to hypoxia may be a common pathophysiological pathway linking a number of other conditions of childhood with cognitive deficit. There is evidence that congenital…

Aspirin Risks in Perspective: A Comparison against Marathon Running

ERIC Educational Resources Information Center

Morgan, Gareth

2014-01-01

Aspirin has public health potential to reduce the risk of ischaemic vascular events and sporadic cancer. One objection to the wider use of aspirin for primary prevention, however, is the undesirable effects of the medicine, which include increasing risk of bleeding and haemorrhagic stroke. Marathons also carry risks of serious events such as…

Antithrombotic therapy in atrial fibrillation: aspirin is rarely the right choice

PubMed Central

Sabir, Ian N; Matthews, Gareth D K; Huang, Christopher L-H

2013-01-01

Atrial fibrillation, the commonest cardiac arrhythmia, predisposes to thrombus formation and consequently increases risk of ischaemic stroke. Recent years have seen approval of a number of novel oral anticoagulants. Nevertheless, warfarin and aspirin remain the mainstays of therapy. It is widely appreciated that both these agents increase the likelihood of bleeding: there is a popular conception that this risk is greater with warfarin. In fact, well-managed warfarin therapy (INR 2-3) has little effect on bleeding risk and is twice as effective as aspirin at preventing stroke. Patients with atrial fibrillation and a further risk factor for stroke (CHA2DS2-VASc >0) should therefore either receive warfarin or a novel oral agent. The remainder who are at the very lowest risk of stroke are better not prescribed antithrombotic therapy. For stroke prevention in atrial fibrillation; aspirin is rarely the right choice. PMID:23404744

Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial.

PubMed

Diener, Hans-Christoph; Eikelboom, John; Connolly, Stuart J; Joyner, Campbell D; Hart, Robert G; Lip, Gregory Y H; O'Donnell, Martin; Hohnloser, Stefan H; Hankey, Graeme J; Shestakovska, Olga; Yusuf, Salim

2012-03-01

In the AVERROES study, apixaban, a novel factor Xa inhibitor, reduced the risk of stroke or systemic embolism in patients with atrial fibrillation who were at high risk of stroke but unsuitable for vitamin K antagonist therapy. We aimed to investigate whether the subgroup of patients with previous stroke or transient ischaemic attack (TIA) would show a greater benefit from apixaban compared with aspirin than would patients without previous cerebrovascular events. In AVERROES, 5599 patients (mean age 70 years) with atrial fibrillation who were at increased risk of stroke and unsuitable for vitamin K antagonist therapy were randomly assigned to receive apixaban (5 mg twice daily) or aspirin (81-324 mg per day). The mean follow-up was 1·1 years. The primary efficacy outcome was stroke or systemic embolism; the primary safety outcome was major bleeding. Patients and investigators were masked to study treatment. In this prespecified subgroup analysis, we used Kaplan-Meier estimates of 1-year event risk and Cox proportional hazards regression models to compare the effects of apixaban in patients with and without previous stroke or TIA. AVERROES is registered at ClinicalTrials.gov, number NCT00496769. In patients with previous stroke or TIA, ten events of stroke or systemic embolism occurred in the apixaban group (n=390, cumulative hazard 2·39% per year) compared with 33 in the aspirin group (n=374, 9·16% per year; hazard ratio [HR] 0·29, 95% CI 0·15-0·60). In those without previous stroke or TIA, 41 events occurred in the apixaban group (n=2417, 1·68% per year) compared with 80 in the aspirin group (n=2415, 3·06% per year; HR 0·51, 95% CI 0·35-0·74). The p value for interaction of the effects of aspirin and apixaban with previous cerebrovascular events was 0·17. Major bleeding was more frequent in patients with history of stroke or TIA than in patients without (HR 2·88, 95% CI 1·77-4·55) but risk of this event did not differ between treatment groups. In patients with atrial fibrillation, apixaban is similarly effective whether or not patients have had a previous stroke or TIA. Given that those with previous stroke or TIA have a higher risk of stroke, the absolute benefits might be greater in these patients. Bristol-Myers Squibb and Pfizer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Prevention of cardiovascular events in elderly people.

PubMed

Andrawes, Wafik Farah; Bussy, Caroline; Belmin, Joël

2005-01-01

Cardiovascular disease has been identified as the leading cause of morbidity and mortality in developed countries. Given the increase in life expectancy and the development of cardiovascular preventive measures, it has become increasingly important to detect and prevent cardiovascular diseases in the elderly. We reviewed the scientific literature concerning cardiovascular prevention to assess the importance of cardiovascular preventive measures in old (> or =65 years of age) individuals. We undertook a systematic search for references relating to prevention of cardiovascular disease in the elderly, mainly ischaemic stroke, coronary artery disease and heart failure, on the MEDLINE database 1962-2005. For cardiovascular prevention by drugs or surgery, emphasis was placed on randomised controlled trials, review articles and meta-analyses. For cardiovascular prevention by lifestyle modification, major cohort studies were also considered. Stroke, coronary heart disease and heart failure were found to be the main targets for cardiovascular prevention in published studies. Antihypertensive treatment has proven its efficacy in primary prevention of fatal or nonfatal stroke in hypertensive and high-risk patients >60 years of age, particularly through treatment of systolic hypertension. Systolic blood pressure reduction is equally important in the secondary prevention of stroke. Similarly, in nonvalvular atrial fibrillation, an adjusted dose of warfarin with a target International Normalized Ratio (INR) of between 2 to 3 prevents ischaemic stroke in elderly patients with an acceptable haemorrhagic risk but is still under prescribed. Antiplatelet agents are indicated in elderly patients with nonembolic strokes. Few large-scale studies have investigated the effect of HMG-CoA reductase inhibitors (statins) on stroke prevention in old individuals. To date, the largest trials suggest a beneficial effect for stroke prevention with use of statins in high-risk elderly subjects < or =82 years of age. Carotid endarterectomy is indicated in carotid artery stenosis >70% and outcomes are even better in elderly than in younger patients. However, medical treatment is still the first-line treatment in asymptomatic elderly patients with <70% stenosis. In ischaemic heart disease, different trials in elderly individuals have shown that use of statins, antithrombotic agents, beta-adrenoceptor antagonists and ACE inhibitors plays an important role either in primary or in secondary cardiovascular prevention. Hormone replacement therapy has been used to treat climacteric symptoms and postmenopausal osteoporosis and was thought to confer a cardiovascular protection. However, controlled trials in elderly individuals changed this false belief when it was found that there was no benefit and even a harmful cardiovascular effect during the first year of treatment. Smoking cessation, regular physical activity and healthy diet are, as in younger individuals, appropriate and effective measures for preventing cardiovascular events in the elderly. Finally, antihypertensive treatment and influenza vaccination are useful for heart failure prevention in elderly individuals. Cardiovascular prevention should be more widely implemented in the elderly, including individuals aged > or =75 years, and this might contribute to improved healthy status and quality of life in this growing population.

Neuroprotection as initial therapy in acute stroke. Third Report of an Ad Hoc Consensus Group Meeting. The European Ad Hoc Consensus Group.

PubMed

1998-01-01

Although a considerable body of scientific data is now available on neuroprotection in acute ischaemic stroke, this field is not yet established in clinical practice. At its third meeting, the European Ad Hoc Consensus Group considered the potential for neuroprotection in acute stroke and the practical problems attendant on the existence of a very limited therapeutic window before irreversible brain damage occurs, and came to the following conclusions. NEUROPROTECTANTS IN CLINICAL DEVELOPMENT: Convincing clinical evidence for an efficacious neuroprotective treatment in acute stroke is still required. Caution should be exercised in interpreting and extrapolating experimental results to stroke patients, who are a very heterogeneous group. The limitations of the time windows and the outcome measures chosen in trials of acute stroke therapy have an important influence on the results. The overall distribution of functional outcomes provides more statistical information than the proportion above a threshold outcome value. Neurological outcome should also be assessed. Neuroprotectants should not be tested clinically in phase II or phase III trials in a time window that exceeds those determined in experimental studies. The harmful effects of a drug in humans may override its neuroprotective potential determined in animals. Agents that act at several different levels in the ischaemic cascade may be more effective than those with a single mechanism of action. CURRENT IN-HOSPITAL MANAGEMENT OF ACUTE STROKE: The four major physiological variables that must be monitored and managed are blood pressure, arterial blood gas levels, body temperature, and glycaemia. The effects of controlling these physiological variables have not been studied in prospective trials, though they may all contribute to the outcome of acute ischaemic stroke and affect the duration of the therapeutic window. Optimal physiological parameters are inherently neuroprotective. Trials of new agents for the treatment of acute stroke should aim to maintain these physiological variables as close to normal as possible, and certainly within strictly defined limits. THE PLACE OF NEUROPROTECTANTS IN ACUTE STROKE MANAGEMENT: Stroke patients are a very heterogeneous group with respect to stroke mechanisms and severity, general condition, age and co-morbidities. At the present time, the only firm guideline than can be proposed for patient selection is the need for early admission to enable neuroprotectant and/or thrombolytic treatment to be started as soon as possible within the therapeutic window. The severity of potential side-effects will largely determine who should assess a patient with suspected stroke and initiate treatment. There is little information on which to base the duration of neuroprotectant therapy, and more experimental data are needed. Even if prehospital treatment proves to be feasible, it should not replace comprehensive stroke management in a specialist hospital unit. Clinical trials of neuroprotectants should only be performed in stroke units. The combined approach of restoring blood flow and providing neuroprotection may be the most productive in human stroke, but current clinical trial design will have to change in order to test combination therapy. Important side-effects are those that interfere with any possible benefit or increase mortality. PHARMACO-ECONOMIC ASPECTS OF NEUROPROTECTANTS: The early increase in hospital cost associated with neuroprotectant therapy may be balanced by the shorter length of hospital stay and lesser degree of disability of the surviving patients. The overall direct financial cost is highly dependent on the number of patients eligible for neuroprotectant therapy, which is itself dependent on the length of the therapeutic window and the severity of potential side-effects. A treatment that achieves a good functional outcome is the most cost-effective approach.

Predictors of Thrombolysis Administration in Mild Stroke: Florida-Puerto Rico Collaboration to Reduce Stroke Disparities.

PubMed

Asdaghi, Negar; Wang, Kefeng; Ciliberti-Vargas, Maria A; Gutierrez, Carolina Marinovic; Koch, Sebastian; Gardener, Hannah; Dong, Chuanhui; Rose, David Z; Garcia, Enid J; Burgin, W Scott; Zevallos, Juan Carlos; Rundek, Tatjana; Sacco, Ralph L; Romano, Jose G

2018-03-01

Mild stroke is the most common cause for thrombolysis exclusion in patients acutely presenting to the hospital. Thrombolysis administration in this subgroup is highly variable among different clinicians and institutions. We aim to study the predictors of thrombolysis in patients with mild ischemic stroke in the FL-PR CReSD registry (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities). Among 73 712 prospectively enrolled patients with a final diagnosis of ischemic stroke or TIA from January 2010 to April 2015, we identified 7746 cases with persistent neurological symptoms and National Institutes of Health Stroke Scale ≤5 who arrived within 4 hours of symptom onset. Multilevel logistic regression analysis with generalized estimating equations was used to identify independent predictors of thrombolytic administration in the subgroup of patients without contraindications to thrombolysis. We included 6826 cases (final diagnosis mild stroke, 74.6% and TIA, 25.4%). Median age was 72 (interquartile range, 21); 52.7% men, 70.3% white, 12.9% black, 16.8% Hispanic; and median National Institutes of Health Stroke Scale, 2 (interquartile range, 3). Patients who received thrombolysis (n=1281, 18.7%) were younger (68 versus 72 years), had less vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia), had lower risk of prior vascular disease (myocardial infarction, peripheral vascular disease, and previous stroke), and had a higher presenting median National Institutes of Health Stroke Scale (4 versus 2). In the multilevel multivariable model, early hospital arrival (arrive by 0-2 hours versus ≥3.5 hours; odds ratio [OR], 8.16; 95% confidence interval [CI], 4.76-13.98), higher National Institutes of Health Stroke Scale (OR, 1.87; 95% CI, 1.77-1.98), aphasia at presentation (OR, 1.35; 95% CI, 1.12-1.62), faster door-to-computed tomography time (OR, 1.81; 95% CI, 1.53-2.15), and presenting to an academic hospital (OR, 2.02; 95% CI, 1.39-2.95) were independent predictors of thrombolysis administration. Mild acutely presenting stroke patients are more likely to receive thrombolysis if they are young, white, or Hispanic and arrive early to the hospital with more severe neurological presentation. Identification of predictors of thrombolysis is important in design of future studies to assess the use of thrombolysis for mild stroke. © 2018 American Heart Association, Inc.

Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records.

PubMed

Bell, Steven; Daskalopoulou, Marina; Rapsomaniki, Eleni; George, Julie; Britton, Annie; Bobak, Martin; Casas, Juan P; Dale, Caroline E; Denaxas, Spiros; Shah, Anoop D; Hemingway, Harry

2017-03-22

Objectives  To investigate the association between alcohol consumption and cardiovascular disease at higher resolution by examining the initial lifetime presentation of 12 cardiac, cerebrovascular, abdominal, or peripheral vascular diseases among five categories of consumption. Design  Population based cohort study of linked electronic health records covering primary care, hospital admissions, and mortality in 1997-2010 (median follow-up six years). Setting  CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records). Participants  1 937 360 adults (51% women), aged ≥30 who were free from cardiovascular disease at baseline. Main outcome measures  12 common symptomatic manifestations of cardiovascular disease, including chronic stable angina, unstable angina, acute myocardial infarction, unheralded coronary heart disease death, heart failure, sudden coronary death/cardiac arrest, transient ischaemic attack, ischaemic stroke, intracerebral and subarachnoid haemorrhage, peripheral arterial disease, and abdominal aortic aneurysm. Results  114 859 individuals received an incident cardiovascular diagnosis during follow-up. Non-drinking was associated with an increased risk of unstable angina (hazard ratio 1.33, 95% confidence interval 1.21 to 1.45), myocardial infarction (1.32, 1.24 to1.41), unheralded coronary death (1.56, 1.38 to 1.76), heart failure (1.24, 1.11 to 1.38), ischaemic stroke (1.12, 1.01 to 1.24), peripheral arterial disease (1.22, 1.13 to 1.32), and abdominal aortic aneurysm (1.32, 1.17 to 1.49) compared with moderate drinking (consumption within contemporaneous UK weekly/daily guidelines of 21/3 and 14/2 units for men and women, respectively). Heavy drinking (exceeding guidelines) conferred an increased risk of presenting with unheralded coronary death (1.21, 1.08 to 1.35), heart failure (1.22, 1.08 to 1.37), cardiac arrest (1.50, 1.26 to 1.77), transient ischaemic attack (1.11, 1.02 to 1.37), ischaemic stroke (1.33, 1.09 to 1.63), intracerebral haemorrhage (1.37, 1.16 to 1.62), and peripheral arterial disease (1.35; 1.23 to 1.48), but a lower risk of myocardial infarction (0.88, 0.79 to 1.00) or stable angina (0.93, 0.86 to 1.00). Conclusions  Heterogeneous associations exist between level of alcohol consumption and the initial presentation of cardiovascular diseases. This has implications for counselling patients, public health communication, and clinical research, suggesting a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary. Registration  clinicaltrails.gov (NCT01864031). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Neuroprotective effect of electroacupuncture and upregulation of hypoxia-inducible factor-1α during acute ischaemic stroke in rats.

PubMed

Li, Ce; Zhang, Tingting; Yu, Kewei; Xie, Hongyu; Bai, Yulong; Zhang, Li; Wu, Yi; Wang, Nianhong

2017-10-01

Acupuncture is a traditional method that has been widely used in various fields of medicine with therapeutic effect. However, evidence of effectiveness to support the application of electroacupuncture (EA) during the process of ischaemia is scarce. To investigate dynamic changes in hypoxia-inducible factor (HIF)-1α expression as well as its association with neurological status in rats subjected to acute ischaemic stroke and EA intervention. Forty adult male rats were randomly divided into three groups that received sham surgery (Control group, n=10) or underwent middle cerebral artery occlusion and EA (MCAO+EA group, n=15) or minimal acupuncture as a control treatment (MCAO+MA group, n=15). The rats in the MCAO+EA and MCAO+MA groups received EA or acupuncture without any electrical current, respectively, during 90 min of ischaemia. Rats in the Control group received the same surgical procedure but without MCAO. EA involved electrical stimulation of needles inserted into the quadriceps at 50 Hz frequency and 3 mA current intensity. Neurological status was evaluated on postoperative day 1, and cerebral infarction volume (IV) and HIF-1α expression 24 hours later. Neurological scores were improved and cerebral IV was decreased in the MCAO+EA group compared to the MCAO+MA group (both p<0.05). Moreover, HIF-1α expression was higher in the MCAO+EA group versus the MCAO+MA group (p<0.05). EA enhanced recovery of neurological function, decreased cerebral IV and increased HIF-1α expression in ischaemic rats. Further research is needed to determine whether EA is effective for stroke treatment through the stimulation of muscle contraction. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The influence of blood pressure management on neurological outcome in endovascular therapy for acute ischaemic stroke.

PubMed

Rasmussen, M; Espelund, U S; Juul, N; Yoo, A J; Sørensen, L H; Sørensen, K E; Johnsen, S P; Andersen, G; Simonsen, C Z

2018-06-01

Observational studies have suggested that low blood pressure and blood pressure variability may partially explain adverse neurological outcome after endovascular therapy with general anaesthesia (GA) for acute ischaemic stroke. The aim of this study was to further examine whether blood pressure related parameters during endovascular therapy are associated with neurological outcome. The GOLIATH trial randomised 128 patients to either GA or conscious sedation for endovascular therapy in acute ischaemic stroke. The primary outcome was 90 day modified Rankin Score. The haemodynamic protocol aimed at keeping the systolic blood pressure >140 mm Hg and mean blood pressure >70 mm Hg during the procedure. Blood pressure related parameters of interest included 20% reduction in mean blood pressure; mean blood pressure <70 mm Hg, <80 mm Hg, and <90 mm Hg, respectively; time with systolic blood pressure <140 mm Hg; procedural minimum and maximum mean and systolic blood pressure; mean blood pressure at the time of groin puncture; postreperfusion mean blood pressure; blood pressure variability; and use of vasopressors. Sensitivity analyses were performed in the subgroup of reperfused patients. Procedural average mean and systolic blood pressures were higher in the conscious sedation group (P<0.001). The number of patients with mean blood pressure <70-90 mm Hg and systolic blood pressure <140 mm Hg, blood pressure variability, and use of vasopressors were all higher in the GA group (P<0.001). There was no statistically significant association between any of the examined blood pressure related parameters and the modified Rankin Score in the overall patient population, and in the subgroup of patients with full reperfusion. We found no statistically significant association between blood pressure related parameters during endovascular therapy and neurological outcome. NCT 02317237. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Triglyceride to high-density lipoprotein cholesterol ratio predicts worse outcomes after acute ischaemic stroke.

PubMed

Deng, Q-W; Wang, H; Sun, C-Z; Xing, F-L; Zhang, H-Q; Zuo, L; Gu, Z-T; Yan, F-L

2017-02-01

The effect of the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) on clinical outcomes of acute ischaemic stroke (AIS) patients is unclear. This study sought to determine whether the TG/HDL-C ratio in AIS patients is associated with worse outcomes at 3 months. Acute ischaemic stroke patients who were admitted from 2011 to 2014 were enrolled in this study. TG, total cholesterol (TC), HDL-C and low-density lipoprotein cholesterol (LDL-C) were collected on admission. Three end-points were defined according to the modified Rankin scale (mRS) score at 3 months after symptom onset (excellent outcome, mRS 0-1; good outcome, mRS 0-2; and death, mRS 6). In all, 1006 patients were included (median age 68.5 years; 58.2% male). Higher TG, non-HDL-C and TG/HDL-C were strongly associated with the three end-points after adjustments: excellent [odds ratio (OR) = 1.39, OR 1.89 and OR 2.34, respectively] and good (OR 1.48, OR 2.90 and OR 4.12) outcomes, and death (OR 0.59, OR 0.29 and OR 0.26). According to receiver operating characteristic (ROC) analysis, the best discriminating factor was a TG/HDL-C ≥ 0.87 for excellent outcomes [area under the ROC curve (AUC) 0.596; sensitivity 73.3%; specificity 42.7%] and non-death (AUC 0.674; sensitivity 67.8%; specificity 60.6%) as well as a TG/HDL-C ≥ 1.01 for a good outcome (AUC 0.652; sensitivity 61.6%; specificity 63.2%). Patients with a TG/HDL-C < 0.87 had a 2.94-fold increased risk of death (95% confidence interval 1.89-4.55) compared with patients with a TG/HDL-C ≥ 0.87. A lower TG/HDL-C was independently associated with death and worse outcome at 3 months in AIS. © 2016 EAN.

Mortality after a cerebrovascular event in age-related macular degeneration patients treated with bevacizumab ocular injections.

PubMed

Hanhart, Joel; Comaneshter, Doron S; Vinker, Shlomo

2018-04-16

To analyse the mortality associated with intravitreal injections of bevacizumab for age-related macular degeneration (AMD) in patients previously diagnosed with stroke or transient ischaemic attack (TIA). We reviewed bevacizumab-treated AMD patients with a diagnosis of stroke or TIA prior to their first bevacizumab injection (n = 948). Those patients, naïve to any anti-vascular endothelial growth factor (anti-VEGF) at the time of stroke/TIA, were then compared to age- and gender-matched patients who had a stroke/TIA at the same time and had never been exposed to anti-VEGF. Survival analysis was performed using adjusted Cox regression. The main outcome measure was survival. Adjusted variables were age, smoking, alcohol abuse, hypertension, diabetes mellitus, obesity, ischaemic heart disease, congestive heart failure and liver cancer. Age and gender distribution of bevacizumab-treated patients and controls were similar (mean age: 83.4 versus 83.7 years, p = 0.3; 51.7% males versus 52.5% males, p = 0.7). The adjusted mortality in patients who received bevacizumab within 3 months after stroke/TIA was significantly different than in patients non-exposed to bevacizumab (OR = 6.92, 95%, CI 1.88-25.43, p < 0.01). Within 6 months after stroke/TIA, the difference in adjusted mortality showed a strong trend (OR = 2.00, 95%, CI 0.96-4.16, p = 0.064). Within 12 months, it was insignificant (OR = 1.30, 95%, CI 0.75-2.26, p = 0.348). We found increased mortality within three months after a cerebrovascular event in patients treated with bevacizumab for AMD compared to patients for whom there was no record of a prescription to any anti-VEGF agent. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Hypertension prevalence, awareness, treatment and control in national surveys from England, the USA and Canada, and correlation with stroke and ischaemic heart disease mortality: a cross-sectional study.

PubMed

Joffres, Michel; Falaschetti, Emanuela; Gillespie, Cathleen; Robitaille, Cynthia; Loustalot, Fleetwood; Poulter, Neil; McAlister, Finlay A; Johansen, Helen; Baclic, Oliver; Campbell, Norm

2013-08-30

Comparison of recent national survey data on prevalence, awareness, treatment and control of hypertension in England, the USA and Canada, and correlation of these parameters with each country stroke and ischaemic heart disease (IHD) mortality. Non-institutionalised population surveys. England (2006 n=6873), the USA (2007-2010 n=10 003) and Canada (2007-2009 n=3485) aged 20-79 years. Stroke and IHD mortality rates were plotted against countries' specific prevalence data. Mean systolic blood pressure (SBP) was higher in England than in the USA and Canada in all age-gender groups. Mean diastolic blood pressure (DBP) was similar in the three countries before age 50 and then fell more rapidly in the USA, being the lowest in the USA. Only 34% had a BP under 140/90 mm Hg in England, compared with 50% in the USA and 66% in Canada. Prehypertension and stages 1 and 2 hypertension prevalence figures were the highest in England. Hypertension prevalence (≥140 mm Hg SBP and/or ≥90 mm Hg DBP) was lower in Canada (19·5%) than in the USA (29%) and England (30%). Hypertension awareness was higher in the USA (81%) and Canada (83%) than in England (65%). England also had lower levels of hypertension treatment (51%; USA 74%; Canada 80%) and control (<140/90 mm Hg; 27%; the USA 53%; Canada 66%). Canada had the lowest stroke and IHD mortality rates, England the highest and the rates were inversely related to the mean SBP in each country and strongly related to the blood pressure indicators, the strongest relationship being between low hypertension awareness and stroke mortality. While the current prevention efforts in England should result in future-improved figures, especially at younger ages, these data still show important gaps in the management of hypertension in these countries, with consequences on stroke and IHD mortality.

Clinical and angiographic risk factors for stroke and death within 30 days after carotid endarterectomy and stent-protected angioplasty: a subanalysis of the SPACE study.

PubMed

Stingele, Robert; Berger, Jürgen; Alfke, Karsten; Eckstein, Hans-Henning; Fraedrich, Gustav; Allenberg, Jens; Hartmann, Marius; Ringleb, Peter A; Fiehler, Jens; Bruckmann, H; Hennerici, M; Jansen, O; Klein, G; Kunze, A; Marx, P; Niederkorn, K; Schmiedt, W; Solymosi, L; Zeumer, H; Hacke, W

2008-03-01

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are used to prevent ischaemic stroke in patients with stenosis of the internal carotid artery. Better knowledge of risk factors could improve assignment of patients to these procedures and reduce overall risk. We aimed to assess the risk of stroke or death associated with CEA and CAS in patients with different risk factors. We analysed data from 1196 patients randomised to CAS or CEA in the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE) trial. The primary outcome event was death or ipsilateral stroke (ischaemic or haemorrhagic) with symptoms that lasted more than 24 h between randomisation and 30 days after therapy. Six predefined variables were assessed as potential risk factors for this outcome: age, sex, type of qualifying event, side of intervention, degree of stenosis, and presence of high-grade contralateral stenosis or occlusion. The SPACE trial is registered at Current Controlled Trials, with the international standard randomised controlled trial number ISRCTN57874028. Risk of ipsilateral stroke or death increased significantly with age in the CAS group (p=0.001) but not in the CEA group (p=0.534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2.7% (8/293) in patients who were 68 years old or younger and 10.8% (34/314) in older patients. Other variables did not differ between the CEA and CAS groups. Of the predefined covariates, only age was significantly associated with the risk of stroke and death. The lower risk after CAS versus CEA in patients up to 68 years of age was not detectable in older patients. This finding should be interpreted with caution because of the drawbacks of post-hoc analyses.

Family history of stroke is potentially associated with arterial stiffness in the Japanese population.

PubMed

Uemura, Hirokazu; Katsuura-Kamano, Sakurako; Yamaguchi, Miwa; Nakamoto, Mariko; Hiyoshi, Mineyoshi; Arisawa, Kokichi

2014-12-01

Studies on the association between family history of cardiovascular disease and arterial stiffness are rare. This study evaluated the possible relationship between family history of cardiovascular disease and arterial stiffness in the Japanese population, by measuring brachial-ankle pulse wave velocity (ba-PWV). A total of 1004 eligible subjects (664 men and 340 women) aged 35-69 years, who were enrolled in the baseline survey of a cohort study in Tokushima Prefecture (Japan) and who underwent ba-PWV measurement, were analysed. Information about their lifestyle characteristics and first-degree family histories of ischaemic heart disease (i.e. myocardial infarction or angina pectoris), stroke or hypertension were obtained from a structural self-administered questionnaire. Subjects of both sexes with a family history of stroke showed significantly higher multivariable-adjusted means of ba-PWV than those without that trait (P values were 0.001 in men and 0.002 in women), while those with a family history of ischaemic heart disease did not. Subjects of both sexes with a family history of hypertension showed significantly higher age-adjusted means of ba-PWV than those without that trait, although these differences disappeared after further adjusting for blood pressure or multivariable covariates. When family histories of these diseases were inserted simultaneously into the same model, these results did not alter substantially. A family history of stroke might be associated with increased arterial stiffness, independent of other known atherosclerotic risk factors, including hypertensive elements, in both sexes in the Japanese population. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Predictors and assessment of cognitive dysfunction resulting from ischaemic stroke

PubMed Central

Gottesman, Rebecca F; Hillis, Argye E

2013-01-01

Stroke remains a primary cause of morbidity throughout the world mainly because of its effect on cognition. Individuals can recover from physical disability resulting from stroke, but might be unable to return to their previous occupations or independent life because of cognitive impairments. Cognitive dysfunction ranges from focal deficits, resulting directly from an area of infarction or from hypoperfusion in adjacent tissue, to more global cognitive dysfunction. Global dysfunction is likely to be related to other underlying subclinical cerebrovascular disease, such as white-matter disease or subclinical infarcts. Study of cognitive dysfunction after stroke is complicated by varying definitions and lack of measurement of cognition before stroke. Additionally, stroke can affect white-matter connectivity, so newer imaging techniques, such as diffusion-tensor imaging and magnetisation transfer imaging, that can be used to assess this subclinical injury are important tools in the assessment of cognitive dysfunction after stroke. As research is increasingly focused on the role of preventable risk factors in the development of dementia, the role of stroke in the development of cognitive impairment and dementia could be another target for prevention. PMID:20723846

Anabolic androgenic steroids, an easily forgotten cause of polycythaemia and cerebral infarction.

PubMed

Low, M S Y; Vilcassim, S; Fedele, P; Grigoriadis, G

2016-04-01

Excessive anabolic androgenic steroids (both exogenous and endogenous) are known causes of polycythaemia and ischaemic cardiovascular events. Despite this, they are commonly forgotten in the workup of patients. We report a case of exogenous anabolic androgenic steroid-induced polycythaemia and stroke and explore possible pitfalls for clinicians. © 2016 Royal Australasian College of Physicians.

Thrombolysis and clinical outcome in patients with stroke after implementation of the Tyrol Stroke Pathway: a retrospective observational study.

PubMed

Willeit, Johann; Geley, Theresa; Schöch, Johannes; Rinner, Heinrich; Tür, Andreas; Kreuzer, Hans; Thiemann, Norbert; Knoflach, Michael; Toell, Thomas; Pechlaner, Raimund; Willeit, Karin; Klingler, Natalie; Praxmarer, Silvia; Baubin, Michael; Beck, Gertrud; Berek, Klaus; Dengg, Christian; Engelhardt, Klaus; Erlacher, Thomas; Fluckinger, Thomas; Grander, Wilhelm; Grossmann, Josef; Kathrein, Hermann; Kaiser, Norbert; Matosevic, Benjamin; Matzak, Heinrich; Mayr, Markus; Perfler, Robert; Poewe, Werner; Rauter, Alexandra; Schoenherr, Gudrun; Schoenherr, Hans-Robert; Schinnerl, Adolf; Spiss, Heinrich; Thurner, Theresa; Vergeiner, Gernot; Werner, Philipp; Wöll, Ewald; Willeit, Peter; Kiechl, Stefan

2015-01-01

Intravenous thrombolysis for ischaemic stroke remains underused worldwide. We aimed to assess whether our statewide comprehensive stroke management programme would improve thrombolysis use and clinical outcome in patients. In 2008-09, we designed the Tyrol Stroke Pathway, which provided information campaigns for the public and standardised the entire treatment pathway from stroke onset to outpatient rehabilitation. It was commenced in Tyrol, Austria, as a long-term routine-care programme and aimed to include all patients with stroke in the survey area. We focused on thrombolysis use and outcome in the first full 4 years of implementation (2010-13). We enrolled 4947 (99%) of 4992 patients with ischaemic stroke who were admitted to hospitals in Tyrol; 675 (14%) of the enrollees were treated with alteplase. Thrombolysis administration in Tyrol increased after programme implementation, from 160 of 1238 patients (12·9%, 95% CI 11·1-14·9) in 2010 to 213 of 1266 patients (16·8%, 14·8-19·0) in 2013 (ptrend 2010-13<0·0001). Differences in use of thrombolysis in the nine counties of Tyrol in 2010 (range, 2·2-22·6%) were reduced by 2013 (12·1-22·5%). Median statewide door-to-needle time decreased from 49 min (IQR 35-60) in 2010 to 44 min (29-60) in 2013; symptomatic post-thrombolysis intracerebral haemorrhages occurred in 28 of 675 patients (4·1%, 95% CI 2·8-5·9) during 2010-13. In four Austrian states without similar stroke programmes, thrombolysis administration remained stable or declined between 2010 and 2013 (mean reduction 14·4%, 95% CI 10·9-17·9). Although the 3-month mortality was not affected by our programme (137 [13%] of 1060 patients in 2010 vs 143 [13%] of 1069 patients in 2013), 3-month functional outcome significantly improved (modified Rankin Scale score 0-1 in 375 [40%] of 944 patients in 2010 vs 493 [53%] of 939 in 2013; score 0-2 in 531 [56%] patients in 2010 and 615 [65%] in 2013; ptrend 2010-13<0·0001). During the period of implementation of our comprehensive stroke management programme, thrombolysis administration increased and clinical outcome significantly improved, although mortality did not change. We hope that these results will guide health authorities and stroke physicians elsewhere when implementing similar programmes for patients with stroke. Reformpool of the Tyrolean Health Care Fund. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy and safety of non-immersive virtual reality exercising in stroke rehabilitation (EVREST): a randomised, multicentre, single-blind, controlled trial.

PubMed

Saposnik, Gustavo; Cohen, Leonardo G; Mamdani, Muhammad; Pooyania, Sepideth; Ploughman, Michelle; Cheung, Donna; Shaw, Jennifer; Hall, Judith; Nord, Peter; Dukelow, Sean; Nilanont, Yongchai; De Los Rios, Felipe; Olmos, Lisandro; Levin, Mindy; Teasell, Robert; Cohen, Ashley; Thorpe, Kevin; Laupacis, Andreas; Bayley, Mark

2016-09-01

Non-immersive virtual reality is an emerging strategy to enhance motor performance for stroke rehabilitation. There has been rapid adoption of non-immersive virtual reality as a rehabilitation strategy despite the limited evidence about its safety and effectiveness. Our aim was to compare the safety and efficacy of virtual reality with recreational therapy on motor recovery in patients after an acute ischaemic stroke. In this randomised, controlled, single-blind, parallel-group trial we enrolled adults (aged 18-85 years) who had a first-ever ischaemic stroke and a motor deficit of the upper extremity score of 3 or more (measured with the Chedoke-McMaster scale) within 3 months of randomisation from 14 in-patient stroke rehabilitation units from four countries (Canada [11], Argentina [1], Peru [1], and Thailand [1]). Participants were randomly allocated (1:1) by a computer-generated assignment at enrolment to receive a programme of structured, task-oriented, upper extremity sessions (ten sessions, 60 min each) of either non-immersive virtual reality using the Nintendo Wii gaming system (VRWii) or simple recreational activities (playing cards, bingo, Jenga, or ball game) as add-on therapies to conventional rehabilitation over a 2 week period. All investigators assessing outcomes were masked to treatment assignment. The primary outcome was upper extremity motor performance measured by total time to complete the Wolf Motor Function Test (WMFT) at the end of the 2 week intervention period, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NTC01406912. The study was done between May 12, 2012, and Oct 1, 2015. We randomly assigned 141 patients: 71 received VRWii therapy and 70 received recreational activity. 121 (86%) patients (59 in the VRWii group and 62 in the recreational activity group) completed the final assessment and were included in the primary analysis. Each group improved WMFT performance time relative to baseline (decrease in median time from 43·7 s [IQR 26·1-68·0] to 29·7 s [21·4-45·2], 32·0% reduction for VRWii vs 38·0 s [IQR 28·0-64·1] to 27·1 s [21·2-45·5], 28·7% reduction for recreational activity). Mean time of conventional rehabilitation during the trial was similar between groups (VRWii, 373 min [SD 322] vs recreational activity, 397 min [345]; p=0·70) as was the total duration of study intervention (VRWii, 528 min [SD 155] vs recreational activity, 541 min [142]; p=0·60). Multivariable analysis adjusted for baseline WMFT score, age, sex, baseline Chedoke-McMaster, and stroke severity revealed no significant difference between groups in the primary outcome (adjusted mean estimate of difference in WMFT: 4·1 s, 95% CI -14·4 to 22·6). There were three serious adverse events during the trial, all deemed to be unrelated to the interventions (seizure after discharge and intracerebral haemorrhage in the recreational activity group and heart attack in the VRWii group). Overall incidences of adverse events and serious adverse events were similar between treatment groups. In patients who had a stroke within the 3 months before enrolment and had mild-to-moderate upper extremity motor impairment, non-immersive virtual reality as an add-on therapy to conventional rehabilitation was not superior to a recreational activity intervention in improving motor function, as measured by WMFT. Our study suggests that the type of task used in motor rehabilitation post-stroke might be less relevant, as long as it is intensive enough and task-specific. Simple, low-cost, and widely available recreational activities might be as effective as innovative non-immersive virtual reality technologies. Heart and Stroke Foundation of Canada and Ontario Ministry of Health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy and safety of non-immersive virtual reality exercising in stroke rehabilitation (EVREST): a randomised, multicentre, single-blind, controlled trial

PubMed Central

Saposnik, Gustavo; Cohen, Leonardo G; Mamdani, Muhammad; Pooyania, Sepideth; Ploughman, Michelle; Cheung, Donna; Shaw, Jennifer; Hall, Judith; Nord, Peter; Dukelow, Sean; Nilanont, Yongchai; De los Rios, Felipe; Olmos, Lisandro; Levin, Mindy; Teasell, Robert; Cohen, Ashley; Thorpe, Kevin; Laupacis, Andreas; Bayley, Mark

2016-01-01

Summary Background Non-immersive virtual reality is an emerging strategy to enhance motor performance for stroke rehabilitation. There has been rapid adoption of non-immersive virtual reality as a rehabilitation strategy despite the limited evidence about its safety and effectiveness. Our aim was to compare the safety and efficacy of virtual reality with recreational therapy on motor recovery in patients after an acute ischaemic stroke. Methods In this randomised, controlled, single-blind, parallel-group trial we enrolled adults (aged 18–85 years) who had a first-ever ischaemic stroke and a motor deficit of the upper extremity score of 3 or more (measured with the Chedoke-McMaster scale) within 3 months of randomisation from 14 in-patient stroke rehabilitation units from four countries (Canada [11], Argentina [1], Peru [1], and Thailand [1]). Participants were randomly allocated (1:1) by a computer-generated assignment at enrolment to receive a programme of structured, task-oriented, upper extremity sessions (ten sessions, 60 min each) of either non-immersive virtual reality using the Nintendo Wii gaming system (VRWii) or simple recreational activities (playing cards, bingo, Jenga, or ball game) as add-on therapies to conventional rehabilitation over a 2 week period. All investigators assessing outcomes were masked to treatment assignment. The primary outcome was upper extremity motor performance measured by total time to complete the Wolf Motor Function Test (WMFT) at the end of the 2 week intervention period, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NTC01406912. Findings The study was done between May 12, 2012, and Oct 1, 2015. We randomly assigned 141 patients: 71 received VRWii therapy and 70 received recreational activity. 121 (86%) patients (59 in the VRWii group and 62 in the recreational activity group) completed the final assessment and were included in the primary analysis. Each group improved WMFT performance time relative to baseline (decrease in median time from 43·7 s [IQR 26·1–68·0] to 29·7 s [21·4–45·2], 32·0% reduction for VRWii vs 38·0 s [IQR 28·0–64·1] to 27·1 s [21·2–45·5], 28·7% reduction for recreational activity). Mean time of conventional rehabilitation during the trial was similar between groups (VRWii, 373 min [SD 322] vs recreational activity, 397 min [345] ; p=0·70) as was the total duration of study intervention (VRWii, 528 min [SD 155] vs recreational activity, 541 min [142]; p=0·60). Multivariable analysis adjusted for baseline WMFT score, age, sex, baseline Chedoke-McMaster, and stroke severity revealed no significant difference between groups in the primary outcome (adjusted mean estimate of difference in WMFT: 4·1 s, 95% CI −14·4 to 22·6). There were three serious adverse events during the trial, all deemed to be unrelated to the interventions (seizure after discharge and intracerebral haemorrhage in the recreational activity group and heart attack in the VRWii group). Overall incidences of adverse events and serious adverse events were similar between treatment groups. Interpretation In patients who had a stroke within the 3 months before enrolment and had mild-to-moderate upper extremity motor impairment, non-immersive virtual reality as an add-on therapy to conventional rehabilitation was not superior to a recreational activity intervention in improving motor function, as measured by WMFT. Our study suggests that the type of task used in motor rehabilitation post-stroke might be less relevant, as long as it is intensive enough and task-specific. Simple, low-cost, and widely available recreational activities might be as effective as innovative non-immersive virtual reality technologies. Funding Heart and Stroke Foundation of Canada and Ontario Ministry of Health. PMID:27365261

Study protocol of the YOU CALL--WE CALL TRIAL: impact of a multimodal support intervention after a "mild" stroke.

PubMed

Rochette, Annie; Korner-Bitensky, Nicol; Bishop, Duane; Teasell, Robert; White, Carole; Bravo, Gina; Côté, Robert; Lachaine, Jean; Green, Teri; Lebrun, Louise-Hélène; Lanthier, Sylvain; Kapral, Moira; Wood-Dauphinee, Sharon

2010-01-06

More than 60% of new strokes each year are "mild" in severity and this proportion is expected to rise in the years to come. Within our current health care system those with "mild" stroke are typically discharged home within days, without further referral to health or rehabilitation services other than advice to see their family physician. Those with mild stroke often have limited access to support from health professionals with stroke-specific knowledge who would typically provide critical information on topics such as secondary stroke prevention, community reintegration, medication counselling and problem solving with regard to specific concerns that arise. Isolation and lack of knowledge may lead to a worsening of health problems including stroke recurrence and unnecessary and costly health care utilization.The purpose of this study is to assess the effectiveness, for individuals who experience a first "mild" stroke, of a sustainable, low cost, multimodal support intervention (comprising information, education and telephone support)--"WE CALL" compared to a passive intervention (providing the name and phone number of a resource person available if they feel the need to)--"YOU CALL", on two primary outcomes: unplanned-use of health services for negative events and quality of life. We will recruit 384 adults who meet inclusion criteria for a first mild stroke across six Canadian sites. Baseline measures will be taken within the first month after stroke onset. Participants will be stratified according to comorbidity level and randomised to one of two groups: YOU CALL or WE CALL. Both interventions will be offered over a six months period. Primary outcomes include unplanned use of heath services for negative event (frequency calendar) and quality of life (EQ-5D and Quality of Life Index). Secondary outcomes include participation level (LIFE-H), depression (Beck Depression Inventory II) and use of health services for health promotion or prevention (frequency calendar). Blind assessors will gather data at mid-intervention, end of intervention and one year follow up. If effective, this multimodal intervention could be delivered in both urban and rural environments. For example, existing infrastructure such as regional stroke centers and existing secondary stroke prevention clinics, make this intervention, if effective, deliverable and sustainable. ISRCTN95662526.

Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis.

PubMed

Whiteley, William N; Emberson, Jonathan; Lees, Kennedy R; Blackwell, Lisa; Albers, Gregory; Bluhmki, Erich; Brott, Thomas; Cohen, Geoff; Davis, Stephen; Donnan, Geoffrey; Grotta, James; Howard, George; Kaste, Markku; Koga, Masatoshi; von Kummer, Rüdiger; Lansberg, Maarten G; Lindley, Richard I; Lyden, Patrick; Olivot, Jean Marc; Parsons, Mark; Toni, Danilo; Toyoda, Kazunori; Wahlgren, Nils; Wardlaw, Joanna; Del Zoppo, Gregory J; Sandercock, Peter; Hacke, Werner; Baigent, Colin

2016-08-01

Randomised trials have shown that alteplase improves the odds of a good outcome when delivered within 4·5 h of acute ischaemic stroke. However, alteplase also increases the risk of intracerebral haemorrhage; we aimed to determine the proportional and absolute effects of alteplase on the risks of intracerebral haemorrhage, mortality, and functional impairment in different types of patients. We used individual patient data from the Stroke Thrombolysis Trialists' (STT) meta-analysis of randomised trials of alteplase versus placebo (or untreated control) in patients with acute ischaemic stroke. We prespecified assessment of three classifications of intracerebral haemorrhage: type 2 parenchymal haemorrhage within 7 days; Safe Implementation of Thrombolysis in Stroke Monitoring Study's (SITS-MOST) haemorrhage within 24-36 h (type 2 parenchymal haemorrhage with a deterioration of at least 4 points on National Institutes of Health Stroke Scale [NIHSS]); and fatal intracerebral haemorrhage within 7 days. We used logistic regression, stratified by trial, to model the log odds of intracerebral haemorrhage on allocation to alteplase, treatment delay, age, and stroke severity. We did exploratory analyses to assess mortality after intracerebral haemorrhage and examine the absolute risks of intracerebral haemorrhage in the context of functional outcome at 90-180 days. Data were available from 6756 participants in the nine trials of intravenous alteplase versus control. Alteplase increased the odds of type 2 parenchymal haemorrhage (occurring in 231 [6·8%] of 3391 patients allocated alteplase vs 44 [1·3%] of 3365 patients allocated control; odds ratio [OR] 5·55 [95% CI 4·01-7·70]; absolute excess 5·5% [4·6-6·4]); of SITS-MOST haemorrhage (124 [3·7%] of 3391 vs 19 [0·6%] of 3365; OR 6·67 [4·11-10·84]; absolute excess 3·1% [2·4-3·8]); and of fatal intracerebral haemorrhage (91 [2·7%] of 3391 vs 13 [0·4%] of 3365; OR 7·14 [3·98-12·79]; absolute excess 2·3% [1·7-2·9]). However defined, the proportional increase in intracerebral haemorrhage was similar irrespective of treatment delay, age, or baseline stroke severity, but the absolute excess risk of intracerebral haemorrhage increased with increasing stroke severity: for SITS-MOST intracerebral haemorrhage the absolute excess risk ranged from 1·5% (0·8-2·6%) for strokes with NIHSS 0-4 to 3·7% (2·1-6·3%) for NIHSS 22 or more (p=0·0101). For patients treated within 4·5 h, the absolute increase in the proportion (6·8% [4·0% to 9·5%]) achieving a modified Rankin Scale of 0 or 1 (excellent outcome) exceeded the absolute increase in risk of fatal intracerebral haemorrhage (2·2% [1·5% to 3·0%]) and the increased risk of any death within 90 days (0·9% [-1·4% to 3·2%]). Among patients given alteplase, the net outcome is predicted both by time to treatment (with faster time increasing the proportion achieving an excellent outcome) and stroke severity (with a more severe stroke increasing the absolute risk of intracerebral haemorrhage). Although, within 4·5 h of stroke, the probability of achieving an excellent outcome with alteplase treatment exceeds the risk of death, early treatment is especially important for patients with severe stroke. UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial.

PubMed

Bath, Philip M; Woodhouse, Lisa J; Appleton, Jason P; Beridze, Maia; Christensen, Hanne; Dineen, Robert A; Duley, Lelia; England, Timothy J; Flaherty, Katie; Havard, Diane; Heptinstall, Stan; James, Marilyn; Krishnan, Kailash; Markus, Hugh S; Montgomery, Alan A; Pocock, Stuart J; Randall, Marc; Ranta, Annemarei; Robinson, Thompson G; Scutt, Polly; Venables, Graham S; Sprigg, Nikola

2018-03-03

Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67-1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05-3·16, p<0·0001). Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice. National Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Predictors and Outcomes of Dysphagia Screening After Acute Ischemic Stroke.

PubMed

Joundi, Raed A; Martino, Rosemary; Saposnik, Gustavo; Giannakeas, Vasily; Fang, Jiming; Kapral, Moira K

2017-04-01

Guidelines advocate screening all acute stroke patients for dysphagia. However, limited data are available regarding how many and which patients are screened and how failing a swallowing screen affects patient outcomes. We sought to evaluate predictors of receiving dysphagia screening after acute ischemic stroke and outcomes after failing a screening test. We used the Ontario Stroke Registry from April 1, 2010, to March 31, 2013, to identify patients hospitalized with acute ischemic stroke and determine predictors of documented dysphagia screening and outcomes after failing the screening test, including pneumonia, disability, and death. Among 7171 patients, 6677 patients were eligible to receive dysphagia screening within 72 hours, yet 1280 (19.2%) patients did not undergo documented screening. Patients with mild strokes were significantly less likely than those with more severe strokes to have documented screening (adjusted odds ratio, 0.51; 95% confidence interval [CI], 0.41-0.64). Failing dysphagia screening was associated with poor outcomes, including pneumonia (adjusted odds ratio, 4.71; 95% CI, 3.43-6.47), severe disability (adjusted odds ratio, 5.19; 95% CI, 4.48-6.02), discharge to long-term care (adjusted odds ratio, 2.79; 95% CI, 2.11-3.79), and 1-year mortality (adjusted hazard ratio, 2.42; 95% CI, 2.09-2.80). Associations were maintained in patients with mild strokes. One in 5 patients with acute ischemic stroke did not have documented dysphagia screening, and patients with mild strokes were substantially less likely to have documented screening. Failing dysphagia screening was associated with poor outcomes, including in patients with mild strokes, highlighting the importance of dysphagia screening for all patients with acute ischemic stroke. © 2017 American Heart Association, Inc.

The global burden of disease attributable to low consumption of fruit and vegetables: implications for the global strategy on diet.

PubMed Central

Lock, Karen; Pomerleau, Joceline; Causer, Louise; Altmann, Dan R.; McKee, Martin

2005-01-01

OBJECTIVE: We estimated the global burden of disease attributable to low consumption of fruit and vegetables, an increasingly recognized risk factor for cardiovascular disease and cancer, and compared its impact with that of other major risk factors for disease. METHODS: The burden of disease attributable to suboptimal intake of fruit and vegetables was estimated using information on fruit and vegetable consumption in the population, and on its association with six health outcomes (ischaemic heart disease, stroke, stomach, oesophageal, colorectal and lung cancer). Data from both sources were stratified by sex, age and by 14 geographical regions. FINDINGS: The total worldwide mortality currently attributable to inadequate consumption of fruit and vegetables is estimated to be up to 2.635 million deaths per year. Increasing individual fruit and vegetable consumption to up to 600 g per day (the baseline of choice) could reduce the total worldwide burden of disease by 1.8%, and reduce the burden of ischaemic heart disease and ischaemic stroke by 31% and 19% respectively. For stomach, oesophageal, lung and colorectal cancer, the potential reductions were 19%, 20%, 12% and 2%, respectively. CONCLUSION: This study shows the potentially large impact that increasing fruit and vegetable intake could have in reducing many noncommunicable diseases. It highlights the need for much greater emphasis on dietary risk factors in public health policy in order to tackle the rise in noncommunicable diseases worldwide, and suggests that the proposed intersectoral WHO/FAO fruit and vegetable promotion initiative is a crucial component in any global diet strategy. PMID:15744402

Head Position in Stroke Trial (HeadPoST)--sitting-up vs lying-flat positioning of patients with acute stroke: study protocol for a cluster randomised controlled trial.

PubMed

Muñoz-Venturelli, Paula; Arima, Hisatomi; Lavados, Pablo; Brunser, Alejandro; Peng, Bin; Cui, Liying; Song, Lily; Billot, Laurent; Boaden, Elizabeth; Hackett, Maree L; Heritier, Stephane; Jan, Stephen; Middleton, Sandy; Olavarría, Verónica V; Lim, Joyce Y; Lindley, Richard I; Heeley, Emma; Robinson, Thompson; Pontes-Neto, Octavio; Natsagdorj, Lkhamtsoo; Lin, Ruey-Tay; Watkins, Caroline; Anderson, Craig S

2015-06-05

Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥ 30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke. We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥ 30°) head position as a 'business as usual' stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period. HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke. ClinicalTrials.gov identifier: NCT02162017 (date of registration: 27 April 2014); ANZCTR identifier: ACTRN12614000483651 (date of registration: 9 May 2014). Protocol version and date: version 2.2, 19 June 2014.

Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study.

PubMed

Ricci, Cristian; Wood, Angela; Muller, David; Gunter, Marc J; Agudo, Antonio; Boeing, Heiner; van der Schouw, Yvonne T; Warnakula, Samantha; Saieva, Calogero; Spijkerman, Annemieke; Sluijs, Ivonne; Tjønneland, Anne; Kyrø, Cecilie; Weiderpass, Elisabete; Kühn, Tilman; Kaaks, Rudolf; Sánchez, Maria-Jose; Panico, Salvatore; Agnoli, Claudia; Palli, Domenico; Tumino, Rosario; Engström, Gunnar; Melander, Olle; Bonnet, Fabrice; Boer, Jolanda M A; Key, Timothy J; Travis, Ruth C; Overvad, Kim; Verschuren, W M Monique; Quirós, J Ramón; Trichopoulou, Antonia; Papatesta, Eleni-Maria; Peppa, Eleni; Iribas, Conchi Moreno; Gavrila, Diana; Forslund, Ann-Sofie; Jansson, Jan-Håkan; Matullo, Giuseppe; Arriola, Larraitz; Freisling, Heinz; Lassale, Camille; Tzoulaki, Ioanna; Sharp, Stephen J; Forouhi, Nita G; Langenberg, Claudia; Saracci, Rodolfo; Sweeting, Michael; Brennan, Paul; Butterworth, Adam S; Riboli, Elio; Wareham, Nick J; Danesh, John; Ferrari, Pietro

2018-05-29

To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. Multicentre case-cohort study. A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Hospital financing of ischaemic stroke: determinants of funding and usefulness of DRG subcategories based on severity of illness.

PubMed

Dewilde, Sarah; Annemans, Lieven; Pincé, Hilde; Thijs, Vincent

2018-05-11

Several Western and Arab countries, as well as over 30 States in the US are using the "All-Patient Refined Diagnosis-Related Groups" (APR-DRGs) with four severity-of-illness (SOI) subcategories as a model for hospital funding. The aim of this study is to verify whether this is an adequate model for funding stroke hospital admissions, and to explore which risk factors and complications may influence the amount of funding. A bottom-up analysis of 2496 ischaemic stroke admissions in Belgium compares detailed in-hospital resource use (including length of stay, imaging, lab tests, visits and drugs) per SOI category and calculates total hospitalisation costs. A second analysis examines the relationship between the type and location of the index stroke, medical risk factors, patient characteristics, comorbidities and in-hospital complications on the one hand, and the funding level received by the hospital on the other hand. This dataset included 2513 hospitalisations reporting on 35,195 secondary diagnosis codes, all medically coded with the International Classification of Disease (ICD-9). Total costs per admission increased by SOI (€3710-€16,735), with severe patients costing proportionally more in bed days (86%), and milder patients costing more in medical imaging (24%). In all resource categories (bed days, medications, visits and imaging and laboratory tests), the absolute utilisation rate was higher among severe patients, but also showed more variability. SOI 1-2 was associated with vague, non-specific stroke-related ICD-9 codes as primary diagnosis (71-81% of hospitalisations). 24% hospitalisations had, in addition to the primary diagnosis, other stroke-related codes as secondary diagnoses. Presence of lung infections, intracranial bleeding, severe kidney disease, and do-not-resuscitate status were each associated with extreme SOI (p < 0.0001). APR-DRG with SOI subclassification is a useful funding model as it clusters stroke patients in homogenous groups in terms of resource use. The data on medical care utilisation can be used with unit costs from other countries with similar healthcare set-ups to 1) assess stroke-related hospital funding versus actual costs; 2) inform economic models on stroke prevention and treatment. The data on diagnosis codes can be used to 3) understand which factors influence hospital funding; 4) raise awareness about medical coding practices.

Performance of stroke risk scores in older people with atrial fibrillation not taking warfarin: comparative cohort study from BAFTA trial.

PubMed

Hobbs, F D R; Roalfe, A K; Lip, G Y H; Fletcher, K; Fitzmaurice, D A; Mant, J

2011-06-23

To compare the predictive power of the main existing and recently proposed schemes for stratification of risk of stroke in older patients with atrial fibrillation. Comparative cohort study of eight risk stratification scores. Trial of thromboprophylaxis in stroke, the Birmingham Atrial Fibrillation in the Aged (BAFTA) trial. 665 patients aged 75 or over with atrial fibrillation based in the community who were randomised to the BAFTA trial and were not taking warfarin throughout or for part of the study period. Events rates of stroke and thromboembolism. 54 (8%) patients had an ischaemic stroke, four (0.6%) had a systemic embolism, and 13 (2%) had a transient ischaemic attack. The distribution of patients classified into the three risk categories (low, moderate, high) was similar across three of the risk stratification scores (revised CHADS(2), NICE, ACC/AHA/ESC), with most patients categorised as high risk (65-69%, n = 460-457) and the remaining classified as moderate risk. The original CHADS(2) (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke) score identified the lowest number as high risk (27%, n = 180). The incremental risk scores of CHADS(2), Rietbrock modified CHADS(2), and CHA(2)DS(2)-VASc (CHA(2)DS(2)-Vascular disease, Age 65-74 years, Sex) failed to show an increase in risk at the upper range of scores. The predictive accuracy was similar across the tested schemes with C statistic ranging from 0.55 (original CHADS(2)) to 0.62 (Rietbrock modified CHADS(2)), with all except the original CHADS(2) predicting better than chance. Bootstrapped paired comparisons provided no evidence of significant differences between the discriminatory ability of the schemes. Based on this single trial population, current risk stratification schemes in older people with atrial fibrillation have only limited ability to predict the risk of stroke. Given the systematic undertreatment of older people with anticoagulation, and the relative safety of warfarin versus aspirin in those aged over 70, there could be a pragmatic rationale for classifying all patients over 75 as "high risk" until better tools are available.

Cognitive outcome following unilateral arterial ischaemic stroke in childhood: effects of age at stroke and lesion location.

PubMed

Westmacott, Robyn; Askalan, Rand; MacGregor, Daune; Anderson, Peter; Deveber, Gabrielle

2010-04-01

Plasticity in the developing brain is a controversial issue. Although language and motor function often recover remarkably well following early brain injury, recent evidence suggests that damage to the developing brain results in significant long-term neuropsychological impairment. Our aim was to investigate the relationship among age at injury, lesion location and intellectual outcome. Using age-appropriate Wechsler scales of intellectual ability, we explored this issue by evaluating a large group (n=145) of children (89 males, 56 females) who experienced unilateral arterial ischaemic stroke during the perinatal period (diagnosed mean 73d, SD 29d), between the ages of 1 month and 5 years (mean 2y 10mo, SD 1y 9mo), or between the ages of 6 and 16 years (mean 11y 1mo SD 3y 6mo). The mean age at assessment was 8 years (SD 3y 10mo) in the perinatal group, 7 years 5 months (SD 2y 9mo) in the 1 month to 5 years group, and 12 years 5 months (SD 3y 9mo) in the 6 to 16 years group. The mean time interval between stroke and assessment was 8 years (SD 18d) for perinatal, 4 years 6 months (SD 1y 5mo) for 1 month to 5 years, and 1 year 4 months (SD 2y 9mo) for 6 to 16 years. The relationship between age at stroke and lesion location (subcortical, cortical, or combined) as it pertains to cognitive outcome was also examined. Measures of overall intelligence, verbal ability, working memory, and processing speed were significantly lower in children who had had a stroke than in the normative sample (all z>2.5, all p<0.01). The perinatal group performed more poorly than the other two groups on most cognitive measures, regardless of lesion location. The combined lesion location group performed more poorly than those with damage to either cortical or subcortical areas alone. Further investigation revealed different periods of peak vulnerability for subcortical lesions (perinatal) and cortical lesions (1mo-5y). Lesion location modulates the relationship between age at stroke and cognitive outcome.

Assessment of mitral apparatus in patients with acute inferoposterior myocardial infarction and ischaemic mitral regurgitation with two-dimensional echocardiography from anatomically correct imaging planes.

PubMed

Mėlinytė, Karolina; Valuckiene, Živile; Jurkevičius, Renaldas

2017-01-01

Ischaemic mitral regurgitation (IMR) is associated with adverse prognosis after myocardial infarction (MI) as a result of left ventricular remodelling and geometric deformation of the mitral apparatus (MA). The aim of this study was to assess MA from anatomically correct imaging planes in acute inferoposterior MI and IMR. Ninety-three patients with no structural cardiac valve abnormalities and the first acute inferoposterior MI were prospectively enrolled into the study. Two-dimensional transthoracic echocardiography for MA assessment was performed within 48 h of presentation after reperfusion therapy. Based on the degree of mitral regurgitation (MR), patients were divided into either a no significant MR (NMR) group (n = 52 with no or mild, grade 0-I MR) or an IMR group (n = 41 with grade ≥ 2 MR). The control group consisted of 45 healthy individuals. Ischaemic MR was related with dilatation of the left ventricle chambers, decrease in ejection fraction, increase in mitral annulus diameter and area, and changes in subvalvular apparatus when compared with the NMR group or healthy individuals. Ischaemic MR in acute inferoposterior MI is related with worse lesions in MA geometry that cause insufficiency of mitral valve function.

Circulating brain derived neurotrophic factor (BDNF) and frequency of BDNF positive T cells in peripheral blood in human ischemic stroke: Effect on outcome.

PubMed

Chan, Adeline; Yan, Jun; Csurhes, Peter; Greer, Judith; McCombe, Pamela

2015-09-15

The aim of this study was to measure the levels of circulating BDNF and the frequency of BDNF-producing T cells after acute ischaemic stroke. Serum BDNF levels were measured by ELISA. Flow cytometry was used to enumerate peripheral blood leukocytes that were labelled with antibodies against markers of T cells, T regulatory cells (Tregs), and intracellular BDNF. There was a slight increase in serum BDNF levels after stroke. There was no overall difference between stroke patients and controls in the frequency of CD4(+) and CD8(+) BDNF(+) cells, although a subgroup of stroke patients showed high frequencies of these cells. However, there was an increase in the percentage of BDNF(+) Treg cells in the CD4(+) population in stroke patients compared to controls. Patients with high percentages of CD4(+) BDNF(+) Treg cells had a better outcome at 6months than those with lower levels. These groups did not differ in age, gender or initial stroke severity. Enhancement of BDNF production after stroke could be a useful means of improving neuroprotection and recovery after stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

Post-Thalamic Stroke Movement Disorders: A Systematic Review.

PubMed

Gupta, Navnika; Pandey, Sanjay

2018-06-05

After a stroke, movement disorders are rare manifestations mainly affecting the deep structures of the brain like the basal ganglia (44%) and thalamus (37%), although there have been case studies of movement disorders in strokes affecting the cerebral cortex also. This review aims to delineate the various movement disorders seen in association with thalamic strokes and tries to identify the location of the nuclei affected in each of the described movement disorders. Cases were identified through a search of PubMed database using different search terms related to post-thalamic stroke movement disorders and a secondary search of references of identified articles. We reviewed 2,520 research articles and only 86 papers met the inclusion criteria. Cases were included if they met criteria for post-thalamic stroke movement disorders. Case-cohort studies were also reviewed and will be discussed further. Key Messages: The most common post-stroke abnormal movement disorder reported in our review was dystonia followed by hemiataxia. There was a higher association between ischaemic stroke and movement disorder. Acute onset movement disorders were more common than delayed. The posterolateral thalamus was most commonly involved in post-thalamic stroke movement disorders. © 2018 S. Karger AG, Basel.

Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study.

PubMed

Lacey, Ben; Lewington, Sarah; Clarke, Robert; Kong, Xiang Ling; Chen, Yiping; Guo, Yu; Yang, Ling; Bennett, Derrick; Bragg, Fiona; Bian, Zheng; Wang, Shaojie; Zhang, Hua; Chen, Junshi; Walters, Robin G; Collins, Rory; Peto, Richard; Li, Liming; Chen, Zhengming

2018-06-01

The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China. 512 891 adults (59% women) aged 30-79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure. During a median follow-up of 9 years (IQR 8-10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40-79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120-180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28-1·34]) and ischaemic stroke (1·30 [1·29-1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65-1·71]). HRs for vascular disease were twice as steep at ages 40-49 years than at ages 70-79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35-1·44]) and diabetes (1·14 [1·12-1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (<80 years of age) annually. Among adults in China, systolic blood pressure was continuously related to major vascular disease with no evidence of a threshold down to 120 mm Hg. Unlike previous studies in high-income countries, blood pressure was more strongly associated with intracerebral haemorrhage than with ischaemic stroke. Even small reductions in mean blood pressure at a population level could be expected to have a major impact on vascular morbidity and mortality. UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, and the National Science Foundation of China. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Impact of Mild Stroke on the Quality of Life of Spouses

ERIC Educational Resources Information Center

Tellier, Myriam; Rochette, Annie; Lefebvre, Helene

2011-01-01

Clients with mild stroke may present subtle deficits that have an impact on complex activities and roles. The purpose of this study was to explore the perceived quality of life of spouses, 3 months after the client with stroke was discharged to go home from acute care. A qualitative design based on a constructivist paradigm was used. Interviews…

Airplane stroke syndrome.

PubMed

Humaidan, Hani; Yassi, Nawaf; Weir, Louise; Davis, Stephen M; Meretoja, Atte

2016-07-01

Only 37 cases of stroke during or soon after long-haul flights have been published to our knowledge. In this retrospective observational study, we searched the Royal Melbourne Hospital prospective stroke database and all discharge summaries from 1 September 2003 to 30 September 2014 for flight-related strokes, defined as patients presenting with stroke within 14days of air travel. We hypothesised that a patent foramen ovale (PFO) is an important, but not the only mechanism, of flight-related stroke. We describe the patient, stroke, and flight characteristics. Over the study period, 131 million passengers arrived at Melbourne airport. Our centre admitted 5727 stroke patients, of whom 42 (0.73%) had flight-related strokes. Flight-related stroke patients were younger (median age 65 versus 73, p<0.001), had similar stroke severity, and received intravenous thrombolysis more often than non-flight-related stroke patients. Seven patients had flight-related intracerebral haemorrhage. The aetiology of the ischaemic strokes was cardioembolic in 14/35 (40%), including seven patients with confirmed PFO, one with atrial septal defect, four with atrial fibrillation, one with endocarditis, and one with aortic arch atheroma. Paradoxical embolism was confirmed in six patients. Stroke related to air travel is a rare occurrence, less than one in a million. Although 20% of patients had a PFO, distribution of stroke aetiologies was diverse and was not limited to PFO and paradoxical embolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure.

PubMed

Ivanes, Fabrice; Susen, Sophie; Mouquet, Frédéric; Pigny, Pascal; Cuilleret, François; Sautière, Karine; Collet, Jean-Philippe; Beygui, Farzin; Hennache, Bernadette; Ennezat, Pierre Vladimir; Juthier, Françis; Richard, Florence; Dallongeville, Jean; Hillaert, Marieke A; Doevendans, Pieter A; Jude, Brigitte; Bertrand, Michel; Montalescot, Gilles; Van Belle, Eric

2012-01-01

Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI. In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001). Our results demonstrate that, in patients with CAD but without heart failure or acute MI, the level of aldosterone is strongly and independently associated with mortality and the occurrence of acute ischaemic events.

mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia

PubMed Central

Yang, Guo-Shuai; Zhou, Xiao-Yan; An, Xue-Fang; Liu, Xuan-Jun; Zhang, Yan-Jun; Yu, Dan

2018-01-01

Stroke is considered an underlying etiology of the development of seizures. Stroke leads to glucose and oxygen deficiency in neurons, resulting in brain dysfunction and injury. Mild hypothermia is a therapeutic strategy to inhibit stroke-induced seizures, which may be associated with the regulation of energy metabolism of the brain. Mammalian target of rapamycin (mTOR) signaling and solute carrier family 2, facilitated glucose transporter member (GLUT)-1 are critical for energy metabolism. Furthermore, mTOR overactivation and GLUT-1 deficiency are associated with genetically acquired seizures. It has been hypothesized that mTOR and GLUT-1 may additionally be involved in seizures elicited by stroke. The present study established global cerebral ischemia (GCI) models of rats. Convulsive seizure behaviors frequently occurred during the first and the second days following GCI, which were accompanied with seizure discharge reflected in the EEG monitor. Expression of phosphor (p)-mTOR and GLUT-1 were upregulated in the cerebral cortex and hippocampus, as evidenced by immunohistochemistry and western blot analyses. Mild hypothermia and/or rapamycin (mTOR inhibitor) treatments reduced the number of epileptic attacks, seizure severity scores and seizure discharges, thereby alleviating seizures induced by GCI. Mild hypothermia and/or rapamycin treatments reduced phosphorylation levels of mTOR and the downstream effecter p70S6 in neurons, and the amount of GLUT-1 in the cytomembrane of neurons. The present study revealed that mTOR is involved in stroke-induced seizures and the anti-seizure effect of mild hypothermia. The role of GLUT-1 in stroke-elicited seizures appears to be different from the role in seizures induced by other reasons. Further studies are necessary in order to elucidate the exact function of GLUT-1 in stroke-elicited seizures. PMID:29484389

Stroke type differentiation using spectrally constrained multifrequency EIT: evaluation of feasibility in a realistic head model.

PubMed

Malone, Emma; Jehl, Markus; Arridge, Simon; Betcke, Timo; Holder, David

2014-06-01

We investigate the application of multifrequency electrical impedance tomography (MFEIT) to imaging the brain in stroke patients. The use of MFEIT could enable early diagnosis and thrombolysis of ischaemic stroke, and therefore improve the outcome of treatment. Recent advances in the imaging methodology suggest that the use of spectral constraints could allow for the reconstruction of a one-shot image. We performed a simulation study to investigate the feasibility of imaging stroke in a head model with realistic conductivities. We introduced increasing levels of modelling errors to test the robustness of the method to the most common sources of artefact. We considered the case of errors in the electrode placement, spectral constraints, and contact impedance. The results indicate that errors in the position and shape of the electrodes can affect image quality, although our imaging method was successful in identifying tissues with sufficiently distinct spectra.

The vascular neural network—a new paradigm in stroke pathophysiology

PubMed Central

Zhang, John H.; Badaut, Jerome; Tang, Jiping; Obenaus, Andre; Hartman, Richard; Pearce, William J.

2013-01-01

The concept of the neurovascular unit as the key brain component affected by stroke is controversial, because current definitions of this entity neglect mechanisms that control perfusion and reperfusion of arteries and arterioles upstream of the cerebral microcirculation. Indeed, although definitions vary, many researchers consider the neurovascular unit to be restricted to endothelial cells, neurons and glia within millimetres of the cerebral capillary microcirculation. This Perspectives article highlights the roles of vascular smooth muscle, endothelial cells and perivascular innervation of cerebral arteries in the initiation and progression of, and recovery from, ischaemic stroke. The concept of the vascular neural network—which includes cerebral arteries, arterioles, and downstream neuronal and glial cell types and structures—is introduced as the fundamental component affected by stroke pathophysiology. The authors also propose that the vascular neural network should be considered the main target for future therapeutic intervention after cerebrovascular insult. PMID:23070610

Thrombolysis for stroke in pregnancy at 39 weeks gestation with a subsequent normal delivery.

PubMed

Ritchie, Joanne; Lokman, Mariam; Panikkar, Jane

2015-08-11

Stroke during pregnancy is fortunately a rare event, however, it can have severe consequences, with 9.5% of all maternal deaths being related to stroke. The most common presentation is an ischaemic stroke. There has been much debate as to the correct treatment for such cases' and whether thrombolysis can be used safely in pregnancy. Our case describes a 28-year-old woman with a previous normal vaginal delivery presenting in her third trimester with a sudden onset of dense left hemiparesis. She was successfully treated with alteplase, an intravenous recombinant tissue-type plasminogen activator, and made a full recovery after normal delivery of a healthy infant. This case report highlights one of the first documented successful outcomes from thrombolysis for this condition in the UK and may help inform future management of these women. 2015 BMJ Publishing Group Ltd.

Impact of posterior communicating artery on basilar artery steno-occlusive disease.

PubMed

Hong, J M; Choi, J Y; Lee, J H; Yong, S W; Bang, O Y; Joo, I S; Huh, K

2009-12-01

Acute brainstem infarction with basilar artery (BA) occlusive disease is the most fatal type of all ischaemic strokes. This report investigates the prognostic impact of the posterior communicating artery (PcoA) and whether its anatomy is a safeguard or not. Consecutive patients who had acute brainstem infarction with at least 50% stenosis of BA upon CT angiography (CTA) were studied. The configuration of PcoA was divided into two groups upon CTA: "textbook" group (invisible PcoA with good P1 and P2 segment) and "fetal-variant of PcoA" group (only visible PcoA with absent P1 segment). Baseline demographics, radiological findings and stroke mechanisms were analysed. A multiple regression analysis was performed to predict clinical outcome at 30 days (modified Rankin disability Scale (mRS

Transient ischaemic attack clinic: an evaluation of diagnoses and clinical decision making.

PubMed

Lee, Will; Frayne, Judith

2015-04-01

The diagnosis of transient ischaemic attack (TIA) is based largely on the patient's symptom recall and clinical judgement. This decision-making process is highly subjective and the inter-observer reliability of TIA diagnosis is at best moderate, even among neurologists. The aim of this study is to examine the presenting features and final diagnoses of referrals to a TIA clinic and to evaluate characteristics that favoured the diagnosis of TIA over other TIA "mimics". Consecutive new referrals to a tertiary metropolitan hospital TIA clinic over a 9month period were examined. Characteristics between TIA and non-TIA diagnoses were compared and analysed. Eighty-two patients were recruited. Eighteen (22%) were given a final diagnosis of TIA or stroke. Major alternative diagnoses included migraine (n=17, 21%), presyncope/syncope (n=13, 16%) and anxiety (n=7, 9%). Four (5%) patients had unclassifiable symptoms with no clear final diagnosis. Mean age was 67±a standard deviation of 17years and patients diagnosed with TIA/stroke were on average older than those with non-TIA diagnoses (77±10 versus 64±17years, p=0.003). A diagnosis of TIA/stroke was favoured in the presence of moderate to severe weakness (p=0.032), dysphasia (p=0.037) or dysarthria (p=0.005). Unclassifiable symptoms (for example, palpitations, confusion, headache) were reported in 27 patients (33%) and their presence favoured non-TIA diagnoses (p=0.0003). TIA constituted a minority of the referrals to our clinic. Accurate clinical diagnosis of TIA facilitates early stroke prevention and avoids unnecessary investigations and prescriptions. Attempts to improve diagnostic accuracy of TIA should target improving the education and awareness of frontline medical practitioners. Copyright © 2014 Elsevier Ltd. All rights reserved.

Repetitive transcranial magnetic stimulation for depression after basal ganglia ischaemic stroke: protocol for a multicentre randomised double-blind placebo-controlled trial.

PubMed

Tang, Ying; Chen, Aimin; Zhu, Shuzhen; Yang, Li; Zhou, Jiyuan; Pan, Suyue; Shao, Min; Zhao, Lianxu

2018-02-03

Studies suggest that repetitive transcranial magnetic stimulation (rTMS) is effective for the treatment of depression and promotes the repair of white matter. This study aims to assess the effectiveness of rTMS in treating depression after basal ganglia ischaemic stroke and to examine whether such effects are related to restoration of white matter integrity. Sixty-six participants will be recruited from Zhujiang Hospital, Nanfang Hospital and Sichuan Bayi Rehabilitation Hospital and randomised in a 1:1 ratio to receive active rTMS treatment or sham rTMS treatment in addition to routine supportive treatments. The data will be collected at 0, 2 and 4 weeks after the commencement of treatment. The primary outcome is the measurement of 24-item Hamilton Depression Rating Scale scores, and the secondary outcomes include diffusion tensor imaging results and the results of neuropsychological tests including the National Institutes of Health Stroke Scale, Activities of Daily Living Scale, Montreal Cognitive Assessment, Clinical Global Impressions scales, Aphasia Battery in Chinese, Social Support Revalued Scale and Medical Coping Modes Questionnaire. This study has been approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University. The findings will be disseminated by publication in a peer-reviewed journal and by presentation at international conferences. NCT03159351. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Upper Limb Kinematics in Stroke and Healthy Controls Using Target-to-Target Task in Virtual Reality.

PubMed

Hussain, Netha; Alt Murphy, Margit; Sunnerhagen, Katharina S

2018-01-01

Kinematic analysis using virtual reality (VR) environment provides quantitative assessment of upper limb movements. This technique has rarely been used in evaluating motor function in stroke despite its availability in stroke rehabilitation. To determine the discriminative validity of VR-based kinematics during target-to-target pointing task in individuals with mild or moderate arm impairment following stroke and in healthy controls. Sixty-seven participants with moderate (32-57 points) or mild (58-65 points) stroke impairment as assessed with Fugl-Meyer Assessment for Upper Extremity were included from the Stroke Arm Longitudinal study at the University of Gothenburg-SALGOT cohort of non-selected individuals within the first year of stroke. The stroke groups and 43 healthy controls performed the target-to-target pointing task, where 32 circular targets appear one after the other and disappear when pointed at by the haptic handheld stylus in a three-dimensional VR environment. The kinematic parameters captured by the stylus included movement time, velocities, and smoothness of movement. The movement time, mean velocity, and peak velocity were discriminative between groups with moderate and mild stroke impairment and healthy controls. The movement time was longer and mean and peak velocity were lower for individuals with stroke. The number of velocity peaks, representing smoothness, was also discriminative and significantly higher in both stroke groups (mild, moderate) compared to controls. Movement trajectories in stroke more frequently showed clustering (spider's web) close to the target indicating deficits in movement precision. The target-to-target pointing task can provide valuable and specific information about sensorimotor impairment of the upper limb following stroke that might not be captured using traditional clinical scale. The trial was registered with register number NCT01115348 at clinicaltrials.gov, on May 4, 2010. URL: https://clinicaltrials.gov/ct2/show/NCT01115348.

Percutaneous closure of patent foramen ovale in patients with cryptogenic embolism: a network meta-analysis.

PubMed

Stortecky, Stefan; da Costa, Bruno R; Mattle, Heinrich P; Carroll, John; Hornung, Marius; Sievert, Horst; Trelle, Sven; Windecker, Stephan; Meier, Bernhard; Jüni, Peter

2015-01-07

Up to 40% of ischaemic strokes are cryptogenic. A strong association between cryptogenic stroke and the prevalence of patent foramen ovale (PFO) suggests paradoxical embolism via PFO as a potential cause. Randomized trials failed to demonstrate superiority of PFO closure over medical therapy. Randomized trials comparing percutaneous PFO closure against medical therapy or devices head-to-head published or presented by March 2013 were identified through a systematic search. We performed a network meta-analysis to determine the effectiveness and safety of PFO closure with different devices when compared with medical therapy. We included four randomized trials (2963 patients with 9309 patient-years). Investigated devices were Amplatzer (AMP), STARFlex (STF), and HELEX (HLX). Patients allocated to PFO closure with AMP were less likely to experience a stroke than patients allocated to medical therapy [rate ratio (RR) 0.39; 95% CI: 0.17-0.84]. No significant differences were found for STF (RR 1.01; 95% CI: 0.44-2.41), and HLX (RR, 0.71; 95% CI: 0.17-2.78) when compared with medical therapy. The probability to be best in preventing strokes was 77.1% for AMP, 20.9% for HLX, 1.7% for STF, and 0.4% for medical therapy. No significant differences were found for transient ischaemic attack and death. The risk of new-onset atrial fibrillation was more pronounced for STF (RR 7.67; 95% CI: 3.25-19.63), than AMP (RR 2.14; 95% CI: 1.00-4.62) and HLX (RR 1.33; 95%-CI 0.33-4.50), when compared with medical therapy. The effectiveness of PFO closure depends on the device used. PFO closure with AMP appears superior to medical therapy in preventing strokes in patients with cryptogenic embolism. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Modelling the role of dietary habits and eating behaviours on the development of acute coronary syndrome or stroke: aims, design, and validation properties of a case-control study.

PubMed

Kastorini, Christina-Maria; Milionis, Haralampos J; Goudevenos, John A; Panagiotakos, Demosthenes B

2010-09-14

In this paper the methodology and procedures of a case-control study that will be developed for assessing the role of dietary habits and eating behaviours on the development of acute coronary syndrome and stroke is presented. Based on statistical power calculations, 1000 participants will be enrolled; of them, 250 will be consecutive patients with a first acute coronary event, 250 consecutive patients with a first ischaemic stroke, and 500 population-based healthy subjects (controls), age and sex matched to the cases. Socio-demographic, clinical, dietary, psychological, and other lifestyle characteristics will be measured. Dietary habits and eating behaviours will be evaluated with a special questionnaire that has been developed for the study.

Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF.

PubMed

Hankey, Graeme J; Patel, Manesh R; Stevens, Susanna R; Becker, Richard C; Breithardt, Günter; Carolei, Antonio; Diener, Hans-Christoph; Donnan, Geoffrey A; Halperin, Jonathan L; Mahaffey, Kenneth W; Mas, Jean-Louis; Massaro, Ayrton; Norrving, Bo; Nessel, Christopher C; Paolini, John F; Roine, Risto O; Singer, Daniel E; Wong, Lawrence; Califf, Robert M; Fox, Keith A A; Hacke, Werner

2012-04-01

In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0-3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio [HR] 0·94, 95% CI 0·77-1·16) and those without (1·44%vs 1·88%; 0·77, 0·58-1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87-1·07) and those without (16·69%vs 15·19%; 1·10, 0·99-1·21; interaction p=0·08). There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF. Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evidence, education and practice.

PubMed

Kaste, Markku

2006-01-01

Stroke causes greater loss of quality-adjusted life years than any other disease and is also one of the most expensive disorders. The burden of stroke will increase in the future due to change in the age structure of populations. We have a vast body of evidence on how to prevent stroke and how to treat stroke patients. Good examples are treatment of hypertension, antithrombotic agents and carotid surgery in stroke prevention, thrombolysis in ischaemic stroke and stroke unit care for all stroke patients. We only have to translate scientific evidence into daily practice. If some pieces are missing, it is our duty to generate them through research. While taking part in randomized clinical trials (RCTs), the discipline, an essential part of RCTs, will improve the daily care of all stroke patients. Besides RCTs there are many other sources of scientific evidence for stroke management, one of which is the European Stroke Initiative (EUSI). The mission of the EUSI is to improve and optimize stroke management in Europe through education and by offering best practice guidelines. Also national and international societies and organizations play an important role in providing education. The human factor is one obstacle to more successful stroke management because to be more effective we must change our own clinical routine. We can make a difference by applying available evidence to our daily practice. Copyright (c) 2006 S. Karger AG, Basel.

Balneotherapy in treatment of spastic upper limb after stroke.

PubMed

Erceg-Rukavina, Tatjana; Stefanovski, Mihajlo

2015-02-01

After stroke, spasticity is often the main problem that prevents functional recovery. Pain occurs in up to 70% of patients during the first year post-stroke. A total of 70 patients (30 female and 45 male) mean age (65.67) participated in prospective, controlled study. ischaemic stroke, developed spasticity of upper limb, post-stroke interval <6 months. contraindications for balneotherapy and inability to follow commands. Experimental group (Ex) (n=35) was treated with sulphurous baths (31°-33°C) and controlled group (Co) with taped water baths, during 21 days. All patients were additionally treated with kinesitherapy and cryotherapy. The outcome was evaluated using Modified Ashworth scale for spasticity and VAS scale for pain. The significance value was sat at p<0.05. To find out the effects of balneotherapy with sulphurous bath on spasticity and pain in affected upper limb. Reduction in tone of affected upper limb muscles was significant in Ex group (p<0.05). Pain decreased significantly in Ex-group (p<0.01). Our results show that balneotherapy with sulphurous water reduces spasticity and pain significantly and can help in treatment of post-stroke patients.

Neuroprotective properties of citicoline: facts, doubts and unresolved issues.

PubMed

Grieb, Pawel

2014-03-01

Citicoline is the generic name of the pharmaceutical substance that chemically is cytidine-5'-diphosphocholine (CDP-choline), which is identical to the natural intracellular precursor of phospholipid phosphatidylcholine. Following injection or ingestion, citicoline is believed to undergo quick hydrolysis and dephosphorylation to yield cytidine and choline, which then enter the brain separately and are used to resynthesize CDP-choline inside brain cells. Neuroprotective activity of citicoline has been repeatedly shown in preclinical models of brain ischaemia and trauma, but two recent, large, pivotal clinical trials have revealed no benefits in ischaemic stroke and traumatic brain injury. However, the substance seems to be beneficial in some slowly advancing neurodegenerative disorders such as glaucoma and mild vascular cognitive impairment. This paper critically discusses issues related to the clinical pharmacology of citicoline, including its pharmacokinetics/biotransformation and pharmacodynamics/mode of action. It is concluded that at present, there is no adequate description of the mechanism(s) of the pharmacological actions of this substance. The possibility should be considered and tested that, in spite of apparently fast catabolism, the intact citicoline molecule or the phosphorylated intermediate products of its hydrolysis, cytidine monophosphate and phosphocholine, are pharmacologically active.

A practical approach to acute hemiparesis in children.

PubMed

Bhate, Sanjay; Ganesan, Vijeya

2015-08-01

Acute hemiparesis in children is a common clinical syndrome presenting to a variety of care settings. The recognition and the differential diagnosis is challenging, particularly in young children. Arterial ischaemic stroke (AIS) is the primary diagnosis to be considered as this requires emergency investigations and management; however, there are several conditions collectively described as 'stroke mimics' that need consideration. Accurate diagnosis is essential for appropriate management. Clinical data combined with neuroimaging are important for accurate diagnosis and management. This review and the accompanying illustrative case vignettes suggest a practical approach to differential diagnosis and management of children presenting with acute hemiparesis. © 2015 Mac Keith Press.

Transient ischaemic attacks clinics provide equivalent and more efficient care than early in-hospital assessment.

PubMed

Martínez-Martínez, M M; Martínez-Sánchez, P; Fuentes, B; Cazorla-García, R; Ruiz-Ares, G; Correas-Callero, E; Lara-Lara, M; Díez-Tejedor, E

2013-02-01

Clinics for early management of transient ischaemic attacks (TIAs) have been developed in some stroke centres, resulting in reduced recurrence rates compared to appointment-based outpatient management, thus saving on hospitalization. We analysed the care process, recurrence rates and economic impact of the first year of work in our early-management TIA clinic and compared these with our previous in-hospital study protocols for low- and moderate-risk TIA patients. This was a prospective evaluation of the management of low- to moderate-risk TIA patients, comparing a new TIA clinic model (2010) with a previous hospitalization model (2009). Demographic data, vascular risk factor profiles, diagnostic test performance, secondary prevention measures, final aetiological diagnoses and cerebrovascular recurrences at 7 and 90 days were compared between in-hospital and TIA clinic assessed patients. We also carried out an economic comparison of the costs of each model's process. Two hundred and eleven low- to moderate-risk TIA patients were included, of whom 40.8% were hospitalized. There were no differences between the TIA clinic assessed and in-hospital assessed patients in terms of risk factor diagnosis and secondary prevention measures. The stroke recurrence rate (2.4% vs. 1.2%; P = 0.65) was low and similar for both groups (CI 95%, 0.214-20.436; P = 0.52). Cost per patient was €393.28 for clinic versus €1931.18 for in-hospital management. Outpatient management resulted in a 77.8% reduction in hospitalizations. Transient ischaemic attacks clinics are efficient for the early management of low- to moderate-risk TIA patients compared to in-hospital assessment, with no higher recurrence rates and at almost one-fifth the cost. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Critical role of matrix metalloprotease-9 in chronic high fat diet-induced cerebral vascular remodelling and increase of ischaemic brain injury in mice†

PubMed Central

Deng, Jiao; Zhang, Junfeng; Feng, Chenzhuo; Xiong, Lize; Zuo, Zhiyi

2014-01-01

Aims About one-third of American adults and 20% of teenagers are obese. Obesity and its associated metabolic disturbances including hyperlipidaemia are risk factors for cardiovascular diseases including stroke. They can worsen neurological outcome after stroke. We determined whether obesity and hyperlipidaemia could induce cerebral vascular remodelling via matrix metalloproteases (MMP) and whether this remodelling affected neurological outcome after brain ischaemia. Methods and results Six-week-old male CD1, C57BL/6J, and MMP-9−/− mice were fed regular diet (RD) or high-fat diet (HFD) for 10 weeks. They were subjected to vascular casting or a 90 min middle cerebral arterial occlusion (MCAO). Mice on HFD were heavier and had higher blood glucose and lipid levels than those on RD. HFD-fed CD1 and C57BL/6J mice had an increased cerebral vascular tortuosity index and decreased inner diameters of the middle cerebral arterial root. HFD increased microvessel density in CD1 mouse cerebral cortex. After MCAO, CD1 and C57BL/6J mice on HFD had a bigger infarct volume, more severe brain oedema and blood–brain barrier damage, higher haemorrhagic transformation rate, greater haemorrhagic volume, and worse neurological function. HFD increased MMP-9 activity in the ischaemic and non-ischaemic brain tissues. Although HFD increased the body weights, blood glucose, and lipid levels in the MMP-9−/− mice on a C57BL/6J genetic background, the HFD-induced cerebral vascular remodelling and worsening of neurological outcome did not occur in these mice. Conclusion HFD induces cerebral vascular remodelling and worsens neurological outcome after transient focal brain ischaemia. MMP-9 activation plays a critical role in these HFD effects. PMID:24935427

Incidence and outcome of subtypes of ischaemic stroke: initial results from the north East melbourne stroke incidence study (NEMESIS).

PubMed

Dewey, Helen M; Sturm, Jonathan; Donnan, Geoffrey A; Macdonell, Richard A L; McNeil, John J; Thrift, Amanda G

2003-01-01

Information about the incidence and outcome of stroke subtypes is necessary to understand the likely impact of stroke prevention and treatment strategies. The purpose of this study was to determine the incidence and outcome of subtypes of cerebral infarction (CI). All strokes occurring in a population of 133816 in Melbourne, Australia, during a 12-month period of 1996 and 1997 were identified and cases of CI subtyped according to the Oxfordshire Community Stroke Project classification. 276 'first-ever-in-a-lifetime' stroke cases were registered. CI accounted for 72% of cases. Annual incidence rates per 100000 persons adjusted to the 'world' population were 11 (95% CI, 4-18) for TACI, 25 (95% CI, 15-35) for PACI, 17 (95% CI, 9-25) for POCI and 18 (95% CI, 10-26) for LACI. 28-day case fatality was highest for TACI (35%; 95% CI, 19-51%) and first year recurrence rate highest for PACI (17%; 95% CI, 8-26%). TACI had the poorest functional outcome at 3 and 12 months. These findings are similar to those of two previous studies conducted in the northern hemisphere. Copyright 2003 S. Karger AG, Basel

Recurrence risk after noncardioembolic mild ischemic stroke in a Japanese population.

PubMed

Kono, Yuji; Yamada, Sumio; Kamisaka, Kenta; Araki, Amane; Fujioka, Yusuke; Yasui, Keizo; Hasegawa, Yasuhiro; Koike, Yasuo

2011-01-01

This study aimed to identify the recurrence rate and risk factors or clinical variables predictive of vascular events after mild ischemic stroke (IS). From December 2006 to September 2007, patients with acute IS with a modified Rankin Scale of 0∼1 were consecutively enrolled in this study. Variables including sex, family history of vascular disease, age, height, weight, stroke subtype, blood pressure, lipid profile, fasting glucose, HbA1c, smoking, alcohol consumption, exercise habits, waist circumference, ankle-brachial pressure index, salt intake and physical activity were assessed. The primary outcome was stroke recurrence or other vascular events such as myocardial infarction, angina pectoris, and peripheral artery disease. Survival curves were calculated by Kaplan-Meier survival analysis, and hazard ratios for recurrence were determined by univariate and multivariate Cox proportional hazards regression models. A total of 102 mild IS patients (78 men and 24 women, mean age 64 years) were successfully followed for 3 years. Of those 102 patients, 25 (24.5%) had stroke recurrence, and 4 (3.9%) had a coronary event. Among the variables studied, abnormal ankle-brachial pressure index, metabolic syndrome, stroke subtypes, salt intake and poor lifestyle management were significant independent predictors of stroke recurrence or cardiovascular events. In mild IS patients within 3 years after onset, not only pathophysiological factors but also lifestyle factors can aid in the identification of patients at high risk for recurrence. Copyright © 2011 S. Karger AG, Basel.

Progress in reducing the burden of stroke.

PubMed

Chalmers, J; Chapman, N

2001-12-01

1. The burden of stroke worldwide is growing rapidly, driven by an ageing population and by the rapid rate of urbanization and industrialization in the developing world. There are approximately 5 million fatal and 15 million non-fatal strokes each year and over 50 million survivors of stroke alive, worldwide, today. 2. The most important determinant of stroke risk is blood pressure, with a strong, continuous relationship between the level of the systolic and diastolic pressures and the risk of initial and recurrent stroke, in both Western and Asian populations. 3. Randomized clinical trials have clearly demonstrated that blood pressure lowering reduces the risk of initial stroke by 35-40% in hypertensive patients; but, until recently, there was no conclusive evidence that blood pressure lowering was effective in the secondary prevention of stroke. 4. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) has provided definitive evidence that blood pressure lowering in patients with previous stroke or transient ischaemic attack (TIA) reduces the incidence of secondary stroke by 28%, of major vascular events by 26% and of major coronary events by 26%. These reductions were all magnified by approximately 50% in a subgroup of patients in whom the angiotensin-converting enzyme inhibitor perindopril was routinely combined with the diuretic indapamide. 5. Successful global implementation of a treatment with perindopril and indapamide in patients with a history of stroke or TIA would markedly reduce the burden of stroke and could avert between 0.5 and one million strokes each year, worldwide.

Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials.

PubMed

Emberson, Jonathan; Lees, Kennedy R; Lyden, Patrick; Blackwell, Lisa; Albers, Gregory; Bluhmki, Erich; Brott, Thomas; Cohen, Geoff; Davis, Stephen; Donnan, Geoffrey; Grotta, James; Howard, George; Kaste, Markku; Koga, Masatoshi; von Kummer, Ruediger; Lansberg, Maarten; Lindley, Richard I; Murray, Gordon; Olivot, Jean Marc; Parsons, Mark; Tilley, Barbara; Toni, Danilo; Toyoda, Kazunori; Wahlgren, Nils; Wardlaw, Joanna; Whiteley, William; del Zoppo, Gregory J; Baigent, Colin; Sandercock, Peter; Hacke, Werner

2014-11-29

Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase. We did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 3-6 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality. Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3·0 h resulted in a good outcome for 259 (32·9%) of 787 patients who received alteplase versus 176 (23·1%) of 762 who received control (OR 1·75, 95% CI 1·35-2·27); delay of greater than 3·0 h, up to 4·5 h, resulted in good outcome for 485 (35·3%) of 1375 versus 432 (30·1%) of 1437 (OR 1·26, 95% CI 1·05-1·51); and delay of more than 4·5 h resulted in good outcome for 401 (32·6%) of 1229 versus 357 (30·6%) of 1166 (OR 1·15, 95% CI 0·95-1·40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [6·8%] of 3391 vs 44 [1·3%] of 3365, OR 5·55, 95% CI 4·01-7·70, p<0·0001; SITS-MOST definition 124 [3·7%] vs 19 [0·6%], OR 6·67, 95% CI 4·11-10·84, p<0·0001) and of fatal intracranial haemorrhage within 7 days (91 [2·7%] vs 13 [0·4%]; OR 7·14, 95% CI 3·98-12·79, p<0·0001). The relative increase in fatal intracranial haemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (17·9%) in the alteplase group versus 556 (16·5%) in the control group (hazard ratio 1·11, 95% CI 0·99-1·25, p=0·07). Taken together, therefore, despite an average absolute increased risk of early death from intracranial haemorrhage of about 2%, by 3-6 months this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 3·0 h and about 5% for patients treated after 3·0 h, up to 4·5 h. Irrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, alteplase significantly improves the overall odds of a good stroke outcome when delivered within 4·5 h of stroke onset, with earlier treatment associated with bigger proportional benefits. UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh. Copyright © 2014 Emberson et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.

[Cryptogenic stroke - patent foramen ovale - migraine with aura: incidental triad or significant relationship? Part II].

PubMed

Łukasik, Maria; Kozubski, Wojciech

2012-01-01

In the second part of the paper, we discuss the relationship between migraine with aura and either patent foramen ovale (PFO) or stroke. The results of the studies suggest that PFO with right-to-left shunt is more prevalent among patients suffering from migraine with aura. Moreover, migraine with aura is a risk factor for ischaemic stroke in women and the risk increases when they have additional vascular risk factors such as taking oral contraception and smoking. However, the pathophysiology of these phenomena remains hypothetical. The most frequently reported theory suggests paradoxical embolism as a mechanism of the above-mentioned pathologies. In this paper we compare the pros and cons of the general theories. We discuss the percutaneous closure of PFO in patients with migraine, regarding the benefit/risk ratio.

Weather types and strokes in the Augsburg region (Southern Germany)

NASA Astrophysics Data System (ADS)

Beck, Christoph; Ertl, Michael; Giemsa, Esther; Jacobeit, Jucundus; Naumann, Markus; Seubert, Stefanie

2017-04-01

Strokes are one of the leading causes of morbidity and mortality worldwide and the main reason for longterm care dependency in Germany. Concerning the economical impact on patients and healthcare systems it is of particular importance to prevent this disease as well as to improve the outcome of the affected persons. Beside the primary well-known risk factors like hypertension, cigarette smoking, physical inactivity and others, also weather seems to have pronounced influence on the occurrence and frequency of strokes. Previous studies most often focused on effects of singular meteorological variables like ambient air temperature, air pressure or humidity. An advanced approach is to link the entire suite of daily weather elements classified to air mass- or weather types to cerebrovascular morbidity or mortality. In a joint pilot study bringing together climatologists, environmental scientists and physicians from the University of Augsburg and the clinical centre Augsburg, we analysed relationships between singular meteorological parameters as well as combined weather effects (e.g. weather types) and strokes in the urban area of Augsburg and the surrounding rural region. A total of 17.501 stroke admissions to Neurological Clinic and Clinical Neurophysiology at Klinikum Augsburg between 2006 and 2015 are classified to either "ischaemic" (16.354) or "haemorrhagic" (1.147) subtype according to etiology (based on the International Classification of Diseases - 10th Revision). Spearman correlations between daily frequencies of ischaemic and haemorrhagic strokes and singular atmospheric parameters (T, Tmin, Tmax, air pressure, humidity etc.) measured at the DWD (German weather service) meteorological station at Augsburg Muehlhausen are rather low. However, higher correlations are achieved when considering sub-samples of "homogenous weather conditions" derived from synoptic circulation classifications: e.g. within almost all of 10 types arising from a classification of central European mean sea level pressure fields into "Großwettertypes" (Beck 2000) the relationships between meteorological variables and stroke frequencies are increasing. Mainly temperature variables (Tmin, Tmax, Tmean) appear to be important particularly in winter and summer. Moreover distinct correlations of similar magnitude are obtained with other variables like wind speed or precipitation for specific weather types (e.g. westerly type). In how far these initial findings do really point to additional health impacts beyond temperature effects is subject of ongoing work.

Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.

PubMed

Easton, J Donald; Lopes, Renato D; Bahit, M Cecilia; Wojdyla, Daniel M; Granger, Christopher B; Wallentin, Lars; Alings, Marco; Goto, Shinya; Lewis, Basil S; Rosenqvist, Mårten; Hanna, Michael; Mohan, Puneet; Alexander, John H; Diener, Hans-Christoph

2012-06-01

In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA. The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. Bristol-Myers Squibb and Pfizer. Copyright © 2012 Elsevier Ltd. All rights reserved.

Plasma Exosomal miRNA-122-5p and miR-300-3p as Potential Markers for Transient Ischaemic Attack in Rats.

PubMed

Li, Dong-Bin; Liu, Jing-Li; Wang, Wei; Luo, Xiu-Mei; Zhou, Xia; Li, Jin-Pin; Cao, Xiao-Li; Long, Xiao-Hong; Chen, Jia-Gui; Qin, Chao

2018-01-01

Background: Differentiation of transient ischaemic attack (TIA) from ischaemic stroke within the thrombolysis time window is difficult. Although TIA may be diagnosed within this window, the latest imaging technologies are complex and costly. Serum markers, which are non-invasive, rapid and economic, are used for diagnosis and prognosis of various diseases. Exosome-derived miRNA markers for TIA are unknown. Methods: We examined focal brain ischaemia produced by occlusion of the middle cerebral artery (MCAo) for 5 min, 10 min, and 2 h in rats. Exosomal miRNAs with consistent trends in cerebrospinal fluid (CSF) and plasma were identified by deep sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). The areas under the curve (AUC) of the receiver operating characteristic (ROC) curve were used to evaluate the diagnostic accuracy of these miRNAs for TIA in rats. Results: Rno-miR-122-5p and rno-miR-300-3p were selected. Plasma exosomal rno-miR-122-5p was significantly downregulated in 10 min ischaemic rats compared with control and 5 min plasma. Plasma exosomal rno-miR-300-3p was significantly upregulated in 5 min ischaemic rats compared with control, 10 min and 2 h rats. Plasma and CSF levels of these miRNAs were correlated. ROC analysis showed high AUC values for rno-miR-122-5p (0.960) and rno-miR-300-3p (0.970) in the 10 and 5 min rats, respectively, compared with controls. Conclusions: Plasma exosomal rno-miR-122-5p and rno-miR-300-3p may be blood-based TIA biomarkers.

[Broad ischemic stroke revealing infective endocarditis in a young patient: about a case].

PubMed

Ravelosaona, Fanomezantsoa Noella; Razafimahefa, Julien; Randrianasolo, Rahamefy Odilon; Rakotoarimanana, Solofonirina; Tehindrazanarivelo, Djacoba Alain

2016-01-01

Broad ischemic stroke is mainly due to a cardiac embolus or to an atheromatous plaque. In young subjects, one of the main causes of ischemic stroke (broad ischemic stroke in particolar) is embolic heart disease including infective endocarditis. Infective endocarditis is a contraindication against the anticoagulant therapy (which is indicated for the treatment of embolic heart disease complicated by ischemic stroke). One neurologic complications of infective endocarditis is ischemic stroke which often occurs in multiple sites. We here report the case of a 44-year old man with afebrile acute onset of severe left hemiplegia associated with a sistolic mitral murmur, who had fever in hospital on day 5 with no other obvious source of infection present. Brain CT scan showed full broad ischaemic stroke of the right middle cerebral artery territory and doppler ultrasound, performed after stroke onset, showed infective endocarditis affecting the small mitral valve. He was treated with 4 weeks of antibiotic therapy without anticoagulant therapy ; evolution was marked by the disappearance of mitral valve vegetations and by movement sequelae involving the left side of the body. In practical terms, our problem was the onset of the fever which didn't accompany or pre-exist patient's deficit, leading us to the misdiagnosis of ischemic stroke of cardioembolic origin. This case study underlines the importance of doppler ultrasound, in the diagnosis of all broad ischemic strokes, especially superficial, before starting anticoagulant therapy.

Validation of a basic neurosonology laboratory for detecting cervical carotid artery stenosis.

PubMed

de la Cruz Cosme, C; Dawid Milner, M S; Ojeda Burgos, G; Gallardo Tur, A; Márquez Martínez, M; Segura, T

2017-03-24

Most of the cases of ischaemic stroke in our setting are of atherothrombotic origin. Detecting intracranial and cervical carotid artery stenosis in patients with ischaemic stroke is therefore essential. Ultrasonography has become the tool of choice for diagnosing carotid artery stenosis because it is both readily accessibility and reliable. However, use of this technique must be validated in each laboratory. The purpose of this study is to validate Doppler ultrasound in our laboratory as a means of detecting severe carotid artery stenosis. We conducted an observational descriptive study to evaluate diagnostic tests. The results from transcranial and cervical carotid Doppler ultrasound scans conducted by neurologists were compared to those from carotid duplex scans performed by radiologists in patients diagnosed with stroke. Arteriography was considered the gold standard (MR angiography, CT angiography, or conventional arteriography). Our sample included 228 patients. Transcranial and cervical carotid Doppler ultrasound showed a sensitivity of 95% and specificity of 100% for detection of carotid artery stenosis > 70%, whereas carotid duplex displayed a sensitivity of 87% and a specificity of 94%. Transcranial carotid Doppler ultrasound achieved a sensitivity of 78% and a specificity of 98% for detection of intracranial stenosis. Doppler ultrasound in our neurosonology laboratory was found to be a useful diagnostic tool for detecting cervical carotid artery stenosis and demonstrated superiority to carotid duplex despite the lack of B-mode. Furthermore, this technique was found to be useful for detecting intracranial stenosis. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Abnormal neurodevelopmental outcomes are very likely in cases of bilateral neonatal arterial ischaemic stroke.

PubMed

Jin, Ju Hyun; Shin, Jeong Eun; Lee, Soon Min; Eun, Ho Seon; Park, Min Soo; Park, Kook In; Namgung, Ran

2017-02-01

Neonatal arterial ischaemic stroke (AIS) is an important cause of severe neurological disability. This study aimed to analyse the clinical manifestations and outcomes of AIS patients. We enrolled neonates with AIS admitted to Severance Children's Hospital and Gangnam Severance Hospital between 2008 and 2015. AIS was confirmed using magnetic resonance imaging (MRI). We retrospectively reviewed the clinical manifestations, MRI findings, electroencephalography (EEG) findings and neurodevelopmental outcomes. The study comprised 29 neonates (18 boys). The mean follow-up period was 15.4 months (range 6-44 months), and the mean age at diagnosis was 8.1 days. Seizure was the most common symptom (66%). Bilateral involvement was more common than unilateral involvement (52%). The middle cerebral artery was the most commonly identified territory (79%). Abnormal EEG findings were noted in 93% of the cases. Neurodevelopment was normal in 11 (38%) patients, while cerebral palsy and delayed development were noted in eight (28%) and six (21%) patients, respectively. Patients with bilateral involvement were very likely to have abnormal neurodevelopmental outcomes. Our study showed that abnormal neurodevelopmental outcomes were very likely after cases of neonatal AIS with bilateral involvement, and clinicians should consider early and more effective interventions in such cases. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

An interesting case of cryptogenic stroke in a young man due to left ventricular non-compaction: role of cardiac MRI in the accurate diagnosis.

PubMed

Kannan, Arun; Das, Anindita; Janardhanan, Rajesh

2014-06-24

A 28-year-old man arrived for an outpatient cardiac MRI (CMR) study to evaluate cardiac structure. At the age of 24 the patient presented with acute onset expressive aphasia and was diagnosed with ischaemic stroke. Echocardiography at that time was reported as 'apical wall thickening consistent with apical hypertrophic cardiomyopathy'. CMR revealed a moderately dilated left ventricle with abnormal appearance of the left ventricular (LV) apical segments. Further evaluation was consistent with a diagnosis of LV non-compaction (LVNC) cardiomyopathy with a ratio of non-compacted to compacted myocardium measuring 3. There was extensive delayed hyperenhancement signal involving multiple segments representing a significant myocardial scar which is shown to have a prognostic role. Our patient, with no significant cerebrovascular risk factors, would likely have had an embolic stroke. This case demonstrates the role of CMR in accurately diagnosing LVNC in a patient with young stroke where prior echocardiography was non-diagnostic. 2014 BMJ Publishing Group Ltd.

Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison.

PubMed

Rothwell, Peter M; Giles, Matthew F; Chandratheva, Arvind; Marquardt, Lars; Geraghty, Olivia; Redgrave, Jessica N E; Lovelock, Caroline E; Binney, Lucy E; Bull, Linda M; Cuthbertson, Fiona C; Welch, Sarah J V; Bosch, Shelley; Alexander, Faye C; Carasco-Alexander, Faye; Silver, Louise E; Gutnikov, Sergei A; Mehta, Ziyah

2007-10-20

The risk of recurrent stroke is up to 10% in the week after a transient ischaemic attack (TIA) or minor stroke. Modelling studies suggest that urgent use of existing preventive treatments could reduce the risk by 80-90%, but in the absence of evidence many health-care systems make little provision. Our aim was to determine the effect of more rapid treatment after TIA and minor stroke in patients who are not admitted direct to hospital. We did a prospective before (phase 1: April 1, 2002, to Sept 30, 2004) versus after (phase 2: Oct 1, 2004, to March 31, 2007) study of the effect on process of care and outcome of more urgent assessment and immediate treatment in clinic, rather than subsequent initiation in primary care, in all patients with TIA or minor stroke not admitted direct to hospital. The study was nested within a rigorous population-based incidence study of all TIA and stroke (Oxford Vascular Study; OXVASC), such that case ascertainment, investigation, and follow-up were complete and identical in both periods. The primary outcome was the risk of stroke within 90 days of first seeking medical attention, with independent blinded (to study period) audit of all events. Of the 1278 patients in OXVASC who presented with TIA or stroke (634 in phase 1 and 644 in phase 2), 607 were referred or presented direct to hospital, 620 were referred for outpatient assessment, and 51 were not referred to secondary care. 95% (n=591) of all outpatient referrals were to the study clinic. Baseline characteristics and delays in seeking medical attention were similar in both periods, but median delay to assessment in the study clinic fell from 3 (IQR 2-5) days in phase 1 to less than 1 (0-3) day in phase 2 (p<0.0001), and median delay to first prescription of treatment fell from 20 (8-53) days to 1 (0-3) day (p<0.0001). The 90-day risk of recurrent stroke in the patients referred to the study clinic was 10.3% (32/310 patients) in phase 1 and 2.1% (6/281 patients) in phase 2 (adjusted hazard ratio 0.20, 95% CI 0.08-0.49; p=0.0001); there was no significant change in risk in patients treated elsewhere. The reduction in risk was independent of age and sex, and early treatment did not increase the risk of intracerebral haemorrhage or other bleeding. Early initiation of existing treatments after TIA or minor stroke was associated with an 80% reduction in the risk of early recurrent stroke. Further follow-up is required to determine long-term outcome, but these results have immediate implications for service provision and public education about TIA and minor stroke.

Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies.

PubMed

Chapman, J; Rand, J H; Brey, R L; Levine, S R; Blatt, I; Khamashta, M A; Shoenfeld, Y

2003-01-01

Although many types of neurological disorders and events have been described in association with antiphospholipid antibodies (aPL) and the antiphospholipid syndrome (APS), only ischaemic stroke is reasonably well established and accepted as a diagnostic criterion for the syndrome. We propose to evaluate, classify and rank the association of other neurological manifestations as possible, probable, or definite according to the data available from clinical studies and animal models. By these criteria, none of the neurological disorders or events such as epilepsy, psychiatric disease, dementia, transverse myelitis, multiple sclerosis-like disease, chorea, migraine, Guillian-Barrè syndrome, and sensory-neural hearing loss, can be definitely associated with aPL or APS.

Pure Motor Stroke Secondary to Cerebral Infarction of Recurrent Artery of Heubner after Mild Head Trauma: A Case Report.

PubMed

Yilmaz, Ali; Kizilay, Zahir; Ozkul, Ayca; Çirak, Bayram

2016-03-15

The recurrent Heubner's artery is the distal part of the medial striate artery. Occlusion of the recurrent artery of Heubner, classically contralateral hemiparesis with fasciobrachiocrural predominance, is attributed to the occlusion of the recurrent artery of Heubner and is widely known as a stroke syndrome in adults. However, isolated occlusion of the deep perforating arteries following mild head trauma also occurs extremely rarely in childhood. Here we report the case of an 11-year-old boy with pure motor stroke. The brain MRI showed an acute ischemia in the recurrent artery of Heubner supply area following mild head trauma. His fasciobrachial hemiparesis and dysarthria were thought to be secondary to the stretching of deep perforating arteries leading to occlusion of the recurrent artery of Heubner. Post-traumatic pure motor ischemic stroke can be secondary to stretching of the deep perforating arteries especially in childhood.

Acute Predictors of Social Integration Following Mild Stroke.

PubMed

Wise, Frances M; Harris, Darren W; Olver, John H; Davis, Stephen M; Disler, Peter B

2018-04-01

Despite an acknowledged need to accurately predict stroke outcome, there is little empirical evidence regarding acute predictors of participation restriction post stroke. The current study examines prediction of social integration following mild stroke, using combinations of acute poststroke factors. In a prospective, longitudinal study, a cohort of 60 stroke survivors was followed up at 6 months post stroke. Hierarchical multiple regression analyses were employed to evaluate the value of acute poststroke variables in predicting social integration at 6 months post stroke. A combination of age, number of comorbidities, stroke severity, social support factors, and general self-efficacy in the acute poststroke period accounted for 42% of the variance in 6-month social integration. The largest amount of variance (20%) was explained by inclusion of social support factors, including number and types of support. Post hoc analysis was conducted to establish whether marital status was the mediating variable through which early poststroke social support factors exerted influence upon subsequent social integration. The new combination of acute variables accounted for 48% of the variance in 6-month social integration. Results suggested that subjects with partners perceived higher levels of functional social support and lower levels of participation restriction. Stroke survivors with partners may receive greater amounts of companionship and encouragement from their partners, which enhances self-esteem and confidence. Such individuals are possibly more able to participate in and maintain relationships, thus improving social integration. Social support factors, mediated via marital status, are the strongest predictors of subsequent social integration following mild stroke. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A stepwise approach to stroke surveillance in Brazil: the EMMA (Estudo de Mortalidade e Morbidade do Acidente Vascular Cerebral) study.

PubMed

Goulart, Alessandra C; Bustos, Iara R; Abe, Ivana M; Pereira, Alexandre C; Fedeli, Ligia M; Benseñor, Isabela M; Lotufo, Paulo A

2010-08-01

Stroke mortality rates in Brazil are the highest in the Americas. Deaths from cerebrovascular disease surpass coronary heart disease. To verify stroke mortality rates and morbidity in an area of São Paulo, Brazil, using the World Health Organization Stepwise Approach to Stroke Surveillance. We used the World Health Organization Stepwise Approach to Stroke Surveillance structure of stroke surveillance. The hospital-based data comprised fatal and nonfatal stroke (Step 1). We gathered stroke-related mortality data in the community using World Health Organization questionnaires (Step 2). The questionnaire determining stroke prevalence was activated door to door in a family-health-programme neighbourhood (Step 3). A total of 682 patients 18 years and above, including 472 incident cases, presented with cerebrovascular disease and were enrolled in Step 1 during April-May 2009. Cerebral infarction (84.3%) and first-ever stroke (85.2%) were the most frequent. In Step 2, 256 deaths from stroke were identified during 2006-2007. Forty-four per cent of deaths were classified as unspecified stroke, 1/3 as ischaemic stroke, and 1/4 due to haemorrhagic subtype. In Step 3, 577 subjects over 35 years old were evaluated at home, and 244 cases of stroke survival were diagnosed via a questionnaire, validated by a board-certified neurologist. The population demographic characteristics were similar in the three steps, except in terms of age and gender. By including data from all settings, World Health Organization stroke surveillance can provide data to help plan future resources that meet the needs of the public-health system.

Balneotherapy in Treatment of Spastic Upper Limb after Stroke

PubMed Central

Erceg-Rukavina, Tatjana; Stefanovski, Mihajlo

2015-01-01

Introduction: After stroke, spasticity is often the main problem that prevents functional recovery. Pain occurs in up to 70% of patients during the first year post-stroke. Materials and methods: A total of 70 patients (30 female and 45 male) mean age (65.67) participated in prospective, controlled study. Inclusion criteria: ischaemic stroke, developed spasticity of upper limb, post-stroke interval <6 months. Exclusion criteria: contraindications for balneotherapy and inability to follow commands. Experimental group (Ex) (n=35) was treated with sulphurous baths (31°-33°C) and controlled group (Co) with taped water baths, during 21 days. All patients were additionally treated with kinesitherapy and cryotherapy. The outcome was evaluated using Modified Ashworth scale for spasticity and VAS scale for pain. The significance value was sat at p<0.05. Goal: To find out the effects of balneotherapy with sulphurous bath on spasticity and pain in affected upper limb. Results: Reduction in tone of affected upper limb muscles was significant in Ex group (p<0.05). Pain decreased significantly in Ex-group (p<0.01). Conclusion: Our results show that balneotherapy with sulphurous water reduces spasticity and pain significantly and can help in treatment of post-stroke patients. PMID:25870474

Alterations in anxiety and social behaviour in Npas4 deficient mice following photochemically-induced focal cortical stroke.

PubMed

Klarić, T S; Jaehne, E J; Koblar, S A; Baune, B T; Lewis, M D

2017-01-01

In addition to causing widespread cell death and loss of brain function, cerebral ischaemia also induces extensive neuroplasticity. In humans, stroke is often accompanied by severe cognitive and psychiatric changes that are thought to arise as a consequence of this infarct-induced remodelling. A candidate for producing these post-stroke neuropsychiatric changes is Npas4, an activity-dependent transcription factor involved in synaptic plasticity whose expression is aberrantly up-regulated following ischaemic injury. In this study we investigated the role of Npas4 in modulating these stroke-induced neuropsychiatric responses by comparing the performance of wildtype and Npas4 -/- mice in various cognitive and behavioural tasks in a photochemical model of focal cortical stroke. We show that this stroke model results in impaired spatial recognition memory and a reduction in despair-like behaviour that affect both genotypes to a similar degree. Moreover, mice lacking Npas4 also show differences in some aspects of post-stroke sociability and anxiety. Specifically, we show that while stroke had no effect on anxiety levels in wildtype mice, Npas4 -/- mice became significantly more anxious following stroke. In addition, Npas4 -/- mice retained a greater level of sociability in the acute post-stroke period in comparison to their wildtype littermates. Thus, our findings suggest that Npas4 may be involved in post-stroke psychiatric changes related to anxiety and sociability. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

The use of virtual reality-based therapy to augment poststroke upper limb recovery.

PubMed

Samuel, Geoffrey S; Choo, Min; Chan, Wai Yin; Kok, Stanley; Ng, Yee Sien

2015-07-01

Stroke remains one of the major causes of disability worldwide. This case report illustrates the complementary use of biomechanical and kinematic in-game markers, in addition to standard clinical outcomes, to comprehensively assess and track a patient's disabilities. A 65-year-old patient was admitted for right-sided weakness and clinically diagnosed with acute ischaemic stroke. She participated in a short trial of standard stroke occupational therapy and physiotherapy with additional daily virtual reality (VR)-based therapy. Outcomes were tracked using kinematic data and conventional clinical assessments. Her Functional Independence Measure score improved from 87 to 113 and Fugl-Meyer motor score improved from 56 to 62, denoting clinically significant improvement. Corresponding kinematic analysis revealed improved hand path ratios and a decrease in velocity peaks. Further research is being undertaken to elucidate the optimal type, timing, setting and duration of VR-based therapy, as well as the use of neuropharmacological adjuncts.

The use of virtual reality-based therapy to augment poststroke upper limb recovery

PubMed Central

Samuel, Geoffrey S; Choo, Min; Chan, Wai Yin; Kok, Stanley; Ng, Yee Sien

2015-01-01

Stroke remains one of the major causes of disability worldwide. This case report illustrates the complementary use of biomechanical and kinematic in-game markers, in addition to standard clinical outcomes, to comprehensively assess and track a patient’s disabilities. A 65-year-old patient was admitted for right-sided weakness and clinically diagnosed with acute ischaemic stroke. She participated in a short trial of standard stroke occupational therapy and physiotherapy with additional daily virtual reality (VR)-based therapy. Outcomes were tracked using kinematic data and conventional clinical assessments. Her Functional Independence Measure score improved from 87 to 113 and Fugl-Meyer motor score improved from 56 to 62, denoting clinically significant improvement. Corresponding kinematic analysis revealed improved hand path ratios and a decrease in velocity peaks. Further research is being undertaken to elucidate the optimal type, timing, setting and duration of VR-based therapy, as well as the use of neuropharmacological adjuncts. PMID:26243983

High-altitude cerebral oedema mimicking stroke.

PubMed

Yanamandra, Uday; Gupta, Amul; Patyal, Sagarika; Varma, Prem Prakash

2014-03-26

High-altitude cerebral oedema (HACO) is the most fatal high-altitude illness seen by rural physicians practising in high-altitude areas. HACO presents clinically with cerebellar ataxia, features of raised intracranial pressure (ICP) and coma. Early identification is important as delay in diagnosis can be fatal. We present two cases of HACO presenting with focal deficits mimicking stroke. The first patient presented with left-sided hemiplegia associated with the rapid deterioration in the sensorium. Neuroimaging revealed features suggestive of vasogenic oedema. The second patient presented with monoplegia of the lower limb. Neuroimaging revealed perfusion deficit in anterior cerebral artery territory. Both patients were managed with dexamethasone and they improved dramatically. Clinical picture and neuroimaging closely resembled acute ischaemic stroke in both cases. Thrombolysis in these patients would have been disastrous. Recent travel to high altitude, young age, absence of atherosclerotic risk factors and features of raised ICP concomitantly directed the diagnosis to HACO.

Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events.

PubMed

Squizzato, Alessandro; Bellesini, Marta; Takeda, Andrea; Middeldorp, Saskia; Donadini, Marco Paolo

2017-12-14

Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease. This is an update to a previously published review from 2011. To review the benefit and harm of adding clopidogrel to aspirin therapy for preventing cardiovascular events in people who have coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or were at high risk of atherothrombotic disease, but did not have a coronary stent. We updated the searches of CENTRAL (2017, Issue 6), MEDLINE (Ovid, 1946 to 4 July 2017) and Embase (Ovid, 1947 to 3 July 2017) on 4 July 2017. We also searched ClinicalTrials.gov and the WHO ICTRP portal, and handsearched reference lists. We applied no language restrictions. We included all randomised controlled trials comparing over 30 days use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in people with coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or at high risk of atherothrombotic disease. We excluded studies including only people with coronary drug-eluting stent (DES) or non-DES, or both. We collected data on mortality from cardiovascular causes, all-cause mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal ischaemic stroke, major and minor bleeding. The overall treatment effect was estimated by the pooled risk ratio (RR) with 95% confidence interval (CI), using a fixed-effect model (Mantel-Haenszel); we used a random-effects model in cases of moderate or severe heterogeneity (I 2 ≥ 30%). We assessed the quality of the evidence using the GRADE approach. We used GRADE profiler (GRADE Pro) to import data from Review Manager to create a 'Summary of findings' table. The search identified 13 studies in addition to the two studies in the previous version of our systematic review. Overall, we included data from 15 trials with 33,970 people. We completed a 'Risk of bias' assessment for all studies. The risk of bias was low in four trials because they were at low risk of bias for all key domains (random sequence generation, allocation concealment, blinding, selective outcome reporting and incomplete outcome data), even if some of them were funded by the pharmaceutical industry.Analysis showed no difference in the effectiveness of aspirin plus clopidogrel in preventing cardiovascular mortality (RR 0.98, 95% CI 0.88 to 1.10; participants = 31,903; studies = 7; moderate quality evidence), and no evidence of a difference in all-cause mortality (RR 1.05, 95% CI 0.87 to 1.25; participants = 32,908; studies = 9; low quality evidence).There was a lower risk of fatal and non-fatal myocardial infarction with clopidogrel plus aspirin compared with aspirin plus placebo or aspirin alone (RR 0.78, 95% CI 0.69 to 0.90; participants = 16,175; studies = 6; moderate quality evidence). There was a reduction in the risk of fatal and non-fatal ischaemic stroke (RR 0.73, 95% CI 0.59 to 0.91; participants = 4006; studies = 5; moderate quality evidence).However, there was a higher risk of major bleeding with clopidogrel plus aspirin compared with aspirin plus placebo or aspirin alone (RR 1.44, 95% CI 1.25 to 1.64; participants = 33,300; studies = 10; moderate quality evidence) and of minor bleeding (RR 2.03, 95% CI 1.75 to 2.36; participants = 14,731; studies = 8; moderate quality evidence).Overall, we would expect 13 myocardial infarctions and 23 ischaemic strokes be prevented for every 1000 patients treated with the combination in a median follow-up period of 12 months, but 9 major bleeds and 33 minor bleeds would be caused during a median follow-up period of 10.5 and 6 months, respectively. The available evidence demonstrates that the use of clopidogrel plus aspirin in people at high risk of cardiovascular disease and people with established cardiovascular disease without a coronary stent is associated with a reduction in the risk of myocardial infarction and ischaemic stroke, and an increased risk of major and minor bleeding compared with aspirin alone. According to GRADE criteria, the quality of evidence was moderate for all outcomes except all-cause mortality (low quality evidence) and adverse events (very low quality evidence).

Mechanical Thrombectomy for Minor and Mild Stroke Patients Harboring Large Vessel Occlusion in the Anterior Circulation: A Multicenter Cohort Study.

PubMed

Dargazanli, Cyril; Arquizan, Caroline; Gory, Benjamin; Consoli, Arturo; Labreuche, Julien; Redjem, Hocine; Eker, Omer; Decroix, Jean-Pierre; Corlobé, Astrid; Mourand, Isabelle; Gaillard, Nicolas; Ayrignac, Xavier; Charif, Mahmoud; Duhamel, Alain; Labeyrie, Paul-Emile; Riquelme, Carlos; Ciccio, Gabriele; Smajda, Stanislas; Desilles, Jean-Philippe; Gascou, Grégory; Lefèvre, Pierre-Henri; Mantilla-García, Daniel; Cagnazzo, Federico; Coskun, Oguzhan; Mazighi, Mikael; Riva, Roberto; Bourdain, Frédéric; Labauge, Pierre; Rodesch, Georges; Obadia, Michael; Bonafé, Alain; Turjman, Francis; Costalat, Vincent; Piotin, Michel; Blanc, Raphaël; Lapergue, Bertrand

2017-12-01

Proximal large vessel occlusion (LVO) is present in up to 30% of minor strokes. The effectiveness of mechanical thrombectomy (MT) in the subgroup of minor stroke with LVO in the anterior circulation is still open to debate. Data about MT in this subgroup of patients are sparse, and their optimal management has not yet been defined. The purpose of this multicenter cohort study was to evaluate the effectiveness of MT in patients experiencing acute ischemic stroke (AIS) because of LVO in the anterior circulation, presenting with minor-to-mild stroke symptoms (National Institutes of Health Stroke Scale score of <8). Multicenter cohort study involving 4 comprehensive stroke centers having 2 therapeutic approaches (urgent thrombectomy associated with best medical treatment [BMT] versus BMT first and MT if worsening occurs) about management of patients with minor and mild acute ischemic stroke harboring LVO in the anterior circulation. An intention-to-treat analysis was conducted. The primary end point was the rate of excellent outcome defined as the achievement of a modified Rankin Scale score of 0 to 1 at 3 months. Three hundred one patients were included, 170 with urgent MT associated with BMT, and 131 with BMT alone as first-line treatment. Patients treated with MT were younger, more often received intravenous thrombolysis, and had shorter time to imaging. Twenty-four patients (18.0%) in the medical group had rescue MT because of neurological worsening. Overall, excellent outcome was achieved in 64.5% of patients, with no difference between the 2 groups. Stratified analysis according to key subgroups did not find heterogeneity in the treatment effect size. Minor-to-mild stroke patients with LVO achieved excellent and favorable functional outcomes at 3 months in similar proportions between urgent MT versus delayed MT associated with BMT. There is thus an urgent need for randomized trials to define the effectiveness of MT in this patient subgroup. © 2017 American Heart Association, Inc.

What is the best imaging strategy for acute stroke?

PubMed

Wardlaw, J M; Keir, S L; Seymour, J; Lewis, S; Sandercock, P A G; Dennis, M S; Cairns, J

2004-01-01

To determine the cost-effectiveness of computed tomographic (CT) scanning after acute stroke. To assess the contribution of brain imaging to the diagnosis and management of stroke, and to estimate the costs, benefits and risks of different imaging strategies in order to provide data to inform national and local policy on the use of brain imaging in stroke. A decision-analysis model was developed to represent the pathway of care in acute stroke using 'scan all patients within 48 hours' as the comparator against which to cost 12 alternative scan strategies. Hospitals in Scotland. Subjects were patients admitted to hospital with a first stroke and those managed as outpatients. The effect on functional outcome after ischaemic or haemorrhagic stroke, tumours or infections, of correctly administered antithrombotic or other treatment; of time to scan and stroke severity on diagnosis by CT or MRI; on management, including length of stay, functional outcome, and quality-adjusted life years (QALYs), of the diagnostic information provided by CT scanning; the cost-effectiveness (cost versus QALYs) of different strategies for use of CT after acute stroke. Death and functional outcome at long-term follow-up; accuracy of CT and MRI; cost of CT scanning by time of day and week; effect of CT diagnosis on change in health outcome, length of stay in hospital and QALYs; cost-effectiveness of various scanning strategies. CT is very sensitive and specific for haemorrhage within the first 8 days of stroke only. Suboptimal scanning used in epidemiology studies suggests that the frequency of primary intracerebral haemorrhage (PICH) has been underestimated. Aspirin increases the risk of PICH. There were no reliable data on functional outcome or on the effect of antithrombotic treatment given long term after PICH. In 60% of patients with recurrent stroke after PICH, the cause is another PICH and mortality is high among PICH patients. A specific MR sequence (gradient echo) is required to identify prior PICH reliably. CT scanners were distributed unevenly in Scotland, 65% provided CT scanning within 48 hours of stroke, and 100% within 7 days for hospital-admitted patients, but access out of hours was very variable, and for outpatients was poor. The average cost of a CT brain scan for stroke was pounds 30.23 to pounds 89.56 in normal working hours and pounds 55.05 to pounds 173.46 out of hours. Average length of stay was greatest for severe strokes and those who survived in a dependent state. For a cohort of 1000 patients aged 70-74 years, the policy 'scan all strokes within 48 hours', cost pounds 10,279,728 and achieved 1982.3 QALYS. The most cost-effective strategy was 'scan all immediately' (pounds 9,993,676 and 1982.4 QALYS). The least cost-effective was to 'scan patients on anticoagulants, in a life-threatening condition immediately and the rest within 14 days'. In general, strategies in which most patients were scanned immediately cost least and achieved the most QALYs, as the cost of providing CT (even out of hours) was less than the cost of inpatient care. Increasing independent survival by even a small proportion through early use of aspirin in the majority with ischaemic stroke, avoiding aspirin in those with haemorrhagic stroke, and appropriate early management of those who have not had a stroke, reduced costs and increased QALYs.

Antithrombotic therapy use and clinical outcomes following thrombo-embolic events in patients with atrial fibrillation: insights from ARISTOTLE.

PubMed

Goto, Shinya; Merrill, Peter; Wallentin, Lars; Wojdyla, Daniel M; Hanna, Michael; Avezum, Alvaro; Easton, J Donald; Harjola, Veli-Pekka; Huber, Kurt; Lewis, Basil S; Parkhomenko, Alexander; Zhu, Jun; Granger, Christopher B; Lopes, Renato D; Alexander, John H

2018-04-01

We investigated baseline characteristics, antithrombotic use, and clinical outcomes of patients with atrial fibrillation (AF) and a thrombo-embolic event in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study to better inform the care of these high-risk patients. Thrombo-embolic events were defined as stroke (ischaemic or unknown cause) or systemic embolism (SE). Clinical outcomes were estimated using the Kaplan-Meier method. All-cause mortality and International Society on Thrombosis and Haemostasis (ISTH) major bleeding after events were analysed using a Cox proportional hazards model with time-dependent covariates. Of 18 201 patients in ARISTOTLE, 365 experienced a thrombo-embolic event [337 strokes (ischaemic or unknown cause), 28 SE]; 46 (12.6%) of which were fatal. In the 30 days before and after a thrombo-embolic event, 11% and 37% of patients, respectively, were not taking an oral anticoagulant. During follow-up (median 1.8 years), 22 patients (7.1%/year) had a recurrent stroke, 97 (30.1%/year) died, and 10 (6.7%/year) had major bleeding. Compared with patients without a thrombo-embolic event, the short- and long-term adjusted hazards of death in patients with a thrombo-embolic event were high [≤30 days: hazard ratio (HR) 54.3%, 95% confidence interval (95% CI) 41.4-71.3; >30 days: HR 3.5, 95% CI 2.5-4.8; both P < 0.001]. The adjusted hazards of major bleeding were also high short-term (HR 10.37, 95% CI 3.87-27.78; P < 0.001) but not long-term (HR 1.7, 95% CI: 0.77-3.88; P = 0.18). Thrombo-embolic events were rare but associated with high short- and long-term morbidity and mortality. Substantial numbers of patients are not receiving oral anticoagulattherapy before and, despite this risk, after a first thrombo-embolic event. ClinicalTrials.gov (NCT00412984).

Vascular and metabolic comorbidities in open-angle glaucoma with low- and high-teen intraocular pressure: a cross-sectional study from South Korea.

PubMed

Lee, Si Hyung; Kim, Gyu Ah; Lee, Wonseok; Bae, Hyoung Won; Seong, Gong Je; Kim, Chan Yun

2017-11-01

To assess the associations between vascular and metabolic comorbidities and the prevalence of open-angle glaucoma (OAG) with low-teen and high-teen intraocular pressure (IOP) in Korea. Cross-sectional data from the Korean National Health and Nutrition Examination Survey from 2008 to 2012 were analysed. Participants diagnosed with OAG with normal IOP were further classified into low-teen IOP (IOP ≤ 15 mmHg) and high-teen IOP (15 mmHg < IOP ≤ 21 mmHg) groups. Using multiple logistic regression analyses, the associations between vascular and metabolic comorbidities and the prevalence of glaucoma were investigated for the low- and high-teen IOP groups. The prevalences of hypertension, hyperlipidemia, ischaemic heart disease, stroke and metabolic syndrome were significantly higher among subjects with low-teen OAG compared with normal subjects, while only the prevalences of hypertension and stroke were higher among subjects with high-teen OAG compared with normal subjects. In multivariate logistic regression models adjusted for confounding factors, low-teen OAG was significantly associated with hypertension (OR, 1.68; 95% CI, 1.30-2.18), hyperlipidemia (OR, 1.49; 95% CI, 1.07-2.08), ischaemic heart disease (OR, 1.83; 95% CI, 1.07-3.11), stroke (OR, 1.91; 95% CI, 1.12-3.25) and metabolic syndrome (OR, 1.46; 95% CI, 1.12-1.90). High-teen OAG was only associated with stroke (OR, 2.58; 95% CI, 1.20-5.53). Various vascular and metabolic comorbidities were significantly associated with low-teen OAG, but not with high-teen OAG. These data support the hypothesis that vascular factors play a more significant role in the pathogenesis of OAG with low-teen baseline IOP. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Associations between results of post-stroke NDT-Bobath rehabilitation in gait parameters, ADL and hand functions.

PubMed

Mikołajewska, Emilia

2013-01-01

In patients after a stroke there are variable disorders. These patients often need rehabilitation in more than one area beceause of multiple limitations of the ability to perform everyday activities. The aim of the study was to assess correlations - statistical relationships between observed gait parameters, ADL and hand functions - results of rehabilitation of patients after ischaemic stroke according to the NDTBobath method for adults. The investigated group consisted of 60 patients after ischaemic stroke, who participated in the rehabilitation programme. 10 sessions of the NDT-Bobath therapy were provided in 2 weeks (10 days of the therapy). The calculation of correlations was made based on changes of parameters: Bobath Scale (to assess hand functions), Barthel Index (to assess ADL), gait velocity, cadence and stride lenght. Measurements were performed in every patient twice: on admission (before the therapy) and after last session of the therapy to assess rehabilitation effects. The main statistically relevant corellations observed in the study were as follows: in the whole group of patients: poor and moderate (negative) correlation between changes of gait parameters and Bobath Scale and Barthel Index, moderate and severe (negative) correlation between changes of gait parameters and Bobath Scale and Barthel Index in the group of women, correlation between changes in Bobath Scale and Barthel Index in the group of patients with left side of paresis, (negative) correlation between changes of gait parameters and Bobath Scale in group of patients younger than 68 years, moderate, high and very high correlations between changes in gait parameters in groups of women, men, younger than 68 years and older than 68 years. There have been observed statistically significant and favourable changes in the health status of patients, described by gait parameters, changes in hand functions and ADL. Based on the presented correlations there is an assumption that it is hard to achieve simultaneous recovery in all areas: gait parameters, hand functions and ADLs in two weeks of rehabilitation.

Improving discharge care: the potential of a new organisational intervention to improve discharge after hospitalisation for acute stroke, a controlled before-after pilot study.

PubMed

Cadilhac, Dominique A; Andrew, Nadine E; Stroil Salama, Enna; Hill, Kelvin; Middleton, Sandy; Horton, Eleanor; Meade, Ian; Kuhle, Sarah; Nelson, Mark R; Grimley, Rohan

2017-08-04

Provision of a discharge care plan and prevention therapies is often suboptimal. Our objective was to design and pilot test an interdisciplinary, organisational intervention to improve discharge care using stroke as the case study using a mixed-methods, controlled before-after observational study design. Acute care public hospitals in Queensland, Australia (n=15). The 15 hospitals were ranked against a benchmark based on a composite outcome of three discharge care processes. Clinicians from a 'top-ranked' hospital participated in a focus group to elicit their success factors. Two pilot hospitals then participated in the organisational intervention that was designed with experts and consumers. Hospital clinicians involved in discharge care for stroke and patients admitted with acute stroke or transient ischaemic attack. A four-stage, multifaceted organisational intervention that included data reviews, education and facilitated action planning. Three discharge processes collected in Queensland hospitals within the Australian Stroke Clinical Registry were used to select study hospitals: (1) discharge care plan; (2) antihypertensive medication prescription and (3) antiplatelet medication prescription (ischaemic events only). Primary measure: composite outcome. Secondary measures: individual adherence changes for each discharge process; sensitivity analyses. The performance outcomes were compared 3 months before the intervention (preintervention), 3 months postintervention and at 12 months (sustainability). Data from 1289 episodes of care from the two pilot hospitals were analysed. Improvements from preintervention adherence were: antiplatelet therapy (88%vs96%, p=0.02); antihypertensive prescription (61%vs79%, p<0.001); discharge planning (72%vs94%, p<0.001); composite outcome (73%vs89%, p<0.001). There was an insignificant decay effect over the 12-month sustainability period (composite outcome: 89% postintervention vs 85% sustainability period, p=0.08). Discharge care in hospitals may be effectively improved and sustained through a staged and peer-informed, organisational intervention. The intervention warrants further application and trialling on a larger scale. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Investigation of the effect of vinpocetine on cerebral blood flow and cognitive functions].

PubMed

Valikovics, Attila

2007-07-30

Vinpocetine has been widely used in the treatment of ischaemic cerebrovascular diseases and dementias of vascular type. Chronic cerebral hypoperfusion plays an important role in the development of certain types of dementia. In consequence of complex mode of action vinpocetine plays a significant role in the improvement of cerebral hypoperfusion. The symptoms of mild cognitive impairment considered as "predementia" are similar to those of dementia, although milder. The authors investigated the characteristics of the blood flow parameters of patients with ischemic stroke and mild cognitive impairment both in resting conditions or following chemical stimulus as well as they investigated the severity of mental deterioration in the two patient groups. In a pilot study the authors examined the influence of 12-week long oral vinpocetine therapy on the blood flow parameters and cognitive functions in the two patient groups. The authors studied the blood flow velocity of a. cerebri media in resting conditions and after 30 sec of breath holding with transcranial Doppler before treatment and after a 12-week long oral vinpocetine treatment. At the same time psychometric tests (MMSE, ADAS-Cog) were used in order to examine cognitive functions, while the general condition of the patients were scored by Clinical Global Impression (CGI) scale. After a 12-week long oral vinpocetine treatment the increase of blood flow velocity in resting conditions compared to the baseline values was significant in the vascular group. The percent increase of mean velocity after the breath holding TCD test showed a significant increase compared to the baseline in both patient groups. The authors found a significant improvement of cognitive functions after a 12-week long oral vinpocetine therapy using psychometric tests. The improvement was identical in both groups. The general condition of patients improved significantly according to both the investigator's and the patients' opinion; patients with mild cognitive impairment judged the improvement higher. Vinpocetine improved the cerebrovascular reserve capacity in both patient groups and favourably influenced the cognitive status and general condition of patients with chronic hypoperfusion. The authors recommend the use of vinpocetine for the treatment of patients with mild cognitive impairment.

Compensatory Versus Noncompensatory Shoulder Movements Used for Reaching in Stroke.

PubMed

Levin, Mindy F; Liebermann, Dario G; Parmet, Yisrael; Berman, Sigal

2016-08-01

Background The extent to which the upper-limb flexor synergy constrains or compensates for arm motor impairment during reaching is controversial. This synergy can be quantified with a minimal marker set describing movements of the arm-plane. Objectives To determine whether and how (a) upper-limb flexor synergy in patients with chronic stroke contributes to reaching movements to different arm workspace locations and (b) reaching deficits can be characterized by arm-plane motion. Methods Sixteen post-stroke and 8 healthy control subjects made unrestrained reaching movements to targets located in ipsilateral, central, and contralateral arm workspaces. Arm-plane, arm, and trunk motion, and their temporal and spatial linkages were analyzed. Results Individuals with moderate/severe stroke used greater arm-plane movement and compensatory trunk movement compared to those with mild stroke and control subjects. Arm-plane and trunk movements were more temporally coupled in stroke compared with controls. Reaching accuracy was related to different segment and joint combinations for each target and group: arm-plane movement in controls and mild stroke subjects, and trunk and elbow movements in moderate/severe stroke subjects. Arm-plane movement increased with time since stroke and when combined with trunk rotation, discriminated between different subject groups for reaching the central and contralateral targets. Trunk movement and arm-plane angle during target reaches predicted the subject group. Conclusions The upper-limb flexor synergy was used adaptively for reaching accuracy by patients with mild, but not moderate/severe stroke. The flexor synergy, as parameterized by the amount of arm-plane motion, can be used by clinicians to identify levels of motor recovery in patients with stroke. © The Author(s) 2015.

The small chill: mild hypothermia for cardioprotection?

PubMed

Tissier, Renaud; Chenoune, Mourad; Ghaleh, Bijan; Cohen, Michael V; Downey, James M; Berdeaux, Alain

2010-12-01

Reducing the heart's temperature by 2-5°C is a potent cardioprotective treatment in animal models of coronary artery occlusion. The anti-infarct benefit depends upon the target temperature and the time at which cooling is instituted. Protection primarily results from cooling during the ischaemic period, whereas cooling during reperfusion or beyond offers little protection. In animal studies, protection is proportional to both the depth and duration of cooling. An optimal cooling protocol must appreciably shorten the normothermic ischaemic time to effectively salvage myocardium. Patients presenting with acute myocardial infarction could be candidates for mild hypothermia since the current door-to-balloon time is typically 90 min. But they would have to be cooled quickly shortly after their arrival. Several strategies have been proposed for ultra-fast cooling, but most like liquid ventilation and pericardial perfusion are too invasive. More feasible strategies might include cutaneous cooling, peritoneal lavage with cold solutions, and endovascular cooling with intravenous thermodes. This last option has been investigated clinically, but the results have been disappointing possibly because the devices lacked capacity to cool the patient quickly or cooling was not implemented soon enough. The mechanism of hypothermia's protection has been assumed to be energy conservation. However, whereas deep hypothermia clearly preserves ATP, mild hypothermia has only a modest effect on ATP depletion during ischaemia. Some evidence suggests that intracellular signalling pathways might be responsible for the protection. It is unknown how cooling could trigger these pathways, but, if true, then it might be possible to duplicate cooling's protection pharmacologically.

Low Morbidity after Extracranial-Intracranial Bypass Operation. The Danish Extracranial-Intracranial Bypass Study: A Nationwide Survey.

PubMed

von Weitzel-Mudersbach, Paul; Andersen, Grethe; Rosenbaum, Sverre

2018-06-07

Patients with symptomatic atherosclerotic carotid artery occlusion (SACAO) have a high risk of a recurrent stroke. Extracranial-intracranial bypass (EC-IC bypass) has been shown not to improve outcome compared with medical treatment alone because long-term prevention of recurrent stroke in operated patients was offset by high perioperative stroke rates. We report our experience with EC-IC bypass operated at an experienced high-volume centre. We conducted a nationwide observational study of EC-IC bypass patients operated in the years 2007-2016 due to SACAO with ongoing clinical symptoms or progression on MRI and severe haemodynamic failure (SHF). Perioperative stroke and death within 30 days after the operation, ipsilateral stroke, bypass patency, transient ischaemic attack, and all-stroke events and deaths during long-term follow-up were registered prospectively. EC-IC bypass was performed in 48 patients with SHF and SACAO. The mean age was 64 (45-83) years. The mean follow-up was 3.6 years. The stroke rate after 30 days was 4.2%. No further ipsilateral strokes occurred during follow-up. Clinical symptoms arrested in all patients. Bypass patency rate was 94%. The perioperative stroke rate in EC-IC bypass operation, performed at a highly experienced centre, was low. During long-term follow-up, no ipsilateral stroke occurred. Consequently, EC-IC-bypass should still be considered for selected patients with SACAO, if operation can be carried out in experienced centres with low perioperative morbidity. © 2018 S. Karger AG, Basel.

EMG based FES for post-stroke rehabilitation

NASA Astrophysics Data System (ADS)

Piyus, Ceethal K.; Anjaly Cherian, V.; Nageswaran, Sharmila

2017-11-01

Annually, 15 million in world population experiences stroke. Nearly 9 million stroke survivors every year experience mild to severe disability. The loss of upper extremity function in stroke survivors still remains a major rehabilitation challenge. The proposed EMG Abstract—Annually, 15 million in world population experiences stroke. Nearly 9 million stroke survivors every year experience mild to severe disability. The loss of upper extremity function in stroke survivors still remains a major rehabilitation challenge. The proposed EMG based FES system can be used for effective upper limb motor re-education in post stroke upper limb rehabilitation. The governing feature of the designed system is its synchronous activation, in which the FES stimulation is dependent on the amplitude of the EMG signal acquired from the unaffected upper limb muscle of the hemiplegic patient. This proportionate operation eliminates the undesirable damage to the patient’s skin by generating stimulus in proportion to voluntary EMG signals. This feature overcomes the disadvantages of currently available manual motor re-education systems. This model can be used in home-based post stroke rehabilitation, to effectively improve the upper limb functions.

Prognostic value of plasma midregional pro-adrenomedullin and C-terminal-pro-endothelin-1 in chronic heart failure outpatients.

PubMed

Adlbrecht, Christopher; Hülsmann, Martin; Strunk, Guido; Berger, Rudolf; Mörtl, Deddo; Struck, Joachim; Morgenthaler, Nils G; Bergmann, Andreas; Jakowitsch, Johannes; Maurer, Gerald; Lang, Irene M; Pacher, Richard

2009-04-01

The identification of chronic heart failure (CHF) patients at high risk of adverse outcome remains a challenge. New peptides are emerging that may give additional information. In CHF patients, endothelin (ET) levels predict mortality risk. Adrenomedullin has been shown to predict mortality in ischaemic heart failure, but not in unselected or non-ischaemic CHF patients. Moreover, ADM and ET have never been assessed in one model. The aim of the present study was to assess the prognostic value of midregional-pro-adrenomedullin (MR-proADM) and C-terminal-pro-endothelin-1 (CT-proET-1) in outpatients with CHF. We measured plasma MR-proADM and CT-proET-1 levels in 786 consecutive CHF outpatients and compared them with B-type natriuretic peptide (BNP) levels. At 24-month follow-up, 233 patients had died. A stepwise forward Cox regression model with age, sex, estimated glomerular filtration rate, NYHA > II, left ventricular ejection fraction (LVEF), MR-proADM, CT-proET-1, and BNP as possible predictors revealed that MR-proADM levels [hazard ratio (HR) = 1.77, P < 0.001] in addition to age (HR = 1.02, P = 0.004), ejection fraction (HR = 0.98, P = 0.004), and NYHA > II (HR = 1.86, P < 0.001) were predictors of death at 24 months. When the analysis was repeated dependent on NYHA-stage, MR-proADM (HR = 2.12, P < 0.001) and LVEF (HR = 0.96, P = 0.006) were significant markers, but only in patients with mild/moderate CHF. Our data suggest that MR-proADM may be an important prognostic humoral marker, especially in mild/moderately symptomatic and non-ischaemic CHF patients.

RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID-TIA): study protocol for a pilot randomised controlled trial.

PubMed

Edwards, Duncan; Fletcher, Kate; Deller, Rachel; McManus, Richard; Lasserson, Daniel; Giles, Matthew; Sims, Don; Norrie, John; McGuire, Graham; Cohn, Simon; Whittle, Fiona; Hobbs, Vikki; Weir, Christopher; Mant, Jonathan

2013-07-02

People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist--that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final TIA clinic diagnosis as the reference standard. This pilot study will be used to estimate key parameters that are needed to design the main study and to estimate the accuracy of primary care diagnosis of TIA. The planned follow-on trial will have important implications for the initial management of people with suspected TIA. ISRCTN62019087.

Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial.

PubMed

1996-09-07

Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation (AF). However, this treatment carries a risk of bleeding and the need for frequent medical monitoring. We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of thromboembolism. 1044 patients with AF and with at least one thromboembolic risk factor (congestive heart failure or left ventricular fractional shortening < or = 25%, previous thromboembolism, systolic blood pressure of more than 160 mm Hg at study enrollment, or being a woman aged over 75 years) were randomly assigned either a combination of low-intensity, fixed-dose warfarin (international normalised ratio [INR] 1.2-1.5 for initial dose adjustment) and aspirin (325 mg/day) or adjusted-dose warfarin (INR 2.0-3.0). Drugs were given open-labelled. The mean INR during follow-up of patients taking combination therapy (n = 521) was 1.3, compared with 2.4 for those taking adjusted-dose warfarin (n = 523). During follow-up, 54% of INRs in patients taking combination therapy were 1.2-1.5 and 34% were less than 1.2. The trial was stopped after a mean, follow-up of 1.1 years when the rate of ischaemic stroke and systemic embolism (primary events) in patients given combination therapy (7.9% per year) was significantly higher than in those given adjusted-dose warfarin (1.9% per year) at an interim analysis (p < 0.0001), an absolute reduction of 6.0% per year (95% Cl 3.4, 8.6) by adjusted-dose warfarin. The annual rates of disabling stroke (5.6% vs 1.7%, p = 0.0007) and of primary event or vascular death (11.8% vs 6.4%, p = 0.002), were also higher with combination therapy. The rates of major bleeding were similar in both treatment groups. Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-dose warfarin (target INR 2.0-3.0) importantly reduces stroke for high-risk patients.

Very early social support following mild stroke is associated with emotional and behavioral outcomes three months later.

PubMed

Villain, Marie; Sibon, Igor; Renou, Pauline; Poli, Mathilde; Swendsen, Joel

2017-01-01

To investigate whether social contact and support received during hospitalization for acute ischemic stroke predict depression and daily life functioning three months later. Prospective observational study using Ecological Momentary Assessments to evaluate the number of social contacts as well as social support received from family, friends and medical staff within 24 hours following admission for stroke. Patients also monitored depression symptoms and behavior in real-time and in daily life contexts three months later. A university hospital acute stroke unit. Thirty-four mild ischemic stroke patients. None. One-day Ecological Momentary Assessments immediately following stroke collected information concerning perceived social support, number of social contacts and depression symptoms. Ecological Momentary Assessments was repeated three months later and addressed depression levels as well as activities of daily living, such as working, cooking, shopping and housework. The number of social interactions received at hospitalization did not predict three-month outcomes. However, a better quality of moral support from friends and family immediately after stroke was associated with decreases in later depression levels ( p = 0.041) and increases in activities of daily living ( p = 0.011). Material support from friends and family was associated with increases in activities of daily living ( p = 0.012). No effect was observed for support received from medical staff. Patient perceptions of better support quality, and not quantity, immediately following mild stroke, are associated with better behavioral and emotional outcomes three months later.

Interventions in the management of serum lipids for preventing stroke recurrence.

PubMed

Manktelow, B; Gillies, C; Potter, J F

2002-01-01

A close association between serum lipid levels and the incidence of coronary heart disease (CHD) has been well proven in middle aged and older persons, up to the age of 70-75 years. Individual studies have shown interventions to reduce total and low density lipoprotein (LDL) cholesterol levels, especially with 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase inhibitors (statins), to be of benefit in reducing CHD and stroke events in those with a history of coronary heart disease. However, the relation of serum cholesterol and cholesterol sub-fractions with cerebrovascular disease is less clear. It is unclear whether lipid levels in the post-stroke period are a predictor of recurrence and whether treatment to alter levels can prevent recurrence of either stroke or cardiovascular events. To investigate the effect of altering serum lipids in the prevention of cardiovascular disease and stroke recurrence in subjects with a history of stroke. The Cochrane Group Trials Register was searched up to 8 May 2001 along with MEDLINE (from 1966), EMBASE (from 1980) and the Cochrane Controlled Trials Register. All pharmaceutical firms known to produce a lipid lowering agent were also contacted and asked to provide information on publications or unpublished work relevant to this review. This review included unconfounded randomised trials of subjects aged 18 years and over with a history of stroke or Transient Ischaemic Attack (TIA). The data were extracted independently by the three reviewers. MetaView 4.1 was used for all statistical analyses. Five studies involving 1700 patients were included in the review. The active intervention in two of the studies was Clofibrate, Pravastatin in another two and Conjugated Oestrogen in the fifth. Fixed effects analysis showed no evidence of a difference in stroke recurrence between the treatment and placebo groups for those with a previous history of stroke or TIA (odds ratio 0.96, 95% confidence interval 0.71 to 1.30). In addition there was also no evidence, based on two studies, that intervention reduced the odds of all cause mortality (odds ratio 0.87, 95% confidence interval 0.55 to 1.39) nor, from one study, that there was any effect on subsequent vascular events (odds ratio 1.27, 95% confidence interval 0.84 to 1.89). These trials do not provide evidence for a benefit, or harm, from interventions to alter serum lipid levels in patients with a history solely of cerebrovascular disease. Their use, therefore, cannot yet be recommended routinely in this patient group, but ischaemic stroke patients with a history of myocardial infarction should receive statin therapy along the lines of the previous recommendations for those patients with a history of myocardial ischaemia. There are currently three ongoing trials which will recruit approximately 30,000 patients, including those with a history of stroke, and the results of these trials may have a significant effect on these conclusions.

[Noopept in the treatment of mild cognitive impairment in patients with stroke].

PubMed

Amelin, A V; Iliukhina, A Iu; Shmonin, A A

2011-01-01

Noopept is a neuroprotector and nootropics. Literature data revealed the treatment effect of noopept on mild cognitive impairment in patients with discirculatory encephalopathy. The present open prospective study included 60 patients with stroke treated with noopept during 12 months. Cognitive functions were assessed before and after treatment using neuropsychological tests. An analysis of MMSE scores and lateral and categorical associations revealed the significant improvement of cognitive functions after 2 months in patients of the main group compared to the controls. The global assessment of efficacy revealed the mild improvement in the main group while no changes were found in the control group. The results have demonstrated that noopept, used in dose 20 mg daily during 2 months, improves cognitive functions in stroke patients and has a high level of safety.

Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial.

PubMed

Hess, David C; Wechsler, Lawrence R; Clark, Wayne M; Savitz, Sean I; Ford, Gary A; Chiu, David; Yavagal, Dileep R; Uchino, Ken; Liebeskind, David S; Auchus, Alexander P; Sen, Souvik; Sila, Cathy A; Vest, Jeffrey D; Mays, Robert W

2017-05-01

Multipotent adult progenitor cells are a bone marrow-derived, allogeneic, cell therapy product that modulates the immune system, and represents a promising therapy for acute stroke. We aimed to identify the highest, well-tolerated, and safest single dose of multipotent adult progenitor cells, and if they were efficacious as a treatment for stroke recovery. We did a phase 2, randomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells in 33 centres in the UK and the USA. We used a computer-generated randomisation sequence and interactive voice and web response system to assign patients aged 18-83 years with moderately severe acute ischaemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 8-20 to treatment with intravenous multipotent adult progenitor cells (400 million or 1200 million cells) or placebo between 24 h and 48 h after symptom onset. Patients were ineligible if there was a change in NIHSS of four or more points during at least a 6 h period between screening and randomisation, had brainstem or lacunar infarct, a substantial comorbid disease, an inability to undergo an MRI scan, or had a history of splenectomy. In group 1, patients were enrolled and randomly assigned in a 3:1 ratio to receive 400 million cells or placebo and assessed for safety through 7 days. In group 2, patients were randomly assigned in a 3:1 ratio to receive 1200 million cells or placebo and assessed for safety through the first 7 days. In group 3, patients were enrolled, randomly assigned, and stratified by baseline NIHSS score to receive 1200 million cells or placebo in a 1:1 ratio within 24-48 h. Patients, investigators, and clinicians were masked to treatment assignment. The primary safety outcome was dose-limiting toxicity effects. The primary efficacy endpoint was global stroke recovery, which combines dichotomised results from the modified Rankin scale, change in NIHSS score from baseline, and Barthel index at day 90. Analysis was by intention to treat (ITT) including all patients in groups 2 and 3 who received the investigational agent or placebo. This study is registered with ClinicalTrials.gov, number NCT01436487. The study was done between Oct 24, 2011, and Dec 7, 2015. After safety assessments in eight patients in group 1, 129 patients were randomly assigned (67 to receive multipotent adult progenitor cells and 62 to receive placebo) in groups 2 and 3 (1200 million cells). The ITT populations consisted of 65 patients who received multipotent adult progenitor cells and 61 patients who received placebo. There were no dose-limiting toxicity events in either group. There were no infusional or allergic reactions and no difference in treatment-emergent adverse events between the groups (64 [99%] of 65 patients in the multipotent adult progenitor cell group vs 59 [97%] of 61 in the placebo group). There was no difference between the multipotent adult progenitor cell group and placebo groups in global stroke recovery at day 90 (odds ratio 1·08 [95% CI 0·55-2·09], p=0·83). Administration of multipotent adult progenitor cells was safe and well tolerated in patients with acute ischaemic stroke. Although no significant improvement was observed at 90 days in neurological outcomes with multipotent adult progenitor cells treatment, further clinical trials evaluating the efficacy of the intervention in an earlier time window after stroke (<36 h) are planned. Athersys Inc. Copyright © 2017 Elsevier Ltd. All rights reserved.

National survey on perioperative anaesthetic management in the endovascular treatment of acute ischaemic stroke.

PubMed

Romero Kräuchi, O; Valencia, L; Iturri, F; Mariscal Ortega, A; López Gómez, A; Valero, R

2018-01-01

To assess the anaesthetic management of treatment for endovascular acute ischaemic stroke (AIS) in Spain. A survey was designed by the SEDAR Neuroscience Section and sent to the Spanish anaesthesiology departments with a primary stroke centre between July and November 2016. Of the 47 hospitals where endovascular treatment of AIS is performed, 37 anaesthesiology departments participated. Thirty responses were obtained; three of which were eliminated due to duplication (response rate of 72.9%). Health coverage for AIS endovascular treatment was available 24hours a day in 63% of the hospitals. The anaesthesiologist in charge of the procedure was physically present in the hospital in 55.3%. There was large inter-hospital variability in non-standard monitoring and type of anaesthesia. The most important criterion for selecting type of anaesthesia was multidisciplinary choice made by the anaesthesiologist, neurologist and neuroradiologist (59.3%). The duration of time from arrival to arterial puncture was 10-15minutes in 59.2%. In 44.4%, systolic blood pressure was maintained between 140-180mmHg, and diastolic blood pressure<105mmHg. Glycaemic levels were taken in 81.5% of hospitals. Intravenous heparinisation was performed during the procedure in 66.7% with different patterns of action. In cases of moderate neurological deterioration with no added complications, 85.2% of the included hospitals awakened and extubated the patients. The wide variability observed in the anaesthetic management and the organization of the endovascular treatment of AIS demonstrates the need to create common guidelines for anaesthesiologists in Spain. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Evidence HDAC9 genetic variant associated with ischaemic stroke increases risk via promoting carotid atherosclerosis

PubMed Central

Markus, Hugh S; Mäkelä, Kari-Matti; Bevan, Steve; Raitoharju, Emma; Oksala, Niku; Bis, Joshua C.; O’Donnell, Chris; Hainsworth, Atticus; Lehtimäki, Terho

2014-01-01

Background and purpose A novel association between a single nucleotide polymorphism (SNP) on chromosome 7p21.1 and large vessel ischaemic stroke, was recently identified. The most likely underlying gene is histone deacetylase 9 (HDAC9). The mechanism by which HDAC9 increases stroke risk is not clear; both vascular and neuronal mechanisms have been proposed. Methods We determined whether the lead SNPs were associated with asymptomatic carotid plaque (N=25179) and carotid intima-media thickness (N=31210) detected by carotid ultrasound in a meta-analysis of population based and community cohorts. Immunohistochemistry was used to determine whether HDAC9 was expressed in healthy human cerebral and systemic arteries. In the Tampere Vascular Study we determined whether HDAC9 mRNA expression was altered in carotid (N=29), abdominal aortic (N=15) and femoral (N=24) atherosclerotic plaques compared with control (left internal thoracic, N=28) arteries. Results Both SNPs (rs11984041 and rs2107595) were associated with common carotid IMT (rs2107595 p=0.0018) and with presence of carotid plaque (rs2107595 p=0.0022). In both cerebral and systemic arteries, HDAC9 labelling was seen in nuclei and cytoplasm of vascular smooth muscle cells, and in endothelial cells. HDAC9 expression was upregulated in carotid plaques compared to left internal thoracic controls (p=0.00000103). It was also up-regulated in aortic and femoral plaques compared to controls, with mRNA expression increased in carotid compared with femoral plaques (p=0.0038). Conclusions Our results are consistent with the 7p21.1 association acting via promoting atherosclerosis, and consistent with alterations in HDAC9 expression mediating this increased risk. Further studies in experimental models are required to confirm this link. PMID:23449258

Aspirin use and chronic diseases: a cohort study of the elderly.

PubMed Central

Paganini-Hill, A.; Chao, A.; Ross, R. K.; Henderson, B. E.

1989-01-01

OBJECTIVE--To evaluate the associations between the use of aspirin and the incidences of cardiovascular diseases, cancers, and other chronic diseases. DESIGN--Postal questionnaire survey to elicit details of aspirin use. SETTING--Californian retirement community. SUBJECTS--All 22,781 residents of the community (white, affluent, and well educated) were sent a questionnaire that included questions on medical history and the use of drugs such as analgesics, laxatives, and vitamin supplements. In all 61% responded (13,987, 8881 women and 5106 men; median age 73). They formed the cohort that was followed up for 6 1/2 years using discharge summaries from three hospitals serving the area and death certificates from the health department. Only 13 respondents were lost to follow up but seemed not to have died. MAIN OUTCOME MEASURES--Incidences of cardiovascular diseases, cancers, gastrointestinal bleeding, ulcers, and cataracts were compared in participants who did and did not take aspirin daily. RESULTS--Age adjusted incidences were computed with an internal standard and five age groups. By 1 January 1988 there had been 25 incident cases of kidney cancer among all participants; 341 incident cases of stroke, 253 of acute myocardial infarction, 220 of ischaemic heart disease, and 317 of other heart disease were reported among respondents without a reported history of angina, myocardial infarction, or stroke. The incidence of kidney cancer was raised among those who took aspirin daily compared with those who did not take it, although the increase was significant only in men (relative risks = 6.3, 95% confidence interval 2.2 to 17, for men and 2.1, 0.53 to 8.5, for women). Those who took aspirin daily showed no increased risk of any other cancer, except colon cancer for both sexes combined (relative risk = 1.5, 1.1 to 2.2). The risk of acute myocardial infarction was reduced slightly among regular users of aspirin in men but not women. The risk of ischaemic heart disease was almost doubled in those who took aspirin daily compared with non-users (relative risks = 1.9, 1.1 to 3.1, for men and 1.7, 1.1 to 2.7, for women). Small, non-significant increased risks of stroke were observed in both sexes. CONCLUSION--The daily use of aspirin increased the risk of kidney cancer and ischaemic heart disease. PMID:2513898

[Prevention of cerebrovascular complications in coronary artery bypass grafting].

PubMed

Mialiuk, P A; Marchenko, A V; Arutiunian, V B; Chragian, V A; Alekseevich, G Iu; Vronskiĭ, A S

The authors carried out a comparative analysis of the incidence rate of cerebrovascular complications following coronary artery bypass grafting performed using either a differentiated approach to surgical policy depending on the findings of epiaortic ultrasonographic scanning or the standard conventional approach. A total of 3,454 operations of coronary artery bypass grafting were performed. All patients were divided into two groups. Patients of the Study Group (n=765) were subjected to obligatory intraoperative epiaortic scanning, with the variant of further surgical intervention depending on the obtained findings of the examination. The Control Group patients (n=2,689) underwent standard coronary artery bypass grafting in the conditions of artificial circulation (AC). In the Study Group patients, depending on the degree and localization of the atherosclerotic lesion of the aorta, determined by the findings of epiaortic scanning, one of the following techniques of coronary artery bypass grafting (CABG) was chosen: cases with no lesion were managed by CABG with AC (585 patients); a local solitary lesion was managed by altering the site of cannulation and application of the clamp (92 patients) or by the operation according to the 'single clamp' technique (43 patients); cases of manifested atherosclerosis of the ascending aorta were treated by the 'on-pump beating-heart' technique in the conditions of AC without placing clamps (27 patients); cases of massive involvement of the ascending aorta and aortic arch were managed by CABG performed according to the 'no-touch aorta' technique (18 patients). The total mortality rate amounted to 1.1%. Thirty-three (0.96%) patients in the postoperative period were found to have ischaemic stroke. The mortality rate in the Control Group amounted to 1.4% and that in the Study Group equalled 0.3%, with the number of cases of ischaemic strokes amounting to 33 (1.4%) and 0, respectively. Perioperative infarction was diagnosed in 16 (0.6%) cases in the Control Group and in 5 (0.7%) patients in the group treated using the differentiated approach. A conclusion was drawn that the differentiated approach to choosing the technique of CABG based on the findings obtained by means of epiaortic scanning was associated with a statistically significant decrease in both the number of ischaemic strokes and the mortality rate after CABG operations.

Systematic preoperative coronary angiography and stenting improves postoperative results of carotid endarterectomy in patients with asymptomatic coronary artery disease: a randomised controlled trial.

PubMed

Illuminati, G; Ricco, J-B; Greco, C; Mangieri, E; Calio', F; Ceccanei, G; Pacilè, M A; Schiariti, M; Tanzilli, G; Barillà, F; Paravati, V; Mazzesi, G; Miraldi, F; Tritapepe, L

2010-02-01

To evaluate the usefulness of systematic coronary angiography followed, if needed, by coronary artery angioplasty (percutaneous coronary intervention (PCI)) on the incidence of cardiac ischaemic events after carotid endarterectomy (CEA) in patients without evidence of coronary artery disease (CAD). From January 2005 to December 2008, 426 patients, candidates for CEA, with no history of CAD and with normal cardiac ultrasound and electrocardiography (ECG), were randomised into two groups. In group A (n=216) all the patients had coronary angiography performed before CEA. In group B, all the patients had CEA without previous coronary angiography. In group A, 66 patients presenting significant coronary artery lesions at angiography received PCI before CEA. They subsequently underwent surgery under aspirin (100 mg day(-1)) and clopidogrel (75 mg day(-1)). CEA was performed within a median delay of 4 days after PCI (range: 1-8 days). Risk factors, indications for CEA and surgical techniques were comparable in both groups (p>0.05). The primary combined endpoint of the study was the incidence of postoperative myocardial ischaemic events combined with the incidence of complications of coronary angiography. Secondary endpoints were death and stroke rates after CEA and incidence of cervical haematoma. Postoperative mortality was 0% in group A and 0.9% in group B (p=0.24). One postoperative stroke (0.5%) occurred in group A, and two (0.9%) in group B (p=0.62). No postoperative myocardial event was observed in group A, whereas nine ischaemic events were observed in group B, including one fatal myocardial infarction (p=0.01). Binary logistic regression analysis demonstrated that preoperative coronary angiography was the only independent variable that predicted the occurrence of postoperative coronary ischaemia after CEA. The odds ratio for coronary angiography (group A) indicated that when holding all other variables constant, a patient having preoperative coronary angiography before carotid surgery was 4 times less likely to have a cardiac ischaemic event after carotid surgery. No complications related to coronary angiography were observed and no cervical haematomas occurred in patients undergoing surgery under aspirin and clopidogrel in this study. Systematic preoperative coronary angiography, possibly followed by PCI, significantly reduces the incidence of postoperative myocardial events after CEA in patients without clinical evidence of CAD. Copyright (c) 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Too good to treat? Outcomes in patients not receiving thrombolysis due to mild deficits or rapidly improving symptoms.

PubMed

Willey, Joshua Z; Stillman, Joshua; Rivolta, Juan A; Vieira, Julio; Doyle, Margaret M; Linares, Guillermo; Marchidann, Adrian; Elkind, Mitchell S V; Boden-Albala, Bernadette; Marshall, Randolph S

2012-04-01

Among ischemic stroke patients arriving within the treatment window, rapidly improving symptoms or having a mild deficit (i.e. too good to treat) is a common reason for exclusion. Several studies have reported poor outcomes in this group. We addressed the question of early neurological deterioration in too good to treat patients in a larger prospective cohort study. Admission and discharge information were collected prospectively in acute stroke patients who presented to the emergency room within three-hours from onset. The primary outcome measure was change in the National Institutes of Health Stroke Scale from baseline to discharge. Secondary outcomes were discharge National Institutes of Health Stroke Scale >4, not being discharged home, and discharge modified Rankin scale. Of 355 patients who presented within three-hours, 127 (35·8%) had too good to treat listed as the only reason for not receiving thrombolysis, with median admission National Institutes of Health Stroke Scale = 1 (range = 0 to 19). At discharge, seven (5·5%) showed a worsening of National Institutes of Health Stroke Scale ≥1, and nine (7·1%) had a National Institutes of Health Stroke Scale >4. When excluding prior stroke (remaining n = 97), discharge status was even more benign: only five (5·2%) had a discharge National Institutes of Health Stroke Scale >4, and two (2·1%) patients were not discharged home. We found that a small proportion of patients deemed too good to treat will have early neurological deterioration, in contrast to other studies. Decisions about whether to treat mild stroke patients depend on the outcome measure chosen, particularly when considering discharge disposition among patients who have had prior stroke. The decision to thrombolyze may ultimately rest on the nature of the presentation and deficit. © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.

PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model.

PubMed

Low, Pei Ching; Manzanero, Silvia; Mohannak, Nika; Narayana, Vinod K; Nguyen, Tam H; Kvaskoff, David; Brennan, Faith H; Ruitenberg, Marc J; Gelderblom, Mathias; Magnus, Tim; Kim, Hyun Ah; Broughton, Brad R S; Sobey, Christopher G; Vanhaesebroeck, Bart; Stow, Jennifer L; Arumugam, Thiruma V; Meunier, Frédéric A

2014-03-14

Stroke is a major cause of death worldwide and the leading cause of permanent disability. Although reperfusion is currently used as treatment, the restoration of blood flow following ischaemia elicits a profound inflammatory response mediated by proinflammatory cytokines such as tumour necrosis factor (TNF), exacerbating tissue damage and worsening the outcomes for stroke patients. Phosphoinositide 3-kinase delta (PI3Kδ) controls intracellular TNF trafficking in macrophages and therefore represents a prospective target to limit neuroinflammation. Here we show that PI3Kδ inhibition confers protection in ischaemia/reperfusion models of stroke. In vitro, restoration of glucose supply following an episode of glucose deprivation potentiates TNF secretion from primary microglia-an effect that is sensitive to PI3Kδ inhibition. In vivo, transient middle cerebral artery occlusion and reperfusion in kinase-dead PI3Kδ (p110δ(D910A/D910A)) or wild-type mice pre- or post-treated with the PI3Kδ inhibitor CAL-101, leads to reduced TNF levels, decreased leukocyte infiltration, reduced infarct size and improved functional outcome. These data identify PI3Kδ as a potential therapeutic target in ischaemic stroke.

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

PubMed

Zanchetti, Alberto; Liu, Lisheng; Mancia, Giuseppe; Parati, Gianfranco; Grassi, Guido; Stramba-Badiale, Marco; Silani, Vincenzo; Bilo, Grzegorz; Corrao, Giovanni; Zambon, Antonella; Scotti, Lorenza; Zhang, Xinhua; Wang, HayYan; Zhang, Yuqing; Zhang, Xuezhong; Guan, Ting Rui; Berge, Eivind; Redon, Josep; Narkiewicz, Krzysztof; Dominiczak, Anna; Nilsson, Peter; Viigimaa, Margus; Laurent, Stéphane; Agabiti-Rosei, Enrico; Wu, Zhaosu; Zhu, Dingliang; Rodicio, José Luis; Ruilope, Luis Miguel; Martell-Claros, Nieves; Pinto, Fernando; Schmieder, Roland E; Burnier, Michel; Banach, Maciej; Cifkova, Renata; Farsang, Csaba; Konradi, Alexandra; Lazareva, Irina; Sirenko, Yuriy; Dorobantu, Maria; Postadzhiyan, Arman; Accetto, Rok; Jelakovic, Bojan; Lovic, Dragan; Manolis, Athanasios J; Stylianou, Philippos; Erdine, Serap; Dicker, Dror; Wei, Gangzhi; Xu, Chengbin; Xie, Hengge; Coca, Antonio; O'Brien, John; Ford, Gary

2014-09-01

The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125  mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8  mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. It has been calculated that 925 patients would reach the primary outcome after a mean 4-year follow-up, and this should provide at least 80% power to detect a 25% stroke difference between SBP targets and a 20% difference between LDL-C targets.

Barriers to medication adherence for the secondary prevention of stroke: a qualitative interview study in primary care.

PubMed

Jamison, James; Graffy, Jonathan; Mullis, Ricky; Mant, Jonathan; Sutton, Stephen

2016-08-01

Medications are highly effective at reducing risk of recurrent stroke, but success is influenced by adherence to treatment. Among survivors of stroke and transient ischaemic attack (TIA), adherence to medication is known to be suboptimal. To identify and report barriers to medication adherence for the secondary prevention of stroke/TIA. A qualitative interview study was conducted within general practice surgeries in the East of England, UK. Patients were approached by letter and invited to take part in a qualitative research study. Semi-structured interviews were undertaken with survivors of stroke, caregivers, and GPs to explore their perspectives and views around secondary prevention and perceived barriers to medication adherence. Key themes were identified using a grounded theory approach. Verbatim quotes describing the themes are presented here. In total, 28 survivors of stroke, including 14 accompanying caregivers and five GPs, were interviewed. Two key themes were identified. Patient level barriers included ability to self-care, the importance people attach to a stroke event, and knowledge of stroke and medication. Medication level barriers included beliefs about medication and beliefs about how pills work, medication routines, changing medications, and regimen complexity and burden of treatment. Patients who have had a stroke are faced with multiple barriers to taking secondary prevention medications in UK general practice. This research suggests that a collaborative approach between caregivers, survivors, and healthcare professionals is needed to address these barriers and facilitate medication-taking behaviour. © British Journal of General Practice 2016.

Acupuncture for neurogenesis in experimental ischemic stroke: a systematic review and meta-analysis.

PubMed

Lu, Lin; Zhang, Xiao-guang; Zhong, Linda L D; Chen, Zi-xian; Li, Yan; Zheng, Guo-qing; Bian, Zhao-xiang

2016-01-20

Acupuncture has been used for patients with stroke and post-stroke rehabilitation for thousands of years. Previous studies reported that acupuncture enhanced stroke recovery through neurogenesis. Hence, we conducted a systematic review and meta-analysis for preclinical studies to assess the current evidence for acupuncture effect on neurogenesis in treating ischaemic stroke. Studies were obtained from six databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, VIP information database, and Chinese Biomedical Literature Database, Ultimately, 34 studies containing 1617 animals were identified. Neurogenesis markers of Brdu, Nestin, PSA-NCAM, NeuN and GFAP were selected as major outcomes. The pooled results of 15 studies marked with Brdu showed significant effects of acupuncture for improving proliferation when compared with control groups (P < 0.01); 13 studies marked with Nestin showed significant effects of acupuncture for increasing proliferation when compared with control groups (P < 0.01); 4 studies marked with PSA-NCAM showed significant effects of acupuncture for enhancing migration when compared with control groups (P < 0.01); 4 studies marked with NeuN showed significant effects of acupuncture for stimulating differentiation when compared with control groups (P < 0.01). The findings suggest that acupuncture is a prospective therapy targeting neurogenesis for ischemic stroke.

Cerebral Metastases of Lung Cancer Mimicking Multiple Ischaemic Lesions - A Case Report and Review of Literature.

PubMed

Zacharzewska-Gondek, Anna; Maksymowicz, Hanna; Szymczyk, Małgorzata; Sąsiadek, Marek; Bladowska, Joanna

2017-01-01

Restricted diffusion that is found on magnetic resonance diffusion-weighted imaging (DWI) typically indicates acute ischaemic stroke. However, restricted diffusion can also occur in other diseases, like metastatic brain tumours, which we describe in this case report. A 57-year-old male, with a diagnosis of small-cell cancer of the right lung (microcellular anaplastic carcinoma), was admitted with focal neurological symptoms. Initial brain MRI revealed multiple, disseminated lesions that were hyperintense on T2-weighted images and did not enhance after contrast administration; notably, some lesions manifested restricted diffusion on DWI images. Based on these findings, disseminated ischaemic lesions were diagnosed. On follow-up MRI that was performed after 2 weeks, we observed enlargement of the lesions; there were multiple, disseminated, sharply outlined, contrast-enhancing, oval foci with persistent restriction of diffusion. We diagnosed the lesions as disseminated brain metastases due to lung cancer. To our knowledge, this is the first description of a patient with brain metastases that were characterised by restricted diffusion and no contrast enhancement. Multiple, disseminated brain lesions, that are characterised by restricted diffusion on DWI, typically indicate acute or hyperacute ischemic infarcts; however, they can also be due to hypercellular metastases, even if no contrast enhancement is observed. This latter possibility should be considered particularly in patients with cancer.

Predictors of short- and long-term mortality in first-ever ischaemic older stroke patients.

PubMed

Hsu, Chia-Yu; Hu, Gwo-Chi; Chen, Yi-Min; Chen, Chiu-Hsiang; Hu, Yu-Ning

2013-12-01

Predictors of short- and long-term all-cause mortality of older stroke patients were explored. Cox regression models were used to estimate the relative risk and 95% confidence intervals (CI) in the database entries of 636 older stroke patients aged 70 years and over. National Institutes of Health Stroke Scale (NIHSS) score on admission, age and coronary heart disease were significantly associated with 28-day death. The hazard ratios for the predictors of long-term mortality were as follows: NIHSS score, 1.1 (95% CI: 1.07-1.1); serum glucose level, 1.08 (95% CI: 1.01-1.2); serum triglyceride level, 0.6 (95% CI: 0.4-0.8); age, 1.04 (95% CI: 1.01-1.08); and coronary heart disease, 2.7 (95% CI: 1.4-5.4). NIHSS score on admission, age and coronary heart disease are independent predictors of short- and long-term mortality. Higher glucose and lower triglyceride level are significantly associated with the long-term mortality. © 2013 The Authors. Australasian Journal on Ageing © 2013 ACOTA.

Internal carotid artery occlusion and stroke as a complication of cisplatin-based chemotherapy for metastatic testicular germ cell tumour.

PubMed

Cerrud-Rodriguez, Roberto Christian; Quinteros, Maria Gabriela; Azam, Mohammed

2017-06-18

Testicular tumours are the most common tumours in young men. Germ cell tumours (GCTs) account for 95% of all testicular cancers, and the non-seminomatous type (NSGCT) accounts for 50% of all GCTs. Cisplatin-based chemotherapy is curative in up to 90% of patients, but it is not without its inherent risks. Ischaemic stroke is a very uncommon, but severe complication of cisplatin-based chemotherapy. Strokes in young patients cause a disproportionately large economic impact by leaving victims disabled during their most productive years and strains the healthcare system with expensive hospital stays. We present a case of a young male patient with past medical history of metastatic NSGCT with the sudden onset of dysarthria, left hemiplegia and ipsilateral hemisensory loss 3 days after receiving cisplatin-based chemotherapy. Subsequent studies revealed a stroke involving the right middle cerebral artery territory secondary to an acute right internal carotid occlusion. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Detection of cerebral amyloid angiopathy by 3-T magnetic resonance imaging and amyloid positron emission tomography in a patient with subcortical ischaemic vascular dementia.

PubMed

Kida, Hirotaka; Satoh, Masayuki; Ii, Yuichiro; Fukuyama, Hidenao; Maeda, Masayuki; Tomimoto, Hidekazu

2017-01-01

The patient was an 81-year-old man who had been treated for hypertension for several decades. In 2012, he developed gait disturbance and mild amnesia. One year later, his gait disturbance worsened, and he developed urinary incontinence. Conventional brain magnetic resonance imaging using T 2 -weighted images and fluid-attenuated inversion recovery showed multiple lacunar infarctions. These findings fulfilled the diagnostic criteria for subcortical ischaemic vascular dementia. However, susceptibility weighted imaging showed multiple lobar microbleeds in the bilateral occipitoparietal lobes, and double inversion recovery and 3-D fluid-attenuated inversion recovery images on 3-T magnetic resonance imaging revealed cortical microinfarctions in the left parietal-temporo-occipito region. Pittsburgh compound B-positron emission tomography revealed diffuse uptake in the cerebral cortex. Therefore, we diagnosed the patient with subcortical ischaemic vascular dementia associated with Alzheimer's disease. The use of the double inversion recovery and susceptibility weighted imaging on 3-T magnetic resonance imaging may be a supplemental strategy for diagnosing cerebral amyloid angiopathy, which is closely associated with Alzheimer's disease. © 2016 The Authors. Psychogeriatrics © 2016 Japanese Psychogeriatric Society.

Estimates of stroke incidence and case fatality in Zabrze, 2005-2006.

PubMed

Wawrzyńczyk, Maciej; Pierzchała, Krystyna; Braczkowska, Bogumiła; Mańka-Gaca, Iwona; Kumor, Klaudiusz; Borowski, Daniel; Grodzicka-Zawisza, Lucyna; Zejda, Jan

2011-01-01

Epidemiological rates for stroke obtained in the United States and Western Europe indicate a decrease in incidence and case fatality. Data published for Poland, as for other Central-Eastern European countries, reported unfavourable results, but this was based on data from the 1990s. The authors evaluated current stroke rates in a population study of the southern Poland city of Zabrze. A retrospective registry of all stroke cases treated in Zabrze, southern Poland, in 2005-2006, was established, based on data from the National Health Fund. Cases were identified by verifying patient files. Epidemiological rates were calculated and standardized to the European population in both groups: all stroke patients, including recurrent (all strokes, AS), and patients with first-ever stroke (FES) in their history. We registered 731 strokes, including 572 FES cases (78.3%) and 159 recurrent strokes (21.7%). There were 385 strokes in men (52.7%), and 346 in women (47.2%); 88.6% were ischaemic strokes (IS), and 11.4% were intra-ce-rebral haemorrhages (ICH). The standardized incidence rate for AS patients was 167/100 000 (211 for men, 130 for women), and in the FES group 131/100 000 (161 for men, 104 for women). Twenty-eight day case fatality for the AS group was 18.3% (15.4% for IS, 41% for ICH), and 16.6% for FES (13.4% for IS, 40.9% for ICH). Incidence rates in this southern Poland city are comparable to those reported previously for Poland. Early case fatality decreased, compared to previous data, probably as a result of improved management of acute stroke and hospitalizing all stroke patients.

Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2

PubMed Central

Diener, Hans-Christoph; Aisenberg, James; Ansell, Jack; Atar, Dan; Breithardt, Günter; Eikelboom, John; Ezekowitz, Michael D.; Granger, Christopher B.; Halperin, Jonathan L.; Hohnloser, Stefan H.; Hylek, Elaine M.; Kirchhof, Paulus; Lane, Deirdre A.; Verheugt, Freek W.A.; Veltkamp, Roland; Lip, Gregory Y.H.

2017-01-01

The choice of oral anticoagulant (OAC) for patients with atrial fibrillation (AF) may be influenced by individual clinical features or by patterns of risk factors and comorbidities. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. non-vitamin K oral anticoagulants (NOACs) for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In addition, we discuss the timing of initiation of anticoagulation. In the second of a two-part review, we discuss the use of NOAC for stroke prevention in the following subgroups of patients with AF: (vii) secondary stroke prevention in patients after stroke or transient ischaemic attack (TIA), (viii) patients with acute stroke requiring thrombolysis or thrombectomy, (ix) those initiating or restarting OAC treatment after stroke or TIA, (x) those with renal impairment on dialysis, (xi) the elderly, (xii) those at high risk of gastrointestinal bleeding, and (xiii) those with hypertension. In addition, we discuss adherence and compliance. Finally, we present a summary of treatment suggestions. In specific subgroups of patients with AF, evidence supports the use of particular NOACs and/or particular doses of anticoagulant. The appropriate choice of treatment for these subgroups will help to promote optimal clinical outcomes. PMID:26848150

Improving the management and referral of patients with transient ischaemic attacks: a change strategy for a health community

PubMed Central

Wright, J; Harrison, S; McGeorge, M; Patterson, C; Russell, I; Russell, D; Small, N; Taylor, M; Walsh, M; Warren, E; Young, J

2006-01-01

Problem Rapid referral and management of patients with transient ischaemic attacks is a key component in the national strategy for stroke prevention. However, patients with transient ischaemic attacks are poorly identified and undertreated. Design and setting Before and after evaluation of quality improvement programme with controlled comparison in three primary care trusts reflecting diverse populations and organisational structures in an urban district in the North of England. Key measures for improvement The proportion of patients receiving antiplatelet drugs and safe driving advice on referral to a speciality clinic, and the numbers of referrals, adjusted for age, to the specialist clinic before and after the improvement programme. Strategies for change Interviews with patient and professionals to identify gaps and barriers to good practice; development of evidence based guidelines for the management of patients with transient ischaemic attacks; interactive multidisciplinary workshops for each primary care trust with feedback of individual audit results of referral practice; outreach visits to teams who were unable to attend the workshops; referral templates and desktop summaries to provide reminders of the guidelines to clinicians; incorporation of standards into professional contracts. Effects of change A significant improvement occurred in identification and referral of patients with transient ischaemic attacks to specialist clinics, with a 41% increase in referrals from trained practices compared with control practices. There were also significant improvements in the early treatment and safety advice provided to patients before referral. Lessons learnt A strategic approach to effective quality improvement across a diverse health community is feasible and achievable. Careful planning with patient and professional involvement to develop a tailored and multifaceted quality improvement programme to implement evidence based practice can work in very different primary care settings. Key components of the effectiveness of the model include contextual analysis, strong professional support, clear recommendations based on robust evidence, simplicity of adoption, good communication, and use of established networks and opinion leaders. PMID:16456203

Improving the management and referral of patients with transient ischaemic attacks: a change strategy for a health community.

PubMed

Wright, J; Harrison, S; McGeorge, M; Patterson, C; Russell, I; Russell, D; Small, N; Taylor, M; Walsh, M; Warren, E; Young, J

2006-02-01

Rapid referral and management of patients with transient ischaemic attacks is a key component in the national strategy for stroke prevention. However, patients with transient ischaemic attacks are poorly identified and undertreated. Before and after evaluation of quality improvement programme with controlled comparison in three primary care trusts reflecting diverse populations and organisational structures in an urban district in the North of England. The proportion of patients receiving antiplatelet drugs and safe driving advice on referral to a specialty clinic, and the numbers of referrals, adjusted for age, to the specialist clinic before and after the improvement programme. Interviews with patient and professionals to identify gaps and barriers to good practice; development of evidence based guidelines for the management of patients with transient ischaemic attacks; interactive multidisciplinary workshops for each primary care trust with feedback of individual audit results of referral practice; outreach visits to teams who were unable to attend the workshops; referral templates and desktop summaries to provide reminders of the guidelines to clinicians; incorporation of standards into professional contracts. A significant improvement occurred in identification and referral of patients with transient ischaemic attacks to specialist clinics, with a 41% increase in referrals from trained practices compared with control practices. There were also significant improvements in the early treatment and safety advice provided to patients before referral. A strategic approach to effective quality improvement across a diverse health community is feasible and achievable. Careful planning with patient and professional involvement to develop a tailored and multifaceted quality improvement programme to implement evidence based practice can work in very different primary care settings. Key components of the effectiveness of the model include contextual analysis, strong professional support, clear recommendations based on robust evidence, simplicity of adoption, good communication, and use of established networks and opinion leaders.

Magnetic resonance imaging detection of multiple ischemic injury produced in an adult rat model of minor stroke followed by mild transient cerebral ischemia.

PubMed

Tuor, Ursula I; Qiao, Min

2017-04-01

To determine whether cumulative brain damage produced adjacent to a minor stroke that is followed by a mild transient ischemia is detectable with MRI and histology, and whether acute or chronic recovery between insults influences this damage. A minor photothrombotic (PT) stroke was followed acutely (1-2 days) or chronically (7 days) by a mild transient middle cerebral artery occlusion (tMCAO). MRI was performed after each insult, followed by final histology. The initial PT produced small hyperintense T 2 and DW infarct lesions and peri-lesion regions of scattered necrosis and modestly increased T 2 . Following tMCAO, in a slice and a region adjacent to the PT, a region of T 2 augmentation was observed when recovery between insults was acute but not chronic. Within the PT slice, a modest region of exacerbated T 2 change proximate to the PT was also observed in the chronic group. Corresponding histological changes within regions of augmented T 2 included increased vacuolation and cell death. Within regions adjacent to an experimental minor stroke, a recurrence of a mild transient cerebral ischemia augmented T 2 above increases produced by tMCAO alone, reflecting increased damage in this region. Exacerbation appeared broader with acute versus chronic recovery between insults.

Facebook: can it be a diagnostic tool for neurologists?

PubMed Central

Mittal, Manoj K; Sloan, Jeff A; Rabinstein, Alejandro A

2012-01-01

A 56-year-old woman presented with acute ischaemic stroke with NIHSS 13. She had right eye ptosis and miosis. She and her husband were not sure if her facial features were different than usual. With her consent, we compared her face with her pictures on Facebook. In the absence of any ptosis or miosis in her pictures, she was diagnosed with acute Horner syndrome. Facebook may be a useful tool for the neurologists to define the timing of facial neurological signs. PMID:22914235

Nitrogen balance in patients with hemiparetic stroke during the subacute rehabilitation phase.

PubMed

Wada, A; Kawakami, M; Otsuka, T; Aoki, H; Anzai, A; Yamada, Y; Liu, F; Otaka, E; Akaboshi, K; Liu, M

2017-06-01

In highly invasive diseases, metabolism commonly changes. Hypercatabolism is frequent in acute stroke, and nitrogen balance tends to be negative. However, there has been no study describing nitrogen balance in subacute and chronic stroke patients. The present study aimed to examine nitrogen balance in the subacute and chronic phases and to identify the factors related to it. Nitrogen balance was calculated from the collected urine of 56 patients with subacute stroke [mean (SD) 53.8 (18.4) days post-stroke] who were admitted for rehabilitation for their first-ever ischaemic or nonsurgical haemorrhagic stroke. In the first experiment, their nitrogen balance was measured during the rehabilitation phase, and factors (type, severity of hemiparesis, activities of daily living, dysphagia and malnutrition status) related to it were evaluated. The second experiment was performed to describe the time course of nitrogen balance in 31 consecutive patients, with assessments made at admission and at discharge. Nitrogen balance was positive in all patients in the subacute phase. A significant difference was seen in nitrogen balance between high and low fat-free mass in male patients. In the chronic phase, nitrogen balance was positive in 96% of the patients. There was no significant difference in nitrogen balance between discharge and admission. In the subacute and chronic phases of stroke, it was confirmed that hypercatabolism had resolved and that intensive rehabilitation is possible in the convalescent period of stroke. © 2017 The British Dietetic Association Ltd.

Code stroke in Asturias.

PubMed

Benavente, L; Villanueva, M J; Vega, P; Casado, I; Vidal, J A; Castaño, B; Amorín, M; de la Vega, V; Santos, H; Trigo, A; Gómez, M B; Larrosa, D; Temprano, T; González, M; Murias, E; Calleja, S

2016-04-01

Intravenous thrombolysis with alteplase is an effective treatment for ischaemic stroke when applied during the first 4.5 hours, but less than 15% of patients have access to this technique. Mechanical thrombectomy is more frequently able to recanalise proximal occlusions in large vessels, but the infrastructure it requires makes it even less available. We describe the implementation of code stroke in Asturias, as well as the process of adapting various existing resources for urgent stroke care in the region. By considering these resources, and the demographic and geographic circumstances of our region, we examine ways of reorganising the code stroke protocol that would optimise treatment times and provide the most appropriate treatment for each patient. We distributed the 8 health districts in Asturias so as to permit referral of candidates for reperfusion therapies to either of the 2 hospitals with 24-hour stroke units and on-call neurologists and providing IV fibrinolysis. Hospitals were assigned according to proximity and stroke severity; the most severe cases were immediately referred to the hospital with on-call interventional neurology care. Patient triage was provided by pre-hospital emergency services according to the NIHSS score. Modifications to code stroke in Asturias have allowed us to apply reperfusion therapies with good results, while emphasising equitable care and managing the severity-time ratio to offer the best and safest treatment for each patient as soon as possible. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials.

PubMed

Bath, Philip M; Woodhouse, Lisa; Krishnan, Kailash; Anderson, Craig; Berge, Eivind; Ford, Gary A; Robinson, Thompson G; Saver, Jeffrey L; Sprigg, Nikola; Wardlaw, Joanna M; In Acute Stroke Collaboration Basc, Blood Pressure

2016-01-01

Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4-6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34-0.78) and reduced death (OR 0.32, 95% CI 0.14-0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.

Barriers and facilitators to staying in work after stroke: insight from an online forum.

PubMed

Balasooriya-Smeekens, Chantal; Bateman, Andrew; Mant, Jonathan; De Simoni, Anna

2016-04-06

To explore barriers and facilitators to staying in work following stroke. Qualitative analysis of posts regarding staying in work following stroke using the archives of an online forum for stroke survivors. 60 stroke survivors (29 male, 23 female, 8 not stated; mean age at stroke 44 years) who have returned to work, identified using terms 'return to work' and 'back at work'. Posts from UK stroke survivors and family members on Talkstroke, the forum of the Stroke Association, between 2004 and 2011. Stroke and transient ischaemic attack (TIA) survivors reported residual impairments that for many had impact on work. Most impairments were 'invisible', including fatigue, problems with concentration, memory and personality changes. Participants described positive (eg, back at work being better than expected) and negative work experiences, including being at risk of losing the job because of stroke-related impairments. Barriers to successfully staying in work included lack of understanding of stroke--in particular invisible impairments--of survivors, employers and general practitioners (GPs), and lack of support in terms of formal adjustments, and 'feeling supported'. Stroke survivors described how they developed their own coping strategies, and how workplace and employer helped them to stay in work. Despite having been able to return to work after a stroke, people may still experience difficulties in staying in work and risking losing their job. There is a need to improve awareness, in particular of invisible stroke-related impairments, among stroke survivors, work personnel and clinicians. This might be achieved through improved assessments of residual impairments in the workplace and in general practice. Future studies should investigate the effect of unrecognised fatigue and invisible impairments on staying in work following stroke, and explore the potential role for primary care in supporting stroke survivors who have returned to employment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Enjoyable company in sharing stroke experiences; - lifestyle groups after stroke.

PubMed

Lund, Anne; Melhus, Mali; Sveen, Unni

2018-03-01

Even people with mild to moderate stroke will experience changes in their abilities to perform everyday occupations. Group interventions may be appropriate in late-stage rehabilitation. The aim of this study was to explore how the participants involved themselves in person-centered lifestyle groups after stroke in Norway. Semi-structured interviews were performed with six older adults with mild-to-moderate stroke who had participated in lifestyle groups over a period of nine months. The interviews were analyzed using qualitative content analysis. The participants involved themselves in the lifestyle groups in a variety of ways by creating enjoyable company in sharing stroke experiences, sharing knowledgeable interest, pushing and forcing each other forward and reflecting on self-worth. Through doing group activities together, they created various ways of being, belonging and becoming, addressing development of strategies for regaining self-belief and a sense of autonomy, and for adapting to everyday life post-stroke. The participants were active contributors in the groups and pushed each other and themselves regarding involvement in meaningful occupations. This active participation seemed to bring the participants' resources into focus and contrasted with the frequent negative perceptions of people post-stroke as 'victims'.

Barriers and facilitators to staying in work after stroke: insight from an online forum

PubMed Central

Balasooriya-Smeekens, Chantal; Bateman, Andrew; Mant, Jonathan; De Simoni, Anna

2016-01-01

Objective To explore barriers and facilitators to staying in work following stroke. Design Qualitative analysis of posts regarding staying in work following stroke using the archives of an online forum for stroke survivors. Participants 60 stroke survivors (29 male, 23 female, 8 not stated; mean age at stroke 44 years) who have returned to work, identified using terms ‘return to work’ and ‘back at work’. Setting Posts from UK stroke survivors and family members on Talkstroke, the forum of the Stroke Association, between 2004 and 2011. Results Stroke and transient ischaemic attack (TIA) survivors reported residual impairments that for many had impact on work. Most impairments were ‘invisible’, including fatigue, problems with concentration, memory and personality changes. Participants described positive (eg, back at work being better than expected) and negative work experiences, including being at risk of losing the job because of stroke-related impairments. Barriers to successfully staying in work included lack of understanding of stroke—in particular invisible impairments—of survivors, employers and general practitioners (GPs), and lack of support in terms of formal adjustments, and ‘feeling supported’. Stroke survivors described how they developed their own coping strategies, and how workplace and employer helped them to stay in work. Conclusions Despite having been able to return to work after a stroke, people may still experience difficulties in staying in work and risking losing their job. There is a need to improve awareness, in particular of invisible stroke-related impairments, among stroke survivors, work personnel and clinicians. This might be achieved through improved assessments of residual impairments in the workplace and in general practice. Future studies should investigate the effect of unrecognised fatigue and invisible impairments on staying in work following stroke, and explore the potential role for primary care in supporting stroke survivors who have returned to employment. PMID:27053267

Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial

PubMed Central

Mahaffey, Kenneth W.; Stevens, Susanna R.; White, Harvey D.; Nessel, Christopher C.; Goodman, Shaun G.; Piccini, Jonathan P.; Patel, Manesh R.; Becker, Richard C.; Halperin, Jonathan L.; Hacke, Werner; Singer, Daniel E.; Hankey, Graeme J.; Califf, Robert M.; Fox, Keith A.A.; Breithardt, Günter

2014-01-01

Aims We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients. Methods and results In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73–1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59–3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10). Conclusion Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events. PMID:24132190

Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial.

PubMed

Mahaffey, Kenneth W; Stevens, Susanna R; White, Harvey D; Nessel, Christopher C; Goodman, Shaun G; Piccini, Jonathan P; Patel, Manesh R; Becker, Richard C; Halperin, Jonathan L; Hacke, Werner; Singer, Daniel E; Hankey, Graeme J; Califf, Robert M; Fox, Keith A A; Breithardt, Günter

2014-01-01

We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients. In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73-1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59-3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10). Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events.

RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID−TIA): study protocol for a pilot randomised controlled trial

PubMed Central

2013-01-01

Background People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist – that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? Methods/Design This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final TIA clinic diagnosis as the reference standard. Discussion This pilot study will be used to estimate key parameters that are needed to design the main study and to estimate the accuracy of primary care diagnosis of TIA. The planned follow-on trial will have important implications for the initial management of people with suspected TIA. Trial registration ISRCTN62019087 PMID:23819476

Perfluorocarbon Enhanced Glasgow Oxygen Level Dependent (GOLD) Magnetic Resonance Metabolic Imaging Identifies the Penumbra Following Acute Ischemic Stroke

PubMed Central

Deuchar, Graeme A; Brennan, David; Holmes, William M; Shaw, Martin; Macrae, I Mhairi; Santosh, Celestine

2018-01-01

The ability to identify metabolically active and potentially salvageable ischaemic penumbra is crucial for improving treatment decisions in acute stroke patients. Our solution involves two complementary novel MRI techniques (Glasgow Oxygen Level Dependant (GOLD) Metabolic Imaging), which when combined with a perfluorocarbon (PFC) based oxygen carrier and hyperoxia can identify penumbra due to dynamic changes related to continued metabolism within this tissue compartment. Our aims were (i) to investigate whether PFC offers similar enhancement of the second technique (Lactate Change) as previously demonstrated for the T2*OC technique (ii) to demonstrate both GOLD metabolic imaging techniques working concurrently to identify penumbra, following administration of Oxycyte® (O-PFC) with hyperoxia. Methods: An established rat stroke model was utilised. Part-1: Following either saline or PFC, magnetic resonance spectroscopy was applied to investigate the effect of hyperoxia on lactate change in presumed penumbra. Part-2; rats received O-PFC prior to T2*OC (technique 1) and MR spectroscopic imaging, which was used to identify regions of tissue lactate change (technique 2) in response to hyperoxia. In order to validate the techniques, imaging was followed by [14C]2-deoxyglucose autoradiography to correlate tissue metabolic status to areas identified as penumbra. Results: Part-1: PFC+hyperoxia resulted in an enhanced reduction of lactate in the penumbra when compared to saline+hyperoxia. Part-2: Regions of brain tissue identified as potential penumbra by both GOLD metabolic imaging techniques utilising O-PFC, demonstrated maintained glucose metabolism as compared to adjacent core tissue. Conclusion: For the first time in vivo, enhancement of both GOLD metabolic imaging techniques has been demonstrated following intravenous O-PFC+hyperoxia to identify ischaemic penumbra. We have also presented preliminary evidence of the potential therapeutic benefit offered by O-PFC. These unique theranostic applications would enable treatment based on metabolic status of the brain tissue, independent of time from stroke onset, leading to increased uptake and safer use of currently available treatment options. PMID:29556351

Preclinical drug evaluation for combination therapy in acute stroke using systematic review, meta-analysis, and subsequent experimental testing

PubMed Central

O'Collins, Victoria E; Macleod, Malcolm R; Cox, Susan F; Van Raay, Leena; Aleksoska, Elena; Donnan, Geoffrey A; Howells, David W

2011-01-01

There is some evidence that in animal models of acute ischaemic stroke, combinations of neuroprotective agents might be more efficacious than the same agents administered alone. Hence, we developed pragmatic, empirical criteria based on therapeutic target, cost, availability, efficacy, administration, and safety to select drugs for testing in combination in animal models of acute stroke. Magnesium sulphate, melatonin, and minocycline were chosen from a library of neuroprotective agents, and were tested in a more ‘realistic' model favoured by the STAIR (Stroke Therapy Academic Industry Roundtable). Outcome was assessed with infarct volume, neurologic score, and two newly developed scales measuring general health and physiologic homeostasis. Owing to the failure to achieve neuroprotection in aged, hypertensive animals with drug delivery at 3 hours, the bar was lowered in successive experiments to determine whether neuroprotection could be achieved under conditions more conducive to recovery. Testing in younger animals showed more favourable homeostasis and general health scores than did testing in older animals, but infarct volume and neurologic scores did not differ with age, and treatment efficacy was again not shown. Testing with shorter occlusions resulted in smaller infarct volumes; nevertheless, treatment efficacy was still not observed. It was concluded that this combination, in these stroke models, was not effective. PMID:20978519

How is stroke thrombolysis portrayed in UK national and London local newspapers? A review and critical discourse analysis.

PubMed

Cluckie, Gillian; Rudd, Anthony G; McKevitt, Christopher

2012-05-01

thrombolysis for stroke has been licensed in the UK since 2007 and needs to be administered within 4.5 h. Given this time critical factor, the media may have an important role in public awareness. this review aimed to find out how stroke thrombolysis was reported in UK national and London local newspapers and how treatment risks and benefits were communicated. Newspapers published between 1 January 2007 and 31 March 2010 were searched for articles on thrombolysis. Fifty-six articles were included and dispositive analysis, a qualitative analysis method, was used to identify themes. four main themes were identified: inaccurate description of thrombolysis, stroke clinicians' involvement, presentation of risks and benefits and patient stories. Inaccuracies included the presentation of thrombolysis as a treatment for transient ischaemic attack. Clinicians were quoted to suggest that thrombolysis produced complete recovery but were not reported to discuss risks or broader stroke management. The articles reported little or no risks of treatment. Patients' stories were used to reinforce that thrombolysis produces full recovery. this review found that newspaper media provides the public with inaccurate perspectives on thrombolysis. Clinicians may wish to check press articles prior to publishing and to consider the impact of reporting thrombolysis as a treatment which produces complete recovery.

Hemodynamic comparison of mild and severe preeclampsia: concept of stroke systemic vascular resistance index.

PubMed

Scardo, J; Kiser, R; Dillon, A; Brost, B; Newman, R

1996-01-01

Our purpose was to compare baseline hemodynamic parameters of mild and severe preeclampsia. Patients admitted to the Medical University Labor and Delivery Unit with the diagnosis of preeclampsia who had not received prior antihypertensive or magnesium sulfate therapy were recruited for noninvasive hemodynamic monitoring with thoracic electrical bioimpedance. After stabilization in the lateral recumbent position, hemodynamic monitoring was begun. Baseline hemodynamic parameters, mean arterial pressure (MAP), heart rate (HR), systemic vascular resistance index (SVRI), cardiac index (CI), and stroke index (SI) were recorded. Stroke systemic vascular resistance index (SSVRI), the resistance imposed by vasculature on each beat of the heart, was calculated for each patient by multiplying SVRI by HR. For statistical analysis, unpaired Student's t-tests (two-tailed) were utilized (P < 0.01). Forty-one preeclamptic patients (20 mild, 21 severe) were enrolled. Mean gestational age of severe patients was 32.2 +/- 4.0 and of mild patients was 37.0 +/- 3.5. MAP, SBP, diastolic blood pressure, HR, and SSVRI were higher in the severe group. SVRI, CI, cardiac output, and SI did not differ significantly between groups. Severe preclampsia appears to be a more intensely vasoconstricted state than mild preeclampsia. Although CI is inversely proportional to SVRI, increased HR in severe preeclampsia prevents this expected decrease in cardiac output.

Thrombolytic Treatment for Ischaemic Stroke: Could the Crisis of Confidence Have Been Avoided by Better Analysis of Trial Data?

PubMed

Barer, David; Berge, Eivind

2017-02-01

In many countries, thrombolysis with intravenous alteplase has become a central part of acute stroke care in recent years, requiring radical restructuring of services. However, a significant minority of emergency and stroke physicians have always had serious doubts about the safety and efficacy of thrombolytic treatment, and in 2015 these prompted a major review of the licensing status of alteplase by the UK regulatory authorities. Subsequent dramatic headlines and media stories have called into question the integrity of researchers and clinicians and undermined public faith in medical research. How did this situation arise and what should be done to prevent a repetition as we enter the era of intra-arterial treatment for stroke?Early intravenous alteplase increases the chances both of good recovery and of severe haemorrhage, so the risk/benefit balance must be assessed for individual patients according to stroke severity. For older patients and those with bigger strokes, the 'good recovery' criterion is an inefficient way of assessing treatment effects since few achieve full independence and differences between levels of functional impairment are ignored. This waste of information can be reduced by applying different criteria for 'good' and 'poor' outcomes in different prognostic groups (as clinicians do intuitively), hence increasing the number of patients contributing useful data. Such 'three-way prognosis-based outcome' analysis of existing and future trials could greatly increase the amount of relevant evidence to guide clinical decisions for individual patients across the range of stroke severity.

Region-specific reduction in brain volume in young adults with perinatal hypoxic-ischaemic encephalopathy.

PubMed

Bregant, Tina; Rados, Milan; Vasung, Lana; Derganc, Metka; Evans, Alan C; Neubauer, David; Kostovic, Ivica

2013-11-01

A severe form of perinatal hypoxic-ischaemic encephalopathy (HIE) carries a high risk of perinatal death and severe neurological sequelae while in mild HIE only discrete cognitive disorders may occur. To compare total brain volumes and region-specific cortical measurements between young adults with mild-moderate perinatal HIE and a healthy control group of the same age. MR imaging was performed in a cohort of 14 young adults (9 males, 5 females) with a history of mild or moderate perinatal HIE. The control group consisted of healthy participants, matched with HIE group by age and gender. Volumetric analysis was done after the processing of MR images using a fully automated CIVET pipeline. We measured gyrification indexes, total brain volume, volume of grey and white matter, and of cerebrospinal fluid. We also measured volume, thickness and area of the cerebral cortex in the parietal, occipital, frontal, and temporal lobe, and of the isthmus cinguli, parahippocampal and cingulated gyrus, and insula. The HIE patient group showed smaller absolute volumetric data. Statistically significant (p < 0.05) reductions of gyrification index in the right hemisphere, of cortical areas in the right temporal lobe and parahippocampal gyrus, of cortical volumes in the right temporal lobe and of cortical thickness in the right isthmus of the cingulate gyrus were found. Comparison between the healthy group and the HIE group of the same gender showed statistically significant changes in the male HIE patients, where a significant reduction was found in whole brain volume; left parietal, bilateral temporal, and right parahippocampal gyrus cortical areas; and bilateral temporal lobe cortical volume. Our analysis of total brain volumes and region-specific corticometric parameters suggests that mild-moderate forms of perinatal HIE lead to reductions in whole brain volumes. In the study reductions were most pronounced in temporal lobe and parahippocampal gyrus. Copyright © 2013 European Paediatric Neurology Society. All rights reserved.

Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Hoffman, Elaine B; Deenadayalu, Naveen; Ezekowitz, Michael D; Camm, A John; Weitz, Jeffrey I; Lewis, Basil S; Parkhomenko, Alexander; Yamashita, Takeshi; Antman, Elliott M

2014-03-15

Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045). This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

Regional brain hematocrit in stroke by single photon emission computed tomography imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loutfi, I.; Frackowiak, R.S.; Myers, M.J.

1987-01-01

Nineteen studies on 18 subjects were performed by single photon emission computed tomography (SPECT) of the head after the successive intravenous administration of a plasma label (/sup 99m/Tc-human serum albumin (HSA)) and /sup 99m/Tc-labeled autologous red blood cells (RBC). Two sets of cerebral tomographic sections were generated: for cerebral /sup 99m/Tc-HSA alone and for combined /sup 99m/Tc-HSA and /sup 99m/Tc-RBC. By relating counts in regions of interest from the cerebral tomograms to counts from blood samples obtained during each tomographic acquisition, regional cerebral haematocrit (Hct) was calculated by the application of a simple formula. Results show 1) lower cerebral Hctmore » than venous Hct (ratio of HCT brain/Hct venous 0.65-0.90) in all subjects, and 2) comparison between right and left hemisphere Hct in 3/3 normal subjects, 6/6 patients with transient ischaemic attacks and 3/8 patients with stroke showed no significant difference. However, in 3/8 patients with stroke (most recent strokes) significant differences were found, the higher Hct value corresponding to the affected side.« less

The effectiveness of low-cost teleconsultation for emergency head computer tomography in patients with suspected stroke.

PubMed

Phabphal, Kanitpong; Hirunpatch, Siriporn

2008-01-01

Teleradiology in an emergency situation can be used to support rapid neurological decision-making when specialists are remote from the hospital concerned. We have developed a low-cost system using a PDA phone as the receiving equipment. The experimental system was based on a notebook PC to send the images and a PDA phone to receive them. We used commercially available toolbar software for transmitting the information through the mobile phone network. A total of 100 images from clinically suspected strokes within the previous 24 hours were transmitted to a neurologist. The mean size of the original picture was 20.9 kByte and the images were compressed by approximately 2:1 before transmission. The mean transmission time was 48 s per image. The diagnosis from the PDA phone image was in complete agreement with the diagnosis from the original image in cases of acute ischaemic stroke, intracerebral haemorrhage, metastasis and in normal scans. However, there was agreement in only 7 of the 8 cases (88%) of subarachnoid haemorrhage. The overall transmission cost was 400 Thai baht per case. The study showed that good accuracy can be achieved with a low-cost system for teleradiology consultation in stroke.

Clinical characteristics, precipitating factors, management and outcome of patients with prior stroke hospitalised with heart failure: an observational report from the Middle East

PubMed Central

Khafaji, Hadi A R; Sulaiman, Kadhim; Singh, Rajvir; AlHabib, Khalid F; Asaad, Nidal; Alsheikh-Ali, Alawi; Al-Jarallah, Mohammed; Bulbanat, Bassam; AlMahmeed, Wael; Ridha, Mustafa; Bazargani, Nooshin; Amin, Haitham; Al-Motarreb, Ahmed; AlFaleh, Hussam; Elasfar, Abdelfatah; Panduranga, Prashanth; Al Suwaidi, Jassim

2015-01-01

Objectives The purpose of this study is to report the prevalence, clinical characteristics, precipitating factors, management and outcome of patients with prior stroke hospitalised with acute heart failure (HF). Design Retrospective analysis of prospectively collected data. Setting Data were derived from Gulf CARE (Gulf aCute heArt failuRe rEgistry), a prospective multicentre study of consecutive patients hospitalised with acute HF in 2012 in seven Middle Eastern countries and analysed according to the presence or absence of prior stroke; demographics, management and outcomes were compared. Participants A total of 5005 patients with HF. Outcome measures In-hospital and 1-year outcome. Results The prevalence of prior stroke in patients with HF was 8.1%. Patients with stroke with HF were more likely to be admitted under the care of internists rather than cardiologists. When compared with patients without stroke, patients with stroke were more likely to be older and to have diabetes mellitus, hypertension, atrial fibrillation, hyperlipidaemia, chronic kidney disease, ischaemic heart disease, peripheral arterial disease and left ventricular dysfunction (p=0.001 for all). Patients with stroke were less likely to be smokers (0.003). There were no significant differences in terms of precipitating risk factors for HF hospitalisation between the two groups. Patients with stroke with HF had a longer hospital stay (mean±SD days; 11±14 vs 9±13, p=0.03), higher risk of recurrent strokes and 1-year mortality rates (32.7% vs 23.2%, p=0.001). Multivariate logistic regression analysis showed that stroke is an independent predictor of in-hospital and 1-year mortality. Conclusions This observational study reports high prevalence of prior stroke in patients hospitalised with HF. Internists rather than cardiologists were the predominant caregivers in this high-risk group. Patients with stroke had higher risk of in-hospital recurrent strokes and long-term mortality rates. Trial registration number NCT01467973. PMID:25908674

Left Atrial Enlargement and Stroke Recurrence: The Northern Manhattan Stroke Study

PubMed Central

Yaghi, Shadi; Moon, Yeseon P.; Mora-McLaughlin, Consuelo; Willey, Joshua Z.; Cheung, Ken; Tullio, Marco R. Di; Homma, Shunichi; Kamel, Hooman; Sacco, Ralph L.; Elkind, Mitchell S. V.

2015-01-01

Background and purpose While left atrial enlargement (LAE) increases incident stroke risk, the association with recurrent stroke is less clear. Our aim was to determine the association of LAE with recurrent stroke most likely related to embolism (cryptogenic and cardioembolic), and all ischemic stroke recurrences. Methods We followed 655 first ischemic stroke patients in the Northern Manhattan Stroke Study for up to 5 years. LA size from 2-D echocardiography was categorized as normal (52.7%), mild LAE (31.6%), and moderate-severe LAE (15.7%). We used Cox proportional hazard models to calculate the hazard ratios and 95% confidence intervals (HR, 95%CI) for the association of LA size and LAE with recurrent cryptogenic/cardioembolic and total recurrent ischemic stroke. Results LA size was available in 529 (81%) patients. Mean age at enrollment was 69±13 years; 45.8% were male, 54.0% Hispanic, and 18.5% had atrial fibrillation. Over a median of 4 years there were 65 recurrent ischemic strokes (29 were cardioembolic or cryptogenic). In multivariable models adjusted for confounders including atrial fibrillation and heart failure, moderate-severe LAE compared to normal LA size was associated with greater risk of recurrent cardioembolic/cryptogenic stroke (adjusted HR 2.83, 95% CI 1.03-7.81), but not total ischemic stroke (adjusted HR 1.06, 95% CI, 0.48-2.30). Mild LAE was not associated with recurrent stroke. Conclusion Moderate to severe LAE was an independent marker of recurrent cardioembolic or cryptogenic stroke in a multiethnic cohort of ischemic stroke patients. Further research is needed to determine whether anticoagulant use may reduce risk of recurrence in ischemic stroke patients with moderate to severe LAE. PMID:25908460

Multi-modal imaging of long-term recovery post-stroke by positron emission tomography and matrix-assisted laser desorption/ionisation mass spectrometry.

PubMed

Henderson, Fiona; Hart, Philippa J; Pradillo, Jesus M; Kassiou, Michael; Christie, Lidan; Williams, Kaye J; Boutin, Herve; McMahon, Adam

2018-05-15

Stroke is a leading cause of disability worldwide. Understanding the recovery process post-stroke is essential; however, longer-term recovery studies are lacking. In vivo positron emission tomography (PET) can image biological recovery processes, but is limited by spatial resolution and its targeted nature. Untargeted mass spectrometry imaging offers high spatial resolution, providing an ideal ex vivo tool for brain recovery imaging. Magnetic resonance imaging (MRI) was used to image a rat brain 48 h after ischaemic stroke to locate the infarcted regions of the brain. PET was carried out 3 months post-stroke using the tracers [ 18 F]DPA-714 for TSPO and [ 18 F]IAM6067 for sigma-1 receptors to image neuroinflammation and neurodegeneration, respectively. The rat brain was flash-frozen immediately after PET scanning, and sectioned for matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) imaging. Three months post-stroke, PET imaging shows minimal detection of neurodegeneration and neuroinflammation, indicating that the brain has stabilised. However, MALDI-MS images reveal distinct differences in lipid distributions (e.g. phosphatidylcholine and sphingomyelin) between the scar and the healthy brain, suggesting that recovery processes are still in play. It is currently not known if the altered lipids in the scar will change on a longer time scale, or if they are stabilised products of the brain post-stroke. The data demonstrates the ability to combine MALD-MS with in vivo PET to image different aspects of stroke recovery. Copyright © 2018 John Wiley & Sons, Ltd.

ASTRAL, DRAGON and SEDAN scores predict stroke outcome more accurately than physicians.

PubMed

Ntaios, G; Gioulekas, F; Papavasileiou, V; Strbian, D; Michel, P

2016-11-01

ASTRAL, SEDAN and DRAGON scores are three well-validated scores for stroke outcome prediction. Whether these scores predict stroke outcome more accurately compared with physicians interested in stroke was investigated. Physicians interested in stroke were invited to an online anonymous survey to provide outcome estimates in randomly allocated structured scenarios of recent real-life stroke patients. Their estimates were compared to scores' predictions in the same scenarios. An estimate was considered accurate if it was within 95% confidence intervals of actual outcome. In all, 244 participants from 32 different countries responded assessing 720 real scenarios and 2636 outcomes. The majority of physicians' estimates were inaccurate (1422/2636, 53.9%). 400 (56.8%) of physicians' estimates about the percentage probability of 3-month modified Rankin score (mRS) > 2 were accurate compared with 609 (86.5%) of ASTRAL score estimates (P < 0.0001). 394 (61.2%) of physicians' estimates about the percentage probability of post-thrombolysis symptomatic intracranial haemorrhage were accurate compared with 583 (90.5%) of SEDAN score estimates (P < 0.0001). 160 (24.8%) of physicians' estimates about post-thrombolysis 3-month percentage probability of mRS 0-2 were accurate compared with 240 (37.3%) DRAGON score estimates (P < 0.0001). 260 (40.4%) of physicians' estimates about the percentage probability of post-thrombolysis mRS 5-6 were accurate compared with 518 (80.4%) DRAGON score estimates (P < 0.0001). ASTRAL, DRAGON and SEDAN scores predict outcome of acute ischaemic stroke patients with higher accuracy compared to physicians interested in stroke. © 2016 EAN.

The Direct Referral to Endovascular Center criteria: a proposal for pre-hospital evaluation of acute stroke in the Madrid Stroke Network.

PubMed

Rodríguez-Pardo, J; Fuentes, B; Alonso de Leciñana, M; Ximénez-Carrillo, Á; Zapata-Wainberg, G; Álvarez-Fraga, J; Barriga, F J; Castillo, L; Carneado-Ruiz, J; Díaz-Guzman, J; Egido-Herrero, J; de Felipe, A; Fernández-Ferro, J; Frade-Pardo, L; García-Gallardo, Á; García-Pastor, A; Gil-Núñez, A; Gómez-Escalonilla, C; Guillán, M; Herrero-Infante, Y; Masjuan-Vallejo, J; Ortega-Casarrubios, M Á; Vivancos-Mora, J; Díez-Tejedor, E

2017-03-01

For patients with acute ischaemic stroke due to large-vessel occlusion, it has recently been shown that mechanical thrombectomy (MT) with stent retrievers is better than medical treatment alone. However, few hospitals can provide MT 24 h/day 365 days/year, and it remains unclear whether selected patients with acute stroke should be directly transferred to the nearest MT-providing hospital to prevent treatment delays. Clinical scales such as Rapid Arterial Occlusion Evaluation (RACE) have been developed to predict large-vessel occlusion at a pre-hospital level, but their predictive value for MT is low. We propose new criteria to identify patients eligible for MT, with higher accuracy. The Direct Referral to Endovascular Center criteria were defined based on a retrospective cohort of 317 patients admitted to a stroke center. The association of age, sex, RACE scale score and blood pressure with the likelihood of receiving MT were analyzed. Cut-off points with the highest association were thereafter evaluated in a prospective cohort of 153 patients from nine stroke units comprising the Madrid Stroke Network. Patients with a RACE scale score ≥ 5, systolic blood pressure <190 mmHg and age <81 years showed a significantly higher probability of undergoing MT (odds ratio, 33.38; 95% confidence interval, 12-92.9). This outcome was confirmed in the prospective cohort, with 68% sensitivity, 84% specificity, 42% positive and 94% negative predictive values for MT, ruling out 83% of hemorrhagic strokes. The Direct Referral to Endovascular Center criteria could be useful for identifying patients suitable for MT. © 2017 EAN.

Mild Aphasia: Is This the Place for an Argument?

ERIC Educational Resources Information Center

Armstrong, Elizabeth; Fox, Sarah; Wilkinson, Ray

2013-01-01

Purpose: Individuals with mild aphasia often report significant disruption to their communication despite seemingly minor impairment. This study explored this phenomenon through examining conversations of a person with mild aphasia engaging in argumentation--a skill she felt had significantly deteriorated after her stroke. Method: A person with…

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data.

PubMed

Campbell, Bruce C V; van Zwam, Wim H; Goyal, Mayank; Menon, Bijoy K; Dippel, Diederik W J; Demchuk, Andrew M; Bracard, Serge; White, Philip; Dávalos, Antoni; Majoie, Charles B L M; van der Lugt, Aad; Ford, Gary A; de la Ossa, Natalia Pérez; Kelly, Michael; Bourcier, Romain; Donnan, Geoffrey A; Roos, Yvo B W E M; Bang, Oh Young; Nogueira, Raul G; Devlin, Thomas G; van den Berg, Lucie A; Clarençon, Frédéric; Burns, Paul; Carpenter, Jeffrey; Berkhemer, Olvert A; Yavagal, Dileep R; Pereira, Vitor Mendes; Ducrocq, Xavier; Dixit, Anand; Quesada, Helena; Epstein, Jonathan; Davis, Stephen M; Jansen, Olav; Rubiera, Marta; Urra, Xabier; Micard, Emilien; Lingsma, Hester F; Naggara, Olivier; Brown, Scott; Guillemin, Francis; Muir, Keith W; van Oostenbrugge, Robert J; Saver, Jeffrey L; Jovin, Tudor G; Hill, Michael D; Mitchell, Peter J

2018-01-01

General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, p<0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14-2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons. Medtronic. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of Right Insular Involvement on Death and Functional Outcome After Acute Ischemic Stroke in the IST-3 Trial (Third International Stroke Trial).

PubMed

Sposato, Luciano A; Cohen, Geoffrey; Wardlaw, Joanna M; Sandercock, Peter; Lindley, Richard I; Hachinski, Vladimir

2016-12-01

In patients with acute ischemic stroke, whether involvement of the insular cortex influences outcome is controversial. Much of the apparent adverse outcome may relate to such strokes usually being severe. We examined the influence of right and left insular involvement on stroke outcomes among patients from the IST-3 study (Third International Stroke Trial) who had visible ischemic stroke on neuroimaging. We used multiple logistic regression to compare outcomes of left versus right insular and noninsular strokes across strata of stroke severity, on death, proportion dead or dependent, and level of disability (ordinalized Oxford Handicap Score) at 6 months, with adjustment for the effects of age, lesion size, and presence of atrial fibrillation. Of 3035 patients recruited, 2099 had visible ischemic strokes limited to a single hemisphere on computed tomography/magnetic resonance scans. Of these, 566 and 714 had infarction of right and left insula. Six months after randomization, right insular involvement was associated with increased odds of death when compared with noninsular strokes on the left side (adjusted odds ratio, 1.83; 95% confidence interval, 1.33-2.52), whereas the adjusted odds ratio comparing mortality after insular versus noninsular strokes on the left side was not significant. Among mild/moderate strokes, outcomes for right insular involvement were worse than for left insular, but among more severe strokes, the difference in outcomes was less substantial. We found an association between right insular involvement and higher odds of death and worse functional outcome. The difference between right- and left-sided insular lesions on outcomes seemed to be most evident for mild/moderate strokes. URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518. © 2016 American Heart Association, Inc.

Ambulatory Status Protects against Venous Thromboembolism in Acute Mild Ischemic Stroke Patients.

PubMed

Sisante, Jason-Flor V; Abraham, Michael G; Phadnis, Milind A; Billinger, Sandra A; Mittal, Manoj K

2016-10-01

Ischemic stroke patients are at high risk (up to 18%) for venous thromboembolism. We conducted a retrospective cross-sectional study to understand the predictors of acute postmild ischemic stroke patient's ambulatory status and its relationship with venous thromboembolism, hospital length of stay, and in-hospital mortality. We identified 522 patients between February 2006 and May 2014 and collected data about patient demographics, admission NIHSS (National Institutes of Health Stroke Scale), venous thromboembolism prophylaxis, ambulatory status, diagnosis of venous thromboembolism, and hospital outcomes (length of stay, mortality). Chi-square test, t-test and Wilcoxon rank-sum test, and binary logistic regression were used for statistical analysis as appropriate. A total of 61 (11.7%), 48 (9.2%), and 23 (4.4%) mild ischemic stroke patients developed venous thromboembolism, deep venous thrombosis, and pulmonary embolism, respectively. During hospitalization, 281 (53.8%) patients were ambulatory. Independent predictors of in-hospital ambulation were being married (OR 1.64, 95% CI 1.10-2.49), being nonreligious (OR 2.19, 95% CI 1.34-3.62), admission NIHSS (per unit decrease in NIHSS; OR 1.62, 95% CI 1.39-1.91), and nonuse of mechanical venous thromboembolism prophylaxis (OR 1.62, 95% CI 1.02-2.61). After adjusting for confounders, ambulatory patients had lower rates of venous thromboembolism (OR .47, 95% CI .25-.89), deep venous thrombosis (OR .36, 95% CI .17-.73), prolonged length of hospital stay (OR .24, 95% CI .16-.37), and mortality (OR .43, 95% CI .21-.84). Our findings suggest that for hospitalized acute mild ischemic stroke patients, ambulatory status is an independent predictor of venous thromboembolism (specifically deep venous thrombosis), hospital length of stay, and in-hospital mortality. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Aspirin resistance are associated with long-term recurrent stroke events after ischaemic stroke.

PubMed

Zhang, Ning; Wang, Zhenhua; Zhou, Lihong

2017-09-01

To investigate the prevalent of aspirin resistance (AR) in stroke and its association with recurrent stroke in 214 patients with ischemic stroke who were receiving aspirin before the stroke onset. Two hundreds and fourteen acute stroke patients who previously received aspirin therapy (100mg/day for ≥7days) were enrolled. Whole blood samples were collected for platelet aggregation testing. The result is expressed in aspirin reaction units (ARU). A cutoff of 550 ARU was used to determine the presence of AR. A follow-up period of 1year was performed to record stroke recurrence events. In this study, the median age was 68 years (IQR, 60-77 years), and 118 (55.1%) were men. A total of 43 of 214 enrolled patients (20.1%) were AR. ARU levels were significantly higher in patients with recurrence than those without (514[IQR: 466-592] vs. 454[IQR: 411-499]; P <0.001). The stroke recurrence distribution across the ARU quartiles ranged between 7.41% (first quartile) to 40.74% (fourth quartile). In multivariate analyses, the 3th and 4th quartile of ARU was significantly associated with stroke recurrence during the observation period compared to the 1st quartile group, and the adjusted risk increased by 215% (OR=3.15 [95% CI 1.96-4.33], P=0.007) and 322% (4.22[2.56-7.16], P<0.001). In multivariate logistic regression analysis, AR was associated with a higher risk of stroke recurrence, and the adjusted risk increased by 365% (OR=4.65; 95% CI=2.99-8.16; P<0.001). In conclusion, AR is not uncommon in Chinese stroke patients who receive anti-platelet medications. Patients with AR may have a greater risk of suffering stroke recurrence events. Copyright © 2017 Elsevier Inc. All rights reserved.

The striatocapsular infarction and its aftermaths

PubMed Central

Amin, Osama S M; Zangana, Hero M; Ameen, Nawa A

2010-01-01

Ischaemic stroke syndromes in the vascular territory of middle cerebral artery may have atypical presentation and radiographic findings because of the variable anatomy of that artery. Therefore, misdiagnosis of these syndromes as neoplastic or infectious processes is not uncommon. This case describes a 69-year-old comatose woman who was referred to us as having ‘a brain tumour with massive surrounding oedema.’ Further work-up revealed that she had a large left-sided lenticular nuclear infarction with some extension into the surrounding areas—the striatocapsular infarction. PMID:22778185

The total cholesterol to high-density lipoprotein cholesterol as a predictor of poor outcomes in a Chinese population with acute ischaemic stroke.

PubMed

Chen, Lifang; Xu, Jianing; Sun, Hao; Wu, Hao; Zhang, Jinsong

2017-11-01

High admission cholesterol has been associated with better outcome after acute ischaemic stroke (AIS), but a paradox not completely illustrated. The purpose of this study was to investigate the effect of the total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) on short-term survival after AIS. Consecutive patients admitted in 2013 and 2015 were enrolled in the present study. The logistic regression analysis was conducted to evaluate predictors of 3-month outcomes. The primary endpoint was death. Secondary endpoint was good (modified Rankin Scale score 0-2 or equal to prestrike modified Rankin Scale score) at 3 months. Of 871 patients enrolled in the final analysis, 94 (10.8%) individuals died during 3 months of observation. The serum TC and TC/HDL-C levels at admission were significantly associated with stroke outcomes at 3 months, and the HDL-C level was only correlated with the good outcomes at 3 months. Mortality risk was markedly decreased for patients with high TC/HDL-C ratio (odds ratio: 0.23, 95% confidence interval [CI]: 0.10-0.50 for Q4:Q1; P-trend <.001) after adjustment. The effect of TC/HDL-C ratio on the probability of good outcomes was still obvious (odds ratio: 2.18, 95% CI: 1.40-3.39 for Q4:Q1; P-trend=.029). According to the receiver operating characteristic analyses, the best discriminating factor was a TG/HDL-C ≥3.37 (area under the ROC curve [AUC]=0.643, sensitivity 61.3%, specificity 61.7%) as well as the TC/HDL-C ≥4.09 for good outcomes (AUC: 0.587, sensitivity 63.9%, specificity 79.7%). High TC/HDL-C ratio may be associated with increased short-term survival and better outcomes after AIS. © 2017 Wiley Periodicals, Inc.

Progression of cognitive impairment in stroke/TIA patients over 3 years.

PubMed

Sachdev, Perminder S; Lipnicki, Darren M; Crawford, John D; Wen, Wei; Brodaty, Henry

2014-12-01

To examine how cognitive deficits progress in the years following a stroke or transient ischaemic attack (TIA). A follow-up study, with neuropsychological and MRI assessments undertaken 3 years after baseline assessments made 3-6 months poststroke in 183 stroke/TIA patients and 97 healthy controls participating in the Sydney Stroke Study. Additional measures included cardiovascular risk factors and apolipoprotein E (APOE) genotype. Stroke/TIA patients had poorer cognitive function and more vascular risk factors than controls at baseline, but did not show greater decline in cognitive function over 3 years except for verbal memory. Patients with a subsequent stroke/TIA showed greater decline in global cognitive function and a number of domains. Rates of incident dementia were 5.9% per year in patients and 0.4% in controls. Both groups showed increased atrophy of the hippocampus, amygdala and whole brain, and an increase in white matter hyperintensities over 3 years; whole brain atrophy was greater in patients. Cognitive decline was greater in women and in those with smaller hippocampi at baseline. For patients without a subsequent stroke/TIA, those with smaller hippocampi or the APOE ε4 allele had greater global cognitive and verbal memory decline. In poststroke patients, cognitive decline was not greater than in comparison subjects, except for verbal memory, unless they had another stroke/TIA. However, dementia incidence was higher in patients, as might be expected from their poorer baseline cognitive functioning. Smaller hippocampi were associated with an increased risk of decline in memory, and APOE ε4 was a risk factor in those without a subsequent stroke/TIA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Mortality following stroke during and after acute care according to neighbourhood deprivation: a disease registry study.

PubMed

Grimaud, Olivier; Leray, Emmanuelle; Lalloué, Benoit; Aghzaf, Radouane; Durier, Jérôme; Giroud, Maurice; Béjot, Yannick

2014-12-01

Neighbourhood deprivation has been shown to be inversely associated with mortality 1 month after stroke. Whether this disadvantage begins while patients are still receiving acute care is unclear. We aimed to study mortality after stroke specifically in the period while patients are under acute care and the ensuing period when they are discharged to home or other care settings. Our sample includes 1760 incident strokes (mean age 75, 48% men, 86% ischaemic) identified between 1998 and 2010 by the population-based stroke registry of Dijon (France). We used Cox regression to study all-cause mortality up to 90 days after stroke occurrence. Overall, 284 (16.1%) patients died during the 90 days following stroke. Prior to stroke, risk factors prevalence (eg, high blood pressure and diabetes) and acute care management did not vary across deprivation levels. There was no association between deprivation and mortality while patients were in acute care (HR comparing the highest to the lowest tertiles of deprivation: 1.01, 95% CI 0.71 to 1.43). After discharge, however, age and gender adjusted mortality gradually increased with deprivation (HR 2.08, 95% CI 1.07 to 4.02). This association was not modified when stroke type and severity were accounted for. The gradient of higher poststroke mortality with increasing neighbourhood deprivation was noticeable only after acute hospital discharge. Quality of postacute care and social support are potential determinants of these variations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical and imaging services for TIA and minor stroke: results of two surveys of practice across the UK

PubMed Central

Brazzelli, Miriam; Shuler, Kirsten; Quayyum, Zahid; Hadley, Donald; Muir, Keith; McNamee, Paul; De Wilde, Janet; Dennis, Martin; Sandercock, Peter; Wardlaw, Joanna M

2013-01-01

Objectives Transient ischaemic attack (TIA) is a medical emergency requiring rapid access to effective, organised, stroke prevention. There are about 90 000 TIAs per year in the UK. We assessed whether stroke-prevention services in the UK meet Government targets. Design Cross-sectional survey. Setting All UK clinical and imaging stroke-prevention services. Intervention Electronic structured survey delivered over the web with automatic recording of responses into a database; reminders to non-respondents. The survey sought information on clinic frequency, staff, case-mix, details of brain and carotid artery imaging, medical and surgical treatments. Results 114 stroke clinical and 146 imaging surveys were completed (both response rates 45%). Stroke-prevention services were available in most (97%) centres but only 31% operated 7 days/week. Half of the clinic referrals were TIA mimics, most patients (75%) were prescribed secondary prevention prior to clinic referral, and nurses performed the medical assessment in 28% of centres. CT was the most common and fastest first-line investigation; MR, used in 51% of centres, mostly after CT, was delayed up to 2 weeks in 26%; 51% of centres omitted blood-sensitive (GRE/T2*) MR sequences. Carotid imaging was with ultrasound in 95% of centres and 59% performed endarterectomy within 1 week of deciding to operate. Conclusions Stroke-prevention services are widely available in the UK. Delays to MRI, its use in addition to CT while omitting key sequences to diagnose haemorrhage, limit the potential benefit of MRI in stroke prevention, but inflate costs. Assessing TIA mimics requires clinical neurology expertise yet nurses run 28% of clinics. Further improvements are still required for optimal stroke prevention. PMID:23929917

Automated data capture from free-text radiology reports to enhance accuracy of hospital inpatient stroke codes.

PubMed

Flynn, Robert W V; Macdonald, Thomas M; Schembri, Nicola; Murray, Gordon D; Doney, Alexander S F

2010-08-01

Much potentially useful clinical information for pharmacoepidemiological research is contained in unstructured free-text documents and is not readily available for analysis. Routine health data such as Scottish Morbidity Records (SMR01) frequently use generic 'stroke' codes. Free-text Computerised Radiology Information System (CRIS) reports have potential to provide this missing detail. We aimed to increase the number of stroke-type-specific diagnoses by augmenting SMR01 with data derived from CRIS reports and to assess the accuracy of this methodology. SMR01 codes describing first-ever-stroke admissions in Tayside, Scotland from 1994 to 2005 were linked to CRIS CT-brain scan reports occurring with 14 days of admission. Software was developed to parse the text and elicit details of stroke type using keyword matching. An algorithm was iteratively developed to differentiate intracerebral haemorrhage (ICH) from ischaemic stroke (IS) against a training set of reports with pathophysiologically precise SMR01 codes. This algorithm was then applied to CRIS reports associated with generic SMR01 codes. To establish the accuracy of the algorithm a sample of 150 ICH and 150 IS reports were independently classified by a stroke physician. There were 8419 SMR01 coded first-ever strokes. The proportion of patients with pathophysiologically clear diagnoses doubled from 2745 (32.6%) to 5614 (66.7%). The positive predictive value was 94.7% (95%CI 89.8-97.3) for IS and 76.7% (95%CI 69.3-82.7) for haemorrhagic stroke. A free-text processing approach was acceptably accurate at identifying IS, but not ICH. This approach could be adapted to other studies where radiology reports may be informative. 2010 John Wiley & Sons, Ltd.

Transcranial magnetic stimulation in mild to severe hemiparesis early after stroke: a proof of principle and novel approach to improve motor function

PubMed Central

Anjos, Sarah M.; Saposnik, Gustavo; Mello, Eduardo A.; Nagaya, Erina M.; Santos, Waldyr; Ferreiro, Karina N.; Melo, Eduardo S.; Reis, Felipe I.; Scaff, Milberto; Cohen, Leonardo G.

2016-01-01

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can enhance function of the paretic hand in patients with mild motor impairment. Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown. In this pilot, randomized, double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpatient customary rehabilitation, in 30 patients within 5–45 days after ischemic stroke, and mild to severe hand paresis. The primary feasibility outcome was compliance with the interventions. The primary safety outcome was the proportion of intervention-related adverse events. Performance of the paretic hand in the Jebsen–Taylor test and pinch strength were secondary outcomes. Outcomes were assessed at baseline, after ten sessions of treatment administered over 2 weeks and at 1 month after end of treatment. Baseline clinical features were comparable across groups. For the primary feasibility outcome, compliance with treatment was 100% in the active group and 94% in the sham group. There were no serious intervention-related adverse events. There were significant improvements in performance in the Jebsen–Taylor test (mean, 12.3% 1 month after treatment) and pinch force (mean, 0.5 Newtons) in the active group, but not in the sham group. Low-frequency rTMS to the contralesional motor cortex early after stroke is feasible, safe and potentially effective to improve function of the paretic hand, in patients with mild to severe hemiparesis. These promising results will be valuable to design larger randomized clinical trials. PMID:22173953

Diffusion-weighted MR of the brain: methodology and clinical application.

PubMed

Mascalchi, Mario; Filippi, Massimo; Floris, Roberto; Fonda, Claudio; Gasparotti, Roberto; Villari, Natale

2005-03-01

Clinical diffusion magnetic resonance (MR) imaging in humans started in the last decade with the demonstration of the capabilities of this technique of depicting the anatomy of the white matter fibre tracts in the brain. Two main approaches in terms of reconstruction and evaluation of the images obtained with application of diffusion sensitising gradients to an echo planar imaging sequence are possible. The first approach consists of reconstruction of images in which the effect of white matter anisotropy is averaged -- known as the isotropic or diffusion weighted images, which are usually evaluated subjectively for possible areas of increased or decreased signal, reflecting restricted and facilitated diffusion, respectively. The second approach implies reconstruction of image maps of the apparent diffusion coefficient (ADC), in which the T2 weighting of the echo planar diffusion sequence is cancelled out, and their objective, i.e. numerical, evaluation with regions of interest or histogram analysis. This second approach enables a quantitative and reproducible assessment of the diffusion changes not only in areas exhibiting signal abnormality in conventional MR images but also in areas of normal signal. A further level of image post-processing requires the acquisition of images after application of sensitising gradients along at least 6 different spatial orientations and consists of computation of the diffusion tensor and reconstruction of maps of the mean diffusivity (D) and of the white matter anisotropic properties, usually in terms of fractional anisotropy (FA). Diffusion-weighted imaging is complementary to conventional MR imaging in the evaluation of the acute ischaemic stroke. The combination of diffusion and perfusion MR imaging has the potential of providing all the information necessary for the diagnosis and management of the individual patient with acute ischaemic stroke. Diffusion-weighted MR, in particular quantitative evaluation based on the diffusion tensor, has a fundamental role in the assessment of brain maturation and of white matter diseases in the fetus, in the neonate and in the child. Diffusion MR imaging enables a better characterisation of the lesions demonstrated by conventional MR imaging, for instance in the hypoxic-ischaemic encephalopathy, in infections and in the inherited metabolic diseases, and is particularly important for the longitudinal evaluation of these conditions. Diffusion-weighted MR imaging has an established role in the differential diagnosis between brain abscess and cystic tumour and between epidermoid tumour and arachnoid cyst. On the other hand, the results obtained with diffusion MR in the characterisation of type and extension of glioma do not yet allow decision making in the individual patient. Diffusion is one of the most relevant MR techniques to have contributed to a better understanding of the pathophysiological mechanisms of multiple sclerosis (MS). In fact, it improves the specificity of MR in characterising the different pathological substrata underlying the rather uniform lesion appearance on the conventional images and enables detection of damage in the normal-appearing white and grey matter. In MS patients the ADC or D values in the normal-appearing white matter are increased as compared to control values, albeit to a lesser degree than in the lesions demonstrated by T2-weighted images. In addition, the D of the normal appearing grey matter is increased in MS patients and this change correlates with the cognitive deficit of these patients. Histogram analysis in MS patients shows that the peak of the brain D is decreased and right-shifted, reflecting an increase of its value, and the two features correlate with the patient's clinical disability. Ageing is associated to a mild but significant increase of the brain ADC or D which is predominantly due to changes in the white matter. Region of interest and histogram studies have demonstrated that D or ADC are increased in either the areas of leukoaraiosis or the normal-appearing white matter in patients with inherited cerebral autosomal dominant arteriopathy with subcortical infarcts and stroke or sporadic ischaemic leukoencephalopathy. Diffusion changes might be a more sensitive marker for progression of the disease than conventional imaging findings. In neurodegenerative diseases of the central nervous system such as Alzheimer's disease, Huntington's disease, hereditary ataxias and motor neuron disease, quantitative diffusion MR demonstrates the cortical and subcortical grey matter damage, which is reflected in a regional increase of D or ADC, but also reveals the concomitant white matter changes that are associated with an increase in D or ADC and decrease in FA. In all these diseases the diffusion changes are correlated to the clinical deficit and are potentially useful for early diagnosis and longitudinal evaluation, especially in the context of pharmacological trials.

Normobaric hyperoxia markedly reduces brain damage and sensorimotor deficits following brief focal ischaemia.

PubMed

Ejaz, Sohail; Emmrich, Julius V; Sitnikov, Sergey L; Hong, Young T; Sawiak, Stephen J; Fryer, Tim D; Aigbirhio, Franklin I; Williamson, David J; Baron, Jean-Claude

2016-03-01

'True' transient ischaemic attacks are characterized not only clinically, but also radiologically by a lack of corresponding changes on magnetic resonance imaging. During a transient ischaemic attack it is assumed that the affected tissue is penumbral but rescued by early spontaneous reperfusion. There is, however, evidence from rodent studies that even brief focal ischaemia not resulting in tissue infarction can cause extensive selective neuronal loss associated with long-lasting sensorimotor impairment but normal magnetic resonance imaging. Selective neuronal loss might therefore contribute to the increasingly recognized cognitive impairment occurring in patients with transient ischaemic attacks. It is therefore relevant to consider treatments to reduce brain damage occurring with transient ischaemic attacks. As penumbral neurons are threatened by markedly constrained oxygen delivery, improving the latter by increasing arterial O2 content would seem logical. Despite only small increases in arterial O2 content, normobaric oxygen therapy experimentally induces significant increases in penumbral O2 pressure and by such may maintain the penumbra alive until reperfusion. Nevertheless, the effects of normobaric oxygen therapy on infarct volume in rodent models have been conflicting, although duration of occlusion appeared an important factor. Likewise, in the single randomized trial published to date, early-administered normobaric oxygen therapy had no significant effect on clinical outcome despite reduced diffusion-weighted imaging lesion growth during therapy. Here we tested the hypothesis that normobaric oxygen therapy prevents both selective neuronal loss and sensorimotor deficits in a rodent model mimicking true transient ischaemic attack. Normobaric oxygen therapy was applied from the onset and until completion of 15 min distal middle cerebral artery occlusion in spontaneously hypertensive rats, a strain representative of the transient ischaemic attack-prone population. Whereas normoxic controls showed normal magnetic resonance imaging but extensive cortical selective neuronal loss associated with microglial activation (present both at Day 14 in vivo and at Day 28 post-mortem) and marked and long-lasting sensorimotor deficits, normobaric oxygen therapy completely prevented sensorimotor deficit (P < 0.02) and near-completely Day 28 selective neuronal loss (P < 0.005). Microglial activation was substantially reduced at Day 14 and completely prevented at Day 28 (P = 0.002). Our findings document that normobaric oxygen therapy administered during ischaemia nearly completely prevents the neuronal death, microglial inflammation and sensorimotor impairment that characterize this rodent true transient ischaemic attack model. Taken together with the available literature, normobaric oxygen therapy appears a promising therapy for short-lasting ischaemia, and is attractive clinically as it could be started at home in at-risk patients or in the ambulance in subjects suspected of transient ischaemic attack/early stroke. It may also be a straightforward adjunct to reperfusion therapies, and help prevent subtle brain damage potentially contributing to long-term cognitive and sensorimotor impairment in at-risk populations. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Body temperature and response to thrombolytic therapy in acute ischaemic stroke.

PubMed

Millán, M; Grau, L; Castellanos, M; Rodríguez-Yáñez, M; Arenillas, J F; Nombela, F; Pérez de la Ossa, N; López-Manzanares, L; Serena, J; Castillo, J; Dávalos, A

2008-12-01

To determine the relationship between body temperature (BT), arterial recanalization, functional outcome, and hemorrhagic transformation (HT) of cerebral infarction in patients treated with i.v. tissue plasminogen activator (tPA). We studied 254 patients treated with tPA within 3 h from stroke onset. National Institute of Health Stroke Scale score, BT, and transcranial Doppler ultrasound (n = 99) on admission and at 24 h were recorded. Hypodensity volume and HT were evaluated on CT at 24-36 h. Poor outcome (Rankin Scale > 2) was evaluated at 3 months. Arterial recanalization at 24 h was found in 70.7% of patients, HT in 24.8% (symptomatic in 4.7%) and poor outcome in 44.1%. Baseline BT was not associated with greater stroke severity at admission or at 24 h, HT or poor outcome. However, BT at 24 h correlated to stroke severity (P < 0.001) and hypodensity volume (P < 0.001) at 24 h, and was higher in patients who did not recanalize (P = 0.001), had symptomatic HT (P = 0.063) and poor outcome (P < 0.001). The adjusted odds ratio of poor outcome for patients with BT at 24 h > or = 37 degrees C was 2.56 (1.19-5.50, P = 0.016). Body temperature > or =37 degrees C at 24 h, but not at baseline, is associated with a lack of recanalization, greater hypodensity volume and worse outcome in stroke patients treated with tPA.

Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target.

PubMed

Hiu, Takeshi; Farzampour, Zoya; Paz, Jeanne T; Wang, Eric Hou Jen; Badgely, Corrine; Olson, Andrew; Micheva, Kristina D; Wang, Gordon; Lemmens, Robin; Tran, Kevin V; Nishiyama, Yasuhiro; Liang, Xibin; Hamilton, Scott A; O'Rourke, Nancy; Smith, Stephen J; Huguenard, John R; Bliss, Tonya M; Steinberg, Gary K

2016-02-01

Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem's potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke.

PubMed

Duricki, Denise A; Hutson, Thomas H; Kathe, Claudia; Soleman, Sara; Gonzalez-Carter, Daniel; Petruska, Jeffrey C; Shine, H David; Chen, Qin; Wood, Tobias C; Bernanos, Michel; Cash, Diana; Williams, Steven C R; Gage, Fred H; Moon, Lawrence D F

2016-01-01

There is an urgent need for a therapy that reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. We show here that intramuscular delivery of neurotrophin-3 (NT3, encoded by NTF3) can induce sensorimotor recovery when treatment is initiated 24 h after stroke. Specifically, in two randomized, blinded preclinical trials, we show improved sensory and locomotor function in adult (6 months) and elderly (18 months) rats treated 24 h following cortical ischaemic stroke with human NT3 delivered using a clinically approved serotype of adeno-associated viral vector (AAV1). Importantly, AAV1-hNT3 was given in a clinically-feasible timeframe using a straightforward, targeted route (injections into disabled forelimb muscles). Magnetic resonance imaging and histology showed that recovery was not due to neuroprotection, as expected given the delayed treatment. Rather, treatment caused corticospinal axons from the less affected hemisphere to sprout in the spinal cord. This treatment is the first gene therapy that reverses disability after stroke when administered intramuscularly in an elderly body. Importantly, phase I and II clinical trials by others show that repeated, peripherally administered high doses of recombinant NT3 are safe and well tolerated in humans with other conditions. This paves the way for NT3 as a therapy for stroke. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target

PubMed Central

Paz, Jeanne T.; Wang, Eric Hou Jen; Badgely, Corrine; Olson, Andrew; Micheva, Kristina D.; Wang, Gordon; Lemmens, Robin; Tran, Kevin V.; Nishiyama, Yasuhiro; Liang, Xibin; Hamilton, Scott A.; O’Rourke, Nancy; Smith, Stephen J.; Huguenard, John R.; Bliss, Tonya M.

2016-01-01

Abstract Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem’s potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery. PMID:26685158

Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis.

PubMed

England, Timothy J; Sprigg, Nikola; Alasheev, Andrey M; Belkin, Andrey A; Kumar, Amit; Prasad, Kameshwar; Bath, Philip M

2016-11-15

Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and type, end-of-trial modified Rankin Scale (mRS), Barthel Index, haematological parameters, serious adverse events and death. Multiple variable analyses were adjusted for age, sex, baseline severity and time-to-treatment. Individual patient data were obtained for 6 of 10 RCTs comprising 196 stroke patients (116 G-CSF, 80 placebo), mean age 67.1 (SD 12.9), 92% ischaemic, median NIHSS 10 (IQR 5-15), randomised 11 days (interquartile range IQR 4-238) post ictus; data from three commercial trials were not shared. G-CSF did not improve mRS (ordinal regression), odds ratio OR 1.12 (95% confidence interval 0.64 to 1.96, p = 0.62). There were more patients with a serious adverse event in the G-CSF group (29.6% versus 7.5%, p = 0.07) with no significant difference in all-cause mortality (G-CSF 11.2%, placebo 7.6%, p = 0.4). Overall, G-CSF did not improve stroke outcome in this individual patient data meta-analysis.

Trajectory formation principles are the same after mild or moderate stroke

PubMed Central

van Dokkum, Liesjet Elisabeth Henriette; Froger, Jérôme; Gouaïch, Abdelkader; Laffont, Isabelle

2017-01-01

When we make rapid reaching movements, we have to trade speed for accuracy. To do so, the trajectory of our hand is the result of an optimal balance between feed-forward and feed-back control in the face of signal-dependant noise in the sensorimotor system. How far do these principles of trajectory formation still apply after a stroke, for persons with mild to moderate sensorimotor deficits who recovered some reaching ability? Here, we examine the accuracy of fast hand reaching movements with a focus on the information capacity of the sensorimotor system and its relation to trajectory formation in young adults, in persons who had a stroke and in age-matched control participants. We find that persons with stroke follow the same trajectory formation principles, albeit parameterized differently in the face of higher sensorimotor uncertainty. Higher directional errors after a stroke result in less feed-forward control, hence more feed-back loops responsible for segmented movements. As a consequence, movements are globally slower to reach the imposed accuracy, and the information throughput of the sensorimotor system is lower after a stroke. The fact that the most abstract principles of motor control remain after a stroke suggests that clinicians can capitalize on existing theories of motor control and learning to derive principled rehabilitation strategies. PMID:28329000

The impact of early specialist management on outcomes of patients with in-hospital stroke.

PubMed

Manawadu, Dulka; Choyi, Jithesh; Kalra, Lalit

2014-01-01

Delays in treatment of in-hospital stroke (IHS) adversely affect patient outcomes. We hypothesised that early referral and specialist management of IHS patients will improve outcomes at 90 days. Baseline characteristics, assessment delays, thrombolysis eligibility, 90-day functional outcomes and all-cause mortality were compared between IHS patients referred for specialist stroke management within 3 hours of symptom onset (early referrals) and later referrals. Patients were identified from a prospective stroke registry between January 2009 and December 2010. Inclusion criteria were primary admission with a non-stroke diagnosis, onset of new neurological deficits after admission and early ischaemic changes on CT or MR imaging. Eighty four (4.6%) of 1836 stroke patients had IHS (mean age 74 year; 51% male, median NIHSS score 10). There were no significant differences in baseline characteristics between 53 (63%) early and 31 (37%) late referrals. Thrombolysis was performed in 29 (76%) of the 37/78 (47%) potentially eligible patients; 7 patients were excluded because specialist referral was delayed beyond 4.5 hours despite symptom recognition within 3 hours of onset. Early referral improved functional outcomes (modified Rankin Scale 0-2 at 90 days 40% v 7%, p = 0.001) and was an independent predictor of mRS 0-2 at 90 days after adjusting for age, pre-morbid function, primary cause for hospital admission and stroke severity [OR 1.13 (95% C.I.  = 1.10-1.27), p = 0.002]. Early referral and specialist management of IHS patients that includes thrombolysis is associated with better functional outcomes at 90 days.

Spotlight on unmet needs in stroke prevention: The PIONEER AF-PCI, NAVIGATE ESUS and GALILEO trials.

PubMed

Hemmrich, Melanie; Peterson, Eric D; Thomitzek, Karen; Weitz, Jeffrey I

2016-09-28

Atrial fibrillation (AF) is a major healthcare concern, being associated with an estimated five-fold risk of ischaemic stroke. In patients with AF, anticoagulants reduce stroke risk to a greater extent than acetylsalicylic acid (ASA) or dual antiplatelet therapy (DAPT) with ASA plus clopidogrel. Non-vitamin K antagonist oral anticoagulants (NOACs) are now a widely-accepted therapeutic option for stroke prevention in non-valvular AF (NVAF). There are particular patient types with NVAF for whom treatment challenges remain, owing to sparse clinical data, their high-risk nature or a need to harmonise anticoagulant and antiplatelet regimens if co-administered. This article focuses on three randomised controlled trials (RCTs) that are investigating the utility of rivaroxaban, a direct, oral, factor Xa inhibitor, in additional areas of stroke prevention where data for anticoagulants are lacking: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment (PIONEER AF-PCI); New Approach riVaroxoban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS); and Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO). Data from these studies present collaborative efforts to build upon existing registrational Phase III data for rivaroxaban, driving the need for effective and safe treatment of a wider range of patients for stroke prevention.

Evidence-Based Carotid Interventions for Stroke Prevention: State-of-the-art Review

PubMed Central

Morris, Dylan R.; Ayabe, Kengo; Inoue, Takashi; Sakai, Nobuyuki; Bulbulia, Richard; Halliday, Alison

2017-01-01

Carotid artery stenosis is responsible for between 10–20% of all ischaemic strokes. Interventions, such as carotid end-arterectomy and carotid stenting, effectively reduce the risk of stroke in selected individuals. This review describes the history of carotid interventions, and summarises reliable evidence on the safety and efficacy of these interventions gained from large randomised clinical trials. Early trials comparing carotid endarterectomy to medical therapy alone in symptomatic patients, and asymptomatic patients, demonstrated that endarterectomy halved the risk of stroke and perioperative death in these two unique populations. The absolute risk reduction was smaller in the asymptomatic carotid trials, consistent with their lower absolute stroke risk. More recent trials in symptomatic patients, suggest that carotid stenting has similar long term durability to carotid endarterectomy, but possibly has higher procedural hazards dominated by non-disabling strokes. The Asymptomatic Carotid Surgery Trial-2, along with individual patient data meta-analysis of all asymptomatic trials, will provide reliable evidence for the choice of intervention in asymptomatic patients in whom a decision has been made for carotid revascularisation. Given improvements in effective cardiovascular medical therapy, in particular lipid-lowering medications, there is renewed uncertainty as to whether carotid interventions still provide meaningful net reductions in stroke risk in asymptomatic populations. Four large trials in Europe and the US are currently underway, and are expected to report longterm results in the next decade. It is essential that surgeons, interventionalists, and physicians continue to randomise large numbers of patients from around the world to clarify current uncertainty around the management of asymptomatic carotid stenosis. PMID:28260723

Multiple therapeutic effects of progranulin on experimental acute ischaemic stroke.

PubMed

Kanazawa, Masato; Kawamura, Kunio; Takahashi, Tetsuya; Miura, Minami; Tanaka, Yoshinori; Koyama, Misaki; Toriyabe, Masafumi; Igarashi, Hironaka; Nakada, Tsutomu; Nishihara, Masugi; Nishizawa, Masatoyo; Shimohata, Takayoshi

2015-07-01

In the central nervous system, progranulin, a glycoprotein growth factor, plays a crucial role in maintaining physiological functions, and progranulin gene mutations cause TAR DNA-binding protein-43-positive frontotemporal lobar degeneration. Although several studies have reported that progranulin plays a protective role against ischaemic brain injury, little is known about temporal changes in the expression level, cellular localization, and glycosylation status of progranulin after acute focal cerebral ischaemia. In addition, the precise mechanisms by which progranulin exerts protective effects on ischaemic brain injury remains unknown. Furthermore, the therapeutic potential of progranulin against acute focal cerebral ischaemia, including combination treatment with tissue plasminogen activator, remains to be elucidated. In the present study, we aimed to determine temporal changes in the expression and localization of progranulin after ischaemia as well as the therapeutic effects of progranulin on ischaemic brain injury using in vitro and in vivo models. First, we demonstrated a dynamic change in progranulin expression in ischaemic Sprague-Dawley rats, including increased levels of progranulin expression in microglia within the ischaemic core, and increased levels of progranulin expression in viable neurons as well as induction of progranulin expression in endothelial cells within the ischaemic penumbra. We also demonstrated that the fully glycosylated mature secretory isoform of progranulin (∼88 kDa) decreased, whereas the glycosylated immature isoform of progranulin (58-68 kDa) markedly increased at 24 h and 72 h after reperfusion. In vitro experiments using primary cells from C57BL/6 mice revealed that the glycosylated immature isoform was secreted only from the microglia. Second, we demonstrated that progranulin could protect against acute focal cerebral ischaemia by a variety of mechanisms including attenuation of blood-brain barrier disruption, neuroinflammation suppression, and neuroprotection. We found that progranulin could regulate vascular permeability via vascular endothelial growth factor, suppress neuroinflammation after ischaemia via anti-inflammatory interleukin 10 in the microglia, and render neuroprotection in part by inhibition of cytoplasmic redistribution of TAR DNA-binding protein-43 as demonstrated in progranulin knockout mice (C57BL/6 background). Finally, we demonstrated the therapeutic potential of progranulin against acute focal cerebral ischaemia using a rat autologous thrombo-embolic model with delayed tissue plasminogen activator treatment. Intravenously administered recombinant progranulin reduced cerebral infarct and oedema, suppressed haemorrhagic transformation, and improved motor outcomes (P = 0.007, 0.038, 0.007 and 0.004, respectively). In conclusion, progranulin may be a novel therapeutic target that provides vascular protection, anti-neuroinflammation, and neuroprotection related in part to vascular endothelial growth factor, interleukin 10, and TAR DNA-binding protein-43, respectively. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Specific and combined subjective responses to noise and their association with cardiovascular diseases.

PubMed

Vandasova, Zdenka; Vencálek, Ondřej; Puklová, Vladimíra

2016-01-01

Noise is one of the most extensive environmental factors affecting the general population. The present study is focused on the association between discomfort caused by noise and the incidence of certain diseases (ischaemic heart disease, stroke and hypertension). This cross-sectional questionnaire study, conducted in 10 cities in the Czech Republic, comprises two stages with 3592 obtained questionnaires in the first phase and 762 in the second phase. Twelve variables describe subjective responses to noise from different sources at different times of day. The intensity of the associations between variables was measured by correlation coefficient. Logistic regression was used for fitting models of morbidity, and confounders such as age and socio-economic status were included. The hypotheses from the first phase were independently validated using data from the second phase. The general rates of noise annoyance/sleep disturbance had greater correlation with traffic noise variables than with neighbourhood noise variables. Factors significantly associated with diseases are: for hypertension - annoyance by traffic noise (the elderly, odds ratio (OR) 1.4) and sleep disturbance by traffic and neighbourhood noise (the elderly, OR 1.6); for ischaemic heart disease - the general rate of noise annoyance (all respondents, OR 1.5 and the adults 30-60 years, OR 1.8) and the general rate of annoyance and sleep disturbance (all respondents, OR 1.3); for stroke - annoyance and sleep disturbance by traffic and neighbourhood noise (all respondents, OR 1.8). Factors that include multiple sources of noise or non-specific noise are associated with the studied diseases more frequently than the source-specific factors.

[Blood pressure lowering therapy for mild hypertensive patients with a history of stroke].

PubMed

Ishikawa, Eiichi; Ibayashi, Setsuro

2008-08-01

Hypertension is the primary and one of the major risk factors for stroke. Many hypertensive patients with a history of stroke might have mild to moderate hypertension at the same time. In order to prevent recurrence of cardiovascular diseases including stroke, we should lower their blood pressure levels, carefully and slowly below less than 140/90 mmHg or much lower. Additionally, the patients having any occlusion or stenoses in their carotid and/or intracranial arteries, or even in old-old patients with atherosclerosis, might need further consideration for the cerebral blood flow insufficiency in the course of blood pressure lowering therapy. Although the advantages of inhibitors of renin-angiotensin system are lionized these days (advertisement based medicine: ABM), we should never forget to select more favorable antihypertensive drugs for each patient in case by case (individual based medicine: IBM), to get the definite blood pressure lowering effects without worsening any complications. We also need further gathering of many evidences in a net-work-meta-analysis way, on blood pressure lowering therapy in those hypertensive patients with a history of stroke (evidence based medicine: EBM).

Effectiveness of two rehabilitation strategies provided by nurses for stroke patients in Mexico.

PubMed

Torres-Arreola, Laura del Pilar; Doubova Dubova, Svetlana Vladislavovna; Hernandez, Sergio F; Torres-Valdez, Laura E; Constantino-Casas, Norma P; Garcia-Contreras, Fernando; Torres-Castro, Sara

2009-11-01

Rehabilitation strategies have been developed to improve functional state in stroke patients. The main objective of this study was to evaluate the effectiveness of the early rehabilitation at hospital and its continuity at home provided by nurses, on the functional recovery of basic and social activities in stroke patients compared with conventional care. A randomised clinical trial was carried out in three general hospitals of the Mexican Institute of Social Security (IMSS) in Mexico City between April 2003-May 2004. Stroke patients. Two rehabilitation strategies provided by nurses for stroke patients were compared: physiotherapy plus caregiver education in rehabilitation (strategy 1, S1) vs. education alone (strategy 2, S2). The main outcome variables were the basic (Barthel index) and social (Frenchay activities index) activities of daily living, of each patient. Age, sex, morbidity, stroke symptoms, complications, neurological damage (Canadian Scale), cognitive state (mini-mental state examination questionnaire) and duration of hospitalisation were defined as the control variables. Patients were evaluated at baseline and months one, three and six thereafter. One hundred and ten patients with ischaemic stroke were enrolled and randomised; 59 were assigned to S1 and 51 to S2. Comparison of the outcome variables showed that patients improved significantly over time, but no differences were observed between groups. We observed no significant difference in strategy performance with regard to the basic and instrumental activities of daily living. Participants who received physiotherapy with additional caregiver education benefit no more than those whose caregivers received education alone. Those countries that do not have integral rehabilitation programmes for stroke patients should understand their importance and budget resources for them. Meanwhile, both caregiver education and nurses trained in specific care and physiotherapy are alternatives that benefit these patients.

Prehospital neurological deterioration in stroke.

PubMed

Slavin, Sabreena J; Sucharew, Heidi; Alwell, Kathleen; Moomaw, Charles J; Woo, Daniel; Adeoye, Opeolu; Flaherty, Matthew L; Ferioli, Simona; McMullan, Jason; Mackey, Jason; De Los Rios La Rosa, Felipe; Martini, Sharyl; Kissela, Brett M; Kleindorfer, Dawn O

2018-04-27

Patients with stroke can experience neurological deterioration in the prehospital setting. We evaluated patients with stroke to determine factors associated with prehospital neurological deterioration (PND). Among the Greater Cincinnati/Northern Kentucky region (population ~1.3 million), we screened all 15 local hospitals' admissions from 2010 for acute stroke and included patients aged ≥20. The GCS was compared between emergency medical services (EMS) arrival and hospital arrival, with decrease ≥2 points considered PND. Data obtained retrospectively included demographics, medical history and medication use, stroke subtype (eg, ischaemic stroke (IS), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH)) and IS subtype (eg, small vessel, large vessel, cardioembolic), seizure at onset, time intervals between symptom onset, EMS arrival and hospital arrival, EMS level of training, and blood pressure and serum glucose on EMS arrival. Of 2708 total patients who had a stroke, 1092 patients (median (IQR) age 74 (61-83) years; 56% women; 21% black) were analysed. PND occurred in 129 cases (12%), including 9% of IS, 24% of ICH and 16% of SAH. In multivariable analysis, black race, atrial fibrillation, haemorrhagic subtype and ALS level of transport were associated with PND. Haemorrhage and atrial fibrillation is associated with PND in stroke, and further investigation is needed to establish whether PND can be predicted. Further studies are also needed to assess whether preferential transport of patients with deterioration to hospitals equipped with higher levels of care is beneficial, identify why race is associated with deterioration and to test therapies targeting PND. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Patent foramen ovale closure following cryptogenic stroke or transient ischaemic attack: Long-term follow-up of 301 cases.

PubMed

Mirzaali, Mikaeil; Dooley, Maureen; Wynne, Dylan; Cooter, Nina; Lee, Lorraine; Haworth, Peter; Saha, Romi; Gainsborough, Nicola; Hildick-Smith, David

2015-11-15

Patent foramen ovale has been identified as a conduit for paradoxical embolism resulting in cryptogenic stroke or transient ischemic attack (TIA). We aimed to establish rates of death, recurrent stroke or TIA among patients undergoing PFO closure for stroke or TIA at our unit. A retrospective analysis of all PFO closure patients was performed between May 2004 and January 2013. Follow up was performed by mortality tracing using the Medical Research Information Service of the Office of National Statistics. With regard to stroke or TIA recurrence, written consent forms and questionnaires were mailed with follow up telephone calls. Medical notes and imaging records were consulted where adverse events were noted. 301 patients aged 48.6 ± 11.0 years, 54.4% male, with ≥1 thromboembolic neurovascular event had percutaneous PFO closure with one of eight devices, with successful implantation in 99% of cases. Follow-up duration was 40.2 ± 26.2 months (range 1.3-105.3); complete in 301 patients for mortality (100%) and 283 patients (94.0%) for neurovascular events. Two patients died during follow-up (respiratory failure n = 1; road traffic accident n = 1). Recurrent stroke (MRI or CT confirmed) was observed in five patients (0.5%; 0.55 per 100 person-years) and TIA in 9 (1.1%; 0.98 per 100 person-years). Atrial fibrillation requiring treatment was documented in 14 patients (1.7%). Percutaneous PFO closure in patients with cryptogenic stroke or TIA is a safe treatment with a low incidence of procedural complications and recurrent neurovascular events. Registry data like these may help to demonstrate the utility of PFO closure in stroke. © 2015 Wiley Periodicals, Inc.

Optimising secondary prevention in the acute period following a TIA of ischaemic origin.

PubMed

Heron, Neil

2016-01-01

Transient ischaemic attacks (TIAs) are highly prevalent conditions, with at least 46 000 people per year in the UK having a TIA for the first time. TIAs are a warning that the patient is at risk of further vascular events and the 90-day risk of vascular events following a TIA, excluding events within the first week after diagnosis when the risk is highest, can be as high as 18%. Immediate assessment of patients with TIA, either at accident and emergency, general practice and/or TIA clinics, is therefore required to address secondary prevention and prevent further vascular events. This article addresses the need for optimising secondary prevention in the acute period following a TIA of ischaemic origin to reduce the risk of further vascular events as per recent Cochrane review advice and presents a novel project, Stroke Prevention Rehabilitation Intervention Trial of Exercise (SPRITE), to do this. One novel way to tackle vascular risk factors and promote secondary prevention in patients with TIA could be to adapt a cardiac rehabilitation programme for these patients. SPRITE, a feasibility and pilot study (ClinicalTrials.gov Identifier: NCT02712385) funded by the National Institute for Health Research, is attempting to adapt a home-based cardiac rehabilitation programme, 'The Healthy Brain Rehabilitation Manual', for use in the acute period following a TIA. The use of cardiac rehabilitation programmes post-TIA requires further research, particularly within the primary care setting.

Association between osteoarthritis and cardiovascular disease: Systematic review and meta-analysis.

PubMed

Hall, Andrew J; Stubbs, Brendon; Mamas, Mamas A; Myint, Phyo K; Smith, Toby O

2016-06-01

To examine for a possible relationship between osteoarthritis and cardiovascular disease. A systematic review and meta-analysis. Published and unpublished literature from: MEDLINE, EMBASE, CINAHL, the Cochrane Library, OpenGrey and clinical trial registers. Search to 22 November 2014. Cohort, case-control, randomised and non-randomised controlled trial papers reporting the prevalence of cardiovascular disease in osteoarthritis were included. Fifteen studies with 32,278,744 individuals were eligible. Pooled prevalence for overall cardiovascular disease pathology in people with osteoarthritis was 38.4% (95% confidence interval (CI): 37.2% to 39.6%). Individuals with osteoarthritis were almost three times as likely to have heart failure (relative risk (RR): 2.80; 95% CI: 2.25 to 3.49) or ischaemic heart disease (RR: 1.78; 95% CI: 1.18 to 2.69) compared with matched non-osteoarthritis cohorts. No significant difference was detected between the two groups for the risk of experiencing myocardial infarction or stroke. There was a three-fold decrease in the risk of experiencing a transient ischaemic attack in the osteoarthritis cohort compared with the non-osteoarthritis group. Prevalence of cardiovascular disease in patients with osteoarthritis is significant. There was an observed increased risk of incident heart failure and ischaemic heart disease in people with osteoarthritis compared with matched controls. However, the relationship between osteoarthritis and cardiovascular disease is not straightforward and there is a need to better understand the potential common pathways linking pathophysiological mechanisms. © The European Society of Cardiology 2015.

1,8-Cineole ameliorates oxygen-glucose deprivation/reoxygenation-induced ischaemic injury by reducing oxidative stress in rat cortical neuron/glia.

PubMed

Ryu, Sangwoo; Park, Hyeon; Seol, Geun Hee; Choi, In-Young

2014-12-01

1,8-Cineole, the main monoterpene in many essential oils, has been used as an ingredient in flavourings and medicine. 1,8-Cineole has been shown to possess pharmacological properties, including anti-oxidative, anti-inflammatory and anti-nociceptive actions. However, to date, no studies have examined the potential of 1,8-cineole to protect against cerebral ischaemic injury. In this study, we investigated the neuroprotective effects of 1,8-cineole against cortical neuronal/glial cell injury caused by oxygen-glucose deprivation/reoxygenation (OGD/R) in an in-vitro model of ischaemia. 1,8-Cineole significantly attenuated OGD/R-induced cortical cell injury, as well as reduced n-methyl-d-aspartate (NMDA)-induced cell injury. However, it did not inhibit NMDA-induced cytosolic calcium overload. Nevertheless, 1,8-cineole significantly reduced the OGD/R- and NMDA-induced overproduction of reactive oxygen species (ROS). These results indicate that 1,8-cineole exerts neuroprotection through its anti-oxidative rather than its anti-excitotoxic, properties. The decrease in OGD/R-induced intracellular superoxide in 1,8-cineole-treated cortical cells was associated with the upregulation of superoxide dismutase activity. Moreover, 1,8-cineole showed direct ROS scavenging activity in an assay of oxygen radical absorbance capacity. Collectively, these results suggest 1,8-cineole as a potentially effective neuroprotective and anti-oxidative candidate for the treatment of patients with ischaemic stroke. © 2014 Royal Pharmaceutical Society.

Randomized clinical trial of remote ischaemic preconditioning versus no preconditioning in the prevention of perioperative myocardial infarction during open surgery for ruptured abdominal aortic aneurysm.

PubMed

Pedersen, T F; Budtz-Lilly, J; Petersen, C N; Hyldgaard, J; Schmidt, J-O; Kroijer, R; Grønholdt, M-L; Eldrup, N

2018-06-01

Remote ischaemic preconditioning (RIPC) has been suggested as a means of protecting vital organs from reperfusion injury during major vascular surgery. This study was designed to determine whether RIPC could reduce the incidence of perioperative myocardial infarction (MI) during open surgery for ruptured abdominal aortic aneurysm (AAA). Secondary aims were to see if RIPC could reduce 30-day mortality, multiple organ failure, acute intestinal ischaemia, acute kidney injury and ischaemic stroke. This randomized, non-blinded clinical trial was undertaken at three vascular surgery centres in Denmark. Patients who had open surgery for ruptured AAA were randomized to intervention with RIPC or control in a 1 : 1 ratio. Postoperative complications and deaths were registered, and ECG and blood samples were obtained daily during the hospital stay. Of 200 patients randomized, 142 (72 RIPC, 70 controls) were included. There was no difference in rates of perioperative MI between the RIPC and control groups (36 versus 43 per cent respectively), or in rates of organ failure. However, in the per-protocol analysis 30-day mortality was significantly reduced in the RIPC group (odds ratio 0·46, 95 per cent c.i. 0·22 to 0·99; P = 0·048). RIPC did not reduce the incidence of perioperative MI in patients undergoing open surgery for ruptured AAA. Registration number: NCT00883363 ( http://www.clinicaltrials.gov).

Memory restoring and neuroprotective effects of the proline-containing dipeptide, GVS-111, in a photochemical stroke model.

PubMed

Ostrovskaya, R U; Romanova, G A; Barskov, I V; Shanina, E V; Gudasheva, T A; Victorov, I V; Voronina, T A; Seredenin, S B

1999-09-01

Local thrombosis of the frontal cortex (Fr1 and Fr3 fields), caused by combination of the intravenous photosensitive dye Rose Bengal administration with focused high-intensity illumination of the frontal bone, was shown to provoke a pronounced deficit in step-through passive avoidance performance in rats without concomitant motor disturbances. N-Phenylacetyl-L-prolylglycine ethyl ester (GVS-111) administered intravenously at a dose of 0.5 mg/kg/day, for the first time 1 h after ischaemic lesion and then for 9 post-operative days, with the last administration 15 min before testing, attenuated the deficit. This treatment significantly diminished the volume of the infarcted area. Thus, post-ischaemic injection of GVS-111 demonstrated both cognition-restoring and neuroprotective properties. The cognition-restoring effect is probably based on an increase in neocortical and hippocampal neuronal plasticity. Neuroprotective effects of GVS-111 combine antioxidant activity with the ability to attenuate glutamate-provoked neurotoxicity and block voltage-gated ionic channels, i.e. the compound mitigates the main metabolic shifts involved in pathogenesis of brain ischaemia.

Effect of nicardipine on somatosensory evoked potentials in patients with acute cerebral infarction.

PubMed Central

Yao, L P; Ding, D Y

1990-01-01

We evaluated the effect of nicardipine, a calcium channel blocker, on somatosensory evoked potentials (SEP) in 26 patients with acute cerebral infarction. Post treatment, 58% (15/26) of the N20 and P25 latencies were prolonged in the affected hemispheres; 8% (2/26) were shortened; and 35% (9/26) did not change. The mean N20 and P25 latencies were significantly prolonged two hours post treatment in the affected hemisphere (N20, P less than 0.01, P25 P less than 0.01). Nicardipine (Ni) had no effect on SEP components in the intact hemispheres. Seventy five per cent of the 12 patients with hypertension had a decrease in blood pressure (BP) after taking nicardipine, but there were no undesirable side effects or worsening of neurological signs. Our study demonstrates that nicardipine prolongs the latencies of short-latency components of SEP in the affected hemisphere after acute ischaemic stroke and also decreases BP. These observations suggest that nicardipine therapy might impair neuronal function in the ischaemic zone. PMID:2266363

Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease.

PubMed

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Wang, Winfred C

2017-01-17

Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Stroke affects around 10% of children with sickle cell anaemia (HbSS). Chronic blood transfusions may reduce the risk of vaso-occlusion and stroke by diluting the proportion of sickled cells in the circulation.This is an update of a Cochrane Review first published in 2002, and last updated in 2013. To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease for primary and secondary stroke prevention (excluding silent cerebral infarcts). We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 04 April 2016.We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 25 April 2016. Randomised controlled trials comparing red blood cell transfusions as prophylaxis for stroke in people with sickle cell disease to alternative or standard treatment. There were no restrictions by outcomes examined, language or publication status. Two authors independently assessed trial eligibility and the risk of bias and extracted data. We included five trials (660 participants) published between 1998 and 2016. Four of these trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of sickle cell disease.Three trials compared regular red cell transfusions to standard care in primary prevention of stroke: two in children with no previous long-term transfusions; and one in children and adolescents on long-term transfusion.Two trials compared the drug hydroxyurea (hydroxycarbamide) and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children); and one in secondary prevention (children and adolescents).The quality of the evidence was very low to moderate across different outcomes according to GRADE methodology. This was due to the trials being at a high risk of bias due to lack of blinding, indirectness and imprecise outcome estimates. Red cell transfusions versus standard care Children with no previous long-term transfusionsLong-term transfusions probably reduce the incidence of clinical stroke in children with a higher risk of stroke (abnormal transcranial doppler velocities or previous history of silent cerebral infarct), risk ratio 0.12 (95% confidence interval 0.03 to 0.49) (two trials, 326 participants), moderate quality evidence.Long-term transfusions may: reduce the incidence of other sickle cell disease-related complications (acute chest syndrome, risk ratio 0.24 (95% confidence interval 0.12 to 0.48)) (two trials, 326 participants); increase quality of life (difference estimate -0.54, 95% confidence interval -0.92 to -0.17) (one trial, 166 participants); but make little or no difference to IQ scores (least square mean: 1.7, standard error 95% confidence interval -1.1 to 4.4) (one trial, 166 participants), low quality evidence.We are very uncertain whether long-term transfusions: reduce the risk of transient ischaemic attacks, Peto odds ratio 0.13 (95% confidence interval 0.01 to 2.11) (two trials, 323 participants); have any effect on all-cause mortality, no deaths reported (two trials, 326 participants); or increase the risk of alloimmunisation, risk ratio 3.16 (95% confidence interval 0.18 to 57.17) (one trial, 121 participants), very low quality evidence. Children and adolescents with previous long-term transfusions (one trial, 79 participants)We are very uncertain whether continuing long-term transfusions reduces the incidence of: stroke, risk ratio 0.22 (95% confidence interval 0.01 to 4.35); or all-cause mortality, Peto odds ratio 8.00 (95% confidence interval 0.16 to 404.12), very low quality evidence.Several review outcomes were only reported in one trial arm (sickle cell disease-related complications, alloimmunisation, transient ischaemic attacks).The trial did not report neurological impairment, or quality of life. Hydroxyurea and phlebotomy versus red cell transfusions and chelationNeither trial reported on neurological impairment, alloimmunisation, or quality of life. Primary prevention, children (one trial, 121 participants)Switching to hydroxyurea and phlebotomy may have little or no effect on liver iron concentrations, mean difference -1.80 mg Fe/g dry-weight liver (95% confidence interval -5.16 to 1.56), low quality evidence.We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: risk of stroke (no strokes); all-cause mortality (no deaths); transient ischaemic attacks, risk ratio 1.02 (95% confidence interval 0.21 to 4.84); or other sickle cell disease-related complications (acute chest syndrome, risk ratio 2.03 (95% confidence interval 0.39 to 10.69)), very low quality evidence. Secondary prevention, children and adolescents (one trial, 133 participants)Switching to hydroxyurea and phlebotomy may: increase the risk of sickle cell disease-related serious adverse events, risk ratio 3.10 (95% confidence interval 1.42 to 6.75); but have little or no effect on median liver iron concentrations (hydroxyurea, 17.3 mg Fe/g dry-weight liver (interquartile range 10.0 to 30.6)); transfusion 17.3 mg Fe/g dry-weight liver (interquartile range 8.8 to 30.7), low quality evidence.We are very uncertain whether switching to hydroxyurea and phlebotomy: increases the risk of stroke, risk ratio 14.78 (95% confidence interval 0.86 to 253.66); or has any effect on all-cause mortality, Peto odds ratio 0.98 (95% confidence interval 0.06 to 15.92); or transient ischaemic attacks, risk ratio 0.66 (95% confidence interval 0.25 to 1.74), very low quality evidence. There is no evidence for managing adults, or children who do not have HbSS sickle cell disease.In children who are at higher risk of stroke and have not had previous long-term transfusions, there is moderate quality evidence that long-term red cell transfusions reduce the risk of stroke, and low quality evidence they also reduce the risk of other sickle cell disease-related complications.In primary and secondary prevention of stroke there is low quality evidence that switching to hydroxyurea with phlebotomy has little or no effect on the liver iron concentration.In secondary prevention of stroke there is low-quality evidence that switching to hydroxyurea with phlebotomy increases the risk of sickle cell disease-related events.All other evidence in this review is of very low quality.