Transient ischemic attack and minor stroke are the most common manifestations of acute cerebrovascular disease: a prospective, population-based study--the Aarhus TIA study.

PubMed

von Weitzel-Mudersbach, Paul; Andersen, Grethe; Hundborg, Heidi H; Johnsen, Søren P

2013-01-01

Severity of acute vascular illness may have changed in the last decades due to improvements in primary and secondary prevention. Population-based data on the severity of acute ischemic cerebrovascular disease are sparse. We aimed to examine incidence, characteristics and severity of acute ischemic cerebrovascular disease in a well-defined population. All patients admitted with transient ischemic attack (TIA) or acute ischemic stroke from March 1, 2007, to February 29, 2008, with residence in the Aarhus area, were included. Incidence rates and characteristics of TIA and ischemic stroke were compared. TIA accounted for 30%, TIA and minor stroke combined for 65% of all acute ischemic cerebrovascular events. Age-adjusted incidence rates of TIA and ischemic stroke were 72.2/100,000 and 129.5/100,000 person-years, respectively. TIA patients were younger than stroke patients (66.3 vs. 72.7 years; p < 0.001). Atrial fibrillation, previous myocardial infarction and previous stroke were significantly more frequent in stroke patients; no differences in other baseline characteristics were found. Minor events are the most common in ischemic cerebrovascular disease, and may constitute a larger proportion than previously reported. TIA and stroke patients share many characteristics; however, TIA patients are younger and have fewer manifestations of atherosclerotic diseases, indicating a high potential for secondary prevention. Copyright © 2012 S. Karger AG, Basel.

Early Rivaroxaban Use After Cardioembolic Stroke May Not Result in Hemorrhagic Transformation: A Prospective Magnetic Resonance Imaging Study.

PubMed

Gioia, Laura C; Kate, Mahesh; Sivakumar, Leka; Hussain, Dulara; Kalashyan, Hayrapet; Buck, Brian; Bussiere, Miguel; Jeerakathil, Thomas; Shuaib, Ashfaq; Emery, Derek; Butcher, Ken

2016-07-01

Early anticoagulation after cardioembolic stroke remains controversial because of the potential for hemorrhagic transformation (HT). We tested the safety and feasibility of initiating rivaroxaban ≤14 days after cardioembolic stroke/transient ischemic attack. A prospective, open-label study of patients with atrial fibrillation treated with rivaroxaban ≤14 days of transient ischemic attack or ischemic stroke (National Institute of Health Stroke Scale <9). All patients underwent magnetic resonance imaging <24 hours of rivaroxaban initiation and day 7. The primary end point was symptomatic HT at day 7. Sixty patients (mean±SD age 71±19 years, 82% stroke/18% transient ischemic attack) were enrolled. Median (interquartile range) time from onset to rivaroxaban was 3 (5) days. At treatment initiation, median National Institute of Health Stroke Scale was 2 (4), and median diffusion-weighted imaging volume was 7.9 (13.7) mL. At baseline, HT was present in 25 (42%) patients (hemorrhagic infarct [HI]1=19, HI2=6). On follow-up magnetic resonance imaging, no patients developed symptomatic HT. New asymptomatic HI1 developed in 3 patients, and asymptomatic progression from HI1 to HI2 occurred in 5 patients; otherwise, HT remained unchanged at day 7. These data support the safety of rivaroxaban initiation ≤14 days of mild-moderate cardioembolic stroke/transient ischemic attack. Magnetic resonance imaging evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT. © 2016 American Heart Association, Inc.

Recurrent Stroke in Minor Ischemic Stroke or Transient Ischemic Attack With Metabolic Syndrome and/or Diabetes Mellitus.

PubMed

Chen, Weiqi; Pan, Yuesong; Jing, Jing; Zhao, Xingquan; Liu, Liping; Meng, Xia; Wang, Yilong; Wang, Yongjun

2017-06-01

We aimed to determine the risk conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent stroke in patients with minor ischemic stroke or transient ischemic attack from the CHANCE (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events) trial. In total, 3044 patients were included. Patients were stratified into 4 groups: neither, METS only, DM only, or both. METS was defined using the Chinese Diabetes Society (CDS) and International Diabetes Foundation (IDF) definitions. The primary outcome was new stroke (including ischemic and hemorrhagic) at 90 days. A multivariable Cox regression model was used to assess the relationship of METS and DM status to the risk of recurrent stroke adjusted for potential covariates. Using the CDS criteria of METS, 53.2%, 17.2%, 19.8%, and 9.8% of patients were diagnosed as neither, METS only, DM only, and both, respectively. After 90 days of follow-up, there were 299 new strokes (293 ischemic, 6 hemorrhagic). Patients with DM only (16.1% versus 6.8%; adjusted hazard ratio 2.50, 95% CI 1.89-3.39) and both (17.1% versus 6.8%; adjusted hazard ratio 2.76, 95% CI 1.98-3.86) had significantly increased rates of recurrent stroke. No interaction effect of antiplatelet therapy by different METS or DM status for the risk of recurrent stroke ( P =0.82 for interaction in the fully adjusted model of CDS) was observed. Using the METS (IDF) criteria demonstrated similar results. Concurrent METS and DM was associated with an increased risk of recurrent stroke in patients with minor stroke and transient ischemic attack. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA.

PubMed

Smith, Wade S; Lev, Michael H; English, Joey D; Camargo, Erica C; Chou, Maggie; Johnston, S Claiborne; Gonzalez, Gilberto; Schaefer, Pamela W; Dillon, William P; Koroshetz, Walter J; Furie, Karen L

2009-12-01

Acute ischemic stroke due to large vessel occlusion (LVO)-vertebral, basilar, carotid terminus, middle and anterior cerebral arteries-likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data have been reported on a cohort of unselected patients with stroke and with transient ischemic attack, the clinical impact of LVO has been difficult to quantify. The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality, was calculated using univariate and multivariate logistic regression. Over a 33-month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as transient ischemic attack. Among patients with stroke, 267 (46%) had LVO accounting for the stroke and 13 (13%) of patients with transient ischemic attack had LVO accounting for transient ischemic attack symptoms. LVO predicted 6-month mortality (OR, 4.5; 95% CI, 2.7 to 7.3; P<0.001). Six-month good outcome (modified Rankin Scale score

Ambulatory Care Data Base (ACDB) Data Dictionary Sequential Files of Phase 2.

DTIC Science & Technology

1992-04-01

ARTERIES 4340 CEREBRAL THROMBOSIS 43491 STROKE , ISCHEMIC 435 TRANSIENT CEREBRAL ISCHEMIA 4359 TRANSIENT ISCHEMIC ATTACK (TIA) 43591 TRANS ISCHEMIC ATTACK W...CRISIS 4373 ANEURYSM, CEREBRAL , NONRUPTURED 4374 ARTERITIS, CEREBRAL 4378 CEREBROVASCULAR DISEASE, OTHER ILL-DEFINED 43781 STROKE , LACUNAR 438 LATE...FOR LOCALIZATION OF CEREBRAL SEIZURE FOC 95999 OTHER NEUROLOGICAL DIAGNOSTIC PROCEDURES 96500 CHEMO INJ, SINGLE, PRE-MIX, PUSH 96501 CHEMO INJ, SINGLE

Stress Hyperglycemia and Prognosis of Minor Ischemic Stroke and Transient Ischemic Attack: The CHANCE Study (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events).

PubMed

Pan, Yuesong; Cai, Xueli; Jing, Jing; Meng, Xia; Li, Hao; Wang, Yongjun; Zhao, Xingquan; Liu, Liping; Wang, David; Johnston, S Claiborne; Wei, Tiemin; Wang, Yilong

2017-11-01

We aimed to determine the association between stress hyperglycemia and risk of new stroke in patients with a minor ischemic stroke or transient ischemic attack. A subgroup of 3026 consecutive patients from 73 prespecified sites of the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) were analyzed. Stress hyperglycemia was measured by glucose/glycated albumin (GA) ratio. Glucose/GA ratio was calculated by fasting plasma glucose divided by GA and categorized into 4 even groups according to the quartiles. The primary outcome was a new stroke (ischemic or hemorrhagic) at 90 days. We assessed the association between glucose/GA ratio and risk of stroke by multivariable Cox regression models adjusted for potential covariates. Among 3026 patients included, a total of 299 (9.9%) new stroke occurred at 3 months. Compared with patients with the lowest quartile, patients with the highest quartile of glucose/GA ratio was associated with an increased risk of stroke at 3 months after adjusted for potential covariates (12.0% versus 9.2%; adjusted hazard ratio, 1.46; 95% confidence interval, 1.06-2.01). Similar results were observed after further adjusted for fasting plasma glucose. We also observed that higher level of glucose/GA ratio was associated with an increased risk of stroke with a threshold of 0.29 using a Cox regression model with restricted cubic spline. Stress hyperglycemia, measured by glucose/GA ratio, was associated with an increased risk of stroke in patients with a minor ischemic stroke or transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2017 American Heart Association, Inc.

Computed tomography identifies patients at high risk for stroke after transient ischemic attack/nondisabling stroke: prospective, multicenter cohort study.

PubMed

Wasserman, Jason K; Perry, Jeffrey J; Sivilotti, Marco L A; Sutherland, Jane; Worster, Andrew; Émond, Marcel; Jin, Albert Y; Oczkowski, Wieslaw J; Sahlas, Demetrios J; Murray, Heather; MacKey, Ariane; Verreault, Steve; Wells, George A; Dowlatshahi, Dar; Stotts, Grant; Stiell, Ian G; Sharma, Mukul

2015-01-01

Ischemia on computed tomography (CT) is associated with subsequent stroke after transient ischemic attack. This study assessed CT findings of acute ischemia, chronic ischemia, or microangiopathy for predicting subsequent stroke after transient ischemic attack. This prospective cohort study enrolled patients with transient ischemic attack or nondisabling stroke that had CT scanning within 24 hours. Primary outcome was subsequent stroke within 90 days. Secondary outcomes were stroke at ≤2 or >2 days. CT findings were classified as ischemia present or absent and acute or chronic or microangiopathy. Analysis used Fisher exact test and multivariate logistic regression. A total of 2028 patients were included; 814 had ischemic changes on CT. Subsequent stroke rate was 3.4% at 90 days and 1.5% at ≤2 days. Stroke risk was greater if baseline CT showed acute ischemia alone (10.6%; P=0.002), acute+chronic ischemia (17.4%; P=0.007), acute ischemia+microangiopathy (17.6%; P=0.019), or acute+chronic ischemia+microangiopathy (25.0%; P=0.029). Logistic regression found acute ischemia alone (odds ratio [OR], 2.61; 95% confidence interval [CI[, 1.22-5.57), acute+chronic ischemia (OR, 5.35; 95% CI, 1.71-16.70), acute ischemia+microangiopathy (OR, 4.90; 95% CI, 1.33-18.07), or acute+chronic ischemia+microangiopathy (OR, 8.04; 95% CI, 1.52-42.63) was associated with a greater risk at 90 days, whereas acute+chronic ischemia (OR, 10.78; 95% CI, 2.93-36.68), acute ischemia+microangiopathy (OR, 8.90; 95% CI, 1.90-41.60), and acute+chronic ischemia+microangiopathy (OR, 23.66; 95% CI, 4.34-129.03) had greater risk at ≤2 days. Only acute ischemia (OR, 2.70; 95% CI, 1.01-7.18; P=0.047) was associated with a greater risk at >2 days. In patients with transient ischemic attack/nondisabling stroke, CT evidence of acute ischemia alone or acute ischemia with chronic ischemia or microangiopathy was associated with increased subsequent stroke risk within 90 days. © 2014 American Heart Association, Inc.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study.

PubMed

Bousser, M G; Amarenco, P; Chamorro, A; Fisher, M; Ford, I; Fox, K; Hennerici, M G; Mattle, H P; Rothwell, P M

2009-01-01

Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event. Copyright 2009 S. Karger AG, Basel.

Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).

PubMed

Easton, J Donald; Aunes, Maria; Albers, Gregory W; Amarenco, Pierre; Bokelund-Singh, Sara; Denison, Hans; Evans, Scott R; Held, Peter; Jahreskog, Marianne; Jonasson, Jenny; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Wong, K S Lawrence; Johnston, S Claiborne

2017-09-05

Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720. © 2017 American Heart Association, Inc.

Internet-based information-seeking behavior for transient ischemic attack.

PubMed

Abedi, Vida; Mbaye, Marieme; Tsivgoulis, Georgios; Male, Shailesh; Goyal, Nitin; Alexandrov, Andrei V; Zand, Ramin

2015-12-01

In recent years, Internet became an increasingly important tool for accessing health information and is being used more frequently to promote public health. To use Google search data to explore information seeking behavior for transient ischemic attack. We selected two groups of keywords related to transient ischemic attack: 'Transient Ischemic Attack' and 'Mini Stroke'. We obtained all available online search data performed in the United States from the Google search engine for a 10-year span--January 2004 to December 2013. The monthly and daily search data for the selected keywords were analyzed--using moving average--to explore the trends, peaks, and declining effects. There were three significant concurrent peaks in the Google search data for the selected keywords. Each peak was directly associated with media coverage and news headlines related to the incident of transient ischemic attack in a public figure. Following each event, it took three- to seven-days for the search trend to return to its respective average value. Furthermore, the trend was steady for 'Transient Ischemic Attack'; however, the search interest for the keyword 'Mini Stroke' shows a steady increase. The overall search interest for the selected keywords was significantly higher in the southeastern United States. Our study shows that changes in online search behavior can be associated with media coverage of key events (in our case transient ischemic attack) in public figures. These findings suggest that multimedia health promotion campaigns might be more effective, if increased promptly after similar media coverage. © 2015 World Stroke Organization.

The CHADS2 Score to Predict Stroke Risk in the Absence of Atrial Fibrillation in Hypertensive Patients Aged 65 Years or Older.

PubMed

Morillas, Pedro; Pallarés, Vicente; Fácila, Lorenzo; Llisterri, Jose Luis; Sebastián, María Eugenia; Gómez, Manuel; Castilla, Elena; Camarasa, Raquel; Sandin, Miriam; García-Honrubia, Antonio

2015-06-01

The CHADS2 score is a proven, essential tool for estimating cardioembolic risk (mainly stroke) in patients with nonvalvular atrial fibrillation, with the purpose of determining the indication for anticoagulant therapy. In this study we analyzed the use of CHADS2 in hypertensive patients without known atrial fibrillation in a Mediterranean population. The study included 887 hypertensive patients aged 65 years or older without atrial fibrillation or anticoagulant therapy, who attended a medical consultation. Data on the patients' main risk factors, cardiovascular history, and medication were collected, basic laboratory analyses and electrocardiography were performed, and the CHADS2 score (heart failure, hypertension, age ≥ 75 years, diabetes mellitus, and previous stroke or transient ischemic attack) was calculated. A clinical follow-up was carried out, recording hospital admissions for a stroke or transient ischemic attack. The median duration of follow-up was 804 days. Mean age was 72.5 (SD,5.7) years, 46.6% were men, 27.8% had diabetes, and 8.6% were smokers. During follow-up, 40 patients were hospitalized for a stroke or transient ischemic attack (4.5%). The event-free survival analysis showed significant differences according to the CHADS2 score (log rank test, P < .001). On multivariate analysis, smoking and CHADS2 ≥3 were independent predictors of stroke or transient ischemic attack. The CHADS2 may be useful for estimating the risk of stroke or transient ischemic attack in hypertensive patients without known atrial fibrillation. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Dolichoectasia and Small Vessel Disease in Young Patients With Transient Ischemic Attack and Stroke.

PubMed

Thijs, Vincent; Grittner, Ulrike; Fazekas, Franz; McCabe, Dominick J H; Giese, Anne-Katrin; Kessler, Christof; Martus, Peter; Norrving, Bo; Ringelstein, Erich Bernd; Schmidt, Reinhold; Tanislav, Christian; Putaala, Jukka; Tatlisumak, Turgut; von Sarnowski, Bettina; Rolfs, Arndt; Enzinger, Christian

2017-09-01

We evaluated whether basilar dolichoectasia is associated with markers of cerebral small vessel disease in younger transient ischemic attack and ischemic stroke patients. We used data from the SIFAP1 study (Stroke in Young Fabry Patients), a large prospective, hospital-based, screening study for Fabry disease in young (<55 years) transient ischemic attack/stroke patients in whom detailed clinical data and brain MRI were obtained, and stroke subtyping with TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment) was performed. Dolichoectasia was found in 508 of 3850 (13.2%) of patients. Dolichoectasia was associated with older age (odds ratio per decade, 1.26; 95% confidence interval, 1.09-1.44), male sex (odds ratio, 1.96; 95% confidence interval, 1.59-2.42), and hypertension (odds ratio, 1.39; 95% confidence interval, 1.13-1.70). Dolichoectasia was more common in patients with small infarctions (33.9% versus 29.8% for acute lesions, P =0.065; 29.1% versus 16.5% for old lesions, P <0.001), infarct location in the brain stem (12.4% versus 6.9%, P <0.001), and in white matter (27.8% versus 21.1%, P =0.001). Microbleeds (16.3% versus 4.7%, P =0.001), higher grades of white matter hyperintensities ( P <0.001), and small vessel disease subtype (18.1% versus 12.4%, overall P for differences in TOAST ( P =0.018) were more often present in patients with dolichoectasia. Dolichoectasia is associated with imaging markers of small vessel disease and brain stem localization of acute and old infarcts in younger patients with transient ischemic attack and ischemic stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2017 American Heart Association, Inc.

Sodium Valproate, a Histone Deacetylase Inhibitor, Is Associated With Reduced Stroke Risk After Previous Ischemic Stroke or Transient Ischemic Attack.

PubMed

Brookes, Rebecca L; Crichton, Siobhan; Wolfe, Charles D A; Yi, Qilong; Li, Linxin; Hankey, Graeme J; Rothwell, Peter M; Markus, Hugh S

2018-01-01

A variant in the histone deacetylase 9 ( HDAC9 ) gene is associated with large artery stroke. Therefore, inhibiting HDAC9 might offer a novel secondary preventative treatment for ischemic stroke. The antiepileptic drug sodium valproate (SVA) is a nonspecific inhibitor of HDAC9. We tested whether SVA therapy given after ischemic stroke was associated with reduced recurrent stroke rate. Data were pooled from 3 prospective studies recruiting patients with previous stroke or transient ischemic attack and long-term follow-up: the South London Stroke Register, The Vitamins to Prevent Stroke Study, and the Oxford Vascular Study. Patients receiving SVA were compared with patients who received antiepileptic drugs other than SVA using survival analysis and Cox Regression. A total of 11 949 patients with confirmed ischemic event were included. Recurrent stroke rate was lower in patient taking SVA (17 of 168) than other antiepileptic drugs (105 of 530; log-rank survival analysis P =0.002). On Cox regression, controlling for potential cofounders, SVA remained associated with reduced stroke (hazard ratio=0.44; 95% confidence interval: 0.3-0.7; P =0.002). A similar result was obtained when patients taking SVA were compared with all cases not taking SVA (Cox regression, hazard ratio=0.47; 95% confidence interval: 0.29-0.77; P =0.003). These results suggest that exposure to SVA, an inhibitor of HDAC, may be associated with a lower recurrent stroke risk although we cannot exclude residual confounding in this study design. This supports the hypothesis that HDAC9 is important in the ischemic stroke pathogenesis and that its inhibition, by SVA or a more specific HDAC9 inhibitor, is worthy of evaluation as a treatment to prevent recurrent ischemic stroke. © 2017 The Authors.

Patent Foramen Ovale Closure for Secondary Prevention of Cryptogenic Stroke: Updated Meta-Analysis of Randomized Clinical Trials.

PubMed

Vaduganathan, Muthiah; Qamar, Arman; Gupta, Ankur; Bajaj, Navkaranbir; Golwala, Harsh B; Pandey, Ambarish; Bhatt, Deepak L

2018-05-01

Patent foramen ovale closure represents a potential secondary prevention strategy for cryptogenic stroke, but available trials have varied by size, device studied, and follow-up. We conducted a systematic search of published randomized clinical trials evaluating patent foramen ovale closure versus medical therapy in patients with recent stroke or transient ischemic attack using PubMED, EMBASE, and Cochrane through September 2017. Weighting was by random effects models. Of 480 studies screened, we included 5 randomized clinical trials in the meta-analysis in which 3440 patients were randomized to patent foramen ovale closure (n = 1829) or medical therapy (n = 1611) and followed for an average of 2.0 to 5.9 years. Index stroke/transient ischemic attack occurred within 6 to 9 months of randomization. The primary end point was composite stroke/transient ischemic attack and death (in 3 trials) or stroke alone (in 2 trials). Patent foramen ovale closure reduced the primary end point (0.70 vs 1.48 events per 100 patient-years; risk ratio [RR], 0.52 [0.29-0.91]; I 2  = 55.0%) and stroke/transient ischemic attack (1.04 vs 2.00 events per 100 patient-years; RR, 0.55 [0.37-0.82]; I 2  = 42.2%) with modest heterogeneity compared with medical therapy. Procedural bleeding was not different between study arms (1.8% vs 1.8%; RR, 0.94 [0.49-1.83]; I 2  = 29.2%), but new-onset atrial fibrillation/flutter was increased with patent foramen ovale closure (6.6% vs 0.7%; RR, 4.69 [2.17-10.12]; I 2  = 29.3%). In patients with recent cryptogenic stroke, patent foramen ovale closure reduces recurrent stroke/transient ischemic attack compared with medical therapy, but is associated with a higher risk of new-onset atrial fibrillation/flutter. Copyright © 2018 Elsevier Inc. All rights reserved.

Association between arterial calcifications and nonlacunar and lacunar ischemic strokes.

PubMed

van Dijk, Anouk C; Fonville, Susanne; Zadi, Taihra; van Hattem, Antonius M G; Saiedie, Ghesrouw; Koudstaal, Peter J; van der Lugt, Aad

2014-03-01

Nonlacunar cerebral infarcts are presumed to be caused by thromboembolism from the heart or extracranial arteries, whereas lacunar infarcts are thought to be caused by small vessel disease. We investigated to what extent arterial calcifications differ between nonlacunar and lacunar ischemic strokes. We studied 820 consecutive patients with transient ischemic attack or ischemic stroke in the anterior circulation who underwent multidetector computed tomography angiography and had no rare cause of stroke. The presence of likely cardioembolic pathogenesis was determined according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The remaining 708 patients were categorized as nonlacunar or lacunar strokes, either transient ischemic attacks or strokes, based on clinical symptoms corrected by brain imaging results. We measured volume of calcifications in the aortic arch, symptomatic extracranial and intracranial carotid artery using multidetector computed tomography angiography. The difference in calcifications between nonlacunar and lacunar strokes was assessed with a multivariable logistic regression analysis. We adjusted for degree of symptomatic carotid artery stenosis and cardiovascular risk factors. We found an independent association between volume of aortic arch calcifications and nonlacunar ischemic strokes (adjusted odds ratio [95% confidence interval], 1.11 [1.02-1.21]). No independent associations between extracranial and intracranial carotid artery calcifications and nonlacunar strokes were present. The only difference we found between nonlacunar and lacunar strokes was a higher calcification volume in the aortic arch in nonlacunar strokes. Our findings only partially confirm the notion of distinct etiologies and suggest that the potential role of other plaque components, plaque morphology, and aortic arch calcifications in ischemic stroke subtypes awaits further evaluation.

New perspectives on the pharmacotherapy of ischemic stroke.

PubMed

Bradberry, J Chris; Fagan, Susan C; Gray, David R; Moon, Yong S K

2004-01-01

To provide an overview of the impact of ischemic stroke and the steps that can be taken to reduce its burden through greater awareness of the disease, improved diagnosis and better treatment, with emphasis on the use of antiplatelet agents. Recent (1995-2003) published scientific literature, as identified by the authors through Medline searches, using the terms stroke, transient ischemic attack, cerebrovascular disease, atherothrombosis, risk factors, pharmacotherapy, prevention, and reviews on treatment. Recent systematic English-language review articles and reports of controlled randomized clinical trials were screened for inclusion. Ischemic stroke is generally the result of an atherothrombotic process leading to vessel obstruction or narrowing. Of the two types of ischemic stroke, thrombotic stroke is caused by a thrombus that develops within the cerebral vasculature, while embolic stroke arises from a distant embolus that lodges in a cerebral artery. The neurologic manifestations of stroke depend on the location of injury in the brain and the degree of ischemia or infarction. Symptoms may be reversible or irreversible and range from sensory deficits to hemiplegia. Risk factors for development of ischemic stroke include hypertension, diabetes, dyslipidemia, smoking, atrial fibrillation, prior stroke, and transient ischemic attack. Tissue plasminogen activator is currently the only available drug treatment for acute ischemic stroke. Stroke recurrence rates are high (about 40% over 5 years), and all ischemic stroke patients should receive antithrombotic therapy (unless contraindicated) for secondary prevention. Of the oral antiplatelet therapies, aspirin, clopidogrel (Plavix--Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership), and the extended-release dipyridamole plus aspirin combination are acceptable first-line agents, while anticoagulants (warfarin) are preferred in patients with atrial fibrillation. Lifestyle changes and drug therapy are important components of primary and secondary prevention strategies in ischemic stroke. Risk factors such as elevated blood pressure and high cholesterol should be aggressively treated. Antiplatelet agents, antihypertensive agents, and cholesterol-lowering agents are therapeutic cornerstones for secondary prevention.

Understanding the Role of Autoimmune Disorders on the Initial Presentation of Cardiovascular Disease

ClinicalTrials.gov

2015-04-20

Myocardial Infarction; Ischemic Stroke; Stroke; Subarachnoid Haemorrhage; Venous Thrombosis; Transient Ischemic Attack; Stable Angina Pectoris; Unstable Angina; Heart Failure; Peripheral Arterial Disease; Abdominal Aortic Aneurysm

Correlation between brain injury and dysphagia in adult patients with stroke

PubMed Central

Nunes, Maria Cristina de Alencar; Jurkiewicz, Ari Leon; Santos, Rosane Sampaio; Furkim, Ana Maria; Massi, Giselle; Pinto, Gisele Sant Ana; Lange, Marcos Christiano

2012-01-01

Summary Introduction: In the literature, the incidence of oropharyngeal dysphagia in patients with cerebrovascular accident (AVE) ranges 20–90%. Some studies correlate the location of a stroke with dysphagia, while others do not. Objective: To correlate brain injury with dysphagia in patients with stroke in relation to the type and location of stroke. Method: A prospective study conducted at the Hospital de Clinicas with 30 stroke patients: 18 women and 12 men. All patients underwent clinical evaluation and swallowing nasolaryngofibroscopy (FEES®), and were divided based on the location of the injury: cerebral cortex, cerebellar cortex, subcortical areas, and type: hemorrhagic or transient ischemic. Results: Of the 30 patients, 18 had ischemic stroke, 10 had hemorrhagic stroke, and 2 had transient stroke. Regarding the location, 10 lesions were in the cerebral cortex, 3 were in the cerebral and cerebellar cortices, 3 were in the cerebral cortex and subcortical areas, and 3 were in the cerebral and cerebellar cortices and subcortical areas. Cerebral cortex and subcortical area ischemic strokes predominated in the clinical evaluation of dysphagia. In FEES®, decreased laryngeal sensitivity persisted following cerebral cortex and ischemic strokes. Waste in the pharyngeal recesses associated with epiglottic valleculae predominated in the piriform cortex in all lesion areas and in ischemic stroke. A patient with damage to the cerebral and cerebellar cortices from an ischemic stroke exhibited laryngeal penetration and tracheal aspiration of liquid and honey. Conclusion: Dysphagia was prevalent when a lesion was located in the cerebral cortex and was of the ischemic type. PMID:25991951

Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.

PubMed

Kernan, Walter N; Ovbiagele, Bruce; Black, Henry R; Bravata, Dawn M; Chimowitz, Marc I; Ezekowitz, Michael D; Fang, Margaret C; Fisher, Marc; Furie, Karen L; Heck, Donald V; Johnston, S Claiborne Clay; Kasner, Scott E; Kittner, Steven J; Mitchell, Pamela H; Rich, Michael W; Richardson, DeJuran; Schwamm, Lee H; Wilson, John A

2014-07-01

The aim of this updated guideline is to provide comprehensive and timely evidence-based recommendations on the prevention of future stroke among survivors of ischemic stroke or transient ischemic attack. The guideline is addressed to all clinicians who manage secondary prevention for these patients. Evidence-based recommendations are provided for control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke. Recommendations are also provided for the prevention of recurrent stroke in a variety of specific circumstances, including aortic arch atherosclerosis, arterial dissection, patent foramen ovale, hyperhomocysteinemia, hypercoagulable states, antiphospholipid antibody syndrome, sickle cell disease, cerebral venous sinus thrombosis, and pregnancy. Special sections address use of antithrombotic and anticoagulation therapy after an intracranial hemorrhage and implementation of guidelines. © 2014 American Heart Association, Inc.

Ambulatory Care Data Base (ACDB) Data Dictionary Sequential Files of Phase 2.

DTIC Science & Technology

1992-04-01

CEREBRAL ARTERIES 4340 CEREBRAL THROMBOSIS 43491 STROKE , ISCHEMIC 435 TRANSIENT CEREBRAL ISCHEMIA 4359 TRANSIENT ISCHEMIC ATTACK (TIA) 43591 TRANS...HYPERTENSIVE CRISIS 4373 ANEURYSM, CEREBRAL , NONRUPTURED 4374 ARTERITIS, CEREBRAL 4378 CEREBROVASCULAR DISEASE, OTHER ILL-DEFINED 43781 STROKE , LACUNAR...95950 MONITORING FOR LOCALIZATION OF CEREBRAL SEIZURE FOC 95999 OTHER NEUROLOGICAL DIAGNOSTIC PROCEDURES 96500 CHEMO INJ, SINGLE, PRE-MIX, PUSH 96501

Ethnicity and Onset of Cardiovascular Disease: A CALIBER Study

ClinicalTrials.gov

2017-06-07

Abdominal Aortic Aneurysm; Coronary Heart Disease; Sudden Cardiac Death; Intracerebral Haemorrhage; Heart Failure; Ischemic Stroke; Myocardial Infarction; Stroke; Peripheral Arterial Disease; Stable Angina Pectoris; Subarachnoid Haemorrhage; Transient Ischemic Attack; Unstable Angina; Cardiac Arrest

Perception of recurrent stroke risk among black, white and Hispanic ischemic stroke and transient ischemic attack survivors: the SWIFT study.

PubMed

Boden-Albala, Bernadette; Carman, Heather; Moran, Megan; Doyle, Margaret; Paik, Myunghee C

2011-01-01

Risk modification through behavior change is critical for primary and secondary stroke prevention. Theories of health behavior identify perceived risk as an important component to facilitate behavior change; however, little is known about perceived risk of vascular events among stroke survivors. The SWIFT (Stroke Warning Information and Faster Treatment) study includes a prospective population-based ethnically diverse cohort of ischemic stroke and transient ischemic attack survivors. We investigate the baseline relationship between demographics, health beliefs, and knowledge on risk perception. Regression models examined predictors of inaccurate perception. Only 20% accurately estimated risk, 10% of the participants underestimated risk, and 70% of the 817 study participants significantly overestimated their risk for a recurrent stroke. The mean perceived likelihood of recurrent ischemic stroke in the next 10 years was 51 ± 7%. We found no significant differences by race-ethnicity with regard to accurate estimation of risk. Inaccurate estimation of risk was associated with attitudes and beliefs [worry (p < 0.04), fatalism (p < 0.07)] and memory problems (p < 0.01), but not history or knowledge of vascular risk factors. This paper provides a unique perspective on how factors such as belief systems influence risk perception in a diverse population at high stroke risk. There is a need for future research on how risk perception can inform primary and secondary stroke prevention. Copyright © 2011 S. Karger AG, Basel.

Sodium Valproate, a Histone Deacetylase Inhibitor, Is Associated With Reduced Stroke Risk After Previous Ischemic Stroke or Transient Ischemic Attack

PubMed Central

Brookes, Rebecca L.; Crichton, Siobhan; Wolfe, Charles D.A.; Yi, Qilong; Li, Linxin; Hankey, Graeme J.; Rothwell, Peter M.

2018-01-01

Background and Purpose— A variant in the histone deacetylase 9 (HDAC9) gene is associated with large artery stroke. Therefore, inhibiting HDAC9 might offer a novel secondary preventative treatment for ischemic stroke. The antiepileptic drug sodium valproate (SVA) is a nonspecific inhibitor of HDAC9. We tested whether SVA therapy given after ischemic stroke was associated with reduced recurrent stroke rate. Methods— Data were pooled from 3 prospective studies recruiting patients with previous stroke or transient ischemic attack and long-term follow-up: the South London Stroke Register, The Vitamins to Prevent Stroke Study, and the Oxford Vascular Study. Patients receiving SVA were compared with patients who received antiepileptic drugs other than SVA using survival analysis and Cox Regression. Results— A total of 11 949 patients with confirmed ischemic event were included. Recurrent stroke rate was lower in patient taking SVA (17 of 168) than other antiepileptic drugs (105 of 530; log-rank survival analysis P=0.002). On Cox regression, controlling for potential cofounders, SVA remained associated with reduced stroke (hazard ratio=0.44; 95% confidence interval: 0.3–0.7; P=0.002). A similar result was obtained when patients taking SVA were compared with all cases not taking SVA (Cox regression, hazard ratio=0.47; 95% confidence interval: 0.29–0.77; P=0.003). Conclusions— These results suggest that exposure to SVA, an inhibitor of HDAC, may be associated with a lower recurrent stroke risk although we cannot exclude residual confounding in this study design. This supports the hypothesis that HDAC9 is important in the ischemic stroke pathogenesis and that its inhibition, by SVA or a more specific HDAC9 inhibitor, is worthy of evaluation as a treatment to prevent recurrent ischemic stroke. PMID:29247141

Inhibition of CD147 (Cluster of Differentiation 147) Ameliorates Acute Ischemic Stroke in Mice by Reducing Thromboinflammation.

PubMed

Jin, Rong; Xiao, Adam Y; Chen, Rui; Granger, D Neil; Li, Guohong

2017-12-01

Inflammation and thrombosis currently are recognized as critical contributors to the pathogenesis of ischemic stroke. CD147 (cluster of differentiation 147), also known as extracellular matrix metalloproteinase inducer, can function as a key mediator of inflammatory and immune responses. CD147 expression is increased in the brain after cerebral ischemia, but its role in the pathogenesis of ischemic stroke remains unknown. In this study, we show that CD147 acts as a key player in ischemic stroke by driving thrombotic and inflammatory responses. Focal cerebral ischemia was induced in C57BL/6 mice by a 60-minute transient middle cerebral artery occlusion. Animals were treated with anti-CD147 function-blocking antibody (αCD147) or isotype control antibody. Blood-brain barrier permeability, thrombus formation, and microvascular patency were assessed 24 hours after ischemia. Infarct size, neurological deficits, and inflammatory cells invaded in the brain were assessed 72 hours after ischemia. CD147 expression was rapidly increased in ischemic brain endothelium after transient middle cerebral artery occlusion. Inhibition of CD147 reduced infarct size and improved functional outcome on day 3 after transient middle cerebral artery occlusion. The neuroprotective effects were associated with (1) prevented blood-brain barrier damage, (2) decreased intravascular fibrin and platelet deposition, which in turn reduced thrombosis and increased cerebral perfusion, and (3) reduced brain inflammatory cell infiltration. The underlying mechanism may include reduced NF-κB (nuclear factor κB) activation, MMP-9 (matrix metalloproteinase-9) activity, and PAI-1 (plasminogen activator inhibitor-1) expression in brain microvascular endothelial cells. Inhibition of CD147 ameliorates acute ischemic stroke by reducing thromboinflammation. CD147 might represent a novel and promising therapeutic target for ischemic stroke and possibly other thromboinflammatory disorders. © 2017 American Heart Association, Inc.

Heart Rate and Initial Presentation of Cardiovascular Diseases (Caliber)

ClinicalTrials.gov

2013-09-17

Abdominal Aortic Aneurysm; Coronary Heart Disease NOS; Unheralded Coronary Death; Intracerebral Haemorrhage; Heart Failure; Ischemic Stroke; Myocardial Infarction; Stroke; Peripheral Arterial Disease; Stable Angina Pectoris; Subarachnoid Haemorrhage; Transient Ischemic Attack; Unstable Angina; Cardiac Arrest, Sudden Cardiac Death

Soluble CD40L Is a Useful Marker to Predict Future Strokes in Patients With Minor Stroke and Transient Ischemic Attack.

PubMed

Li, Jiejie; Wang, Yilong; Lin, Jinxi; Wang, David; Wang, Anxin; Zhao, Xingquan; Liu, Liping; Wang, Chunxue; Wang, Yongjun

2015-07-01

Elevated soluble CD40 ligand (sCD40L) was shown to be related to cardiovascular events, but the role of sCD40L in predicting recurrent stroke remains unclear. Baseline sCD40L levels were measured in 3044 consecutive patients with acute minor stroke and transient ischemic attack, who had previously been enrolled in the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Cox proportional-hazards model was used to assess the association of sCD40L with recurrent stroke. Patients in the top tertile of sCD40L levels had increased risk of recurrent stroke comparing with those in the bottom tertile, after adjusted for conventional confounding factors (hazard ratio, 1.49; 95% confidence interval, 1.11-2.00; P=0.008). The patients with elevated levels of both sCD40L and high-sensitive C-reactive protein also had increased risk of recurrent stroke (hazard ratio, 1.81; 95% confidence interval, 1.23-2.68; P=0.003). Elevated sCD40L levels independently predict recurrent stroke in patients with minor stroke and transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2015 American Heart Association, Inc.

[Preditive clinical factors for epileptic seizures after ischemic stroke].

PubMed

Fukujima, M M; Cardeal, J O; Lima, J G

1996-06-01

Preditive clinical factors for epileptic seizures after ischemic stroke. Clinical features of 35 patients with ischemic stroke who developed epilepsy (Group 1) were compared with those of 35 patients with ischemic stroke without epilepsy (Group 2). The age of the patients did not differ between the groups. There were more men than women and more white than other races in both groups. Diabetes melitus, hypertension, transient ischemic attack, previous stroke, migraine, Chagas disease, cerebral embolism of cardiac origin and use of oral contraceptive did not differ between the groups. Smokers and alcohol users were more frequent in Group 1 (p < 0.05). Most patients of Group 1 presented with hemiparesis; none presented cerebellar or brainstem involvement. Perhaps strokes in smokers have some different aspects, that let them more epileptogenic than in non smokers.

Prevalence of stroke symptoms among stroke-free residents: first national data from Lebanon.

PubMed

Farah, Rita; Zeidan, Rouba Karen; Chahine, Mirna N; Asmar, Roland; Chahine, Ramez; Salameh, Pascale; Hosseini, Hassan

2015-10-01

Stroke symptoms are common among people without a history of stroke or transient ischemic attack. Reported stroke symptoms may represent stroke episodes that failed to reach the threshold for clinical diagnosis. This study aimed to assess in the Lebanese population the prevalence of self-reported stroke symptoms in a stroke- and transient ischemic attack-free population, and the association of these symptoms with major risk factors for stroke. We carried out a cross-sectional study using a multistage cluster sample across Lebanon. We interviewed residents aged 40 years and more. Stroke symptoms were assessed using the Questionnaire for Verifying Stroke-Free Status. We included 1515 individuals (mean age was 57·2 ± 12·4 years, 783 women, 51·7%). Among 1460 participants stroke- and transient ischemic attack-free, 175 had experienced at least one stroke symptom (12·1%, 95% CI 9·9%-14·3%). Arterial hypertension (adjOR 4·37, 95% CI 2·68-7·12), history of heart disease (adjOR 3·34, 95% CI 2·00-5·56), current waterpipe smoking (adjOR 3·88, 95% CI 2·33-6·48), current and former cigarette smoking (adjOR 1·84, 95% CI 1·18-2·87 and adjOR 2·01, 95% CI 1·13-3·5, respectively), psychological distress (adjOR 1·04, 95% CI 1·02-1·05), the Mediterranean diet score (adjOR 0·87, 95% CI 0·76-0·99), and regular physical activity (adjOR 0·45, 95% CI 0·26-0·77) were independently associated with stroke symptoms. This is the first study conducted in the Middle East, assessing self-reported stroke symptoms among stroke-free residents. Our study showed that almost one in eight residents without a history of stroke or transient ischemic attack has had stroke symptoms. Major vascular risk factors are associated with these symptoms, thus allowing for prevention strategies. © 2015 World Stroke Organization.

The complexity of atrial fibrillation newly diagnosed after ischemic stroke and transient ischemic attack: advances and uncertainties

PubMed Central

Cerasuolo, Joshua O.; Cipriano, Lauren E.; Sposato, Luciano A.

2017-01-01

Purpose of review Atrial fibrillation is being increasingly diagnosed after ischemic stroke and transient ischemic attack (TIA). Patient characteristics, frequency and duration of paroxysms, and the risk of recurrent ischemic stroke associated with atrial fibrillation detected after stroke and TIA (AFDAS) may differ from atrial fibrillation already known before stroke occurrence. We aim to summarize major recent advances in the field, in the context of prior evidence, and to identify areas of uncertainty to be addressed in future research. Recent findings Half of all atrial fibrillations in ischemic stroke and TIA patients are AFDAS, and most of them are asymptomatic. Over 50% of AFDAS paroxysms last less than 30 s. The rapid initiation of cardiac monitoring and its duration are crucial for its timely and effective detection. AFDAS comprises a heterogeneous mix of atrial fibrillation, possibly including cardiogenic and neurogenic types, and a mix of both. Over 25 single markers and at least 10 scores have been proposed as predictors of AFDAS. However, there are considerable inconsistencies across studies. The role of AFDAS burden and its associated risk of stroke recurrence have not yet been investigated. Summary AFDAS may differ from atrial fibrillation known before stroke in several clinical dimensions, which are important for optimal patient care strategies. Many questions remain unanswered. Neurogenic and cardiogenic AFDAS need to be characterized, as it may be possible to avoid some neurogenic cases by initiating timely preventive treatments. AFDAS burden may differ in ischemic stroke and TIA patients, with distinctive diagnostic and treatment implications. The prognosis of AFDAS and its risk of recurrent stroke are still unknown; therefore, it is uncertain whether AFDAS patients should be treated with oral anticoagulants. PMID:27984303

Social Deprivation and Initial Presentation of 12 Cardiovascular Diseases: a CALIBER Study

ClinicalTrials.gov

2013-09-03

Abdominal Aortic Aneurysm; Coronary Heart Disease NOS; Unheralded Corronary Death; Intracerebral Haemorrhage; Heart Failure; Ischemic Stroke; Myocardial Infarction; Stroke; Peripheral Arterial Disease; Stable Angina Pectoris; Subarachnoid Haemorrhage; Transient Ischemic Attack; Unstable Angina; Cardiac Arrest, Sudden Cardiac Death

Frequency of Inverted Electrocardiographic T Waves (Cerebral T Waves) in Patients With Acute Strokes and Their Relation to Left Ventricular Wall Motion Abnormalities.

PubMed

Stone, Jeremy; Mor-Avi, Victor; Ardelt, Agnieszka; Lang, Roberto M

2018-01-01

Transient, symmetric, and deep inverted electrocardiogram (ECG) T waves in the setting of stroke, commonly referred to as cerebral T waves, are rare, and the underlying mechanism is unclear. Our study aimed to test the hypothesis that cerebral T waves are associated with transient cardiac dysfunction. This retrospective study included 800 patients admitted with the primary diagnosis of hemorrhagic or ischemic stroke. ECGs were examined for cerebral T waves, defined as T-wave inversion of ≥5 mm depth in ≥4 contiguous precordial leads. Echocardiograms of those meeting these criteria were examined for the presence of left ventricular (LV) wall motion abnormalities. Follow-up evaluation included both ECG and echocardiogram. Of the 800 patients, 17 had cerebral T waves on ECG (2.1%). All 17 patients had ischemic strokes, of which 11 were in the middle cerebral artery distribution (65%), and 2 were cerebellar (12%), whereas the remaining 4 involved other locations. Follow-up ECG showed resolution of the T-wave changes in all 17 patients. Of these patients, 14 (82%) had normal wall motion, and 3 had transient wall motion abnormalities (18%). Two of these patients had Takotsubo-like cardiomyopathy with apical ballooning, and the third had globally reduced LV function. Coronary angiography showed no significant disease to explain the LV dysfunction. In summary, in our cohort of patients with acute stroke, cerebral T waves were rare and occurred only in ischemic stroke. Eighteen percent of patients with cerebral T waves had significant transient wall motion abnormalities. Patients with stroke with cerebral T waves, especially in those with ischemic strokes, should be assessed for cardiac dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: An updated systematic review and meta-analysis of randomized controlled trials.

PubMed

Ntaios, George; Papavasileiou, Vasileios; Diener, Hans-Chris; Makaritsis, Konstantinos; Michel, Patrik

2017-08-01

Background In a previous systematic review and meta-analysis, we assessed the efficacy and safety of nonvitamin-K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and stroke or transient ischemic attack. Since then, new information became available. Aim The aim of the present work was to update the results of the previous systematic review and meta-analysis. Methods We searched PubMed until 24 August 2016 for randomized controlled trials using the following search items: "atrial fibrillation" and "anticoagulation" and "warfarin" and "previous stroke or transient ischemic attack." Eligible studies had to be phase III trials in patients with atrial fibrillation comparing warfarin with nonvitamin-K antagonist oral anticoagulants currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause, and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding, and major gastrointestinal bleeding. We performed fixed effects analyses on intention-to-treat basis. Results Among 183 potentially eligible articles, four were included in the meta-analysis. In 20,500 patients, compared to warfarin, nonvitamin-K antagonist oral anticoagulants were associated with a significant reduction of stroke/systemic embolism (relative risk reduction: 13.7%, absolute risk reduction: 0.78%, number needed to treat to prevent one event: 127), hemorrhagic stroke (relative risk reduction: 50.0%, absolute risk reduction: 0.63%, number needed to treat: 157), any stroke (relative risk reduction: 13.1%, absolute risk reduction: 0.7%, number needed to treat: 142), and intracranial hemorrhage (relative risk reduction: 46.1%, absolute risk reduction: 0.88%, number needed to treat: 113) over 1.8-2.8 years. Conclusions This updated meta-analysis in 20,500 atrial fibrillation patients with previous stroke or transient ischemic attack shows that compared to warfarin non-vitamin-K antagonist oral anticoagulants are associated with a significant reduction of stroke, stroke or systemic embolism, hemorrhagic stroke, and intracranial bleeding.

Cerebral microbleeds and recurrent stroke risk: systematic review and meta-analysis of prospective ischemic stroke and transient ischemic attack cohorts.

PubMed

Charidimou, Andreas; Kakar, Puneet; Fox, Zoe; Werring, David J

2013-04-01

To evaluate cerebral microbleeds (CMBs) and future stroke risk (including intracerebral hemorrhage [ICH]) in patients with ischemic stroke (IS) or transient ischemic attack. A systematic review and meta-analysis of prospective cohorts with recent IS/transient ischemic attack. We critically appraised studies and calculated pooled odds ratios (ORs), using the Mantel-Haenszel fixed-effects method, for ICH or recurrent IS, in patients with versus without CMBs. We pooled data from 10 cohorts, including 3067 patients. CMBs were associated with a significant increased risk of any recurrent stroke (OR, 2.25; 95% confidence interval [95% CI], 1.70-2.98; P<0.0001), ICH (OR, 8.52; 95%CI, 4.23-17.18; P=0.007), and IS (OR, 1.55; 95%CI, 1.12-2.13; P<0.0001). When stratified by study population ethnicity (Asian versus Western [mainly white European]), the association of CMBs with ICH was significant for Asian cohorts (5 studies; n=1915; OR, 10.43; 95%CI, 4.59-23.72; P<0.0001) but borderline and of lower magnitude for Western cohorts (4 studies; n=885; OR, 3.87; 95%CI, 0.91-16.4; P=0.066). By contrast, there was a significant association of CMBs with recurrent IS in Western (3 studies; n=899) but not Asian cohorts (4 studies; n=1357; OR, 2.23; 95%CI, 1.29-3.85; P=0.004 compared with OR, 1.30; 95%CI, 0.88-1.93; P=0.192, respectively). There is consistent evidence of an increased risk of recurrent stroke after IS or transient ischemic attack in patients with CMBs. The risk for spontaneous ICH appears to be greater than the risk for recurrent IS. Our findings also suggest that the balance of risk for ICH versus IS differs between Asian and Western cohorts.

Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis.

PubMed

Rink, Cameron; Christoforidis, Greg; Khanna, Savita; Peterson, Laura; Patel, Yojan; Khanna, Suchin; Abduljalil, Amir; Irfanoglu, Okan; Machiraju, Raghu; Bergdall, Valerie K; Sen, Chandan K

2011-11-01

Vitamin E consists of tocopherols and tocotrienols, in which α-tocotrienol is the most potent neuroprotective form that is also effective in protecting against stroke in rodents. As neuroprotective agents alone are insufficient to protect against stroke, we sought to test the effects of tocotrienol on the cerebrovascular circulation during ischemic stroke using a preclinical model that enables fluoroscopy-guided angiography. Mongrel canines (mean weight=26.3±3.2 kg) were supplemented with tocotrienol-enriched (TE) supplement (200 mg b.i.d, n=11) or vehicle placebo (n=9) for 10 weeks before inducing transient middle cerebral artery (MCA) occlusion. Magnetic resonance imaging was performed 1 hour and 24 hours post reperfusion to assess stroke-induced lesion volume. Tocotrienol-enriched supplementation significantly attenuated ischemic stroke-induced lesion volume (P<0.005). Furthermore, TE prevented loss of white matter fiber tract connectivity after stroke as evident by probabilistic tractography. Post hoc analysis of cerebral angiograms during MCA occlusion revealed that TE-supplemented canines had improved cerebrovascular collateral circulation to the ischemic MCA territory (P<0.05). Tocotrienol-enriched supplementation induced arteriogenic tissue inhibitor of metalloprotease 1 and subsequently attenuated the activity of matrix metalloproteinase-2. Outcomes of the current preclinical trial set the stage for a clinical trial testing the effects of TE in patients who have suffered from transient ischemic attack and are therefore at a high risk for stroke.

Perception of Recurrent Stroke Risk among Black, White and Hispanic Ischemic Stroke and Transient Ischemic Attack Survivors: The SWIFT Study

PubMed Central

Boden-Albala, Bernadette; Carman, Heather; Moran, Megan; Doyle, Margaret; Paik, Myunghee C.

2011-01-01

Objectives Risk modification through behavior change is critical for primary and secondary stroke prevention. Theories of health behavior identify perceived risk as an important component to facilitate behavior change; however, little is known about perceived risk of vascular events among stroke survivors. Methods The SWIFT (Stroke Warning Information and Faster Treatment) study includes a prospective population-based ethnically diverse cohort of ischemic stroke and transient ischemic attack survivors. We investigate the baseline relationship between demographics, health beliefs, and knowledge on risk perception. Regression models examined predictors of inaccurate perception. Results Only 20% accurately estimated risk, 10% of the participants underestimated risk, and 70% of the 817 study participants significantly overestimated their risk for a recurrent stroke. The mean perceived likelihood of recurrent ischemic stroke in the next 10 years was 51 ± 7%. We found no significant differences by race-ethnicity with regard to accurate estimation of risk. Inaccurate estimation of risk was associated with attitudes and beliefs [worry (p < 0.04), fatalism (p < 0.07)] and memory problems (p < 0.01), but not history or knowledge of vascular risk factors. Conclusion This paper provides a unique perspective on how factors such as belief systems influence risk perception in a diverse population at high stroke risk. There is a need for future research on how risk perception can inform primary and secondary stroke prevention. Copyright © 2011 S. Karger AG, Basel PMID:21894045

Ischemic Stroke Patients Demonstrate Increased Carotid Plaque Microvasculature Compared to (Ocular) Transient Ischemic Attack Patients

PubMed Central

van Hoof, Raf H.M.; Schreuder, Floris H.B.M.; Nelemans, Patty; Truijman, Martine T.B.; van Orshoven, Narender P.; Schreuder, Tobien H.; Mess, Werner H.; Heeneman, Sylvia; van Oostenbrugge, Robert J.; Wildberger, Joachim E.; Kooi, M. Eline

2017-01-01

Background Patients with a recent ischemic stroke have a higher risk of recurrent stroke compared to (ocular) transient ischemic attack (TIA) patients. Plaque microvasculature is considered as a feature of plaque vulnerability and can be quantified with carotid dynamic contrast-enhanced MRI (DCE-MRI). The purpose of this cross-sectional study was to explore the association between plaque microvasculature and the type of recent cerebrovascular events in symptomatic patients with mild-to-moderate carotid stenosis. Methods A total of 87 symptomatic patients with a recent stroke (n = 35) or (ocular) TIA (n = 52) underwent carotid DCE-MRI examination. Plaque microvasculature was studied in the vessel wall and adventitia using DCE-MRI and the pharmacokinetic modeling parameter Ktrans. Statistical analysis was performed with logistic regression, correcting for associated clinical risk factors. Results The 75th percentile adventitial (OR 1.97, 95% CI 1.18–3.29) Ktrans was significantly associated with a recent ischemic stroke compared to (ocular) TIA in multivariate analysis, while clinical risk factors were not significantly associated with the type of event. Conclusions This study indicates a positive association of leaky plaque microvasculature with a recent ischemic stroke compared to (ocular) TIA. Prospective longitudinal studies are needed to investigate whether Ktrans or other plaque characteristics may serve as an imaging marker for predicting (the type of) future cerebrovascular events. PMID:28946147

Patent Foramen Ovale and Cryptogenic Strokes in the Stroke in Young Fabry Patients Study.

PubMed

Huber, Roman; Grittner, Ulrike; Weidemann, Frank; Thijs, Vincent; Tanislav, Christian; Enzinger, Christian; Fazekas, Franz; Wolf, Markus; Hennerici, Michael G; McCabe, Dominick J H; Putaala, Jukaa; Tatlisumak, Turgut; Kessler, Christoph; von Sarnowski, Bettina; Martus, Peter; Kolodny, Edwin; Norrving, Bo; Rolfs, Arndt

2017-01-01

A patent foramen ovale (PFO) is disproportionately prevalent in patients with cryptogenic stroke. Without alternative explanations, it is frequently considered to be causative. A detailed stratification of these patients may improve the identification of incidental PFO. We investigated the PFO prevalence in 3497 transient ischemic attack and ischemic stroke patients aged 18 to 55 years in the prospective multicenter SIFAP1 study (Stroke in Young Fabry Patients 1) using the ASCO classification. Patients without an obvious cause for transient ischemic attack/stroke (ASCO 0) were divided into subgroups with and without vascular risk factors (ASCO 0+ and 0-). In addition, we looked for PFO-related magnetic resonance imaging lesion patterns. PFO was identified in 25% of patients. Twenty percent of patients with a definite or probable cause of transient ischemic attack/stroke (≥1 grade 1 or 2 ASCO criterion; n=1769) had a PFO compared with 29% of cryptogenic stroke patients (ASCO 0 and 3; n=1728; P<0,001); subdivision of cryptogenic strokes revealed a PFO in 24% of 978 ASCO 3 patients (n.s. versus ASCO 1 and 2) and a higher prevalence of 36% in 750 ASCO 0 cases (P<0.001 versus ASCO 3 and versus ASCO 1 and 2). PFO was more commonly observed in ASCO 0- (n=271) than in ASCO 0+ patients (n=479; 48 versus 29%; P<0.001). There was no PFO-associated magnetic resonance imaging lesion pattern. Cryptogenic stroke patients demonstrate a heterogeneous PFO prevalence. Even in case of less conclusive diseases like nonstenotic arteriosclerosis, patients should preferentially be considered to have a non-PFO-mediated stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2016 American Heart Association, Inc.

Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack.

PubMed

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

2016-07-07

Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia. We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days. During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%. In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).

Association Between CYP2C19 Loss-of-Function Allele Status and Efficacy of Clopidogrel for Risk Reduction Among Patients With Minor Stroke or Transient Ischemic Attack.

PubMed

Wang, Yilong; Zhao, Xingquan; Lin, Jinxi; Li, Hao; Johnston, S Claiborne; Lin, Yi; Pan, Yuesong; Liu, Liping; Wang, David; Wang, Chunxue; Meng, Xia; Xu, Jianfeng; Wang, Yongjun

2016-07-05

Data are limited regarding the association between CYP2C19 genetic variants and clinical outcomes of patients with minor stroke or transient ischemic attack treated with clopidogrel. To estimate the association between CYP2C19 genetic variants and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack. Three CYP2C19 major alleles (*2, *3, *17) were genotyped among 2933 Chinese patients from 73 sites who were enrolled in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) randomized trial conducted from January 2, 2010, to March 20, 2012. Patients with acute minor ischemic stroke or transient ischemic attack in the trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone. The primary efficacy outcome was new stroke. The secondary efficacy outcome was a composite of new composite vascular events (ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death). Bleeding was the safety outcome. Among 2933 patients, 1948 (66.4%) were men, with a mean age of 62.4 years. Overall, 1207 patients (41.2%) were noncarriers and 1726 patients (58.8%) were carriers of loss-of-function alleles (*2, *3). After day 90 follow-up, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the loss-of-function alleles (P = .02 for interaction; events among noncarriers, 41 [6.7%] with clopidogrel-aspirin vs 74 [12.4%] with aspirin; hazard ratio [HR], 0.51 [95% CI, 0.35-0.75]; events among carriers, 80 [9.4%] with clopidogrel-aspirin vs 94 [10.8%] with aspirin; HR, 0.93 [95% CI, 0.69 to 1.26]). Similar results were observed for the secondary composite efficacy outcome (noncarriers: 41 [6.7%] with clopidogrel-aspirin vs 75 [12.5%] with aspirin; HR, 0.50 [95% CI, 0.34-0.74]; carriers: 80 [9.4%] with clopidogrel-aspirin vs 95 [10.9%] with aspirin; HR, 0.92 [95% CI, 0.68-1.24]; P = .02 for interaction). The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the loss-of-function alleles (2.3% for carriers and 2.5% for noncarriers in the clopidogrel-aspirin group vs 1.4% for carriers and 1.7% for noncarriers in the aspirin only group; P = .78 for interaction). Among patients with minor ischemic stroke or transient ischemic attack, the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who were not carriers of the CYP2C19 loss-of-function alleles. These findings support a role of CYP2C19 genotype in the efficacy of this treatment. clinicaltrials.gov Identifier: NCT00979589.

Stroke Risk Factors and Symptoms

MedlinePlus

... » [ pdf, 433 kb ] Order Materials » Stroke Risk Factors and Symptoms Risk Factors for a Stroke Stroke prevention is still ... it. Treatment can delay complications that increase the risk of stroke. Transient ischemic attacks (TIAs). Seek help. ...

Prevalence of Depression Among Stroke Survivors: Racial-Ethnic Differences.

PubMed

Fei, Kezhen; Benn, Emma K T; Negron, Rennie; Arniella, Guedy; Tuhrim, Stanley; Horowitz, Carol R

2016-02-01

Although poststroke depression is common, racial-ethnic disparities in depression among stroke survivors remain underexplored. Thus, we investigated the relationship between race/ethnicity and depression in a multiracial-ethnic stroke cohort. Baseline survey data of validated scales of depression and functional status, demographics, comorbidities, and socioeconomic status were used from a recurrent stroke prevention study among community-dwelling urban stroke/transient ischemic attack survivors. The cohort included 556 participants with a mean age of 64 years. The majorities were black (44%) or latino (42%) and female (60%), had their last stroke/transient ischemic attack nearly 2 years before study enrollment, and lived below the poverty level (58%). Nearly 1 in 2 latinos, 1 in 4 blacks, and 1 in 8 whites were depressed. Multivariate logistic regression showed that survivors who were younger, were female, had ≥3 comorbid conditions, were functionally disabled from stroke, lacked emotional-social support, and who took antidepressants before study entry had higher risk of depression. Time since last stroke/transient ischemic attack did not affect the chance of depression. After adjusting for all above risk factors, latinos had 3× the odds of depression (95% confidence interval: 1.18-6.35) than whites; blacks and whites had similar odds of depression. This study reveals that latino stroke survivors have a significantly higher prevalence of depression compared with their non-latino counterparts. © 2015 American Heart Association, Inc.

Four-year follow-up of transient ischemic attacks, strokes, and mimics: a retrospective transient ischemic attack clinic cohort study.

PubMed

Dutta, Dipankar; Bowen, Emily; Foy, Chris

2015-05-01

There is limited information on outcomes from rapid access transient ischemic attack (TIA) clinics. We present 4-year outcomes of TIAs, strokes, and mimics from a UK TIA clinic database. All patients referred between April 2010 and May 2012 were retrospectively identified and outcomes determined. End points were stroke, myocardial infarction, any vascular event (TIA, stroke, or myocardial infarction), and all-cause death. Data were analyzed by survival analysis. Of 1067 patients, 31.6% were TIAs, 18% strokes, and 50.4% mimics. Median assessment time was 4.5 days from onset and follow-up was for 34.9 months. Subsequent strokes occurred in 7.1% of patients with TIA, 10.9% of patients with stroke, and 2.0% of mimics at the end of follow-up. Stroke risk at 90 days was 1.3% for patients diagnosed as TIA or stroke. Compared with mimics, hazard ratios for subsequent stroke were 3.88 (1.90-7.91) for TIA and 5.84 (2.81-12.11) for stroke. Hazard ratio for any subsequent vascular event was 2.91 (1.97-4.30) for TIA and 2.83 (1.81-4.41) for stroke. Hazard ratio for death was 1.68 (1.10-2.56) for TIA and 2.19 (1.38-3.46) for stroke. Our results show a lower 90-day stroke incidence after TIA or minor stroke than in earlier studies, suggesting that rapid access daily TIA clinics may be having a significant effect on reducing strokes. © 2015 American Heart Association, Inc.

Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis.

PubMed

Kishore, Amit; Vail, Andy; Majid, Arshad; Dawson, Jesse; Lees, Kennedy R; Tyrrell, Pippa J; Smith, Craig J

2014-02-01

Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%-14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%-18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%-8.3%). There was substantial heterogeneity even within specified subgroups. Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF.

Neuroprotective Effect of a New Synthetic Aspirin-decursinol Adduct in Experimental Animal Models of Ischemic Stroke

PubMed Central

Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

2013-01-01

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants. PMID:24073226

Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental animal models of ischemic stroke.

PubMed

Yan, Bing Chun; Park, Joon Ha; Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

2013-01-01

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.

The effect of antihypertensive treatment on the incidence of stroke and cognitive decline in the elderly: a meta-analysis.

PubMed

Parsons, Christine; Murad, Mohammad Hassan; Andersen, Stuart; Mookadam, Farouk; Labonte, Helene

2016-03-01

To evaluate the effectiveness of antihypertensives in reducing neurocognitive outcomes in elderly patients. We conducted a systematic literature search of randomized trials in which hypertensive patients with a mean age ≥65 years received antihypertensive or control treatment. Outcomes were stroke, transient ischemic attack, cognitive decline and dementia. We included 14 trials for meta-analysis. Compared to placebo, antihypertensive treatment reduced the risk of stroke (RR: 0.67 [95% CI: 0.57-0.79]). Reduced risk was significant for transient ischemic attack, fatal stroke, nonfatal stroke and total stroke. There were insufficient data to compare individual agents. Antihypertensive treatment is associated with a significant reduction in stroke in elderly individuals. Reductions in dementia and cognitive decline were not significant; however, there was short follow-up. Comparative effectiveness evidence is limited.

Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis

PubMed Central

Rink, Cameron; Christoforidis, Greg; Khanna, Savita; Peterson, Laura; Patel, Yojan; Khanna, Suchin; Abduljalil, Amir; Irfanoglu, Okan; Machiraju, Raghu; Bergdall, Valerie K; Sen, Chandan K

2011-01-01

Vitamin E consists of tocopherols and tocotrienols, in which α-tocotrienol is the most potent neuroprotective form that is also effective in protecting against stroke in rodents. As neuroprotective agents alone are insufficient to protect against stroke, we sought to test the effects of tocotrienol on the cerebrovascular circulation during ischemic stroke using a preclinical model that enables fluoroscopy-guided angiography. Mongrel canines (mean weight=26.3±3.2 kg) were supplemented with tocotrienol-enriched (TE) supplement (200 mg b.i.d, n=11) or vehicle placebo (n=9) for 10 weeks before inducing transient middle cerebral artery (MCA) occlusion. Magnetic resonance imaging was performed 1 hour and 24 hours post reperfusion to assess stroke-induced lesion volume. Tocotrienol-enriched supplementation significantly attenuated ischemic stroke-induced lesion volume (P<0.005). Furthermore, TE prevented loss of white matter fiber tract connectivity after stroke as evident by probabilistic tractography. Post hoc analysis of cerebral angiograms during MCA occlusion revealed that TE-supplemented canines had improved cerebrovascular collateral circulation to the ischemic MCA territory (P<0.05). Tocotrienol-enriched supplementation induced arteriogenic tissue inhibitor of metalloprotease 1 and subsequently attenuated the activity of matrix metalloproteinase-2. Outcomes of the current preclinical trial set the stage for a clinical trial testing the effects of TE in patients who have suffered from transient ischemic attack and are therefore at a high risk for stroke. PMID:21673716

Recent advances in the management of transient ischemic attacks

PubMed Central

Gomez, Camilo R.; Schneck, Michael J.; Biller, Jose

2017-01-01

Significant advances in our understanding of transient ischemic attack (TIA) have taken place since it was first recognized as a major risk factor for stroke during the late 1950's. Recently, numerous studies have consistently shown that patients who have experienced a TIA constitute a heterogeneous population, with multiple causative factors as well as an average 5–10% risk of suffering a stroke during the 30 days that follow the index event. These two attributes have driven the most important changes in the management of TIA patients over the last decade, with particular attention paid to effective stroke risk stratification, efficient and comprehensive diagnostic assessment, and a sound therapeutic approach, destined to reduce the risk of subsequent ischemic stroke. This review is an outline of these changes, including a discussion of their advantages and disadvantages, and references to how new trends are likely to influence the future care of these patients. PMID:29263784

Methodological factors in determining rates of dementia in transient ischemic attack and stroke: (I) impact of baseline selection bias.

PubMed

Pendlebury, Sarah T; Chen, Ping-Jen; Bull, Linda; Silver, Louise; Mehta, Ziyah; Rothwell, Peter M

2015-03-01

Many previous studies on dementia in stroke have restrictive inclusion criteria, which may result in underestimation of dementia rates. We undertook a large prospective population-based study of all transient ischemic attack and stroke to determine the impact of study entry criteria on measured rates of pre- and postevent dementia. All patients with acute transient ischemic attack or stroke from a defined population of 92 728 are referred from primary care or at hospital admission to the Oxford Vascular Study (2002-2007) and have baseline clinical and cognitive assessment and follow-up. We examined the impact of early death, other nonavailability, and commonly used selection criteria, on measured rates of dementia. Among 1236 patients (mean age/SD 75.2/12.1 years, 582 men, 403 transient ischemic attack), 139 died or were otherwise unavailable for baseline assessment, 319 had prior dependency, 425 had comorbidity, 512 were aged ≥80 years, 85 were dysphasic, and 502 were hospitalized. Pre-event dementia was 3-fold higher in patients dying preascertainment (10/47, 21%) and twice as high in other nonassessed (14/92, 15%) versus assessed patients (69/1097, 6%; P=0.0006 and P=0.002) and was several-fold higher in those with prior functional impairment (24% versus 3%; P<0.0001), age >80 years (13% versus 3%; P<0.0001), dysphasia (11% versus 7%; P<0.0001), and comorbidity (10% versus 6%; P=0.04). Findings for postevent dementia were similar: prior functional impairment (40% versus 13%; P<0.0001), age >80 years (28% versus 10%; P<0.0001), dysphasia (39% versus 15%; P<0.0001), and comorbidity (20% versus 15%; P=0.04). Exclusion of patients unavailable for assessment, and other widely used selection criteria, results in underestimation of the measured rate of dementia associated with transient ischemic attack and stroke. © 2015 American Heart Association, Inc.

Antiplatelet Agents for the Secondary Prevention of Ischemic Stroke or Transient Ischemic Attack: A Network Meta-Analysis.

PubMed

Wang, Wen; Zhang, Lu; Liu, Weiming; Zhu, Qin; Lan, Qing; Zhao, Jizong

2016-05-01

Stroke can cause high morbidity and mortality, and ischemic stroke (IS) and transient ischemic attack (TIA) patients have a high stroke recurrence rate. Antiplatelet agents are the standard therapy for these patients, but it is often difficult for clinicians to select the best therapy from among the multiple treatment options. We therefore performed a network meta-analysis to estimate the efficacy of antiplatelet agents for secondary prevention of recurrent stroke. We systematically searched 3 databases (PubMed, Embase, and Cochrane) for relevant studies published through August 2015. The primary end points of this meta-analysis were overall stroke, hemorrhagic stroke, and fatal stroke. A total of 30 trials were included in our network meta-analysis and abstracted data. Among the therapies evaluated in the included trials, the estimates for overall stroke and hemorrhagic stroke for cilostazol (Cilo) were significantly better than those for aspirin (odds ratio [OR] = .64, 95% credibility interval [CrI], .45-.91; OR = .23, 95% CrI, .08-.58). The estimate for fatal stroke was highest for Cilo plus aspirin combination therapy, followed by Cilo therapy. The results of our meta-analysis indicate that Cilo significantly improves overall stroke and hemorrhagic stroke in IS or TIA patients and reduces fatal stroke, but with low statistical significance. Our results also show that Cilo was significantly more efficient than other therapies in Asian patients; therefore, future trials should focus on Cilo treatment for secondary prevention of recurrent stroke in non-Asian patients. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

External Validation of Risk Scores for Major Bleeding in a Population-Based Cohort of Transient Ischemic Attack and Ischemic Stroke Patients.

PubMed

Hilkens, Nina A; Li, Linxin; Rothwell, Peter M; Algra, Ale; Greving, Jacoba P

2018-03-01

The S 2 TOP-BLEED score may help to identify patients at high risk of bleeding on antiplatelet drugs after a transient ischemic attack or ischemic stroke. The score was derived on trial populations, and its performance in a real-world setting is unknown. We aimed to externally validate the S 2 TOP-BLEED score for major bleeding in a population-based cohort and to compare its performance with other risk scores for bleeding. We studied risk of bleeding in 2072 patients with a transient ischemic attack or ischemic stroke on antiplatelet agents in the population-based OXVASC (Oxford Vascular Study) according to 3 scores: S 2 TOP-BLEED, REACH, and Intracranial-B 2 LEED 3 S. Performance was assessed with C statistics and calibration plots. During 8302 patient-years of follow-up, 117 patients had a major bleed. The S 2 TOP-BLEED score showed a C statistic of 0.69 (95% confidence interval [CI], 0.64-0.73) and accurate calibration for 3-year risk of major bleeding. The S 2 TOP-BLEED score was much more predictive of fatal bleeding than nonmajor bleeding (C statistics 0.77; 95% CI, 0.69-0.85 and 0.50; 95% CI, 0.44-0.58). The REACH score had a C statistic of 0.63 (95% CI, 0.58-0.69) for major bleeding and the Intracranial-B 2 LEED 3 S score a C statistic of 0.60 (95% CI, 0.51-0.70) for intracranial bleeding. The ratio of ischemic events versus bleeds decreased across risk groups of bleeding from 6.6:1 in the low-risk group to 1.8:1 in the high-risk group. The S 2 TOP-BLEED score shows modest performance in a population-based cohort of patients with a transient ischemic attack or ischemic stroke. Although bleeding risks were associated with risks of ischemic events, risk stratification may still be useful to identify a subgroup of patients at particularly high risk of bleeding, in whom preventive measures are indicated. © 2018 The Authors.

De novo Diagnosis of Fabry Disease among Italian Adults with Acute Ischemic Stroke or Transient Ischemic Attack.

PubMed

Romani, Ilaria; Borsini, Walter; Nencini, Patrizia; Morrone, Amelia; Ferri, Lorenzo; Frusconi, Sabrina; Donadio, Vincenzo Angelo; Liguori, Rocco; Donati, Maria Alice; Falconi, Serena; Pracucci, Giovanni; Inzitari, Domenico

2015-11-01

Cerebrovascular complications are often the first cause of hospitalization in patients with Fabry disease (FD). Screenings for FD among stroke patients have yielded discrepant results, likely as a result of heterogeneous or incomplete assessment. We designed a study to identify FD among adults 60 years of age or younger who were consecutively admitted for acute ischemic stroke or transient ischemic attack (TIA) to a stroke neurology service in Italy. Patients with first-ever or recurrent events were included, irrespective of gender, risk factors, or stroke type. We screened male patients using α-galactosidase A enzyme assay, and female patients using DNA sequencing. FD was eventually established after a broad multidisciplinary discussion. We screened 108 patients (61% males, median age: 48 years); 84% of these patients had stroke. De novo FD diagnosis was established in 3 patients (2.8%; 95% confidence interval, .57-8.18): a 59-year-old man with recurrent lacunar-like strokes and multiple risk factors; a 42-year-old woman with recurrent cryptogenic minor strokes; and a 32-year-old woman with recurrent strokes previously attributed to Behçet's disease. Screened patients were systematically asked for typical FD symptoms; each of the de novo patients reported one or more of the following: episodes of hand/foot pain during fever, angiokeratoma, and family history of heart disease. In all of the patients events were recurrent, and lacunar-like infarcts characterized their brain imaging. Prevalence of FD among nonselected adults 60 years of age or younger with acute ischemic stroke or TIA is not negligible. A systematic search for FD in a stroke setting, using a comprehensive clinical, biochemical, and genetic screening protocol, may be worthwhile. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Anxiety After Stroke

PubMed Central

Whiteley, William N.; Dennis, Martin S.; Mead, Gillian E.; Carson, Alan J.

2018-01-01

Background and Purpose— Anxiety after stroke is common and disabling. Stroke trialists have treated anxiety as a homogenous condition, and intervention studies have followed suit, neglecting the different treatment approaches for phobic and generalized anxiety. Using diagnostic psychiatric interviews, we aimed to report the frequency of phobic and generalized anxiety, phobic avoidance, predictors of anxiety, and patient outcomes at 3 months poststroke/transient ischemic attack. Methods— We followed prospectively a cohort of new diagnosis of stroke/transient ischemic attack at 3 months with a telephone semistructured psychiatric interview, Fear Questionnaire, modified Rankin Scale, EuroQol-5D5L, and Work and Social Adjustment Scale. Results— Anxiety disorder was common (any anxiety disorder, 38 of 175 [22%]). Phobic disorder was the predominant anxiety subtype: phobic disorder only, 18 of 175 (10%); phobic and generalized anxiety disorder, 13 of 175 (7%); and generalized anxiety disorder only, 7 of 175 (4%). Participants with anxiety disorder reported higher level of phobic avoidance across all situations on the Fear Questionnaire. Younger age (per decade increase in odds ratio, 0.64; 95% confidence interval, 0.45–0.91) and having previous anxiety/depression (odds ratio, 4.38; 95% confidence interval, 1.94–9.89) were predictors for anxiety poststroke/transient ischemic attack. Participants with anxiety disorder were more dependent (modified Rankin Scale score 3–5, [anxiety] 55% versus [no anxiety] 29%; P<0.0005), had poorer quality of life on EQ-5D5L, and restricted participation (Work and Social Adjustment Scale: median, interquartile range, [anxiety] 19.5, 10–27 versus [no anxiety] 0, 0–5; P<0.001). Conclusions— Anxiety after stroke/transient ischemic attack is predominantly phobic and is associated with poorer patient outcomes. Trials of anxiety intervention in stroke should consider the different treatment approaches needed for phobic and generalized anxiety. PMID:29437982

Anxiety After Stroke: The Importance of Subtyping.

PubMed

Chun, Ho-Yan Yvonne; Whiteley, William N; Dennis, Martin S; Mead, Gillian E; Carson, Alan J

2018-03-01

Anxiety after stroke is common and disabling. Stroke trialists have treated anxiety as a homogenous condition, and intervention studies have followed suit, neglecting the different treatment approaches for phobic and generalized anxiety. Using diagnostic psychiatric interviews, we aimed to report the frequency of phobic and generalized anxiety, phobic avoidance, predictors of anxiety, and patient outcomes at 3 months poststroke/transient ischemic attack. We followed prospectively a cohort of new diagnosis of stroke/transient ischemic attack at 3 months with a telephone semistructured psychiatric interview, Fear Questionnaire, modified Rankin Scale, EuroQol-5D5L, and Work and Social Adjustment Scale. Anxiety disorder was common (any anxiety disorder, 38 of 175 [22%]). Phobic disorder was the predominant anxiety subtype: phobic disorder only, 18 of 175 (10%); phobic and generalized anxiety disorder, 13 of 175 (7%); and generalized anxiety disorder only, 7 of 175 (4%). Participants with anxiety disorder reported higher level of phobic avoidance across all situations on the Fear Questionnaire. Younger age (per decade increase in odds ratio, 0.64; 95% confidence interval, 0.45-0.91) and having previous anxiety/depression (odds ratio, 4.38; 95% confidence interval, 1.94-9.89) were predictors for anxiety poststroke/transient ischemic attack. Participants with anxiety disorder were more dependent (modified Rankin Scale score 3-5, [anxiety] 55% versus [no anxiety] 29%; P <0.0005), had poorer quality of life on EQ-5D5L, and restricted participation (Work and Social Adjustment Scale: median, interquartile range, [anxiety] 19.5, 10-27 versus [no anxiety] 0, 0-5; P <0.001). Anxiety after stroke/transient ischemic attack is predominantly phobic and is associated with poorer patient outcomes. Trials of anxiety intervention in stroke should consider the different treatment approaches needed for phobic and generalized anxiety. © 2018 The Authors.

Ticagrelor in Acute Stroke or Transient Ischemic Attack in Asian Patients: From the SOCRATES Trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes).

PubMed

Wang, Yongjun; Minematsu, Kazuo; Wong, Ka Sing Lawrence; Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Jonasson, Jenny; Molina, Carlos A; Johnston, S Claiborne

2017-01-01

In the SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), ticagrelor was not superior to aspirin. Because of differences in patient demographics and stroke disease pattern in Asia, outcomes of ticagrelor versus aspirin were assessed among Asian patients in a prespecified exploratory analysis. Baseline demographics, treatment effects, and safety of ticagrelor and aspirin were assessed among Asian patients. Differences in outcomes between groups were assessed using Cox proportional hazard model. A total of 3858 (29.2%) SOCRATES participants were recruited in Asia. Among the Asian patients, the primary end point event occurred in 186 (9.6%) of the 1933 patients treated with ticagrelor, versus 224 (11.6%) of the 1925 patients treated with aspirin (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99). The exploratory P value for treatment-by-region interaction was 0.27. The primary end point event rate in the Asian subgroup was numerically higher than that in the non-Asian group (10.6% versus 5.7%; nominal P<0.01). Among the Asian patients, the rate of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeding was similar in the ticagrelor group and the aspirin group (0.6% versus 0.8%; hazard ratio, 0.76; 95% confidence interval, 0.36-1.61). The event rates were numerically higher in the Asian patients. Among the Asian patients with acute stroke or transient ischemic attacks, there was a trend toward a lower hazard ratio in reducing risk of the primary end point of stroke, myocardial infarction, or death in the ticagrelor group. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720. © 2016 American Heart Association, Inc.

Atrial fibrillation is not uncommon among patients with ischemic stroke and transient ischemic stroke in China.

PubMed

Yang, Xiaomeng; Li, Shuya; Zhao, Xingquan; Liu, Liping; Jiang, Yong; Li, Zixiao; Wang, Yilong; Wang, Yongjun

2017-12-04

Atrial fibrillation (AF) is reported to be a less frequent cause of ischemic stroke in China than in Europe and North America, but it is not clear whether this is due to underestimation. Our aim was to define the true frequency of AF-associated stroke, to determine the yield of 6-day Holter ECG to detect AF in Chinese stroke patients, and to elucidate predictors of newly detected AF. Patients with acute ischemic stroke or transient ischemic attack (TIA) were enrolled in a prospective, multicenter cohort study of 6-day Holter monitoring within 7 days after stroke onset at 20 sites in China between 2013 and 2015. Independent predictors of newly-detected AF were determined by multivariate analysis. Among 1511 patients with ischemic stroke and TIA (mean age 63 years, 33.1% women), 305 (20.2%) had either previously known (196, 13.0%) or AF newly-detected by electrocardiography (53, 3.5%) or by 6-day Holter monitoring (56/1262, 4.4%). A history of heart failure (OR = 4.70, 95%CI, 1.64-13.5), advanced age (OR = 1.06, 95%CI, 1.04-1.09), NIHSS at admission (OR = 1.06, 95%CI, 1.02-1.10), blood high density lipoprotein (HDL) (OR = 1.52, 95%CI, 1.09-2.13), together with blood triglycerides (OR = 0.64, 95%CI, 0.45-0.91) were independently associated with newly-detected AF. Contrary to previous reports, AF-associated stroke is frequent (20%) in China if systemically sought. Prolonged noninvasive cardiac rhythm monitoring importantly increases AF detection in patients with recent ischemic stroke and TIA in China. Advanced age, history of heart failure, and higher admission NIHSS and higher level of HDL were independent indicators of newly-detected AF. NCT02156765 (June 5, 2014).

Validation of Diagnoses of Transient Ischemic Attack in the Swedish Stroke Register (Riksstroke) TIA-Module.

PubMed

Buchwald, Fredrik; Ström, Jakob O; Norrving, Bo; Petersson, Jesper

2015-01-01

In 2010, the Swedish Stroke Register (Riksstroke; RS) established a module for transient ischemic attacks (RS-TIA). We report a diagnostic validation study of patients included in RS-TIA. During the first year, 7,825 patients were registered at 59 out of 74 Swedish hospitals. A time-based TIA definition was applied. A sample of 180 patients (30 patients each from 6 hospitals), with a similar distribution of age and sex as in RS-TIA, was prepared. Two independent observers assessed medical records for quality of documentation and assigned a diagnosis of likely, possible, unlikely TIA or ischemic stroke, according to prespecified criteria. The 2 observers agreed in 77% of cases that the event was a likely or possible TIA, in 3% that the event was an ischemic stroke, and in 2% that the event was an unlikely TIA. The observers disagreed in 8% of patients on TIA vs. ischemic stroke, and in 11% on a vascular vs. non-vascular cause. Quality of documentation was fair. There was interobserver agreement on diagnosis of TIA in the majority of patients included in RS-TIA. Diagnostic accuracy may be further improved by more systematic documentation of symptoms and signs. © 2015 S. Karger AG, Basel.

Effect of ticagrelor with clopidogrel on high on-treatment platelet reactivity in acute stroke or transient ischemic attack (PRINCE) trial: Rationale and design.

PubMed

Wang, Yilong; Lin, Yi; Meng, Xia; Chen, Weiqi; Chen, Guohua; Wang, Zhimin; Wu, Jialing; Wang, Dali; Li, Jianhua; Cao, Yibin; Xu, Yuming; Zhang, Guohua; Li, Xiaobo; Pan, Yuesong; Li, Hao; Liu, Liping; Zhao, Xingquan; Wang, Yongjun

2017-04-01

Rationale and aim Little is known about the safety and efficacy of the combination of ticagrelor and aspirin in acute ischemic stroke. This study aimed to evaluate whether the combination of ticagrelor and aspirin was superior to that of clopidogrel and aspirin in reducing the 90-day high on-treatment platelet reactivity for acute minor stroke or transient ischemic attack, especially for carriers of cytochrome P450 2C19 loss-of-function allele. Sample size and design This study was designed as a prospective, multicenter, randomized, open-label, active-controlled, and blind-endpoint, phase II b trial. The required sample size was 952 patients. It was registered with ClinicalTrials.gov (NCT02506140). Study outcomes The primary outcome was the proportion of patients with high on-treatment platelet reactivity at 90 days. High on-treatment platelet reactivity is defined as the P2Y12 reaction unit >208 measured using the VerifyNow P2Y12 assay. Conclusion The Platelet Reactivity in Acute Non-disabling Cerebrovascular Events study explored whether ticagrelor combined with aspirin could reduce further the proportion of patients with high on-treatment platelet reactivity at 90 days after acute minor stroke or transient ischemic attack compared with clopidogrel and aspirin.

Copeptin and Long-Term Risk of Recurrent Vascular Events After Transient Ischemic Attack and Ischemic Stroke: Population-Based Study.

PubMed

Greisenegger, Stefan; Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Rothwell, Peter M

2015-11-01

Copeptin, the c-terminal portion of provasopressin, is a useful prognostic marker in patients after myocardial infarction and heart failure. More recently, high levels of copeptin have also been associated with worse functional outcome and increased mortality within the first year after ischemic stroke and transient ischemic attack (TIA). However, to date, there are no published data on whether copeptin predicts long-term risk of vascular events after TIA and stroke. We measured copeptin levels in consecutive patients with TIA or ischemic stroke in a population-based study (Oxford Vascular Study) recruited from 2002 to 2007 and followed up to 2014. Associations with risk of recurrent vascular events were determined by Cox-regression. During ≈6000 patient-years in 1076 patients, there were 357 recurrent vascular events, including 174 ischemic strokes. After adjustment for age, sex, and risk factors, copeptin was predictive of recurrent vascular events (adjusted hazard ratio per SD, 1.47; 95% confidence interval, 1.31-1.64; P=0.0001), vascular death (1.85; 1.60-2.14; P<0.0001), all-cause death (1.75; 1.58-1.93; P<0.0001), and recurrent ischemic stroke (1.22; 1.04-1.44; P=0.017); and improved model-discrimination significantly: net reclassification improvement for recurrent vascular events (32%; P<0.0001), vascular death (55%; P<0.0001), death (66%; P<0.0001), and recurrent stroke (16%; P=0.044). The predictive value of copeptin was largest in patients with cardioembolic index events (adjusted hazard ratio, 1.84; 95% confidence interval, 1.53-2.20 versus 1.31, 1.14-1.50 in noncardioembolic stroke; P=0.0025). In patients with cardioembolic stroke, high copeptin levels were associated with a 4-fold increased risk of vascular events within the first year of follow-up (adjusted hazard ratio, 4.02; 95% confidence interval, 2.13-7.70). In patients with TIA and ischemic stroke, copeptin predicted recurrent vascular events and death, particularly after cardioembolic TIA/stroke. Further validation is required, in particular, in studies using more extensive cardiac evaluation. © 2015 American Heart Association, Inc.

Functional Stroke Mimics: Incidence and Characteristics at a Primary Stroke Center in the Middle East

PubMed Central

Wilkins, Stacy Schantz; Bourke, Paula; Salam, Abdul; Akhtar, Naveed; D'Souza, Atlantic; Kamran, Saadat; Bhutta, Zain; Shuaib, Ashfaq

2018-01-01

ABSTRACT Objective Approximately 30% of individuals who initially present with stroke are found to be stroke mimics (SM), with functional/psychological SM (FSM) accounting for up to 6.4% of all stroke presentations. Middle Eastern countries may have higher rates of somatization of emotional distress. The aim of this study was to evaluate the incidence and characteristics of FSM at a large general hospital in the Middle East. Methods All patients presenting with an initial diagnosis of stroke from June 2015 to September 2016 were eligible for this study. Clinical and sociodemographic data were obtained from the hospital's stroke database. All SM and strokes were diagnosed by Joint Commission International–certified stroke program neurologists. SM was defined as any discharge diagnosis (other than acute stroke) for symptoms that prompted initial admission for suspected stroke. FSM were compared with medical stroke mimics (MSM) and strokes (ischemic, hemorrhagic, and transient ischemic attacks). Results A total of 1961 patients were identified; 161 FSM (8.2%), 390 MSM (19.9%), and 1410 strokes (71.9%) (985 ischemic strokes, 196 transient ischemic attacks, 229 intracerebral hemorrhages). Admission with FSM was related to patients' nationality, with the highest frequency in Arabic (15.6%) and African (16.8%) patients. FSM patients were younger, more often female, and had fewer cardiovascular risk factors except for smoking compared with the strokes. FSM patients presented with more left-sided weakness and had more magnetic resonance imagings than the stroke and MSM groups. A total of 9.9% of FSM patients received thrombolysis versus only 0.5% of the MSM and 16.4% of ischemic strokes. Conclusions FSM frequencies varied by nationality, with Arab and African nationals being twice as prevalent. Stress, vulnerable status as expats, sociopolitical instability, and exposure to trauma are proposed as potential factors contributing to FSM. PMID:29394187

Transient Ischemic Attack (TIA)

MedlinePlus

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Incidental Statin Use and the Risk of Stroke or Transient Ischemic Attack after Radiotherapy for Head and Neck Cancer

PubMed Central

Addison, Daniel; Lawler, Patrick R.; Emami, Hamed; Janjua, Sumbal A.; Staziaki, Pedro V.; Hallett, Travis R.; Hennessy, Orla; Lee, Hang; Szilveszter, Bálint; Lu, Michael; Mousavi, Negar; Nayor, Matthew G.; Delling, Francesca N.; Romero, Javier M.; Wirth, Lori J.; Chan, Annie W.; Hoffmann, Udo; Neilan, Tomas G.

2018-01-01

Background and Purpose Interventions to reduce the risk for cerebrovascular events (CVE; stroke and transient ischemic attack [TIA]) after radiotherapy (RT) for head and neck cancer (HNCA) are needed. Among broad populations, statins reduce CVEs; however, whether statins reduce CVEs after RT for HNCA is unclear. Therefore, we aimed to test whether incidental statin use at the time of RT is associated with a lower rate of CVEs after RT for HNCA. Methods From an institutional database we identified all consecutive subjects treated with neck RT from 2002 to 2012 for HNCA. Data collection and event adjudication was performed by blinded teams. The primary outcome was a composite of ischemic stroke and TIA. The secondary outcome was ischemic stroke. The association between statin use and events was determined using Cox proportional hazard models after adjustment for traditional and RT-specific risk factors. Results The final cohort consisted of 1,011 patients (59±13 years, 30% female, 44% hypertension) with 288 (28%) on statins. Over a median follow-up of 3.4 years (interquartile range, 0.1 to 14) there were 102 CVEs (89 ischemic strokes and 13 TIAs) with 17 in statin users versus 85 in nonstatins users. In a multivariable model containing known predictors of CVE, statins were associated with a reduction in the combination of stroke and TIA (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2 to 0.8; P=0.01) and ischemic stroke alone (HR, 0.4; 95% CI, 0.2 to 0.8; P=0.01). Conclusions Incidental statin use at the time of RT for HNCA is associated with a lower risk of stroke or TIA. PMID:29402065

Transient ischemic attack: reviewing the evolution of the definition, diagnosis, risk stratification, and management for the emergency physician.

PubMed

Siket, Matthew S; Edlow, Jonathan A

2012-08-01

A transient ischemic attack (TIA) is an episode of reversible neurologic deficit caused by temporary focal central nervous system hypoperfusion. TIA is a medical emergency. Because patients with TIA in the emergency department (ED) have a high risk for stroke within the next 48 hours, it is imperative for the clinician to recognize this golden opportunity to prevent a disabling stroke. This article reviews our conceptual understanding of TIA, its definition, diagnosis, ways to stratify stroke risk, the acute management and disposition in the ED, and the potential future role of diagnostic biomarkers. Copyright © 2012 Elsevier Inc. All rights reserved.

The Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) registry: design, rationale, and baseline patient characteristics.

PubMed

Bushnell, Cheryl; Zimmer, Louise; Schwamm, Lee; Goldstein, Larry B; Clapp-Channing, Nancy; Harding, Tina; Drew, Laura; Zhao, Xin; Peterson, Eric

2009-03-01

Approximately one third of the 780,000 people in the United States who have a stroke each year have recurrent events. Although efficacious secondary prevention measures are available, levels of adherence to these strategies in patients who have had stroke are largely unknown. Understanding medication-taking behavior in this population is an important step to optimizing the appropriate use of proven secondary preventive therapies and reducing the risk of recurrent stroke. The Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) registry is a prospective study of adherence to stroke prevention medications from hospital discharge to 1 year in patients admitted with stroke or transient ischemic attack. The primary outcomes are medication usage as determined by patient interviews after 3 and 12 months. Potential patient-, provider-, and system-level barriers to persistence of medication use are also collected. Secondary outcomes include the rates of recurrent stroke or transient ischemic attack, vascular events, and rehospitalization and functional status as measured by the modified Rankin score. The AVAIL enrolled about 2,900 subjects from 106 hospitals from July 2006 through July 2008. The 12-month follow-up will be completed in August 2009. The AVAIL registry will document the current state of adherence and persistence to stroke prevention medications among a nationwide sample of patients. These data will be used to design interventions to improve the quality of care post acute hospitalization and reduce the risks of future stroke and cardiovascular events.

Carotid Artery Disease

MedlinePlus

... have the condition may be a stroke or transient ischemic attack (TIA). A TIA is a temporary shortage of blood flow to ... your brain of blood, causing a stroke or TIA. Signs and symptoms of a stroke or TIA ...

Epidemiology of Stroke in Costa Rica: A 7-Year Hospital-Based Acute Stroke Registry of 1319 Consecutive Patients.

PubMed

Torrealba-Acosta, Gabriel; Carazo-Céspedes, Kenneth; Chiou, Sy Han; O'Brien, Anthony Terrence; Fernández-Morales, Huberth

2018-05-01

Limited data on stroke exist for Costa Rica. Therefore, we created a stroke registry out of patients with stroke seen in the Acute Stroke Unit of the Hospital Calderon Guardia. We analyzed 1319 patients enrolled over a 7-year period, which incorporated demographic, clinical, laboratory, and neuroimaging data. The mean age of patients with stroke was 68.0 ± 15.5 years. Seven hundred twenty-five were men and the age range was 13-104 years. The most prevalent risk factors were hypertension (78.8%), dyslipidemia (36.3%), and diabetes (31.9%). Fifteen percent had atrial fibrillation and 24.7% had a previous stroke or transient ischemic attack. Prevalence of hypertension and atrial fibrillation increased with age; however, younger patients were more associated with thrombophilia. We documented 962 (72.9%) ischemic and 270 (20.5%) hemorrhagic strokes. Of the ischemic strokes, 174 (18.1%) were considered secondary to large-artery atherothrombosis, 175 (18.2%) were due to cardiac embolism, 19 (2.0%) were due to lacunar infarcts, and 25 (2.6%) were due to other determined causes. Five hundred sixty-nine (59.1%) remained undetermined. Atherothrombotic strokes were mostly associated with dyslipidemia, diabetes, metabolic syndrome, and obesity, whereas lacunar infarcts were associated with hypertension, smoking, sedentary lifestyle, and previous stroke or transient ischemic attack. Of our patients, 69.9% scored between 0 and 9 in the initial National Institutes of Health Stroke Scale (NIHSS). We found differences in sociodemographic features, risk factors, and stroke severity among stroke subtypes. Risk factor prevalence was similar to other registries involving Hispanic populations. Copyright © 2018 National Stroke Association. All rights reserved.

[Contribution of vascular ultrasonography in patients with ischemic strokes in Brazzaville (Congo)].

PubMed

Ikama, S M; Nsitou, B M; Ossou-Nguiet, P M; Otiobanda, G F; Matali, E

2014-05-01

To determine the prevalence of the carotid lesions during ischemic strokes. This was a descriptive cross-sectional study, conducted in Brazzaville from January 2011 to June 2012 in a consecutive series of 73 patients, victims of a transient ischemic attack or ischemic stroke, documented by a brain computed tomography. All patients underwent vascular ultrasonography of the supra-aortic trunks, carried out within the framework of etiological assessment. The examination searched for plaques, parietal infiltration (measurement of intima-media thickness), and carotid stenosis or occlusion. There were 49 men (67%) and 24 women (33%), mean age 58.7 ± 11.8 years. Eleven patients (15%) had a transient ischemic attack and 62 (85%) an ischemic stroke. The identified independent vascular risk factors were known and treated hypertension (n=66, 90.4%), dyslipidemia (n=16, 22%), diabetes mellitus (n=9, 12.3%), and smoking (n=5, 6.8%), with on average 2.5 factors per individual. Vascular ultrasonography of the supra-aortic trunks, normal in 44 patients (60.3%) was pathological in the other 29 (39.7%). The main anomalies were atheromatous plaque (n=10, 13.7%), parietal infiltration (n=19, 26%). On average intima-media thickness was 0.86 ± 0.11 mm on the left and 0.83 ± 0.11 mm on the right. Two cases of moderate stenosis were noted on the right and left internal carotids, respectively. This preliminary study confirms the existence of carotid atherosclerosis anomalies during ischemic strokes. These lesions, though non-significant, must nevertheless be taken into consideration when searching for the cause of stroke in high-risk vascular patients. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Acciarresi, Monica; D'Amore, Cataldo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Bubba, Valentina; Silvestri, Ilenia; Lees, Kennedy R

2015-08-01

The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants. © 2015 American Heart Association, Inc.

Decline in physical performance among women with a recent transient ischemic attack or ischemic stroke: opportunities for functional preservation a report of the Women's Estrogen Stroke Trial.

PubMed

Kernan, Walter N; Viscoli, Catherine M; Brass, Lawrence M; Gill, Thomas M; Sarrel, Philip M; Horwitz, Ralph I

2005-03-01

Physical performance for walking, reaching, turning, and other common tasks is a major determinant of functional independence after stroke. Current strategies to preserve physical performance focus on prevention of recurrent stroke. Loss of physical performance, however, may occur in the absence of recurrence. To examine this possibility, we measured change in physical performance, independent of subsequent stroke, among women with a recent ischemic stroke or transient ischemic attack (TIA). Among 664 postmenopausal women who participated in a clinical trial of estrogen therapy after stroke or TIA, we administered the Physical Performance Test (PPT) at baseline (mean 58 days from the cerebrovascular event) and annually. Women who died or had a stroke during follow-up were censored. Decline or improvement in physical performance was defined as a change in the PPT score from baseline of at least 3 points. Sustained decline or improvement was defined as 2 consecutive years during which the score had declined or improved, respectively, relative to the baseline score. With each year of follow-up, a smaller proportion of the cohort demonstrated improvement (16% in year 1, 6% in year 5) and a larger proportion demonstrated decline (15% in year 1, 35% in year 5). In an analysis restricted to 259 women with 3 years of follow-up, 46 (18%) experienced a nonsustained decline in physical performance, and 39 (15%) experienced a sustained decline. Decline in physical performance is common after an ischemic stroke or TIA even in the absence of a recurrent neurological event. Our findings suggest that specific interventions to maintain and improve physical performance may be important for reducing long-term disability.

The Effects of Various Weather Conditions as a Potential Ischemic Stroke Trigger in Dogs

PubMed Central

Silver, Gena M.

2017-01-01

Stroke is the fifth leading cause of death in the United States, and is the leading cause of serious, long-term disability worldwide. There are at least 795,000 new or recurrent strokes each year, and approximately 85% of all stroke occurrences are ischemic. Unfortunately, companion animals are also at risk for ischemic stroke. Although the exact incidence of ischemic stroke in companion animals is unknown, some studies, and the veterinary information network (VIN), report that approximately 3% of neurological case referrals are due to a stroke. There is a long list of predisposing factors associated with the risk of ischemic stroke in both humans and canines; however, these factors do not explain why a stroke happens at a particular time on a particular day. Our understanding of these potential stroke “triggers” is limited, and the effect of transient environmental exposures may be one such “trigger”. The present study investigated the extent to which the natural occurrence of canine ischemic stroke was related to the weather conditions in the time-period immediately preceding the onset of stroke. The results of the present study demonstrated that the change in weather conditions could be a potential stroke trigger, with the strokes evaluated occurring after periods of rapid, large fluctuations in weather conditions. There are currently no epidemiological data on the seasonal variability of ischemic stroke in dogs, and determining whether canine stroke parallels human stroke would further validate the use of companion dogs as an appropriate naturally occurring model. PMID:29144407

Human Papillomavirus Status and the Risk of Cerebrovascular Events Following Radiation Therapy for Head and Neck Cancer.

PubMed

Addison, Daniel; Seidelmann, Sara B; Janjua, Sumbal A; Emami, Hamed; Staziaki, Pedro V; Hallett, Travis R; Szilveszter, Bálint; Lu, Michael T; Cambria, Richard P; Hoffmann, Udo; Chan, Annie W; Wirth, Lori J; Neilan, Tomas G

2017-08-30

Radiation therapy (RT) is a standard treatment for head and neck cancer; however, it is associated with inflammation, accelerated atherosclerosis, and cerebrovascular events (CVEs; stroke or transient ischemic attack). Human papillomavirus (HPV) is found in nearly half of head and neck cancers and is associated with inflammation and atherosclerosis. Whether HPV confers an increased risk of CVEs after RT is unknown. Using an institutional database, we identified all consecutive patients treated with RT from 2002 to 2012 for head and neck cancer who were tested for HPV. The outcome of interest was the composite of ischemic stroke and transient ischemic attack, and the association between HPV and CVEs was assessed using Cox proportional hazard models, competing risk analysis, and inverse probability weighting. Overall, 326 participants who underwent RT for head and neck cancer were tested for HPV (age 59±12 years, 75% were male, 9% had diabetes mellitus, 45% had hypertension, and 61% were smokers), of which 191 (59%) were tumor HPV positive. Traditional risk factors for CVEs were similar between HPV-positive and -negative patients. Over a median follow-up of 3.4 years, there were 18 ischemic strokes and 5 transient ischemic attacks (event rate of 1.8% per year). The annual event rate was higher in the HPV-positive patients compared with the HPV-negative patients (2.6% versus 0.9%, P =0.002). In a multivariable model, HPV-positive status was associated with a >4 times increased risk of CVEs (hazard ratio: 4.4; 95% confidence interval, 1.5-13.2; P =0.008). In this study, HPV-positive status is associated with an increased risk of stroke or transient ischemic attack following RT for head and neck cancer. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Risk Factors and Cognitive Relevance of Cortical Cerebral Microinfarcts in Patients With Ischemic Stroke or Transient Ischemic Attack.

PubMed

Wang, Zhaolu; van Veluw, Susanne J; Wong, Adrian; Liu, Wenyan; Shi, Lin; Yang, Jie; Xiong, Yunyun; Lau, Alexander; Biessels, Geert Jan; Mok, Vincent C T

2016-10-01

It was recently demonstrated that cerebral microinfarcts (CMIs) can be detected in vivo using 3.0 tesla (T) magnetic resonance imaging. We investigated the prevalence, risk factors, and the longitudinal cognitive consequence of cortical CMIs on 3.0T magnetic resonance imaging, in patients with ischemic stroke or transient ischemic attack. A total of 231 patients undergoing 3.0T magnetic resonance imaging were included. Montreal Cognitive Assessment was used to evaluate global cognitive functions and cognitive domains (memory, language, and attention visuospatial and executive functions). Cognitive changes were represented by the difference in Montreal Cognitive Assessment score between baseline and 28-month after stroke/transient ischemic attack. The cross-sectional and longitudinal associations between cortical CMIs and cognitive functions were explored using ANCOVA and regression models. Cortical CMIs were observed in 34 patients (14.7%), including 13 patients with acute (hyperintense on diffusion-weighted imaging) and 21 with chronic CMIs (isointense on diffusion-weighted imaging). Atrial fibrillation was a risk factor for all cortical CMIs (odds ratio, 4.8; 95% confidence interval, 1.5-14.9; P=0.007). Confluent white matter hyperintensities was associated with chronic CMIs (odds ratio, 2.8; 95% confidence interval, 1.0-7.8; P=0.047). The presence of cortical CMIs at baseline was associated with worse visuospatial functions at baseline and decline over 28-month follow-up (β=0.5; 95% confidence interval, 0.1-1.0; P=0.008, adjusting for brain atrophy, white matter hyperintensities, lacunes, and microbleeds). Cortical CMIs are a common finding in patients with stroke/transient ischemic attack. Associations between CMI with atrial fibrillation and white matter hyperintensities suggest that these lesions have a heterogeneous cause, involving microembolism and cerebral small vessel disease. CMI seemed to preferentially impact visuospatial functions as assessed by a cognitive screening test. © 2016 American Heart Association, Inc.

Vertebrobasilar circulatory disorders

MedlinePlus

... nih.gov/pubmed/26763920 . Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the ...

Secondary stroke prevention: from guidelines to clinical practice.

PubMed

Graham, Glenn D

2008-10-01

Stroke remains a leading cause of mortality and is associated with substantial morbidity in the United States. The majority of strokes are of ischemic origin, with an atherothrombotic trigger, and the clinical manifestation of atherothrombosis depends on the affected vascular site. The systemic nature of atherosclerosis means that stroke patients are at increased risk of ischemic events in several vascular beds, including cerebral, coronary and peripheral sites. Because stroke patients are at heightened risk of more ischemic events, secondary prevention is an important therapeutic goal. Recently, the American Heart Association and its division, the American Stroke Association, released new evidence-based guidelines for secondary stroke prevention in patients with ischemic stroke or transient ischemic attack. The new guidelines emphasize an individualized, patient-oriented approach to treatment based on clinical evidence. Evidence-based recommendations are set forth for the management of risk factors, including hypertension, dyslipidemia and diabetes, through lifestyle modifications and pharmacological interventions. The purpose of this paper is to review the topic of stroke prevention in light of current guidelines and clinical implementation patterns for primary care physicians, and to discuss new and emerging clinical evidence, with a focus on antiplatelet treatment.

High ABCD2 Scores and In-Hospital Interventions following Transient Ischemic Attack

PubMed Central

Cutting, Shawna; Regan, Elizabeth; Lee, Vivien H.; Prabhakaran, Shyam

2016-01-01

Background and Purpose Following transient ischemic attack (TIA), there is increased risk for ischemic stroke. The American Heart Association recommends admission of patients with ABCD2 scores ≥3 for observation, rapid performance of diagnostic tests, and potential acute intervention. We aimed to determine if there is a relationship between ABCD2 scores, in-hospital ischemic events, and in-hospital treatments after TIA admission. Methods We reviewed consecutive patients admitted between 2006 and 2011 following a TIA, defined as transient focal neurological symptoms attributed to a specific vascular distribution and lasting <24 h. Three interventions were prespecified: anticoagulation for atrial fibrillation, carotid or intracranial revascularization, and intravenous or intra-arterial reperfusion therapies. We compared rates of in-hospital recurrent TIA or ischemic stroke and the receipt of interventions among patients with low (<3) versus high (≥3) ABCD2 scores. Results Of 249 patients, 11 patients (4.4%) had recurrent TIAs or strokes during their stay (8 TIAs, 3 strokes). All 11 had ABCD2 scores ≥3, and no neurological events occurred in patients with lower scores (5.1 vs. 0%; p = 0.37). Twelve patients (4.8%) underwent revascularization for large artery stenosis, 16 (6.4%) were started on anticoagulants, and no patient received intravenous or intra-arterial reperfusion therapy. The ABCD2 score was not associated with anticoagulation (p = 0.59) or revascularization (p = 0.20). Conclusions Higher ABCD2 scores may predict early ischemic events after TIA but do not predict the need for intervention. Outpatient evaluation for those with scores <3 would potentially have delayed revascularization or anticoagulant treatment in nearly one-fifth of ‘low-risk’ patients. PMID:27721312

Neurology Concepts: Young Women and Ischemic Stroke-Evaluation and Management in the Emergency Department.

PubMed

Chang, Bernard P; Wira, Charles; Miller, Joseph; Akhter, Murtaza; Barth, Bradley E; Willey, Joshua; Nentwich, Lauren; Madsen, Tracy

2018-01-01

Ischemic stroke is a leading cause of morbidity and mortality worldwide. While the incidence of ischemic stroke is highest in older populations, incidence of ischemic stroke in adults has been rising particularly rapidly among young (e.g., premenopausal) women. The evaluation and timely diagnosis of ischemic stroke in young women presents a challenging situation in the emergency department, due to a range of sex-specific risk factors and to broad differentials. The goals of this concepts paper are to summarize existing knowledge regarding the evaluation and management of young women with ischemic stroke in the acute setting. A panel of six board-certified emergency physicians, one with fellowship training in stroke and one with training in sex- and sex-based medicine, along with one vascular neurologist were coauthors involved in the paper. Each author used various search strategies (e.g., PubMed, PsycINFO, and Google Scholar) for primary research and reviewed articles related to their section. The references were reviewed and evaluated for relevancy and included based on review by the lead authors. Estimates on the incidence of ischemic stroke in premenopausal women range from 3.65 to 8.9 per 100,000 in the United States. Several risk factors for ischemic stroke exist for young women including oral contraceptive (OCP) use and migraine with aura. Pregnancy and the postpartum period (up to 12 weeks) is also an important transient state during which risks for both ischemic stroke and cerebral hemorrhage are elevated, accounting for 18% of strokes in women under 35. Current evidence regarding the management of acute ischemic stroke in young women is also summarized including use of thrombolytic agents (e.g., tissue plasminogen activator) in both pregnant and nonpregnant individuals. Unique challenges exist in the evaluation and diagnosis of ischemic stroke in young women. There are still many opportunities for future research aimed at improving detection and treatment of this population. © 2017 by the Society for Academic Emergency Medicine.

Comparison of Risk Factor Control in the Year After Discharge for Ischemic Stroke Versus Acute Myocardial Infarction.

PubMed

Bravata, Dawn M; Daggy, Joanne; Brosch, Jared; Sico, Jason J; Baye, Fitsum; Myers, Laura J; Roumie, Christianne L; Cheng, Eric; Coffing, Jessica; Arling, Greg

2018-02-01

The Veterans Health Administration has engaged in quality improvement to improve vascular risk factor control. We sought to examine blood pressure (<140/90 mm Hg), lipid (LDL [low-density lipoprotein] cholesterol <100 mg/dL), and glycemic control (hemoglobin A1c <9%), in the year post-hospitalization for acute ischemic stroke or acute myocardial infarction (AMI). We identified patients who were hospitalized (fiscal year 2011) with ischemic stroke, AMI, congestive heart failure, transient ischemic attack, or pneumonia/chronic obstructive pulmonary disease. The primary analysis compared risk factor control after incident ischemic stroke versus AMI. Facilities were included if they cared for ≥25 ischemic stroke and ≥25 AMI patients. A generalized linear mixed model including patient- and facility-level covariates compared risk factor control across diagnoses. Forty thousand two hundred thirty patients were hospitalized (n=75 facilities): 2127 with incident ischemic stroke and 4169 with incident AMI. Fewer stroke patients achieved blood pressure control than AMI patients (64%; 95% confidence interval, 0.62-0.67 versus 77%; 95% confidence interval, 0.75-0.78; P <0.0001). After adjusting for patient and facility covariates, the odds of blood pressure control were still higher for AMI than ischemic stroke patients (odds ratio, 1.39; 95% confidence interval, 1.21-1.51). There were no statistical differences for AMI versus stroke patients in hyperlipidemia ( P =0.534). Among patients with diabetes mellitus, the odds of glycemic control were lower for AMI than ischemic stroke patients (odds ratio, 0.72; 95% confidence interval, 0.54-0.96). Given that hypertension control is a cornerstone of stroke prevention, interventions to improve poststroke hypertension management are needed. © 2017 The Authors.

A multicenter, randomized trial on neuroprotection with remote ischemic per-conditioning during acute ischemic stroke: the REmote iSchemic Conditioning in acUtE BRAin INfarction study protocol.

PubMed

Pico, Fernando; Rosso, Charlotte; Meseguer, Elena; Chadenat, Marie-Laure; Cattenoy, Amina; Aegerter, Philippe; Deltour, Sandrine; Yeung, Jennifer; Hosseini, Hassan; Lambert, Yves; Smadja, Didier; Samson, Yves; Amarenco, Pierre

2016-10-01

Rationale Remote ischemic per-conditioning-causing transient limb ischemia to induce ischemic tolerance in other organs-reduces final infarct size in animal stroke models. Aim To evaluate whether remote ischemic per-conditioning during acute ischemic stroke (<6 h) reduces brain infarct size at 24 h. Methods and design This study is being performed in five French hospitals using a prospective randomized open blinded end-point design. Adults with magnetic resonance imaging confirmed ischemic stroke within 6 h of symptom onset and clinical deficit of 5-25 according to National Institutes of Health Stroke Scale will be randomized 1:1 to remote ischemic per-conditioning or control (stratified by center and intravenous fibrinolysis use). Remote ischemic per-conditioning will consist of four cycles of electronic tourniquet inflation (5 min) and deflation (5 min) to a thigh within 6 h of symptom onset. Magnetic resonance imaging is repeated 24 h after stroke onset. Sample size estimates For a difference of 15 cm 3 in brain infarct growth between groups, 200 patients will be included for 5% significance and 80% power. Study outcomes The primary outcome will be the difference in brain infarct growth from baseline to 24 h in the intervention versus control groups (by diffusion-weighted image magnetic resonance imaging). Secondary outcomes include: National Institutes of Health Stroke Scale score absolute difference between baseline and 24 h, three-month modified Rankin score and daily living activities, mortality, and tolerance and side effects of remote ischemic per-conditioning. Discussion The only remote ischemic per-conditioning trial in humans with stroke did not show remote ischemic per-conditioning to be effective. REmote iSchemic Conditioning in acUtE BRAin INfarction, which has important design differences, should provide more information on the use of this intervention in patients with acute ischemic stroke.

Confounding by Pre-Morbid Functional Status in Studies of Apparent Sex Differences in Severity and Outcome of Stroke

PubMed Central

Coulombe, Janie; Li, Linxin; Ganesh, Aravind; Silver, Louise; Rothwell, Peter M.

2017-01-01

Background and Purpose— Several studies have reported unexplained worse outcomes after stroke in women but none included the full spectrum of symptomatic ischemic cerebrovascular events while adjusting for prior handicap. Methods— Using a prospective population-based incident cohort of all transient ischemic attack/stroke (OXVASC [Oxford Vascular Study]) recruited between April 2002 and March 2014, we compared pre-morbid and post-event modified Rankin Scale score (mRS) in women and men and change in mRS score 1 month, 6 months, 1 year, and 5 years after stroke. Baseline stroke-related neurological impairment was measured with the National Institutes of Health Stroke Scale. Results— Among 2553 patients (50.6% women) with a first transient ischemic attack/ischemic stroke, women had a worse handicap 1 month after ischemic stroke (age-adjusted odds ratio for mRS score, 1.35; 95% confidence interval, 1.12–1.63). However, women also had a higher pre-morbid mRS score compared with men (age-adjusted odds ratio, 1.58; 95% confidence interval, 1.36–1.84). There was no difference in stroke severity when adjusting for age and pre-morbid mRS (odds ratio, 1.10; 95% confidence interval, 0.90–1.35) and no difference in the pre-/poststroke change in mRS at 1 month (age-adjusted odds ratio, 1.00; 95% confidence interval, 0.82–1.21), 6 months, 1 year, and 5 years. Women had a lower mortality rate, and there was no sex difference in risk of recurrent stroke. Conclusions— We found no evidence of a worse outcome of stroke in women when adjusting for age and pre-morbid mRS. Failure to account for sex differences in pre-morbid handicap could explain contradictory findings in previous studies. Properties of the mRS may also contribute to these inconsistencies. PMID:28798261

Confounding by Pre-Morbid Functional Status in Studies of Apparent Sex Differences in Severity and Outcome of Stroke.

PubMed

Renoux, Christel; Coulombe, Janie; Li, Linxin; Ganesh, Aravind; Silver, Louise; Rothwell, Peter M

2017-10-01

Several studies have reported unexplained worse outcomes after stroke in women but none included the full spectrum of symptomatic ischemic cerebrovascular events while adjusting for prior handicap. Using a prospective population-based incident cohort of all transient ischemic attack/stroke (OXVASC [Oxford Vascular Study]) recruited between April 2002 and March 2014, we compared pre-morbid and post-event modified Rankin Scale score (mRS) in women and men and change in mRS score 1 month, 6 months, 1 year, and 5 years after stroke. Baseline stroke-related neurological impairment was measured with the National Institutes of Health Stroke Scale. Among 2553 patients (50.6% women) with a first transient ischemic attack/ischemic stroke, women had a worse handicap 1 month after ischemic stroke (age-adjusted odds ratio for mRS score, 1.35; 95% confidence interval, 1.12-1.63). However, women also had a higher pre-morbid mRS score compared with men (age-adjusted odds ratio, 1.58; 95% confidence interval, 1.36-1.84). There was no difference in stroke severity when adjusting for age and pre-morbid mRS (odds ratio, 1.10; 95% confidence interval, 0.90-1.35) and no difference in the pre-/poststroke change in mRS at 1 month (age-adjusted odds ratio, 1.00; 95% confidence interval, 0.82-1.21), 6 months, 1 year, and 5 years. Women had a lower mortality rate, and there was no sex difference in risk of recurrent stroke. We found no evidence of a worse outcome of stroke in women when adjusting for age and pre-morbid mRS. Failure to account for sex differences in pre-morbid handicap could explain contradictory findings in previous studies. Properties of the mRS may also contribute to these inconsistencies. Copyright © 2017 The Author(s).

The Relationship between Frontal Lobe Lesions, Course of Post-Stroke Depression, and 1-year Prognosis in Patients with First-Ever Ischemic Stroke

PubMed Central

Shi, Yu-Zhi; Xiang, Yu-Tao; Wu, Shuo-Lin; Zhang, Ning; Zhou, Juan; Bai, Ying; Wang, Shuo; Wang, Yi-Long; Zhao, Xing-Quan; Ungvari, Gabor S.; Chiu, Helen F. K.; Wang, Yong-Jun; Wang, Chun-Xue

2014-01-01

Background and Purpose Most studies on post-stroke depression (PSD) have focused on a certain time point after stroke instead of the time course of PSD. The aim of this study was to determine the relationship between frontal lobe lesions, course of PSD over a year following the stroke onset, and the 1-year prognosis in patients with first-ever ischemic stroke. Methods A total of 1067 patients from the prospective cohort study on the incidence and outcome of patients with post stroke depression in China who were diagnosed with first-ever ischemic stroke and attended 4 follow-up visits at 14±2 days, 3 months, 6 months, and 1 year after stroke onset, were enrolled in the study. PSD was diagnosed according to DSM-IV. The course of PSD was divided into the following two categories: persistent/recurrent depression and no/transient depression. Patients with any ischemic lesion responsible for the indexed stroke event located in the frontal lobe were defined as patients with frontal lobe lesions. Modified Rankin Scale (mRS) ≥2 at 1-year was considered to be poor prognosis. Results There were 109 patients with and 958 patients without frontal lobe lesions that formed the frontal lobe (FL) and no-frontal lobe (NFL) groups, respectively. After adjusting for confounding variables, frontal lobe lesion was significantly associated with persistent/recurrent PSD (OR 2.025, 95%CI 1.039–3.949). Overall, 32.7% of patients in the FL group had poor prognosis at 1- year compared with 22.7% in the NFL group (P = 0.021). Compared with no/transient depression, persistent/recurrent depression was found to be an independent predictor of poor prognosis at 1-year both in FL and NFL groups. Conclusions Long-term and periodical screening, evaluation and treatment are needed for PSD after the onset of ischemic stroke, particularly for patients with frontal lobe infarction. PMID:25003990

The relationship between frontal lobe lesions, course of post-stroke depression, and 1-year prognosis in patients with first-ever ischemic stroke.

PubMed

Shi, Yu-Zhi; Xiang, Yu-Tao; Wu, Shuo-Lin; Zhang, Ning; Zhou, Juan; Bai, Ying; Wang, Shuo; Wang, Yi-Long; Zhao, Xing-Quan; Ungvari, Gabor S; Chiu, Helen F K; Wang, Yong-Jun; Wang, Chun-Xue

2014-01-01

Most studies on post-stroke depression (PSD) have focused on a certain time point after stroke instead of the time course of PSD. The aim of this study was to determine the relationship between frontal lobe lesions, course of PSD over a year following the stroke onset, and the 1-year prognosis in patients with first-ever ischemic stroke. A total of 1067 patients from the prospective cohort study on the incidence and outcome of patients with post stroke depression in China who were diagnosed with first-ever ischemic stroke and attended 4 follow-up visits at 14±2 days, 3 months, 6 months, and 1 year after stroke onset, were enrolled in the study. PSD was diagnosed according to DSM-IV. The course of PSD was divided into the following two categories: persistent/recurrent depression and no/transient depression. Patients with any ischemic lesion responsible for the indexed stroke event located in the frontal lobe were defined as patients with frontal lobe lesions. Modified Rankin Scale (mRS) ≥2 at 1-year was considered to be poor prognosis. There were 109 patients with and 958 patients without frontal lobe lesions that formed the frontal lobe (FL) and no-frontal lobe (NFL) groups, respectively. After adjusting for confounding variables, frontal lobe lesion was significantly associated with persistent/recurrent PSD (OR 2.025, 95%CI 1.039-3.949). Overall, 32.7% of patients in the FL group had poor prognosis at 1- year compared with 22.7% in the NFL group (P = 0.021). Compared with no/transient depression, persistent/recurrent depression was found to be an independent predictor of poor prognosis at 1-year both in FL and NFL groups. Long-term and periodical screening, evaluation and treatment are needed for PSD after the onset of ischemic stroke, particularly for patients with frontal lobe infarction.

CHA2DS2-VASc Score (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65-74, Female) for Stroke in Asian Patients With Atrial Fibrillation: A Korean Nationwide Sample Cohort Study.

PubMed

Kim, Tae-Hoon; Yang, Pil-Sung; Uhm, Jae-Sun; Kim, Jong-Youn; Pak, Hui-Nam; Lee, Moon-Hyoung; Joung, Boyoung; Lip, Gregory Y H

2017-06-01

The CHA 2 DS 2 -VASc stroke score (congestive heart failure, hypertension, age ≥75 (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 65-74, female) is used in most guidelines for risk stratification in atrial fibrillation (AF), but most data for this score have been derived in Western populations. Ethnic differences in stroke risk may be present. Our objective was to investigate risk factors for stroke in AF and application of the CHA 2 DS 2 -VASc score in an Asian AF population from Korea. A total of 5855 oral anticoagulant-naive nonvalvular AF patients aged ≥20 years were enrolled from Korea National Health Insurance Service Sample cohort from 2002 to 2008 and were followed up until December 2013. The incidence rates (per 100 person-years) of ischemic stroke were 3.32 in the total population, being 0.23 in low-risk (CHA 2 DS 2 -VASc score 0 [male] or 1 [female]) and 4.59 in high-risk patients (CHA 2 DS 2 -VASc ≥2). Incidence rates of ischemic stroke or the composite thromboembolism end point showed a clear increase with increasing CHA 2 DS 2 -VASc score. On multivariable analysis, significant associations between CHA 2 DS 2 -VASc risk factors and ischemic stroke were observed; however, the significance of vascular disease or diabetes mellitus was attenuated after multivariate adjustment, and female sex (hazard ratio, 0.73; 95% confidence interval, 0.64-0.84) had a lower risk of ischemic stroke than males. Patients who were categorized as low risk consistently had an event rate <1% per year. The performance of CHA 2 DS 2 -VASc score in Asians is comparable with that in Western populations. The score shows good performance in defining the truly-low-risk AF patients for stroke/thromboembolism. © 2017 American Heart Association, Inc.

Transient receptor potential melastatin subfamily member 2 cation channel regulates detrimental immune cell invasion in ischemic stroke.

PubMed

Gelderblom, Mathias; Melzer, Nico; Schattling, Benjamin; Göb, Eva; Hicking, Gordon; Arunachalam, Priyadharshini; Bittner, Stefan; Ufer, Friederike; Herrmann, Alexander M; Bernreuther, Christian; Glatzel, Markus; Gerloff, Christian; Kleinschnitz, Christoph; Meuth, Sven G; Friese, Manuel A; Magnus, Tim

2014-11-01

Brain injury during stroke results in oxidative stress and the release of factors that include extracellular Ca(2+), hydrogen peroxide, adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate. These alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. Our goal was to evaluate the contribution of TRPM2 to the tissue damage after stroke. In accordance with current quality guidelines, we independently characterized Trpm2 in a murine ischemic stroke model in 2 different laboratories. Gene deficiency of Trpm2 resulted in significantly improved neurological outcome and decreased infarct size. Besides an already known moderate neuroprotective effect of Trpm2 deficiency in vitro, ischemic brain invasion by neutrophils and macrophages was particularly reduced in Trpm2-deficient mice. Bone marrow chimeric mice revealed that Trpm2 deficiency in the peripheral immune system is responsible for the protective phenotype. Furthermore, experiments with mixed bone marrow chimeras demonstrated that Trpm2 is essential for the migration of neutrophils and, to a lesser extent, also of macrophages into ischemic hemispheres. Notably, the pharmacological TRPM2 inhibitor, N-(p-amylcinnamoyl)anthranilic acid, was equally protective in the stroke model. Although a neuroprotective effect of TRPM2 in vitro is well known, we can show for the first time that the detrimental role of TRPM2 in stroke primarily depends on its role in activating peripheral immune cells. Targeting TRPM2 systemically represents a promising therapeutic approach for ischemic stroke. © 2014 American Heart Association, Inc.

Early Initiation of Anticoagulation with Direct Oral Anticoagulants in Patients after Transient Ischemic Attack or Ischemic Stroke.

PubMed

Macha, Kosmas; Volbers, Bastian; Bobinger, Tobias; Kurka, Natalia; Breuer, Lorenz; Huttner, Hagen B; Schwab, Stefan; Köhrmann, Martin

2016-09-01

Direct oral anticoagulants (DOACs) are increasingly used for secondary prevention of cardioembolic stroke. While DOACs are associated with a long-term reduced risk of intracranial hemorrhage compared to vitamin K antagonists, pivotal trials avoided the very early period after stroke and few data exist on early initiation of DOAC therapy post stroke. We retrospectively analyzed data from our prospective database of all consecutive transient ischemic attack (TIA) or ischemic stroke patients with atrial fibrillation treated with DOACs during hospital stay. As per our institutional treatment algorithm for patients with cardioembolic ischemia DOACs are started immediately in TIA and minor stroke (group 1), within days 3-5 in patients with infarcts affecting one third or less of the middle cerebral artery, the anterior cerebral artery, or the posterior cerebral artery territories (group 2) as well as in infratentorial stroke (group 3) and after 1-2 weeks in patients with large infarcts (>⅓MCA territory, group 4). We investigated baseline characteristics, time to initiation of DOAC therapy after symptom onset, and hemorrhagic complications. In 243 included patients, administration of DOAC was initiated 40.5 hours (interquartile range [IQR] 23.0-65.5) after stroke onset in group 1 (n = 41) and after 76.7 hours (IQR 48.0-134.0), 108.4 hours (IQR 67.3-176.4), and 161.8 hours (IQR 153.9-593.8) in groups 2-4 (n = 170, 28, and 4), respectively. Two cases of asymptomatic intracranial hemorrhage (.8%) and 1 case of symptomatic intracranial hemorrhage (.4%) were observed, both in group 2. No severe safety issues were observed in early initiation of DOACs for secondary prevention after acute stroke in our in-patient cohort. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Clopidogrel with aspirin in acute minor stroke or transient ischemic attack.

PubMed

Wang, Yongjun; Wang, Yilong; Zhao, Xingquan; Liu, Liping; Wang, David; Wang, Chunxue; Wang, Chen; Li, Hao; Meng, Xia; Cui, Liying; Jia, Jianping; Dong, Qiang; Xu, Anding; Zeng, Jinsheng; Li, Yansheng; Wang, Zhimin; Xia, Haiqin; Johnston, S Claiborne

2013-07-04

Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone. In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect. Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel-aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the rate of hemorrhagic stroke was 0.3% in each group. Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage. (Funded by the Ministry of Science and Technology of the People's Republic of China; CHANCE ClinicalTrials.gov number, NCT00979589.).

Rheumatoid arthritis significantly increased recurrence risk after ischemic stroke/transient ischemic attack.

PubMed

Chen, Yih-Ru; Hsieh, Fang-I; Lien, Li-Ming; Hu, Chaur-Jong; Jeng, Jiann-Shing; Peng, Giia-Sheun; Tang, Sung-Chun; Chi, Nai-Fang; Sung, Yueh-Feng; Chiou, Hung-Yi

2018-06-02

The effect of RA on recurrent stroke is unknown. Therefore, we examined effects of rheumatoid arthritis (RA) on risk of stroke recurrence and investigated the interaction between RA and traditional cardiovascular risk factors on recurrence risk after ischemic stroke (IS) or transient ischemic attack (TIA). Of 3190 patients with IS or TIA recruited in this cohort study, 638 were comorbid with RA and 2552 without RA. Stroke recurrence, RA, lifestyle, lipid variables and other comorbidities were identified through linkage between a nationwide stroke database in Taiwan and the National Health Insurance claims database. Cox proportional hazard models with competing risk adjustment were used to evaluate the relationship between RA and recurrent stroke. Patients with RA showed a significantly increased risk of recurrent stroke, particular in recurrent IS/TIA. The increased risk of recurrent IS/TIA in RA patients may through the changes of triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio. A positive additive interaction was observed between RA and current smoking on the risk of recurrent IS/TIA. Significantly increased risks for recurrent IS/TIA were observed among RA patients who smoked > 40 years or those who smoked > 20 cigarettes/day. This study provides the first evidence that RA significantly increased recurrence IS/TIA risk. The changes of TG/HDL-C ratio may play some roles in the recurrence IS/TIA risk in RA patients. In addition, our results suggest that smoking increases the risk of recurrent IS/TIA in RA patients and reinforces the need for aggressive smoking cessation efforts in RA patients.

Smartphone electrographic monitoring for atrial fibrillation in acute ischemic stroke and transient ischemic attack.

PubMed

Tu, Hans T; Chen, Ziyuan; Swift, Corey; Churilov, Leonid; Guo, Ruibing; Liu, Xinfeng; Jannes, Jim; Mok, Vincent; Freedman, Ben; Davis, Stephen M; Yan, Bernard

2017-10-01

Rationale Paroxysmal atrial fibrillation is a common and preventable cause of devastating strokes. However, currently available monitoring methods, including Holter monitoring, cardiac telemetry and event loop recorders, have drawbacks that restrict their application in the general stroke population. AliveCor™ heart monitor, a novel device that embeds miniaturized electrocardiography (ECG) in a smartphone case coupled with an application to record and diagnose the ECG, has recently been shown to provide an accurate and sensitive single lead ECG diagnosis of atrial fibrillation. This device could be used by nurses to record a 30-s ECG instead of manual pulse taking and automatically provide a diagnosis of atrial fibrillation. Aims To compare the proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring with current standard practice. Sample size 296 Patients. Design Consecutive ischemic stroke and transient ischemic attack patients presenting to participating stroke units without known atrial fibrillation will undergo intermittent AliveCor™ ECG monitoring administered by nursing staff at the same frequency as the vital observations of pulse and blood pressure until discharge, in addition to the standard testing paradigm of each participating stroke unit to detect paroxysmal atrial fibrillation. Study outcome Proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring compared to 12-lead ECG, 24-h Holter monitoring and cardiac telemetry. Discussion Use of AliveCor™ heart monitor as part of routine stroke unit nursing observation has the potential to be an inexpensive non-invasive method to increase paroxysmal atrial fibrillation detection, leading to improvement in stroke secondary prevention.

Renal impairment in stroke patients: A comparison between the haemorrhagic and ischemic variants.

PubMed

Shrestha, Pratyush; Thapa, Shalima; Shrestha, Shikher; Lohani, Subash; Bk, Suresh; MacCormac, Oscar; Thapa, Lekhjung; Devkota, Upendra Prasad

2017-01-01

Background: Renal impairment is regularly seen in hospitalized stroke patients, affecting the outcome of patients, as well as causing difficulties in their management. A prospective cohort study was conducted to assess the trend of renal function in hospitalized ischemic and haemorrhagic stroke patients. The incidence of renal impairment in these subgroups, the contributing factors and the need for renal replacement in renal impaired patients was evaluated. Methods: Alternate day renal function testing was performed in hospitalized stroke patients. Estimated glomerular filtration rate (e-GFR) was calculated and the trend of renal function in the two stroke subgroups (haemorrhagic and ischemic) was assessed, with renal impairment defined as e-GFR < 60mL/ minute per 1.73m 2 . Results: Among 52 patients, 25 had haemorrhagic stroke (mean age 59.81 ± 14.67) and 27 had ischemic stroke (mean age 56.12 ± 13.08). The mean e-GFR (mL/minute per 1.732m 2 ) at admission in the haemorrhagic stroke subgroup was 64.79 ± 25.85 compared to 86.04 ± 26.09 in the ischemic stroke subgroup (p=0.005). Sixteen out of 25 (64%) patients in the haemorrhagic stroke subgroup and 9 out of 27 (33.3%) patients in the ischemic subgroup developed renal impairment (p=0.027). The location of the bleed (p=0.8), volume of hematoma (p=0.966) and surgical intervention (p=0.4) did not predispose the patients to renal impairment. One out of 16 patients with haemorrhagic stroke (who eventually died), and 2 out of 9 patients with ischemic stroke required renal replacement. Conclusion : Renal impairment is commonly seen in stroke patients, more so in patients who suffered haemorrhagic strokes.  The impairment, however, is transient and rarely requires renal replacement therapy.

Optical-resolution photoacoustic microscopy of ischemic stroke

NASA Astrophysics Data System (ADS)

Hu, Song; Gonzales, Ernie; Soetikno, Brian; Gong, Enhao; Yan, Ping; Maslov, Konstantin; Lee, Jin-Moo; Wang, Lihong V.

2011-03-01

A major obstacle in understanding the mechanism of ischemic stroke is the lack of a tool to noninvasively or minimally invasively monitor cerebral hemodynamics longitudinally. Here, we applied optical-resolution photoacoustic microscopy (OR-PAM) to longitudinally study ischemic stroke induced brain injury in a mouse model with transient middle cerebral artery occlusion (MCAO). OR-PAM showed that, during MCAO, the average hemoglobin oxygen saturation (sO2) values of feeder arteries and draining veins within the stroke core region dropped ~10% and ~34%, respectively. After reperfusion, arterial sO2 recovered back to the baseline; however, the venous sO2 increased above the baseline value by ~7%. Thereafter, venous sO2 values were close to the arterial sO2 values, suggesting eventual brain tissue infarction.

Huang-Lian-Jie-Du-Decotion induced protective autophagy against the injury of cerebral ischemia/reperfusion via MAPK-mTOR signaling pathway.

PubMed

Wang, Peng-Ran; Wang, Jun-Song; Zhang, Chao; Song, Xing-Fang; Tian, Na; Kong, Ling-Yi

2013-08-26

Huang-Lian-Jie-Du-Decotion (HLJDD, Hwangryun-Hae-Dok-Decotion in Japan), an ancient antipyretic and detoxifying traditional Chinese medicine formula, was reported to have protective effect on ischemic stroke. To investigate the therapeutic effect of HLJDD on ischemic stroke and explore its mode of action. A model of ischemic stroke in the rat was established after transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Rats were assigned randomly to groups of control, sham, transient ischemia/reperfusion (I/R), and three treatment groups by HLJDD at 2.5, 5.0, 10.0mg/kg. The neurological deficit, the cerebral infarct size, morphology abnormality, biochemical parameters were examined, and the levels of relevant proteins were determined by immunoblotting analysis to evaluate the protective effects of HLJDD on ischemic stroke and explore the underlying mechanism. Compared with I/R group, HLJDD significantly ameliorated neurological deficit and histopathology changes, decreased infarct area, and restored the levels of biochemical indicators including nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), total superoxide dismutase (T-SOD), Cu/Zn-SOD, Mn-SOD and glutathione peroxidase (GSH-PX). HLJDD also notably elevated the levels of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, and other autophagy related genes (Atgs), promoted the activation of extracellular signal-regulated kinases (ERK), protein kinase B (Akt), 3-phosphoinositide-dependent kinase (PDK1), and inhibited the activation of mammalian target of rapamycin (mTOR), c-Jun N-terminal protein kinases (JNK), p38, phosphatase and tensin homolog (PTEN). HLJDD showed neuroprotective effects on ischemic stroke, at least in part to the induced protective autophagy via the regulation of mitogen-activated protein kinase (MAPK) signals. This Akt-independent protective autophagy is favorable in the treatment of stroke, avoiding unfavorable side-effects associated with the inactivation of Akt. The efficacy of HLJDD on ischemic stroke and its safety warranted by its long-term clinical use in traditional Chinese medicine favored further study to develop HLJDD as an effective therapeutic agent to treat ischemic stroke. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Neuronal PirB Upregulated in Cerebral Ischemia Acts as an Attractive Theranostic Target for Ischemic Stroke.

PubMed

Wang, Jie; Zhang, Ying; Xia, Jing; Cai, Tingting; Du, Jiawei; Chen, Jinpeng; Li, Ping; Shen, Yuqing; Zhang, Aifeng; Fu, Bo; Gao, Xueren; Miao, Fenqin; Zhang, Jianqiong; Teng, Gaojun

2018-01-29

Ischemic stroke is a complex disease with multiple etiologies and clinical manifestations. Paired immunoglobulin-like receptor B (PirB), which is originally thought to function exclusively in the immune system, is now also known to be expressed by neurons. A growing number of studies indicate that PirB can inhibit neurite outgrowth and restrict neuronal plasticity. The aim of the study is to investigate whether PirB can be an attractive theranostic target for ischemic stroke. First, we investigated the spatial-temporal expression of PirB in multiple ischemic stroke models, including transient middle cerebral artery occlusion, photothrombotic cerebral cortex ischemia, and the neuronal oxygen glucose deprivation model. Then, anti-PirB immunoliposome nanoprobe was developed by thin-film hydration method and investigated its specific targeting in vitro and in vivo. Finally, soluble PirB ectodomain (sPirB) protein delivered by polyethylene glycol-modified nanoliposome was used as a therapeutic reagent for ischemic stroke by blocking PirB binding to its endogenous ligands. These results showed that PirB was significantly upregulated after cerebral ischemic injury in ischemic stroke models. Anti-PirB immunoliposome nanoprobe was successfully developed and specifically bound to PirB in vitro. There was accumulation of anti-PirB immunoliposome nanoprobe in the ischemic hemisphere in vivo. Soluble PirB ectodomains remarkably improved ischemic stroke model recovery by liposomal delivery system. These data indicated that PirB was a significant element in the pathological process of cerebral ischemia. Therefore, PirB may act as a novel theranostic target for ischemic stroke. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Predicting Major Bleeding in Ischemic Stroke Patients With Atrial Fibrillation.

PubMed

Hilkens, Nina A; Algra, Ale; Greving, Jacoba P

2017-11-01

Performance of risk scores for major bleeding in patients with atrial fibrillation and a previous transient ischemic attack or ischemic stroke is not well established. We aimed to validate risk scores for major bleeding in patients with atrial fibrillation treated with oral anticoagulants after cerebral ischemia and explore the net benefit of oral anticoagulants among bleeding risk categories. We analyzed 3623 patients with a history of transient ischemic attack or stroke included in the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). We assessed performance of HEMORR 2 HAGES (hepatic or renal disease, ethanol abuse, malignancy, older age, reduced platelet count or function, hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke), Shireman, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and ORBIT scores (older age, reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) with C statistics and calibration plots. Net benefit of oral anticoagulants was explored by comparing risk reduction in ischemic stroke with risk increase in major bleedings on warfarin. During 6922 person-years of follow-up, 266 patients experienced a major bleed (3.8 per 100 person-years). C statistics ranged from 0.62 (Shireman) to 0.67 (ATRIA). Calibration was poor for ATRIA and moderate for other models. The reduction in recurrent ischemic strokes on warfarin was larger than the increase in major bleeding risk, irrespective of bleeding risk category. Performance of prediction models for major bleeding in patients with cerebral ischemia and atrial fibrillation is modest but comparable with performance in patients with only atrial fibrillation. Bleeding risk scores cannot guide treatment decisions for oral anticoagulants but may still be useful to identify modifiable risk factors for bleeding. Clinical usefulness may be best for ORBIT, which is based on a limited number of easily obtainable variables and showed reasonable performance. © 2017 American Heart Association, Inc.

Guideline-directed low-density lipoprotein management in high-risk patients with ischemic stroke: findings from Get with the Guidelines-Stroke 2003 to 2012.

PubMed

Saposnik, Gustavo; Fonarow, Gregg C; Pan, Wenquin; Liang, Li; Hernandez, Adrian F; Schwamm, Lee H; Smith, Eric E

2014-11-01

Limited information is available on stroke prevention in high-risk patients with preexisting cardiovascular disease. Our aim was to use admission low-density lipoprotein (LDL) values to evaluate differences in the attainment of National Cholesterol Education Program-Adult Treatment Panel III guidelines goals at the time of the index event in high-risk patients with stroke and preexisting cardio- or cerebrovascular disease. Observational study, using data from the Get-With-The-Guidelines-Stroke Registry including 913 436 patients with an acute ischemic stroke or transient ischemic attack from April 2003 to September 2012. Participants were classified as high risk if they had history of transient ischemic attack (TIA), stroke (cardiovascular disease), and coronary artery disease (CAD). Of the 913 436 patients admitted with an acute stroke or TIA, 194 557 (21.3%) had previous stroke/TIA, 148 833 (16.3%) had previous CAD, and 88 605 (9.7%) had concomitant CAD and cardiovascular disease. Overall, only 68% of patients with stroke were at their preadmission National Cholesterol Education Program III guideline-recommended LDL target; 51.3% had LDL <100 mg/dL; and only 19.8% had LDL<70 mg/dL. Among those presenting with a recurrent stroke, >45% had LDL>100 mg/dL. When compared with patients with CAD, patients with previous TIA/stroke were less likely to have LDL<100 or <70 mg/dL. In multivariable analysis, older age, men, white race, lack of major vascular risk factors, previous use of cholesterol-lowering therapy, and care provided in larger hospitals were associated with meeting LDL targets on admission testing. Management of dyslipidemia in high-risk patients with preexistent CAD or stroke continues to be suboptimal. Only 1 in 5 patients with prior TIA/stroke had LDL levels <70 mg/dL. © 2014 American Heart Association, Inc.

Effect of a provincial system of stroke care delivery on stroke care and outcomes

PubMed Central

Kapral, Moira K.; Fang, Jiming; Silver, Frank L.; Hall, Ruth; Stamplecoski, Melissa; O’Callaghan, Christina; Tu, Jack V.

2013-01-01

Background: Systems of stroke care delivery have been promoted as a means of improving the quality of stroke care, but little is known about their effectiveness. We assessed the effect of the Ontario Stroke System, a province-wide strategy of regionalized stroke care delivery, on stroke care and outcomes in Ontario, Canada. Methods: We used population-based provincial administrative databases to identify all emergency department visits and hospital admissions for acute stroke and transient ischemic attack from Jan. 1, 2001, to Dec. 31, 2010. Using piecewise regression analyses, we assessed the effect of the full implementation of the Ontario Stroke System in 2005 on the proportion of patients who received care at stroke centres, and on rates of discharge to long-term care facilities and 30-day mortality after stroke. Results: We included 243 287 visits by patients with acute stroke or transient ischemic attack. The full implementation of the Ontario Stroke System in 2005 was associated with an increase in rates of care at stroke centres (before implementation: 40.0%; after implementation: 46.5%), decreased rates of discharge to long-term care facilities (before implementation: 16.9%; after implementation: 14.8%) and decreased 30-day mortality for hemorrhagic (before implementation: 38.3%; after implementation: 34.4%) and ischemic stroke (before implementation: 16.3%; after implementation: 15.7%). The system’s implementation was also associated with marked increases in the proportion of patients who received neuroimaging, thrombolytic therapy, care in a stroke unit and antithrombotic therapy. Interpretation: The implementation of an organized system of stroke care delivery was associated with improved processes of care and outcomes after stroke. PMID:23713072

Relapse of Takayasu arteritis as a cause of suicidal poisoning and subsequent major ischemic stroke successfully treated with thrombolytic therapy.

PubMed

Komatina, Neneal; Lepić, Toplica; Labović, Boban; Stevović, Tatjana; Petronijević, Milan; Radovinović-Tasić, Sanja; Obradović, Dragana

2016-08-01

Takayasu arteritis (TA) is a rare large vessel arteritis, affecting primarily aorta and its major branches. Its clinical manifestations can vary significantly - from asymptomatic to serious vascular events. Acute neurological complications are frequent at the onset of the disease and in relapses. Anxiety and depression are more frequent in TA patients than in general population as well as during relapses. Prevalence of transient ischemic attack or ischemic stroke in TA patients is approximately 10-20%. We presented a patient with TA that began with a depressive episode resulting in attempted suicide by bromazepame poisoning. This was subsequently followed by major ischemic stroke caused by thrombosis of the left middle cerebral artery (probably due to aortic arch embolism) successfully treated with intravenous thrombolysis. Intravenous thrombolysis appears to be safe and effective in patients with TA and stroke.

Comprehensive cardiac rehabilitation for secondary prevention after transient ischemic attack or mild stroke: I: feasibility and risk factors.

PubMed

Prior, Peter L; Hachinski, Vladimir; Unsworth, Karen; Chan, Richard; Mytka, Sharon; O'Callaghan, Christina; Suskin, Neville

2011-11-01

Comprehensive cardiac rehabilitation (CCR), which integrates structured lifestyle interventions and medications, reduces morbidity and mortality among cardiac patients. CCR has not typically been used with cerebrovascular populations, despite important commonalities with heart patients. We tested feasibility and effectiveness of 6-month outpatient CCR for secondary prevention after transient ischemic attack or mild, nondisabling stroke. This article presents risk factors. A future article will discuss psychological outcomes. Consecutive consenting subjects having sustained a transient ischemic attack or mild, nondisabling stroke within the previous 12 months (mean, 11.5 weeks; event-to-CCR entry) with ≥1 vascular risk factor, were recruited from a stroke prevention clinic providing usual care. We measured 6-month CCR outcomes following a prospective cohort design. Of 110 subjects recruited from January 2005 to April 2006, 100 subjects (mean age, 64.9 years; 46 women) entered and 80 subjects completed CCR. We obtained favorable, significant intake-to-exit changes in: aerobic capacity (+31.4%; P<0.001), total cholesterol (-0.30 mmol/L; P=0.008), total cholesterol/high-density lipoprotein (-11.6%; P<0.001), triglycerides (-0.27 mmol/L; P=0.003), waist circumference (-2.44 cm; P<0.001), body mass index (-0.53 kg/m(2); P=0.003), and body weight (-1.43 kg; P=0.001). Low-density lipoprotein (-0.24 mmol/L), high-density lipoprotein (+0.06 mmol/L), systolic (-3.21 mm Hg) and diastolic (-2.34 mm Hg) blood pressure changed favorably, but nonsignificantly. A significant shift toward nonsmoking occurred (P=0.008). Compared with intake, 11 more individuals (25.6% increase) finished CCR in the lowest-mortality risk category of the Duke Treadmill Score (P<0.001). CCR is feasible and effective for secondary prevention after transient ischemic attack or mild, nondisabling stroke, offering a promising model for vascular protection across chronic disease entities. We know of no similar previous investigation, and are now conducting a randomized trial.

Risk Factors in the Initial Presentation of Specific Cardiovascular Disease Syndromes

ClinicalTrials.gov

2013-03-03

Heart Diseases; Cardiovascular Diseases; Acute Myocardial Infarction; Unstable Angina; Chronic Stable Angina; Ischemic Stroke; Cerebrovascular Accident; Subarachnoid Hemorrhage; Transient Ischemic Attack; Abdominal Aortic Aneurysm; Peripheral Arterial Disease; Sudden Coronary Death; Ventricular Arrhythmia; Sudden Death; Cardiac Arrest; Heart Failure

Prediction of Recurrent Stroke or Transient Ischemic Attack After Noncardiogenic Posterior Circulation Ischemic Stroke.

PubMed

Zhang, Changqing; Wang, Yilong; Zhao, Xingquan; Liu, Liping; Wang, ChunXue; Pu, Yuehua; Zou, Xinying; Pan, Yuesong; Wong, Ka Sing; Wang, Yongjun

2017-07-01

Posterior circulation ischemic stroke (IS) is generally considered an illness with a poor prognosis. However, there are no effective rating scales to predict recurrent stroke following it. Therefore, our aim was to identify clinical or radiological measures that could assist in predicting recurrent cerebral ischemic episodes. We prospectively enrolled 723 noncardiogenic posterior circulation IS patients with onset of symptoms <7 days. Stroke risk factors, admission symptoms and signs, topographical distribution and responsible cerebral artery of acute infarcts, and any recurrent IS or transient ischemic attack (TIA) within 1 year were assessed. Cox regression was used to identify risk factors associated with recurrent IS or TIA within the year after posterior circulation IS. A total of 40 patients (5.5%) had recurrent IS or TIA within 1 year of posterior circulation IS. Multivariate Cox regression identified chief complaint with dysphagia (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.69-10.2; P =0.002), repeated TIAs within 3 months before the stroke (HR, 15.4; 95% CI, 5.55-42.5; P <0.0001), responsible artery stenosis ≥70% (HR, 7.91; 95% CI, 1.00-62.6; P =0.05), multisector infarcts (HR, 5.38; 95% CI, 1.25-23.3; P =0.02), and not on antithrombotics treatment at discharge (HR, 3.06; 95% CI, 1.09-8.58; P =0.03) as independent predictors of recurrent IS or TIA. Some posterior circulation IS patients are at higher risk for recurrent IS or TIA. Urgent assessment and preventive treatment should be offered to these patients as soon as possible. © 2017 American Heart Association, Inc.

Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial.

PubMed

Hart, Robert G; Pearce, Lesly A; Bakheet, Majid F; Benavente, Oscar R; Conwit, Robin A; McClure, Leslie A; Talbert, Robert L; Anderson, David C

2014-04-01

Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high versus low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. Multivariable analyses of 3020 participants with recent magnetic resonance imaging-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. Prior symptomatic lacunar stroke or transient ischemic attack (TIA) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.6, 2.9), diabetes (HR 2.0, 95% CI 1.5, 2.5), black race (HR 1.7, 95% CI 1.3, 2.3), and male sex (HR 1.5, 95% CI 1.1, 1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3% per year (95% CI 3.4, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1% per year (95% CI 2.6, 3.9) in those with more than 1 of the other 3 risk factors (27% of the cohort), and 1.3% per year (95% CI 1.0, 1.7) in those with 0-1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, black race, and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk. Copyright © 2014 National Stroke Association. All rights reserved.

Niche astrocytes promote the survival, proliferation and neuronal differentiation of co-transplanted neural stem cells following ischemic stroke in rats

PubMed Central

Luo, Li; Guo, Kaihua; Fan, Wenguo; Lu, Yinghong; Chen, Lizhi; Wang, Yang; Shao, Yijia; Wu, Gongxiong; Xu, Jie; Lü, Lanhai

2017-01-01

Niche astrocytes have been reported to promote neuronal differentiation through juxtacrine signaling. However, the effects of astrocytes on neuronal differentiation following ischemic stroke are not fully understood. In the present study, transplanted astrocytes and neural stem cells (NSCs) were transplanted into the ischemic striatum of transient middle cerebral artery occlusion (MCAO) model rats 48 h following surgery. It was observed that the co-transplantation of astrocytes and NSCs resulted in a higher ratio of survival and proliferation of the transplanted NSCs, and neuronal differentiation, in MCAO rats compared with NSC transplantation alone. These results demonstrate that the co-administration of astrocytes promotes the survival and neuronal differentiation of NSCs in the ischemic brain. These results suggest that the co-transplantation of astrocytes and NSCs is more effective than NSCs alone in the production of neurons following ischemic stroke in rats. PMID:28352345

Elevation of Autoantibody in Patients with Ischemic Stroke.

PubMed

Yoshida, Yoichi; Hiwasa, Takaki; Machida, Toshio; Kobayashi, Eiichi; Mine, Seiichiro; Matsushima, Jun; Takiguchi, Masaki; Iwadate, Yasuo

2018-05-31

Recent clinical research has revealed a significant correlation between atherosclerosis, one of the primary etiologies of ischemic stroke, and the immune system. Assuming that "disease-specific autoantibodies are produced in the sera of patients with ischemic stroke," we investigated multiple arteriosclerosis-related antibodies using the serological identification of antigens by recombinant cDNA expression cloning (SEREX), an established method for identifying antigenic proteins. We either screened a human aortic endothelial cell cDNA library or conducted protein array screening using the sera from patients with ischemic stroke, such as carotid artery stenosis or transient ischemic attack (TIA). Next, we measured serum antibody levels using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in patient/healthy donor (HD) cohorts and identified several antigens, the antibody levels of which were significantly higher in patients with ischemic stroke than in HDs. This review introduced the method of identifying antigens by the SEREX and protein microarray and summarized antigenic proteins. In particular, it focused on anti-replication protein A2 antibody and anti-programmed cell death 11 antibody, which are significantly related to atherosclerotic plaque and ischemic brain tissue, respectively, and proposed the mechanism of elevated autoantibody levels against them. Furthermore, this review suggests a possibility of clinical application as an atherosclerotic disease diagnostic marker for TIA or cerebral infarction.

Risk of Stroke/Transient Ischemic Attack or Myocardial Infarction with Herpes Zoster: A Systematic Review and Meta-Analysis.

PubMed

Zhang, Yanting; Luo, Ganfeng; Huang, Yuanwei; Yu, Qiuyan; Wang, Li; Li, Ke

2017-08-01

Accumulating evidence indicates that herpes zoster (HZ) may increase the risk of stroke/transient ischemic attack (TIA) or myocardial infarction (MI), but the results are inconsistent. We aim to explore the relationship between HZ and risk of stroke/TIA or MI and between herpes zoster ophthalmicus (HZO) and stroke. We estimated the relative risk (RR) and 95% confidence intervals (CIs) with the meta-analysis. Cochran's Q test and Higgins I 2 statistic were used to check for heterogeneity. HZ infection was significantly associated with increased risk of stroke/TIA (RR = 1.30, 95% CI: 1.17-1.46) or MI (RR = 1.18, 95% CI: 1.07-1.30). The risk of stroke after HZO was 1.91 (95% CI 1.32-2.76), higher than that after HZ. Subgroup analyses revealed increased risk of ischemic stroke after HZ infection but not hemorrhagic stroke. The risk of stroke was increased more at 1 month after HZ infection than at 1-3 months, with a gradual reduced risk with time. The risk of stroke after HZ infection was greater with age less than 40 years than 40-59 years and more than 60 years. Risk of stroke with HZ infection was greater without treatment than with treatment and was greater in Asia than Europe and America but did not differ by sex. Our study indicated that HZ infection was associated with increased risk of stroke/TIA or MI, and HZO infection was the most marked risk factor for stroke. Further studies are needed to explore whether zoster vaccination could reduce the risk of stoke/TIA or MI. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Risk factors and incidence of ischemic stroke in Taiwanese with nonvalvular atrial fibrillation-- a nation wide database analysis.

PubMed

Lin, Lian-Yu; Lee, Chang-Hsing; Yu, Chih-Chieh; Tsai, Chia-Ti; Lai, Ling-Pin; Hwang, Juey-Jen; Chen, Pau-Chung; Lin, Jiunn-Lee

2011-07-01

Atrial fibrillation (AF) is a risk factor for ischemic stroke. Stroke-prevention strategies based on risk schemes have been developed but most of the data are from western people. Our goal is to investigate the risk factors of ischemic stroke in Taiwanese with AF in a nation-wide database. A universal national health insurance (NHI) program has been implemented in Taiwan since 1995. We used system sampling database from 1997 to 2008 with a total of 1,000,000 subjects. By using ambulatory and inpatient claim data, we included subjects with AF and were above 20 years old. We excluded those who had ever taken warfarin or aspirin or had valvular heart diseases. A total of 7920 patients (3633 women, 4287 men) were included in the final analyses. Cox regression analysis showed that the risk factors for ischemic stroke were age (OR=1.338 for age 65-74 years vs. age 20-64 years, P=0.014; OR=1.652 for age over 75 years vs. age 20-64 years, P<0.001), hypertension (HTN) (OR=2.656, P<0.001), diabetes mellitus (DM) (OR=1.341, P=0.005), heart failure (OR=1.611, P<0.001), previous ischemic stroke or transient ischemic accident (TIA) (OR=2.752, P<0.001) and peripheral arterial disease (PAD) (OR=1.814, P=0.006). The gender, coronary artery disease, history of myocardial infarction and chronic renal insufficiency were not associated with ischemic stroke. The rate of ischemic stroke was much lower in current cohort as compared with that in whites. Frequent used risk schemes including CHADS₂ and CHA₂DS₂-VASC had comparable but only limited ability to predict ischemic stroke in subjects with AF. Compare with western people, hypertension plays a more important role in ischemic stroke in Taiwanese with AF and the incidence is lower. A substantial number of ischemic strokes cannot be accurately predicted by current risk schemes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Systematic implementation of transthoracic echocardiography, transesophageal echocardiography and 24-hour Holter ECG for the detection of cardiac sources of embolism in patients with stroke or transient ischemic attack. A retrospective study of 220 patients].

PubMed

Vinsonneau, U; Leblanc, A; Buchet, J-F; Pangnarind-Heintz, V; Le Gal, G; Rohel, G; Paleiron, N; Piquemal, M; Blanchard, C; Zagnoli, F; Paule, P

2014-09-01

Embolism of cardiac origin accounts for around 20% of ischemic strokes. ECG and transthoracic echocardiography (TTE) are commonly obtained during the evaluation of patient of ischemic stroke but specific indications for the transesophageal (TEE) echocardiography and 24-hour Holter ECG (Holter) remain uncertain. The aim of this study is to report the contribution of TTE, TEE and Holter performed as a routine during the evaluation of patients with ischemic stroke (IS) or transient ischemic attack (TIA). This is a retrospective single-center study of 220 patients hospitalized between 1st January 2007 and 31st December 2010 for a first IS or TIA. One hundred and forty-three IS and 77 TIA are identified. The average age of patients was 66 years (18-88 years). TTE/TEE/24-hour Holter allowed the diagnosis of cardiac sources of embolism in 135 patents (61.3%). TTE/TEE identified potential source of cardiogenic embolism in 126 patients (52.2%). Twenty four-hour Holter ECG tracked supraventricular arrhythmia in 15 patients (6.7%), 9 (4%) which had non-contributory ultrasound assessment. The systematic implementation of TTE/TEE/Holter is useful for identifying potential sources of cardiogenic embolism. The performance of TEE remains above the TTE. Holter should be recommended because it is a cost effective and non-invasive tool. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

PubMed

Kernan, Walter N; Viscoli, Catherine M; Furie, Karen L; Young, Lawrence H; Inzucchi, Silvio E; Gorman, Mark; Guarino, Peter D; Lovejoy, Anne M; Peduzzi, Peter N; Conwit, Robin; Brass, Lawrence M; Schwartz, Gregory G; Adams, Harold P; Berger, Leo; Carolei, Antonio; Clark, Wayne; Coull, Bruce; Ford, Gary A; Kleindorfer, Dawn; O'Leary, John R; Parsons, Mark W; Ringleb, Peter; Sen, Souvik; Spence, J David; Tanne, David; Wang, David; Winder, Toni R

2016-04-07

Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003). In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

Relationship of Preexisting Cardiovascular Comorbidities to Newly Diagnosed Atrial Fibrillation After Ischemic Stroke.

PubMed

Bisson, Arnaud; Clementy, Nicolas; Bodin, Alexandre; Angoulvant, Denis; Babuty, Dominique; Lip, Gregory Y H; Fauchier, Laurent

2017-10-01

There remains uncertainty as whether newly diagnosed atrial fibrillation (AF) after ischemic stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic mechanisms. We aimed to determine whether cardiovascular comorbidities in patients with new AF after ischemic stroke differ from patients with previous known AF or without AF. This French longitudinal cohort study was based on the database covering hospital care from 2009 to 2012 for the entire population. Of 336 291 patients with ischemic stroke, 240 459 (71.5%) had no AF and 95 832 (28.5%) had previously known AF at baseline. Patients without previous AF had a mean CHA 2 DS 2 -VASc score of 4.98±1.63 SD. During a mean follow-up of 7.9±11.5 months, 14 095 (5.9%) of these patients had incident AF, representing an annual incidence of AF after ischemic stroke of 8.9 per 100 person-years (95% confidence interval, 8.8-9.0). New AF patients had higher CHA 2 DS 2 -VASc score, more likely comorbidities, and more frequent history of previous transient ischemic attack than patients with previous known AF or without AF. Preexisting cardiovascular comorbidities underlie AF newly diagnosed after stroke. Consequently, these high-risk patients should be closely monitored for incident AF to facilitate an earlier diagnosis of AF and avoid stroke with appropriate thromboprophylaxis. © 2017 American Heart Association, Inc.

Prevalence of ex vivo high on-treatment platelet reactivity on antiplatelet therapy after transient ischemic attack or ischemic stroke on the PFA-100(®) and VerifyNow(®).

PubMed

Kinsella, Justin A; Tobin, W Oliver; Cox, Dermot; Coughlan, Tara; Collins, Ronan; O'Neill, Desmond; Murphy, Raymond P; McCabe, Dominick J H

2013-10-01

The prevalence of ex vivo high on-treatment platelet reactivity (HTPR) to commonly prescribed antiplatelet regimens after transient ischemic attack (TIA) or ischemic stroke is uncertain. Platelet function inhibition was simultaneously assessed with modified light transmission aggregometry (VerifyNow; Accumetrics Inc, San Diego, CA) and with a moderately high shear stress platelet function analyzer (PFA-100; Siemens Medical Solutions USA, Inc, Malvern, PA) in a pilot, cross-sectional study of TIA or ischemic stroke patients. Patients were assessed on aspirin-dipyridamole combination therapy (n = 51) or clopidogrel monotherapy (n = 25). On the VerifyNow, HTPR on aspirin was identified in 4 of 51 patients (8%) on aspirin-dipyridamole combination therapy (≥ 550 aspirin reaction units on the aspirin cartridge). Eleven of 25 (44%) patients had HTPR on clopidogrel (≥ 194 P2Y12 reaction units on the P2Y12 cartridge). On the PFA-100, 21 of 51 patients (41%) on aspirin-dipyridamole combination therapy had HTPR on the collagen-epinephrine (C-EPI) cartridge. Twenty-three of 25 patients (92%) on clopidogrel had HTPR on the collagen-adenosine diphosphate (C-ADP) cartridge. The proportion of patients with antiplatelet HTPR was lower on the VerifyNow than PFA-100 in patients on both regimens (P < .001). The prevalence of ex vivo antiplatelet HTPR after TIA or ischemic stroke is markedly influenced by the method used to assess platelet reactivity. The PFA-100 C-ADP cartridge is not sensitive at detecting the antiplatelet effects of clopidogrel ex vivo. Larger prospective studies with the VerifyNow and with the PFA-100 C-EPI and recently released Innovance PFA P2Y cartridges (Siemens Medical Solutions USA, Inc) in addition to newer tests of platelet function are warranted to assess whether platelet function monitoring predicts clinical outcome in ischemic cerebrovascular disease. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Development, Validation, and Assessment of an Ischemic Stroke or Transient Ischemic Attack-Specific Prediction Tool for Obstructive Sleep Apnea.

PubMed

Sico, Jason J; Yaggi, H Klar; Ofner, Susan; Concato, John; Austin, Charles; Ferguson, Jared; Qin, Li; Tobias, Lauren; Taylor, Stanley; Vaz Fragoso, Carlos A; McLain, Vincent; Williams, Linda S; Bravata, Dawn M

2017-08-01

Screening instruments for obstructive sleep apnea (OSA), as used routinely to guide clinicians regarding patient referral for polysomnography (PSG), rely heavily on symptomatology. We sought to develop and validate a cerebrovascular disease-specific OSA prediction model less reliant on symptomatology, and to compare its performance with commonly used screening instruments within a population with ischemic stroke or transient ischemic attack (TIA). Using data on demographic factors, anthropometric measurements, medical history, stroke severity, sleep questionnaires, and PSG from 2 independently derived, multisite, randomized trials that enrolled patients with stroke or TIA, we developed and validated a model to predict the presence of OSA (i.e., Apnea-Hypopnea Index ≥5 events per hour). Model performance was compared with that of the Berlin Questionnaire, Epworth Sleepiness Scale (ESS), the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender instrument, and the Sleep Apnea Clinical Score. The new SLEEP Inventory (Sex, Left heart failure, ESS, Enlarged neck, weight [in Pounds], Insulin resistance/diabetes, and National Institutes of Health Stroke Scale) performed modestly better than other instruments in identifying patients with OSA, showing reasonable discrimination in the development (c-statistic .732) and validation (c-statistic .731) study populations, and having the highest negative predictive value of all in struments. Clinicians should be aware of these limitations in OSA screening instruments when making decisions about referral for PSG. The high negative predictive value of the SLEEP INventory may be useful in determining and prioritizing patients with stroke or TIA least in need of overnight PSG. Published by Elsevier Inc.

Parvovirus B19 Infection in Children With Arterial Ischemic Stroke.

PubMed

Fullerton, Heather J; Luna, Jorge M; Wintermark, Max; Hills, Nancy K; Tokarz, Rafal; Li, Ying; Glaser, Carol; DeVeber, Gabrielle A; Lipkin, W Ian; Elkind, Mitchell S V

2017-10-01

Case-control studies suggest that acute infection transiently increases the risk of childhood arterial ischemic stroke. We hypothesized that an unbiased pathogen discovery approach utilizing MassTag-polymerase chain reaction would identify pathogens in the blood of childhood arterial ischemic stroke cases. The multicenter international VIPS study (Vascular Effects of Infection in Pediatric Stroke) enrolled arterial ischemic stroke cases, and stroke-free controls, aged 29 days through 18 years. Parental interview included questions on recent infections. In this pilot study, we used MassTag-polymerase chain reaction to test the plasma of the first 161 cases and 34 controls enrolled for a panel of 28 common bacterial and viral pathogens. Pathogen DNA was detected in no controls and 14 cases (8.7%): parvovirus B19 (n=10), herpesvirus 6 (n=2), adenovirus (n=1), and rhinovirus 6C (n=1). Parvovirus B19 infection was confirmed by serologies in all 10; infection was subclinical in 8. Four cases with parvovirus B19 had underlying congenital heart disease, whereas another 5 had a distinct arteriopathy involving a long-segment stenosis of the distal internal carotid and proximal middle cerebral arteries. Using MassTag-polymerase chain reaction, we detected parvovirus B19-a virus known to infect erythrocytes and endothelial cells-in some cases of childhood arterial ischemic stroke. This approach can generate new, testable hypotheses about childhood stroke pathogenesis. © 2017 American Heart Association, Inc.

Evidence for human leukocyte antigen-related susceptibility in idiopathic childhood ischemic stroke.

PubMed

Zou, Li-Ping; Guo, Yu-Hong; Fang, Fang; Jin, Hong; Wu, Hu-Sheng; Mix, Eilhard

2002-01-01

Stroke in children is a relatively uncommon condition and frequently associated with other diseases like cardiopathies, sickle cell disease and chronic smoking. In contrast to stroke in adults, it is rarely caused by atherosclerosis, hypertension or diabetes mellitus. Childhood stroke of unknown causes is called idiopathic stroke. The etiology of idiopathic stroke is unknown. However, several so-called idiopathic diseases develop on the basis of a genetic predisposition. As an approach to investigate this possibility in idiopathic childhood ischemic stroke, we studied the relationship between clinical and immunogenetic features in this disease. We demonstrate that the gene frequencies and relative risk of HLA-B51 were markedly increased in our patients compared with controls (p < 0.001). Thirteen of seventeen HLA-B51-positive patients had had a preceding respiratory infection, which was a higher proportion than in the control group (p < 0.05). In the patient group, the alleles HLA-DRB1*0802, -DRAI*0401 and -DQBI*0402 were also significantly increased, defining the haplotype DRB1*0802-DRA1*0401-DQB1*0402 as a high-risk haplotype for idiopathic childhood ischemic stroke. Transient viral or bacterial infections, which involve vasculitis and vascular occlusion in the brain, can trigger idiopathic childhood ischemic stroke on the basis of an genetic predisposition. Copyright 2002 S. Karger AG, Basel

Association between gastrointestinal bleeding and 3-year mortality in patients with acute, first-ever ischemic stroke.

PubMed

Chou, Yu-Fang; Weng, Wei-Chieh; Huang, Wen-Yi

2017-10-01

The influence of gastrointestinal bleeding on clinical presentation and outcomes of patients with acute ischemic stroke remains controversial. We investigate the effect of gastrointestinal bleeding on the outcomes of patients with acute, first-ever ischemic stroke. We enrolled 934 patients with acute, first-ever ischemic stroke and followed up them for 3years. Patients were divided into 2 groups according to the presence or absence of gastrointestinal bleeding during acute stroke stage. Clinical presentation, stroke risk factors, laboratory data, co-morbidities, and outcomes were recorded. Seventy-six (8.1%) patients had gastrointestinal bleeding at admission. The prevalence of old age, atrial fibrillation, and previous transient ischemic attack was higher in patients with gastrointestinal bleeding (P<0.001, P=0.038, and P=0.018, respectively). Total anterior circulation syndrome occurred more frequently among patients with gastrointestinal bleeding (P<0.001). The mean length of acute ward stay, initial impaired consciousness, and stroke in evolution were higher in patients with gastrointestinal bleeding (P<0.001, P<0.001, and P<0.001, respectively). The occurrence of pneumonia and dependent functional outcome were higher in patients with gastrointestinal bleeding (P<0.001 and P<0.001, respectively). A multivariate Cox regression analysis revealed that gastrointestinal bleeding is a significant risk factor for 3-year all-cause mortality (hazard ratio=2.76; 95% confidence interval=1.61-4.72; P<0.001). In conclusion, gastrointestinal bleeding is associated with increased risk of 3-year mortality in patients with acute, first-ever ischemic stroke. Prophylactic therapies for gastrointestinal bleeding might improve ischemic stroke outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

Patent foramen ovale and stroke in childhood: A systematic review of the literature.

PubMed

Khan, Rubeena; Chan, Anthony K; Mondal, Tapas K; Paes, Bosco A

2016-07-01

Stroke in association with a patent foramen ovale (PFO) may be due to paradoxical embolization via a right to left intracardiac shunt but the exact contribution of PFO to stroke or stroke recurrence in childhood remains unclear. To review the relationship of a PFO with stroke, and evaluate associated co-morbidities. An electronic database literature search of Pubmed, Cochrane and EMBASE was performed from January 2000-December 2014. 149 articles were retrieved, with overlap for diagnosis, management, treatment and outcome. 65 reports were utilized for the comprehensive review. Majority of childhood arterial ischemic stroke and transient ischemic attacks are associated with prothrombotic disorders or arteriopathy. Transthoracic echocardiography with a Valsalva maneuver is highly sensitive as a screening tool but may be falsely positive. Transthoracic echocardiography with color Doppler and a concurrent bubble contrast study are excellent for visualizing the atrial septum and PFO and identifying a right to left shunt. Current literature does not support PFO closure for cryptogenic stroke in young adults without an associated risk of thromboembolism. High quality research in the pediatric population is lacking and most of the data is extrapolated from adults. Paradoxical embolism from a PFO as a cause of transient ischemic attack or stroke is a diagnosis of exclusion. PFO closure should be individualized based on significant shunting and risk factors such that maximum benefit is derived from the procedure. A young person with a PFO and stroke should be thoroughly investigated to rule out other etiologies. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Trends in risk factor prevalence and management before first stroke: data from the South London Stroke Register 1995-2011.

PubMed

Marshall, Iain J; Wang, Yanzhong; McKevitt, Christopher; Rudd, Anthony G; Wolfe, Charles D A

2013-07-01

Vascular risk factors are suboptimally managed internationally. This study investigated time trends in risk factors diagnosed before stroke and their treatment, and factors associated with appropriate medication use. A total of 4416 patients with a first stroke were registered in the population-based South London Stroke Register from 1995 to 2011. Previously diagnosed risk factors and usual medications were collected from patients' primary care and hospital records. Trends and associations were assessed using multivariate logistic regression. Seventy-two percent of patients were diagnosed previously with 1 or more risk factors; 30% had diagnosed risk factors that were untreated. Hypercholesterolemia increased significantly during the study period; myocardial infarction and transient ischemic attack prevalences decreased. Antiplatelet prescription increased in atrial fibrillation (AF), myocardial infarction, and transient ischemic attack (AF, 37%-51%, P<0.001; myocardial infarction, 48%-69%, P<0.001; transient ischemic attack, 49%-61%, P=0.015). Anticoagulant prescription for AF showed a nonsignificant increase (12%-23%; P=0.059). Fewer older patients with AF were prescribed anticoagulants (age, >85 versus <65 years; adjusted relative risk, 0.19; 95% confidence interval, 0.08-0.41). Black ethnicity (adjusted relative risk, 1.17; 95% confidence interval, 1.10-1.23) and female sex (adjusted relative risk, 1.09; 95% confidence interval, 1.03-1.15) were associated with increased antihypertensive drug prescription; other medications did not vary by ethnicity or sex. Antiplatelet and cholesterol-lowering treatment prescribing have improved significantly over time; however, only a minority with AF received anticoagulants, and this did not improve significantly. Overall, 30% of strokes occurred in patients with previously diagnosed but untreated risk factors.

A fast multiparameter MRI approach for acute stroke assessment on a 3T clinical scanner: preliminary results in a non-human primate model with transient ischemic occlusion.

PubMed

Zhang, Xiaodong; Tong, Frank; Li, Chun-Xia; Yan, Yumei; Nair, Govind; Nagaoka, Tsukasa; Tanaka, Yoji; Zola, Stuart; Howell, Leonard

2014-04-01

Many MRI parameters have been explored and demonstrated the capability or potential to evaluate acute stroke injury, providing anatomical, microstructural, functional, or neurochemical information for diagnostic purposes and therapeutic development. However, the application of multiparameter MRI approach is hindered in clinic due to the very limited time window after stroke insult. Parallel imaging technique can accelerate MRI data acquisition dramatically and has been incorporated in modern clinical scanners and increasingly applied for various diagnostic purposes. In the present study, a fast multiparameter MRI approach including structural T1-weighted imaging (T1W), T2-weighted imaging (T2W), diffusion tensor imaging (DTI), T2-mapping, proton magnetic resonance spectroscopy, cerebral blood flow (CBF), and magnetization transfer (MT) imaging, was implemented and optimized for assessing acute stroke injury on a 3T clinical scanner. A macaque model of transient ischemic stroke induced by a minimal interventional approach was utilized for evaluating the multiparameter MRI approach. The preliminary results indicate the surgical procedure successfully induced ischemic occlusion in the cortex and/or subcortex in adult macaque monkeys (n=4). Application of parallel imaging technique substantially reduced the scanning duration of most MRI data acquisitions, allowing for fast and repeated evaluation of acute stroke injury. Hence, the use of the multiparameter MRI approach with up to five quantitative measures can provide significant advantages in preclinical or clinical studies of stroke disease.

Interferon-β Modulates Inflammatory Response in Cerebral Ischemia.

PubMed

Kuo, Ping-Chang; Scofield, Barbara A; Yu, I-Chen; Chang, Fen-Lei; Ganea, Doina; Yen, Jui-Hung

2016-01-08

Stroke is a leading cause of death in the world. In >80% of strokes, the initial acute phase of ischemic injury is due to the occlusion of a blood vessel resulting in severe focal hypoperfusion, excitotoxicity, and oxidative damage. Interferon-β (IFNβ), a cytokine with immunomodulatory properties, was approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis for more than a decade. Its anti-inflammatory properties and well-characterized safety profile suggest that IFNβ has therapeutic potential for the treatment of ischemic stroke. We investigated the therapeutic effect of IFNβ in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNβ not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNβ modulates ischemic brain inflammation were identified. IFNβ reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD4(+) T cells, and γδ T cells; inhibited the production of inflammatory mediators; suppressed the expression of adhesion molecules on brain endothelial cells; and repressed microglia activation in the ischemic brain. Our results demonstrate that IFNβ exerts a protective effect against ischemic stroke through its anti-inflammatory properties and suggest that IFNβ is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis.

PubMed

Nave, Alexander H; Lange, Kristin S; Leonards, Christopher O; Siegerink, Bob; Doehner, Wolfram; Landmesser, Ulf; Steinhagen-Thiessen, Elisabeth; Endres, Matthias; Ebinger, Martin

2015-10-01

Lipoprotein (a) [Lp(a)] harbors atherogenic potential but its role as a risk factor for ischemic stroke remains controversial. We conducted a meta-analysis to determine the relative strength of the association between Lp(a) and ischemic stroke and identify potential subgroup-specific risk differences. A systematic search using the MeSH terms "lipoproteins" OR "lipoprotein a" AND "stroke" was performed in PubMed and ScienceDirect for case-control studies from June 2006 and prospective cohort studies from April 2009 until December 20th 2014. Data from eligible papers published before these dates were reviewed and extracted from previous meta-analyses. Studies that assessed the relationship between Lp(a) levels and ischemic stroke and reported generic data-i.e. odds ratio [OR], hazard ratio, or risk ratio [RR]-were eligible for inclusion. Studies that not distinguish between ischemic and hemorrhagic stroke and transient ischemic attack were excluded. Random effects meta-analyses with mixed-effects meta-regression were performed by pooling adjusted OR or RR. A total of 20 articles comprising 90,904 subjects and 5029 stroke events were eligible for the meta-analysis. Comparing high with low Lp(a) levels, the pooled estimated OR was 1.41 (95% CI, 1.26-1.57) for case-control studies (n = 11) and the pooled estimated RR was 1.29 (95% CI, 1.06-1.58) for prospective studies (n = 9). Sex-specific differences in RR were inconsistent between case-control and prospective studies. Study populations with a mean age of ≤55 years had an increased RR compared to older study populations. Reported Lp(a) contrast levels and ischemic stroke subtype significantly contributed to the heterogeneity observed in the analyses. Elevated Lp(a) is an independent risk factor for ischemic stroke and may be especially relevant for young stroke patients. Sex-specific risk differences remain conflicting. Further studies in these subgroups may be warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Closure of Patent Foramen Ovale Versus Medical Therapy in Patients With Cryptogenic Stroke or Transient Ischemic Attack: Updated Systematic Review and Meta-Analysis.

PubMed

Ntaios, George; Papavasileiou, Vasileios; Sagris, Dimitrios; Makaritsis, Konstantinos; Vemmos, Konstantinos; Steiner, Thorsten; Michel, Patrik

2018-02-01

Previous systematic reviews and meta-analyses compared the efficacy and safety of patent foramen ovale (PFO) closure versus medical treatment in patients with cryptogenic stroke or transient ischemic attack (TIA). Recently, new evidence from randomized trials became available. We searched PubMed until September 24, 2017, for trials comparing PFO closure with medical treatment in patients with cryptogenic stroke/TIA using the items: stroke or cerebrovascular accident or TIA and patent foramen ovale or paradoxical embolism and trial or study. Among 851 identified articles, 5 were eligible. In 3627 patients with 3.7-year mean follow-up, there was significant difference in ischemic stroke recurrence (0.53 versus 1.1 per 100 patient-years, respectively; odds ratio [OR], 0.43; 95% confidence intervals (CI), 0.21-0.90; relative risk reduction, 50.5%; absolute risk reduction, 2.11%; and number needed to treat to prevent 1 event, 46.5 for 3.7 years). There was no significant difference in TIAs (0.78 versus 0.98 per 100 patient-years, respectively; OR, 0.80; 95% CI, 0.53-1.19) and all-cause mortality (0.18 versus 0.23 per 100 patient-years, respectively; OR, 0.73; 95% CI, 0.34-1.56). New-onset atrial fibrillation occurred more frequently in the PFO closure arm (1.3 versus 0.25 per 100 patient-years, respectively; OR, 5.15; 95% CI, 2.18-12.15) and resolved in 72% of cases within 45 days, whereas rates of myocardial infarction (0.12 versus 0.09 per 100 patient-years, respectively; OR, 1.22; 95% CI, 0.25-5.91) and any serious adverse events (7.3 versus 7.3 per 100 patient-years, respectively; OR, 1.07; 95% CI, 0.92-1.25) were similar. In patients with cryptogenic stroke/TIA and PFO who have their PFO closed, ischemic stroke recurrence is less frequent compared with patients receiving medical treatment. Atrial fibrillation is more frequent but mostly transient. There is no difference in TIA, all-cause mortality, or myocardial infarction. © 2018 American Heart Association, Inc.

Current management of symptomatic intracranial stenosis.

PubMed

Taylor, Robert A; Weigele, John B; Kasner, Scott E

2011-08-01

Intracranial arterial stenosis (IAS) is the cause of about 10% of all ischemic strokes in the United States, but may account for about 40% of strokes in some populations. After a stroke or transient ischemic attack due to IAS, patients face a 12% annual risk of recurrent stroke on medical therapy, with most strokes occurring in the first year. Warfarin is no better than aspirin in preventing recurrent strokes but poses a higher risk of serious bleeding and death. Groups with the highest risk of recurrent stroke are those with high-grade (≥ 70%) stenosis, those with recent symptom onset, those with symptoms precipitated by hemodynamic maneuvers, and women. Endovascular treatment of IAS is a rapidly evolving therapeutic option. Antiplatelet agents are currently recommended as the primary treatment for symptomatic IAS, with endovascular therapy reserved for appropriate high-risk cases refractory to medical therapy.

Amelioration of ischemic brain damage by peritoneal dialysis

PubMed Central

Godino, María del Carmen; Romera, Victor G.; Sánchez-Tomero, José Antonio; Pacheco, Jesus; Canals, Santiago; Lerma, Juan; Vivancos, José; Moro, María Angeles; Torres, Magdalena; Lizasoain, Ignacio; Sánchez-Prieto, José

2013-01-01

Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patients. PMID:23999426

Impact of MCA stenosis on the early outcome in acute ischemic stroke patients

PubMed Central

Jeng, Jiann-Shing; Hsieh, Fang-I; Yeh, Hsu-Ling; Chen, Wei-Hung; Chiu, Hou-Chang; Tang, Sung-Chun; Liu, Chung-Hsiang; Lin, Huey-Juan; Hsu, Shih-Pin; Lo, Yuk-Keung; Chan, Lung; Chen, Chih-Hung; Lin, Ruey-Tay; Chen, Yu-Wei; Lee, Jiunn-Tay; Yeh, Chung-Hsin; Sun, Ming-Hui; Lai, Ta-Chang; Sun, Yu; Sun, Mu-Chien; Chen, Po-Lin; Chiang, Tsuey-Ru; Lin, Shinn-Kuang; Yip, Bak-Sau; Chen, Chin-I; Bai, Chi-Huey; Chen, Sien-Tsong; Chiou, Hung-Yi; Lien, Li-Ming; Hsu, Chung Y.

2017-01-01

Background Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR). Methods Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (<50%) in the extracranial internal carotid artery (ICA) and MCA, respectively. Logistic regression analysis, Kaplan-Meier method and Cox proportional hazard model were applied to assess relevant variables between groups. Results Of 6003 patients, 23.3% had MCA stenosis, 10.1% ICA stenosis, and 3.9% both MCA and ICA stenosis. Patients with MCA stenosis had greater initial NIHSS, higher likelihood of stroke-in-evolution, and more severe disability than those without (all p<0.001). Patients with MCA stenosis had higher prevalence of hypertension, diabetes and hypercholesterolemia. Patients with combined MCA and extracranial ICA stenosis had even higher NIHSS, worse functional outcome, higher risk of stroke recurrence or death (hazard ratio, 2.204; 95% confidence intervals, 1.440–3.374; p<0.001) at 3 months after stroke than those without MCA stenosis. Conclusions In conclusion, MCA stenosis was more prevalent than extracranial ICA stenosis in ischemic stroke patients in Taiwan. Patients with MCA stenosis, especially combined extracranial ICA stenosis, had more severe neurological deficit and worse outcome. PMID:28388675

1.4 times increase in atrial fibrillation-related ischemic stroke and TIA over 12years in a stroke center.

PubMed

Yang, Qiong; Churilov, Leonid; Fan, Dongsheng; Davis, Stephen; Yan, Bernard

2017-08-15

Prevalence of atrial fibrillation (AF) has quadrupled in the past 50years in the general population. However, there is uncertainty regarding prevalence of AF over time in ischemic stroke patients given the aging population and enhanced surveillance of AF. We aimed to explore the changing prevalence of AF as well as other risk factors, stroke subtypes, investigations and pre-stroke medications among ischemic stroke and transient ischemic attack (TIA) patients. We performed a retrospective analysis of data from a prospective database of consecutive patients with acute ischemic stroke and TIA from 2004 to 2015. Trends in risk factors and other variables year by year were analyzed using logistic regression or median regression. Among 6275 patients (median age [interquartile range] 74 [62-82] years, 56% males), the prevalence of AF increased 1.4 times over 12years (from 23.3% to 32.7%, P<0.001). The increase in the prevalence of AF remained significant after adjustment for age and the use of Holter monitoring. There was also a significant increase in prevalence of hypertension (67.4% to 77.3%), structural heart disease (9.8% to 10.5%), and previous TIA (10.9% to 13.7%) and a significant decrease in prevalence of dyslipidemia (71.8% to 49.4%). There was a 1.4 times increase in the prevalence of AF among consecutive ischemic stroke and TIA patients in the past 12years in a hospital-based registry. More active screening of the general population for AF may be warranted in order to decrease the overall stroke burden. Copyright © 2017 Elsevier B.V. All rights reserved.

[Registry of patients with stroke stated in a public hospital of Peru, 2000-2009].

PubMed

Castañeda-Guarderas, Ana; Beltrán-Ale, Guillermo; Casma-Bustamante, Renzo; Ruiz-Grosso, Paulo; Málaga, Germán

2011-12-01

We performed a descriptive study taking on account the characteristics of the registries of the patients hospitalized at the Hospital Nacional Cayetano Heredia between the years 2000 and 2009 with stroke as hospitalization diagnosis. 2225 records were obtained from patients older than 18, with stroke. According to ICD-10, 1071 had diagnosis of ischemic stroke, 554 were hemorrhagic, 183 were subarachnoid hemorrhage, 49 were ischemic plus hemorrhagic, 10 were transient ischemic attack (TIA) and in 358 we were unable to specify the type of stroke. 352 deaths were recorded (19.6 %), most of them during the first 3 days. The male / female ratio was 1.09, the mean age 64.1 ± 17.2 years and the median length of hospital stay was 9 days. The most common associated conditions were high blood pressure, atrial fibrillation and type 2 diabetes mellitus. The mortality found is the highest reported in our country, constant in all age groups and higher in women.

Burden of Intracranial Atherosclerosis Is Associated With Long-Term Vascular Outcome in Patients With Ischemic Stroke.

PubMed

Kim, Byung-Su; Chung, Pil-Wook; Park, Kwang-Yeol; Won, Hong-Hee; Bang, Oh Young; Chung, Chin-Sang; Lee, Kwang Ho; Kim, Gyeong-Moon

2017-10-01

Ischemic stroke patients often have intracranial atherosclerosis (ICAS), despite heterogeneity in the cause of stroke. We tested the hypothesis that ICAS burden can independently reflect the risk of long-term vascular outcome. This was a retrospective cohort study analyzing data from a prospective stroke registry enrolling consecutive patients with acute ischemic stroke or transient ischemic attack. A total of 1081 patients were categorized into no ICAS, single ICAS, and advanced ICAS (ICAS ≥2 different intracranial arteries) groups. Primary and secondary end points were time to occurrence of recurrent ischemic stroke and composite vascular outcome, respectively. Study end points by ICAS burden were compared using Cox proportional hazards models in overall and propensity-matched patients. ICAS was present in 405 patients (37.3%). During a median 5-year follow-up, recurrent stroke and composite vascular outcome occurred in 6.8% and 16.8% of patients, respectively. As the number of ICAS increased, the risk for study end points increased after adjustment of potential covariates (hazard ratio per 1 increase in ICAS, 1.19; 95% confidence interval, 1.01-1.42 for recurrent ischemic stroke and hazard ratio, 1.18; 95% confidence interval, 1.05-1.33 for composite vascular outcome). The hazard ratios (95% confidence interval) for recurrent stroke and composite vascular outcome in patients with advanced ICAS compared with those without ICAS were 1.56 (0.88-2.74) and 1.72 (1.17-2.53), respectively, in the overall patients. The corresponding values in the propensity-matched patients were 1.28 (0.71-2.30) and 1.95 (1.27-2.99), respectively. ICAS burden was independently associated with the risk of subsequent composite vascular outcome in patients with ischemic stroke. These findings suggest that ICAS burden can reflect the risk of long-term vascular outcome. © 2017 American Heart Association, Inc.

Delayed-onset dementia after stroke or transient ischemic attack.

PubMed

Mok, Vincent C T; Lam, Bonnie Y K; Wang, Zhaolu; Liu, Wenyan; Au, Lisa; Leung, Eric Y L; Chen, Sirong; Yang, Jie; Chu, Winnie C W; Lau, Alexander Y L; Chan, Anne Y Y; Shi, Lin; Fan, Florence; Ma, Sze H; Ip, Vincent; Soo, Yannie O Y; Leung, Thomas W H; Kwok, Timothy C Y; Ho, Chi L; Wong, Lawrence K S; Wong, Adrian

2016-11-01

Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Epidemiology of non-fatal cerebrovascular stroke and transient ischemic attacks in Al Quseir, Egypt.

PubMed

El-Tallawy, Hamdy N; Farghaly, Wafaa M A; Shehata, Ghaydaa A; Abdel-Hakeem, Nabil M; Rageh, Tarek A; Badry, Reda; Kandil, Mahmoud R

2013-01-01

Stroke is a medical emergency that can cause permanent neurological damage, complications, and disability. We aim to determine the epidemiology of non-fatal cerebrovascular stroke (CVS) and transient ischemic attacks (TIAs) in Al Quseir City, Red Sea, Egypt. The total population (n=33,285) was screened through a door to door study by three specialists of neurology and 15 female social workers (for demographic data collection). All suspected stroke patients were subjected to a full clinical examination, computerized tomography (CT) and/or magnetic resonance imaging (MRI) of their brain, blood sugar, lipogram, serum uric acid, complete blood cells, blood urea, and serum creatinine, as well as evaluated by Barthel Index and Scandinavian Stroke Scale. Carotid doppler, echocardiography, and thyroid functions were done for selected cases. CVS was recorded among 130 patients out of 19,848 subjects aged 20 years and more, yielding a total prevalence of 6.55/1,000 population. From June 1, 2010 to May 31, 2011, 36 patients were recorded to have stroke within 1-year, yielding an incidence rate of 1.81/1,000. Prevalence and incidence rates were higher among males than females, and both indices increased steadily with advancing age to reach the highest prevalence (37.02/1,000) and incidence rate (9.5/1,000) among aged persons 60 years and more. The prevalence of non-fatal stroke in Al Quseir city (6.55/1,000) was at the lower range of that recorded in developing countries (5-10/1,000) and slightly higher than that recorded in industrialized countries (5/1,000 population). Ischemic stroke is the most common type of stroke. The prevalence of TIAs was 0.15/1,000.

Glibenclamide for the treatment of ischemic and hemorrhagic stroke.

PubMed

Caffes, Nicholas; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc

2015-03-04

Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1-transient receptor potential melastatin 4 (Sur1-Trpm4) channels and, in some cases, microglial KATP (Sur1-Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.

Long-term survival and regeneration of neuronal and vasculature cells inside the core region after ischemic stroke in adult mice.

PubMed

Jiang, Michael Qize; Zhao, Ying-Ying; Cao, Wenyuan; Wei, Zheng Zachory; Gu, Xiaohuan; Wei, Ling; Yu, Shan Ping

2017-07-01

Focal cerebral ischemia results in an ischemic core surrounded by the peri-infarct region (penumbra). Most research attention has been focused on penumbra while the pattern of cell fates inside the ischemic core is poorly defined. In the present investigation, we tested the hypothesis that, inside the ischemic core, some neuronal and vascular cells could survive the initial ischemic insult while regenerative niches might exist many days after stroke in the adult brain. Adult mice were subjected to focal cerebral ischemia induced by permanent occlusion of distal branches of the middle cerebral artery (MCA) plus transient ligations of bilateral common carotid artery (CCA). The ischemic insult uniformly reduced the local cerebral blood flow (LCBF) by 90%. Massive cell death occurred due to multiple mechanisms and a significant infarction was cultivated in the ischemic cortex 24 h later. Nevertheless, normal or even higher levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) persistently remained in the core tissue, some NeuN-positive and Glut-1/College IV-positive cells with intact ultrastructural features resided in the core 7-14 days post stroke. BrdU-positive but TUNEL-negative neuronal and endothelial cells were detected in the core where extensive extracellular matrix infrastructure developed. Meanwhile, GFAP-positive astrocytes accumulated in the penumbra and Iba-1-positive microglial/macrophages invaded the core several days after stroke. The long term survival of neuronal and vascular cells inside the ischemic core was also seen after a severe ischemic stroke induced by permanent embolic occlusion of the MCA. We demonstrate that a therapeutic intervention of pharmacological hypothermia could save neurons/endothelial cells inside the core. These data suggest that the ischemic core is an actively regulated brain region with residual and newly formed viable neuronal and vascular cells acutely and chronically after at least some types of ischemic strokes. © 2016 International Society of Neuropathology.

Front-loading with clopidogrel plus aspirin followed by dual antiplatelet therapy in the prevention of early stroke recurrence.

PubMed

Censori, Bruno

2014-07-01

Dual antiplatelet therapy with aspirin plus clopidogrel is not recommended for secondary stroke prevention because of lack of effectiveness and increased hemorrhagic risk. Recent studies show that in patients with a very recent transient ischemic attack or minor ischemic stroke loading with 300 mg clopidogrel plus aspirin, followed by clopidogrel 75 mg plus aspirin once daily for up to 90 days significantly decreases the rate of recurrent stroke, especially strokes that occur within few days from the event that led to medical attention, without an increase in severe bleedings. This article reviews the pharmacokinetics and pharmacodynamics of clopidogrel, focusing on loading doses, and summarizes the results of the studies that have shown the effectiveness of the front-loading approach in the early secondary prevention of stroke.

Three Variations in Rabbit Angiographic Stroke Models

PubMed Central

Culp, William C.; Woods, Sean D.; Brown, Aliza T.; Lowery, John D.; Hennings, Leah J.; Skinner, Robert D.; Borrelli, Michael J.; Roberson, Paula K.

2012-01-01

Purpose To develop angiographic models of embolic stroke in the rabbit using pre-formed clot or microspheres to model clinical situations ranging from transient ischemic events to severe ischemic stroke. Materials and Methods New Zealand White rabbits (N=151) received angiographic access to the internal carotid artery (ICA) from a femoral approach. Variations of emboli type and quantity of emboli were tested by injection into the ICA. These included fresh clots (1.0-mm length, 3–6 h), larger aged clots (4.0-mm length, 3 days), and 2 or 3 insoluble microspheres (700–900 μm). Neurological assessment scores (NAS) were based on motor, sensory, balance, and reflex measures. Rabbits were euthanized at 4, 7, or 24 hours after embolization, and infarct volume was measured as a percent of total brain volume using 2,3,5-triphenyltetrazolium chloride (TTC). Results Infarct volume percent at 24 hours after stroke was lower for rabbits embolized with fresh clot (0.45% ± 0.14%), compared with aged clot (3.52% ± 1.31%) and insoluble microspheres (3.39% ± 1.04%). Overall NAS (including posterior vessel occlusions) were positively correlated to infarct volume percent measurements in the fresh clot (r=0.50), aged clot (r=0.65) and microsphere (r=0.62) models (p<0.001). Conclusion The three basic angiographic stroke models may be similar to human transient ischemic attacks (TIA) (fresh clot), major strokes that can be thrombolysed (aged clot), or major strokes with insoluble emboli such as atheromata (microspheres). Model selection can be tailored to specific research needs. PMID:23142182

Heavy cannabis users at elevated risk of stroke: evidence from a general population survey.

PubMed

Hemachandra, Dilini; McKetin, Rebecca; Cherbuin, Nicolas; Anstey, Kaarin J

2016-06-01

Case reports and hospital-based case-control studies suggest that cannabis use may increase the risk of stroke. We examined the risk of non-fatal stroke or transient ischemic attack (TIA) among cannabis users in the general community. A general population survey of Australians aged 20-24 years (n=2,383), 40-44 years (n=2,525) and 60-64 years (n=2,547) was used to determine the odds of lifetime stroke or TIA among participants who had smoked cannabis in the past year while adjusting for other stroke risk factors. There were 153 stroke/TIA cases (2.1%). After adjusting for age cohort, past year cannabis users (n=1,043) had 3.3 times the rate of stroke/TIA (95% CI 1.8-6.3, p<0.001). The incidence rate ratio (IRR) reduced to 2.3 after adjustment for covariates related to stroke, including tobacco smoking (95% CI 1.1-4.5). Elevated stroke/TIA was specific to participants who used cannabis weekly or more often (IRR 4.7, 95% CI 2.1-10.7) with no elevation among participants who used cannabis less often. Heavy cannabis users in the general community have a higher rate of non-fatal stroke or transient ischemic attack than non-cannabis users. © 2015 Public Health Association of Australia.

3H-1,2-Dithiole-3-thione as a novel therapeutic agent for the treatment of ischemic stroke through Nrf2 defense pathway.

PubMed

Kuo, Ping-Chang; Yu, I-Chen; Scofield, Barbara A; Brown, Dennis A; Curfman, Eric T; Paraiso, Hallel C; Chang, Fen-Lei; Yen, Jui-Hung

2017-05-01

Cerebral ischemic stroke accounts for more than 80% of all stroke cases. During cerebral ischemia, reactive oxygen species produced in brain tissue induce oxidative stress and inflammatory responses. D3T, the simplest compound of the cyclic, sulfur-containing dithiolethiones, is found in cruciferous vegetables and has been reported to induce antioxidant genes and glutathione biosynthesis through activation of Nrf2. In addition to antioxidant activity, D3T was also reported to possess anti-inflammatory effects. In this study, we evaluated the therapeutic potential of D3T for the treatment of ischemic stroke and investigated the mechanisms underlying the protective effects of D3T in ischemic stroke. Mice subjected to transient middle cerebral artery occlusion/reperfusion (tMCAO/R) were administered with vehicle or D3T to evaluate the effect of D3T in cerebral brain injury. We observed D3T reduced infarct size, decreased brain edema, lessened blood-brain barrier disruption, and ameliorated neurological deficits. Further investigation revealed D3T suppressed microglia (MG) activation and inhibited peripheral inflammatory immune cell infiltration of CNS in the ischemic brain. The protective effect of D3T in ischemic stroke is mediated through Nrf2 induction as D3T-attenuated brain injury was abolished in Nrf2 deficient mice subjected to tMCAO/R. In addition, in vitro results indicate the induction of Nrf2 by D3T is required for its suppressive effect on MG activation and cytokine production. In summary, we demonstrate for the first time that D3T confers protection against ischemic stroke, which is mediated through suppression of MG activation and inhibition of CNS peripheral cell infiltration, and that the protective effect of D3T in ischemic stroke is dependent on the activation of Nrf2. Copyright © 2017 Elsevier Inc. All rights reserved.

Clopidogrel plus aspirin versus aspirin alone for preventing early neurological deterioration in patients with acute ischemic stroke.

PubMed

He, Fan; Xia, Cheng; Zhang, Jing-Hua; Li, Xiao-Qiu; Zhou, Zhong-He; Li, Feng-Peng; Li, Wei; Lv, Yan; Chen, Hui-Sheng

2015-01-01

Recent studies have suggested that combination antiplatelet therapy may be superior to monotherapy in the treatment of acute stroke. However, additional prospective studies are needed to confirm this finding. The present trial compared the efficacy and safety of clopidogrel plus aspirin versus aspirin alone in the treatment of non-cardioembolic ischemic stroke within 72 hours of onset. Six hundred and ninety patients aged ⩾ 40 years with minor stroke or transient ischemic attack (TIA) were identified for enrollment. Experienced physicians determined baseline National Institutes of Health Stroke Scale scores at the time of admission. All patients were randomly allocated (1:1) to receive aspirin alone (300 mg/day) or clopidogrel (300 mg for the first day, 75 mg/day thereafter) plus aspirin (100mg/day). The main endpoints were neurological deterioration, recurrent stroke, and development of stroke in patients with TIA within 14 days of admission. After 43 patients were excluded, 321 patients in the dual therapy group and 326 patients in the monotherapy group completed the treatment. Baseline characteristics were similar between groups. During the 2 week period, stroke deterioration occurred in nine patients in the dual therapy group and 19 patients in the monotherapy group. Stroke occurred after TIA in one patient in the dual therapy group and three patients in the monotherapy group. Similar numbers of adverse events occurred in both groups. This study showed that early dual antiplatelet treatment reduced early neurological deterioration in patients with acute ischemic stroke, compared with antiplatelet monotherapy. These results imply that dual antiplatelet therapy is superior to monotherapy in the early treatment of acute ischemic stroke. Copyright © 2014 Elsevier Ltd. All rights reserved.

C-reactive protein predicts further ischemic events in first-ever transient ischemic attack or stroke patients with intracranial large-artery occlusive disease.

PubMed

Arenillas, Juan F; Alvarez-Sabín, José; Molina, Carlos A; Chacón, Pilar; Montaner, Joan; Rovira, Alex; Ibarra, Bernardo; Quintana, Manuel

2003-10-01

The role of inflammation in intracranial large-artery occlusive disease is unclear. We sought to investigate the relationship between high-sensitivity C-reactive protein (CRP) levels and the risk of further ischemic events in first-ever transient ischemic attack (TIA) or stroke patients with intracranial large-artery occlusive disease. Of a total of 127 consecutive first-ever TIA or ischemic stroke patients with intracranial stenoses detected by transcranial Doppler ultrasonography, 71 fulfilled all inclusion criteria, which included angiographic confirmation. Serum high-sensitivity CRP level was determined a minimum of 3 months after the qualifying event. Patients were followed up during 1 year after blood sampling. Thirteen patients (18.3%) with intracranial large-artery occlusive disease experienced an end point event: 9 cerebral ischemic events, 7 of which were attributable to intracranial large-artery occlusive disease, and 4 myocardial infarctions. Patients in the highest quintile of high-sensitivity CRP level had a significantly higher adjusted odds ratio for new events compared with those in the first quintile (odds ratio, 8.66; 95% CI, 1.39 to 53.84; P=0.01). A high-sensitivity CRP level above the receiver operating characteristic curve cutoff value of 1.41 mg/dL emerged as an independent predictor of new end point events (hazard ratio, 7.14; 95% CI, 1.77 to 28.73; P=0.005) and of further intracranial large-artery occlusive disease-related ischemic events (hazard ratio, 30.67; 95% CI, 3.6 to 255.5; P=0.0015), after adjustment for age, sex, and risk factors. Kaplan-Meier curves showed that a significantly lower proportion of patients with a high-sensitivity CRP >1.41 mg/dL remained free of a new ischemic event (P<0.0001). High-sensitivity CRP serum level predicts further intracranial large-artery occlusive disease-related and any major ischemic events in patients with first-ever TIA or stroke with intracranial large-artery occlusive disease. These findings are consistent with the hypothesis that inflammation may be involved in the progression and complication of intracranial large-artery occlusive disease.

Efficacy and Safety of Cilostazol Therapy in Ischemic Stroke: A Meta-analysis.

PubMed

Tan, Liang; Margaret, Barnhart; Zhang, John H; Hu, Rong; Yin, Yi; Cao, Liu; Feng, Hua; Zhang, Yanqi

2015-05-01

Antiplatelet therapy is recommended for patients who have experienced ischemic stroke. We performed a meta-analysis to compare the efficacy and safety of cilostazol with other antiplatelet therapies in patients with ischemic stroke. PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched for randomized controlled trials published in English from May 1999 to May 2013. Clinical outcomes were compared by pooled and meta-regression analyses. Nine studies involving 6328 patients satisfied our inclusion criteria. Stroke recurrence (including hemorrhagic and ischemic) with cilostazol use was 5.3% (157) versus 8.3% (248) in control group (risk ratio .63 [.52-.76], 95% confidence interval [CI]). Poststroke intracranial hemorrhage was .5% (16) with cilostazol versus 1.6% (46) in control group (risk ratio .36 [.21-.63], 95% CI). Poststroke extracranial bleeding complications occurred in 2.4% (66) of the patients taking cilostazol versus 3.9% (108) in control group (risk ratio .62 [.46-.83], 95% CI). No significant difference in cerebrovascular events (nonfatal stroke, intracranial hemorrhage, and transient ischemic attack) was found between the cilostazol group (8.2%, 246) versus control group (12.0%, 360; risk ratio .71 [.50-1.01], 95% CI). In addition, the cilostazol therapy brought about a nonsignificant reduction of cardiac adverse events (heart failure, myocardial infarction, and angina pectoris) comparing with control groups, with 3.8% (99) of the cilostazol group versus 4.7% (123) of control group (risk ratio, .81 [.62-1.04], 95% CI). Cilostazol, alone or in combination with aspirin, significantly reduces stroke recurrence, poststroke intracranial hemorrhage, and extracranial bleeding in patients with a prior ischemic stroke as compared with other antiplatelet therapies. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Risk of Ischemic Stroke and Transient Ischemic Attack Is Increased up to 90 Days after Non-Carotid and Non-Cardiac Surgery.

PubMed

Grau, Armin J; Eicke, Martin; Burmeister, Christoph; Hardt, Roland; Schmitt, Eberhard; Dienlin, Sieghard

2017-01-01

The risk of stroke after cardiac and carotid surgery is well established. In contrast, stroke risk in association with non-cardiac and non-carotid surgery and its time course are insufficiently known. We investigated the prevalence of recent and planned surgery among patients with stroke and transient ischemic attack (TIA), time dependency of stroke risk, stroke etiology, and interruption of antithrombotic medication in association with surgery. Data on type and date of surgery and similar interventions within the last year or planned for the next 2 weeks were anonymously collected together with demographic data, vascular risk factors, stroke severity, handicap before stroke and stroke etiology within a state-wide, mandatory, hospital-based acute stroke care quality monitoring project (Rhineland-Palatinate, Germany) for 1 year (2010). Non-carotid and non-cardiothoracic surgery was reported as performed within 1 year before the index event or as planned for the next 2 weeks thereafter in 532 out of 12,120 patients with ischemic stroke/TIA (4.4%). Compared to 91-365 days before stroke/TIA as reference period, risk of cerebral ischemia (per day analysis) was increased for surgery within 61-90 days before ischemia (rate ratio 2.0, 95% CI 1.5-2.8) and continuously increased along shorter intervals between stroke and surgery (31-60 days: rate ratio 3.6, 95% CI 2.9-4.5; 15-30 days: rate ratio 8.2, 95% CI 6.7-10.1; 8-14 days: rate ratio 13.2, 95% CI 10.3-16.8; 4-7 days: rate ratio 16.5, 95% CI 12.2-22.1) peaking at an interval of 1-3 days before ischemia (rate ratio 34.0, 95% CI 26.9-42.8). On the day of surgery, rate ratio was 14.8 (95% CI 7.8-27.9) and for planned surgery it was 2.7 (95% CI 1.8-4.0). Results were similar for first-ever and for recurrent ischemic stroke. Perioperative stroke/TIA was positively associated with atrial fibrillation and cardioembolic stroke etiology, higher mortality, more severe neurological deficits at discharge, and longer hospital stay; and it was inversely associated with microangiopathic etiology and discharge at home. In 34.5% of patients with recent/planned surgery, prior antithrombotic or anticoagulant medication had been interrupted. Recent or planned surgery imposes a considerable short-term stroke risk particularly by cardioembolism with cessation of medication as an important contributor. Stroke after surgery is associated with poor outcome and high mortality. Better strategies to reduce the burden of perioperative stroke are urgently required. © 2017 S. Karger AG, Basel.

Prevention of ischemic stroke in clinical practice: a role of internists and general practitioners.

PubMed

Niewada, Maciej; Członkowska, Anna

2014-01-01

Stroke constitutes a substantial clinical and socio-economic burden. It is currently the third cause of death worldwide and results in mortality or disability in every third patient at the end of the first year following an acute cerebrovascular event. Although in-hospital mortality rates in stroke patients have decreased, prevention and cardiovascular risk control remain critical for improving the prognosis and reducing stroke burden worldwide. The definitions of stroke and transient ischemic attack (TIA) have been recently modified following the findings from neuroimaging and thrombolysis research. Both stroke and TIA are recurrent and preventable disorders. Both patients with stroke and those with TIA require prompt clinical workup, risk assessment, and appropriate management because the risk of recurrence, stroke, and coronary events is significant. The 5 most common cardiovascular risk factors (high blood pressure, smoking, abdominal obesity, diet, and lack of physical activity) are responsible for 80% of the cases. Stroke prevention involves lifestyle modification and specific treatment. Secondary prevention of ischemic stroke involves early treatment (antiplatelets and carotid interventions) and long-term management including lifestyle changes, antihypertensive therapy, antiplatelets, antithrombotic drugs in patients with atrial fibrillation, and the use of statins and other lipid-lowering drugs. Stroke patients are at risk of depression, dementia, epilepsy, and other complications that also require targeted treatment.

YC‑1 reduces inflammatory responses by inhibiting nuclear factor‑κB translocation in mice subjected to transient focal cerebral ischemia.

PubMed

Lee, Wei-Ting; Tai, Shih-Huang; Lin, Yu-Wen; Wu, Tian-Shung; Lee, E-Jian

2018-06-15

3‑(5‑hydroxymethyl‑2‑furyl)‑1‑benzyl‑indazole (YC‑1) is understood to protect against ischemic stroke, but the molecular basis for its neuroprotection remains to be fully characterized. The present study investigated the influence of YC‑1 on inflammatory responses following experimental stroke. Previous studies indicated that nuclear factor (NF)‑κB‑driven signals serve a pivotal role in mediating inflammatory responses following stroke. Ischemic stroke results in activation of NF‑κB to induce gene expression of factors including inducible nitric oxide synthase, interleukin (IL)‑1β, IL‑6 and matrix metalloproteinases (MMPs). The results of the present study demonstrated that YC‑1 effectively reduced brain infarction and brain edema, and improved blood‑brain barrier leakage. Additionally, animals treated with YC‑1 exhibited significant reductions in neutrophil and macrophage infiltration into the ischemic brain. Furthermore, YC‑1 effectively inhibited NF‑κB translocation and binding activity, and the activity and expression of MMP‑9 following ischemic stroke. In conclusion, YC‑1 may effectively attenuate NF‑κB‑induced inflammatory damage following cerebral ischemia‑reperfusion.

National survey of emergency physicians for transient ischemic attack (TIA) risk stratification consensus and appropriate treatment for a given level of risk.

PubMed

Perry, Jeffrey J; Losier, Justin H; Stiell, Ian G; Sharma, Mukul; Abdulaziz, Kasim

2016-01-01

Five percent of transient ischemic attack (TIA) patients have a subsequent stroke within 7 days. The Canadian TIA Score uses clinical findings to calculate the subsequent stroke risk within 7 days. Our objectives were to assess 1) anticipated use; 2) component face validity; 3) risk strata for stroke within 7 days; and 4) actions required, for a given risk for subsequent stroke. After a rigorous development process, a survey questionnaire was administered to a random sample of 300 emergency physicians selected from those registered in a national medical directory. The surveys were distributed using a modified Dillman technique. From a total of 271 eligible surveys, we received 131 (48.3%) completed surveys; 96.2% of emergency physicians would use a validated Canadian TIA Score; 8 of 13 components comprising the Canadian TIA Score were rated as Very Important or Important by survey respondents. Risk categories for subsequent stroke were defined as minimal-risk: 10% risk of subsequent stroke within 7 days. A validated Canadian TIA Score will likely be used by emergency physicians. Most components of the TIA Score have high face validity. Risk strata are definable, which may allow physicians to determine immediate actions, based on subsequent stroke risk, in the emergency department.

Symptomatic and asymptomatic carotid artery plaque

PubMed Central

Mughal, Majid M; Khan, Mohsin K; DeMarco, J Kevin; Majid, Arshad; Shamoun, Fadi; Abela, George S

2011-01-01

Carotid atherosclerotic plaques represent both stable and unstable atheromatous lesions. Atherosclerotic plaques that are prone to rupture owing to their intrinsic composition such as a large lipid core, thin fibrous cap and intraplaque hemorrhage are associated with subsequent thromboembolic ischemic events. At least 15–20% of all ischemic strokes are attributable to carotid artery atherosclerosis. Characterization of plaques may enhance the understanding of natural history and ultimately the treatment of atherosclerotic disease. MRI of carotid plaque and embolic signals during transcranial Doppler have identified features beyond luminal stenosis that are predictive of future transient ischemic attacks and stroke. The value of specific therapies to prevent stroke in symptomatic and asymptomatic patients with severe carotid artery stenosis are the subject of current research and analysis of recently published clinical trials that are discussed in this article. PMID:21985544

Recent surgery or invasive procedures and the risk of stroke.

PubMed

Urbanek, Christian; Palm, Frederick; Buggle, Florian; Wolf, Joachim; Safer, Anton; Becher, Heiko; Grau, Armin J

2014-01-01

A recent surgery may be one of the trigger factors precipitating stroke and transient ischemic attack (TIA). While stroke in cardiac and carotid surgery has been well studied, less is known on stroke risk after surgery outside the heart and brain supplying arteries. We tested the hypothesis that preceding non-neurosurgical, non-cardiothoracic, and non-carotid surgery and other interventions temporarily increase the risk of stroke and transient ischemic attack (TIA) and investigated the risk related to different time periods between interventions and stroke/TIA. In the Ludwigshafen Stroke Study, a population-based stroke registry, we assessed surgery and other interventions within the year preceding stroke and TIA. The risk factor profiles of patients with and without prior intervention were compared and rate ratios (RR) were calculated for different time periods with 91-365 days before stroke and TIA serving as reference period. In 2006 and 2007, 803 patients without and 116 patients with non-neurosurgical, non-cardiothoracic, and non-carotid intervention within the preceding year were identified. Elective (n = 21) and posttraumatic orthopedic (n = 14), eye (n = 14), and visceral surgery (n = 11) dominated. Interventions within 0-30 days (n = 34; RR 4.72; 95% confidence interval (CI) 2.70-8.26) but not within 31-60 or 61-90 days before stroke/TIA were observed more often than in the reference period. Interventions were more common within day 8-30 before stroke/TIA (RR 3.26; 95% CI 1.66-6.39), particularly common within the preceding week (RR 9.52; 95% CI 3.77-24.1) and most common in the preceding 2 days (RR 27.1; 95% CI 5.97-123) as compared to the reference period. Atrial fibrillation (AF) but not other risk factors was more common in patients with interventions within 30 days (n = 15; 44.1%) as compared to patients with more antecedent interventions (n = 19; 23.2%, p = 0.022) and those without surgery (n = 222; 27.6%, p = 0.031). Interventions within 30 days before stroke/TIA, were associated with total ischemic stroke (RR 6.11; 95% CI 3.32-11.2), first-ever in a lifetime ischemic stroke (RR 5.62; 95% CI 2.83-11.1) and recurrent ischemic stroke (RR 7.50; 95% CI 2.88-19.6). Recent non-cardiothoracic, non-carotid, and non-neurosurgical interventions are associated with an increased risk of stroke lasting for about 1 month and being particularly high within the first days. AF may be among the mechanisms linking interventions and stroke besides induction of a procoagulant state and interruption of medication. © 2014 S. Karger AG, Basel.

Stroke and transient ischemic attack incidence rate in Spain: the IBERICTUS study.

PubMed

Díaz-Guzmán, Jaime; Egido, Jose-A; Gabriel-Sánchez, Rafael; Barberá-Comes, Gloria; Fuentes-Gimeno, Blanca; Fernández-Pérez, Cristina

2012-01-01

In Spain, stroke is a major public health concern, but large population-based studies are scarce and date from the 1990s. We estimated the incidence and in-hospital mortality of stroke through a multicentered population-based stroke register in 5 geographical areas of Spain, i.e. Lugo, Almería, Segovia, Talavera de la Reina and Mallorca, representing north, south, central (×2) and Mediterranean areas of Spain, respectively, the aim and novelty being that all methodologies were standardized, and diagnoses were verified by a neurologist using neuroimaging techniques. The register identified subjects >17 years of age who suffered a first-ever stroke or transient ischemic attack (TIA) between 1 January and 31 December 2006. Stroke and TIA were defined according to the WHO criteria. The Lausanne Stroke Registry definitions were used to classify ischemic stroke subtypes, as follows: (1) large-artery atherosclerosis (LAA); (2) cardioembolism (CE); (3) lacunar stroke or small-artery occlusion (SAO); (4) stroke of other infrequent cause (SIC), and (5) stroke of undetermined cause (UND). We used several complementary data sources such as hospital discharge registers, emergency room registers and primary care surveillance systems. In the 1-year study period, we identified 2,700 first-ever cerebrovascular episodes (53% men; 2,257 strokes + 443 TIA episodes). Brain CT in the acute stage was performed in 99% of cases. Of a total of 2,257 stroke patients, 1,817 (81%) had cerebral infarction, 350 (16%) had intracerebral hemorrhage, 59 (3%) had subarachnoid hemorrhage (SAH) and 31 (1%) had unclassifiable stroke. The overall unadjusted annual incidence for all cerebrovascular events was 187 per 100,000 [95% confidence interval (CI) 180-194; incidence for men: 202, 95% CI 189-210; incidence for women: 187, 95% CI 180-194]. The subtype of ischemic stroke could be determined in 1,779 patients and was classified as LAA in 624 (35%), CE in 352 (20%), SAO in 316 (18%), SIC in 56 (3%) and UND in 431 (24%). The incidence rates per 100,000 (95% CI) standardized to the 2006 European population were as follows: all cerebrovascular events, 176 (169-182); all stroke (non-TIA), 147 (140-153); TIA, 29 (26-32); ischemic stroke, 118 (112-123); intracerebral hemorrhage, 23 (21-26), and SAH, 4.2 (3.1-5.2). Incidence rates clearly increased with age in both genders, with a peak at or above 85 years of age. The in-hospital mortality was 14%. Our results show that the incidence of stroke and TIA in Spain is moderate compared to other Western and European countries. However, it is expected that these figures will change due to progressively aging populations. Copyright © 2012 S. Karger AG, Basel.

Incidental primary mediastinal choriocarcinoma diagnosed by endobronchial ultrasound-guided fine needle aspiration in a patient presenting with transient ischemic attack and stroke.

PubMed

Francischetti, Ivo M B; Cajigas, Antonio; Suhrland, Mark; Farinhas, Joaquim M; Khader, Samer

2017-08-01

We describe a case of a 41-year old male patient with no significant prior medical history who presents with symptoms of Transient Ischemic Attack and stroke. Magnetic Resonance Imaging (MRI) of the brain identified areas of ischemia in the left side, and angiography showed occlusion of the left Medial Cerebral Artery (MCA). Cardiac Transthoracic Echocardiogram (TTE) for stroke evaluation incidentally noted a mediastinal abnormality leading to cancer work-up. Computer Tomography (CT) and 18 F-fluorodeoxyglucose (FDG) PET-CT scan of the chest incidentally revealed an avid 6 cm paraesophagial/subcarinal mass. Further diagnostic work-up with endoscopic and endobronchial ultra sound (EBUS)-guided fine needle aspiration (FNA) of the mass yielded a cytology diagnosis of Germ Cell Tumor (GCT), with choriocarcinoma component. Additionally, high plasma levels of β-human chorionic gonadotrophin (β-HCG) were detected with no evidence of testicular tumor. This exceedingly rare presentation for a primary mediastinal choriocarcinoma underscores the importance of complete investigation of young patients presenting with neurological symptoms compatible with ischemic events. Diagn. Cytopathol. 2017;45:738-743. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Caso, Valeria; Tsivgoulis, Georgios; Furie, Karen L; Tadi, Prasanna; Becattini, Cecilia; Falocci, Nicola; Zedde, Marialuisa; Abdul-Rahim, Azmil H; Lees, Kennedy R; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Procopio, Antonio; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Cappellari, Manuel; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Bandini, Fabio; Marcheselli, Simona; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Masotti, Luca; Vannucchi, Vieri; Sohn, Sung-Il; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Ntaios, George; Karagkiozi, Efstathia; Athanasakis, George; Makaritsis, Kostantinos; Vadikolias, Kostantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Mumoli, Nicola; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Colombo, Giovanna; Silvestrelli, Giorgio; Ciccone, Alfonso; Scoditti, Umberto; Denti, Licia; Mancuso, Michelangelo; Maccarrone, Miriam; Orlandi, Giovanni; Giannini, Nicola; Gialdini, Gino; Tassinari, Tiziana; De Lodovici, Maria Luisa; Bono, Giorgio; Rueckert, Christina; Baldi, Antonio; D'Anna, Sebastiano; Toni, Danilo; Letteri, Federica; Giuntini, Martina; Lotti, Enrico Maria; Flomin, Yuriy; Pieroni, Alessio; Kargiotis, Odysseas; Karapanayiotides, Theodore; Monaco, Serena; Baronello, Mario Maimone; Csiba, Laszló; Szabó, Lilla; Chiti, Alberto; Giorli, Elisa; Del Sette, Massimo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Michel, Patrik; Vanacker, Peter; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Gourbali, Vanessa; Yaghi, Shadi

2017-03-01

This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P =0.10) for major bleedings. The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P =0.009) for ischemic outcome events and 0.407 (0.275-0.540; P =0.14) for hemorrhagic outcome events. In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc.

Risk of cerebrovascular events in patients with patent foramen ovale and intracardiac devices.

PubMed

Poddar, Kanhaiya L; Nagarajan, Vijaiganesh; Krishnaswamy, Amar; Bajaj, Navkaranbir S; Kumari, Meera; Bdair, Hazem; Modi, Dhruv; Agarwal, Shikhar; Goel, Sachin S; Parashar, Akhil; Tuzcu, E Murat; Kapadia, Samir R

2014-11-01

This study investigated whether patients with patent foramen ovale (PFO) have an increased risk of stroke due to permanent pacemaker (PPM)/implantable cardioverter-defibrillator (ICD) implantation. Data are lacking on the risk of stroke in patients with PFO and implantable intracardiac devices, either a PPM or an ICD. We investigated whether patients with PFO have increased risk of stroke due to PPM/ICD implantation. Between 2001 and 2008, 2,921 consecutive patients with PFO (67.5 ± 16.4 years of age, 52.2% male) were identified from our echocardiography database. These patients were divided into a device group (patients had PPM/ICD implantation for any reason after receiving a diagnosis of PFO) and a no device group (patients did not have PPM or ICD implantation). Patients who had PFO closure during follow-up were excluded. Both groups were matched for baseline characteristics and medications. The incidence of ischemic stroke was assessed in each group after propensity score matching (case:control ratio of 1:1 yielding 231 pairs). All patients completed at least 4 years of follow-up until May 2012. There were 2,690 patients in the n device group (67.3 ± 16.4 years of age, 51.6% male) and 231 patients in the device group (75.4 ± 14.6 years of age, 59.3% male). Six patients (2.6%) in the no device group and 6 (2.6%) in the device group had a stroke during the follow-up period. No difference in the rate of stroke, transient ischemic stroke, or stroke/transient ischemic stroke was observed between the 2 groups. The risk of stroke in patients with PFO and an implantable intracardiac device is similar to those without an intracardiac device. In patients with PFO, without a history of stroke, device implantation might not be considered a risk factor for future stroke occurrence. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cerebral collaterals and collateral therapeutics for acute ischemic stroke.

PubMed

Winship, Ian R

2015-04-01

Cerebral collaterals are vascular redundancies in the cerebral circulation that can partially maintain blood flow to ischemic tissue when primary conduits are blocked. After occlusion of a cerebral artery, anastomoses connecting the distal segments of the MCA with distal branches of the ACA and PCA (known as leptomeningeal or pial collaterals) allow for partially maintained blood flow in the ischemic penumbra and delay or prevent cell death. However, collateral circulation varies dramatically between individuals, and collateral extent is significant predictor of stroke severity and recanalization rate. Collateral therapeutics attempt to harness these vascular redundancies by enhancing blood flow through pial collaterals to reduce ischemia and brain damage after cerebral arterial occlusion. While therapies to enhance collateral flow remain relatively nascent neuroprotective strategies, experimental therapies including inhaled NO, transient suprarenal aortic occlusion, and electrical stimulation of the parasympathetic sphenopalatine ganglion show promise as collateral therapeutics with the potential to improve treatment of acute ischemic stroke. © 2014 John Wiley & Sons Ltd.

Indications and applications of arterial stents for stroke prevention in atherosclerotic intracranial stenosis.

PubMed

Fields, Jeremy D; Liu, Kenneth C; Barnwell, Stanley L; Clark, Wayne M; Lutsep, Helmi L

2010-01-01

Intracranial stenosis accounts for 8-10% of all ischemic strokes in North America, a frequency slightly less than that of extracranial carotid stenosis. Among patients presenting with transient ischemic attack or stroke due to intracranial stenosis, the risk of recurrent stroke in the first year after initial symptoms is about 14%. Those with high-risk features (recent stroke and severe stenosis) have up to a 23% rate of recurrent stroke in the year after their initial event. Angioplasty with stenting has emerged as a potential treatment strategy, particularly in high-risk patients, although evidence is currently limited to uncontrolled prospective trials and retrospective case series. In this article, we critically review the clinical results supporting the use of stenting and highlight some key considerations in the application of this technology, including patient selection, procedural management, technical issues, and risk factors for complications and in-stent restenosis.

A Systematic Review of Validated Methods for Identifying Cerebrovascular Accident or Transient Ischemic Attack Using Administrative Data

PubMed Central

Andrade, Susan E.; Harrold, Leslie R.; Tjia, Jennifer; Cutrona, Sarah L.; Saczynski, Jane S.; Dodd, Katherine S.; Goldberg, Robert J.; Gurwitz, Jerry H.

2012-01-01

Purpose To perform a systematic review of the validity of algorithms for identifying cerebrovascular accidents (CVAs) or transient ischemic attacks (TIAs) using administrative and claims data. Methods PubMed and Iowa Drug Information Service (IDIS) searches of the English language literature were performed to identify studies published between 1990 and 2010 that evaluated the validity of algorithms for identifying CVAs (ischemic and hemorrhagic strokes, intracranial hemorrhage and subarachnoid hemorrhage) and/or TIAs in administrative data. Two study investigators independently reviewed the abstracts and articles to determine relevant studies according to pre-specified criteria. Results A total of 35 articles met the criteria for evaluation. Of these, 26 articles provided data to evaluate the validity of stroke, 7 reported the validity of TIA, 5 reported the validity of intracranial bleeds (intracerebral hemorrhage and subarachnoid hemorrhage), and 10 studies reported the validity of algorithms to identify the composite endpoints of stroke/TIA or cerebrovascular disease. Positive predictive values (PPVs) varied depending on the specific outcomes and algorithms evaluated. Specific algorithms to evaluate the presence of stroke and intracranial bleeds were found to have high PPVs (80% or greater). Algorithms to evaluate TIAs in adult populations were generally found to have PPVs of 70% or greater. Conclusions The algorithms and definitions to identify CVAs and TIAs using administrative and claims data differ greatly in the published literature. The choice of the algorithm employed should be determined by the stroke subtype of interest. PMID:22262598

Transient ischameic attack/stroke electronic decision support: a 14-month safety audit.

PubMed

Lavin, Timothy L; Ranta, Annemarei

2014-02-01

To assess the safety of a Transient Ischameic Attack (TIA)/Stroke Electronic Decision Support (EDS) tool in the primary care setting intended to aid general practitioners in the timely management of transient ischemic attacks (TIAs). A 14-month safety audit reviewing all patients managed with the help of the TIA/Stroke EDS tool. Major morbidity and mortality were assessed by screening patients for subsequent hospital admissions and investigating potential links to EDS use. Seventy-nine patients were managed with the aid of the TIA/Stroke EDS. EDS use resulted in 8 appropriate immediate hospital admissions because of patients being at high risk of stroke. Three patients had delayed admission, but care was fully guideline based and patients had no adverse outcome. Eleven admissions were unrelated to EDS use. Two deaths occurred; these did not result from inappropriate EDS advice. Results suggest that TIA/Stroke EDS use is not associated with major morbidity or mortality. Larger studies are needed to draw more definite conclusions regarding the utility of this TIA/Stroke EDS in preventing strokes. Copyright © 2014 National Stroke Association. All rights reserved.

XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.

PubMed

Jiang, Meng; Yu, Shu; Yu, Zhui; Sheng, Huaxin; Li, Ying; Liu, Shuai; Warner, David S; Paschen, Wulf; Yang, Wei

2017-06-01

Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke. To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated. A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation). Stroke impairs endoplasmic reticulum function, which activates unfolded protein response. The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke. Mice with Xbp1 loss and gain of function in neurons were generated. Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice. Thiamet-G was used to increase O-GlcNAcylation. Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion. After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent. This activation of O-GlcNAcylation was impaired in aged mice. Pharmacological increase of O-GlcNAcylation before or after stroke improved outcome in both young and aged mice. Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome. O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice. Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains. © 2017 American Heart Association, Inc.

Which risk factors are more associated with ischemic rather than hemorrhagic stroke in black Africans?

PubMed

Owolabi, Mayowa O; Agunloye, Atinuke M

2013-10-01

To comprehensively examine the relationship of vascular risk factors to stroke type in native black Africans. We explored 34 candidate demographic, clinical, and laboratory variables in 282 consecutive adult stroke patients with brain imaging. Ischemic stroke (IS) was found in 61.7% (174). Gender, alcohol, cigarette, homocysteine, C-reactive peptide, anthropometry, and carotid parameters were not significantly associated with stroke type (p>0.05). Patients with IS had relatively lower BP, were significantly older, and more frequently had diabetes mellitus, cardiac disease, or previous transient ischemic attack than patients with hemorrhagic stroke (HS). However, in multivariate regression model predicting 69% of stroke type correctly, age≥62 years (OR: 4.0, 95% CI: 2.0-7.9), previous TIA (OR: 4.3, 95% CI: 1.2-15.7) and systolic BP≥140 mmHg (OR: 0.4, 95% CI: 0.2-0.9) were the only independent significant predictors of IS. With increasing proportion of the population over 61 years and better BP control, the proportion of IS is expected to rise in black African countries currently undergoing epidemiological transition (changing lifestyle/disease pattern). Therefore, relevant components of the stroke intervention quadrangle (stroke surveillance, acute care, preventive and rehabilitation services) should be tailored toward this need. Copyright © 2013 Elsevier B.V. All rights reserved.

Heart rate as a predictor of stroke in high-risk, hypertensive patients with previous stroke or transient ischemic attack.

PubMed

Sandset, Else Charlotte; Berge, Eivind; Kjeldsen, Sverre E; Julius, Stevo; Holzhauer, Björn; Krarup, Lars-Henrik; Hua, Tsushung A

2014-01-01

Risk factors for first stroke are well established, but less is known about risk factors for recurrent stroke. In the present analysis, we aimed to assess the effect of heart rate and other possible predictors of stroke in a hypertensive population with previous stroke or transient ischemic attack (TIA). The Valsartan Antihypertensive Long-Term Use Evaluation trial was a multicentre, double-masked, randomized controlled, parallel group trial comparing the effects of an angiotensin receptor blocker (valsartan) and a calcium channel blocker (amlodipine) in patients with hypertension and high cardiovascular risk. We used Cox proportional hazard models to investigate the effect of baseline variables on the risk of stroke. Quadratic terms of the continuous variables were entered in the models to test for linearity. Of 15,245 patients included in the trial, 3014 had a previous stroke or TIA at baseline and were included in the present analysis. Stroke recurrence occurred in 239 patients (7.9%) during a median of 4.5 years of follow-up. Resting heart rate (per 10 beats per minute; hazard ratio [HR], 2.78; 95% confidence interval [CI], 1.18-6.58) and diabetes mellitus at baseline (HR, 1.47; 95% CI, 1.03-2.10) were significantly associated with an increased risk of stroke recurrence in the multivariable analysis. In high-risk, hypertensive patients with previous stroke or TIA, resting heart rate was the strongest predictor of recurrent stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

[Understanding the reasons behind the low utilization of thrombolysis in hyperacute ischemic stroke].

PubMed

Zhang, Xiaoxue; Zhang, Jingfen; Li, Ruiming; Cheng, Guojuan; Chen, Qiang

2016-03-22

The study aimed to analyze the influencing factors of thrombolysis therapy in acute ischemic stroke patients with onset time less than 4.5 hours. We consecutively prospectively screened acute ischemic stroke patients with onset time less than 4.5 hours from emergency department, outpatients and inpatients of neurology department, and image center in our hospital over a 31-month time period (April 2012-November 2014). The rate of thrombolysis and the reasons for not receiving thrombolysis were analyzed. A total of 538 patients who met the inclusion criteria were included (68.2% males, mean age 67±13 years old). Only 104 (19.3%) patients received thrombolysis. The main reasons for the patients not receiving thrombolysis included minor symptoms (172 cases, 39.6%), rapidly improving symptoms and high possibility of transient ischemic attack (TIA) (59 cases, 13.6%), patients or families refusing thrombolysis (44, 10.1%), in-hospital delay (38, 8.8%), elderly people with age over than 80 years old (38, 8.8%). The thrombolysis rate within time window of acute ischemic stroke is remarkably higher than that of several years ago in China. The main reasons for not receiving thrombolysis are minor and rapidly improving symptoms, patients or families' refusal, in-hospital delay, elderly people with age over than 80 years old.

Patient and Provider Assessment of Lipid Management Registry

ClinicalTrials.gov

2016-02-15

Hyperlipidemia; Hypercholesterolemia; Cardiovascular Disease; Diabetes; Chronic Kidney Disease (CKD); Hypertension; Smoking; Myocardial Infarction (MI); Unstable Angina; Angina; Coronary Artery Disease (CAD); Stroke; Transient Ischemic Attack (TIA); Carotid Stenosis; Peripheral Arterial Disease; Atherosclerosis; Claudication

Study design of the CLOSURE I Trial: a prospective, multicenter, randomized, controlled trial to evaluate the safety and efficacy of the STARFlex septal closure system versus best medical therapy in patients with stroke or transient ischemic attack due to presumed paradoxical embolism through a patent foramen ovale.

PubMed

Furlan, Anthony J; Reisman, Mark; Massaro, Joseph; Mauri, Laura; Adams, Harold; Albers, Gregory W; Felberg, Robert; Herrmann, Howard; Kar, Saibal; Landzberg, Michael; Raizner, Albert; Wechsler, Lawrence

2010-12-01

Some strokes of unknown etiology may be the result of a paradoxical embolism traversing through a nonfused foramen ovale (patent foramen ovale [PFO]). The utility of percutaneously placed devices for treatment of patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO is unknown. In addition, there are no clear data about the utility of medical interventions or other surgical procedures in this situation. Despite limited data, many patients are being treated with PFO closure devices. Thus, there is a strong need for clinical trials that test the potential efficacy of PFO occlusive devices in this situation. To address this gap in medical knowledge, we designed the CLOSURE I trial, a randomized, clinical trial comparing the use of a percutaneously placed PFO occlusive device and best medical therapy versus best medical therapy alone for prevention of recurrent ischemic neurologic symptoms among persons with TIA or ischemic stroke. This prospective, multicenter, randomized, controlled trial has finished enrollment. Two-year follow-up for all 910 patients is required. The primary end point is the 2-year incidence of stroke or TIA, all-cause mortality for the first 30 days, and neurologic mortality from ≥ 31 days of follow-up, as adjudicated by a panel of physicians who are unaware of treatment allocation. This article describes the rationale and study design of CLOSURE I. This trial should provide information as to whether the STARFlex septal closure system is safe and more effective than best medical therapy alone in preventing recurrent stroke/TIA and mortality in patients with PFO and whether the STARFlex septal closure device can demonstrate superiority compared with best medical therapy alone. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00201461.

Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury: Implications for Perioperative Neuroprotection

PubMed Central

Sun, Yu-Yo; Li, Yikun; Wali, Bushra; Li, Yuancheng; Lee, Jolly; Heinmiller, Andrew; Abe, Koji; Stein, Donald G.; Mao, Hui; Sayeed, Iqbal; Kuan, Chia-Yi

2015-01-01

Background and Purpose Hypoperfusion-induced thrombosis is an important mechanism for post-surgery stroke and cognitive decline, but there are no perioperative neuroprotectants to date. This study investigated whether prophylactic application of Edaravone, a free radical scavenger already used in treating ischemic stroke in Japan, can prevent infarct and cognitive deficits in a murine model of transient cerebral hypoxia-ischemia. Methods Adult male C57BL/6 mice were subjected to transient hypoxic-ischemic (tHI) insult that consists of 30-min occlusion of the unilateral common carotid artery and exposure to 7.5% oxygen. Edaravone or saline was prophylactically applied to compare their effects on cortical oxygen saturation, blood flow, coagulation, oxidative stress, metabolites, and learning-memory using methods that include photoacoustic imaging, laser speckle contrast imaging, solid state NMR and Morris water maze. The effects on infarct size by Edaravone application at different time-points after tHI were also compared. Results Prophylactic administration of Edaravone (4.5 mg/kg × 2, IP, 1 h before and 1 h after tHI) improved vascular reperfusion, oxygen saturation, and the maintenance of brain metabolites, while reducing oxidative stress, thrombosis, white-matter injury, and learning impairment after tHI insult. Delayed Edaravone treatment after 3 h post-tHI became unable to reduce infarct size. Conclusions Acute application of Edaravone may be a useful strategy to prevent post-surgery stroke and cognitive impairment, especially in patients with severe carotid stenosis. PMID:26060244

Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury: Implications for Perioperative Neuroprotection.

PubMed

Sun, Yu-Yo; Li, Yikun; Wali, Bushra; Li, Yuancheng; Lee, Jolly; Heinmiller, Andrew; Abe, Koji; Stein, Donald G; Mao, Hui; Sayeed, Iqbal; Kuan, Chia-Yi

2015-07-01

Hypoperfusion-induced thrombosis is an important mechanism for postsurgery stroke and cognitive decline, but there are no perioperative neuroprotectants to date. This study investigated whether prophylactic application of Edaravone, a free radical scavenger already used in treating ischemic stroke in Japan, can prevent infarct and cognitive deficits in a murine model of transient cerebral hypoxia-ischemia. Adult male C57BL/6 mice were subjected to transient hypoxic-ischemic (tHI) insult that consists of 30-minute occlusion of the unilateral common carotid artery and exposure to 7.5% oxygen. Edaravone or saline was prophylactically applied to compare their effects on cortical oxygen saturation, blood flow, coagulation, oxidative stress, metabolites, and learning-memory using methods that include photoacoustic imaging, laser speckle contrast imaging, solid-state NMR, and Morris water maze. The effects on infarct size by Edaravone application at different time points after tHI were also compared. Prophylactic administration of Edaravone (4.5 mg/kg×2, IP, 1 hour before and 1 hour after tHI) improved vascular reperfusion, oxygen saturation, and the maintenance of brain metabolites, reducing oxidative stress, thrombosis, white-matter injury, and learning impairment after tHI insult. Delayed Edaravone treatment after 3 h post-tHI became unable to reduce infarct size. Acute application of Edaravone may be a useful strategy to prevent postsurgery stroke and cognitive impairment, especially in patients with severe carotid stenosis. © 2015 American Heart Association, Inc.

Left-sided strokes are more often recognized than right-sided strokes: the Rotterdam study.

PubMed

Portegies, Marileen L P; Selwaness, Mariana; Hofman, Albert; Koudstaal, Peter J; Vernooij, Meike W; Ikram, M Arfan

2015-01-01

Left-sided strokes are reported to be more common than right-sided strokes, but it is unknown whether they occur more often or are simply recognized more easily by clinicians. In a large unselected community-dwelling population, we examined the frequency of clinical left- and right-sided strokes and transient ischemic attacks (TIAs) and compared it with the frequency of left- and right-sided infarcts on MRI. This study was conducted within the population-based Rotterdam Study. Between 1990 and 2012, 13 894 participants were followed up for first-ever stroke and TIA. MRI scans were performed within a random subgroup of 5081 persons and were rated for the presence of supratentorial cortical and lacunar infarcts. We compared frequencies of left- and right-sided strokes, TIAs, or MRI infarcts using binomial and Fisher exact tests. After a mean follow-up of 9.6 (±6.0) years, 1252 patients had a stroke, of which 704 were ischemic, and 799 participants had a TIA. Within the subgroup with MRI, we identified 673 infarcts. Ischemic strokes were more frequently left-sided (57.7%; 95% confidence interval, 53.7-61.6) than right-sided, similar to TIAs (57.8% left-sided; 53.4-62.3). In contrast, we found no left-right difference in distribution of infarcts on MRI (51.9% left-sided; 48.1-55.6). Clinical ischemic strokes and TIAs are more frequently left-sided than right-sided, whereas this difference is not present for infarcts on MRI. This suggests that left-sided strokes and TIAs are more easily recognized. Consequently, there should be more attention for symptoms of right-sided strokes and TIAs. © 2014 American Heart Association, Inc.

Innate inflammation as the common pathway of risk factors leading to TIAs and stroke.

PubMed

del Zoppo, Gregory J; Gorelick, Philip B

2010-10-01

In the early moments of ischemic stroke, the processes of thrombosis, ischemia, and inflammation are intimately interrelated, setting in motion an injury that leads to infarction and permanent damage. Of these, the potential roles that innate inflammation can play in the evolution of brain tissue damage in response to the ischemic injury are not well understood. Observations in the settings of atherosclerotic cardiovascular disease and cerebral ischemia have much to teach each other. The following provides an introductory overview of the conference "Innate Inflammation as the Common Pathway of Risk Factors Leading to Transient Ischemic Attacks and Stroke: Pathophysiology and Potential Interventions," which took place May 9-10, 2010 at the New York Academy of Sciences. This meeting was convened to explore aspects of the cellular and tissue responses to innate inflammation. A faculty of leading experts was assembled to discuss the role of inflammation in laboratory models of stroke and myocardial infarction, define possible novel means from laboratory evidence to alleviate or prevent inflammation underlying stroke and cardiovascular disease, and present information on current examples of clinical translation of these understandings in relation to human stroke and myocardial infarction. © 2010 New York Academy of Sciences.

Accuracy of paramedic identification of stroke and transient ischemic attack in the field.

PubMed

Smith, W S; Isaacs, M; Corry, M D

1998-01-01

To determine the accuracy of acute stroke identification by paramedics in an urban emergency medical services system. Retrospective chart review of all patient encounters by paramedics resulting in transport to two university hospitals during a six-month period. Subjects were identified by paramedic coding of stroke/transient ischemic attach (TIA) or final hospital discharge ICD-9 diagnosis of acute stroke and TIA. The sensitivity and positive predictive value for paramedic identification of stroke were calculated, and the time intervals from symptom onset to various points along the patients' prehospital and hospital courses were identified. Ninety-six patients were identified, of whom 81 met the diagnosis of acute stroke or TIA. Paramedics identified 49 of these 81 patients (sensitivity 61%). Fifteen patients were identified by paramedics as having a stroke when the patient ultimately had a different diagnosis (positive predictive value 77%) Patients or their families waited on average 2.5 +/- 3.6 (SD) hours before accessing 911, and a mean of 5.1 +/- 4.0 (SD) hours elapsed from symptom onset until head imaging studies were obtained. Paramedics in San Francisco County were correct three-fourths of the time when their documentation listed patients as having stroke/TIA. However, they did not identify 39% of stroke victims, a patient population who may benefit from urgent therapy. A substantial period elapses before stroke victims access 911. This highlights the need to develop an educational program for the community at risk for stroke, and another for paramedics directed toward more accurate identification of acute stroke victims.

Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcome (AIM-HIGH) trial.

PubMed

Teo, Koon K; Goldstein, Larry B; Chaitman, Bernard R; Grant, Shannon; Weintraub, William S; Anderson, David C; Sila, Cathy A; Cruz-Flores, Salvador; Padley, Robert J; Kostuk, William J; Boden, William E

2013-10-01

In Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial, addition of extended-release niacin (ERN) to simvastatin in participants with established cardiovascular disease, low high-density lipoprotein cholesterol, and high triglycerides had no incremental benefit, despite increases in high-density lipoprotein cholesterol. Preliminary analysis based on incomplete end point adjudication suggested increased ischemic stroke risk among participants randomized to ERN. This final analysis was conducted after complete AIM-HIGH event ascertainment to further explore potential relationship between niacin therapy and ischemic stroke risk. There was no group difference in trial primary composite end point at a mean 36-month follow-up among 3414 patients (85% men; mean age, 64±9 years) randomized to simvastatin plus ERN (1500-2000 mg/d) versus simvastatin plus matching placebo. In the intention-to-treat analysis, there were 50 fatal or nonfatal ischemic strokes: 18 (1.06%) in placebo arm versus 32 (1.86%) in ERN arm (hazard ratio [HR], 1.78 [95% confidence interval {CI}, 1.00-3.17; P=0.050). Multivariate analysis showed independent associations between ischemic stroke risk and >65 years of age (HR, 3.58; 95% CI, 1.82-7.05; P=0.0002), history of stroke/transient ischemic attack/carotid disease (HR, 2.18; 95% CI, 1.23-3.88; P=0.0079), elevated baseline Lp(a) (HR, 2.80; 95% CI, 1.25-6.27 comparing the middle with the lowest tertile; HR, 2.31; 95% CI, 1.002-5.30 comparing the highest with the lowest tertile; overall P=0.042) but a nonsignificant association with ERN (HR, 1.74; 95% CI, 0.97-3.11; P=0.063). Although there were numerically more ischemic strokes with addition of ERN to simvastatin that reached nominal significance, the number was small, and multivariable analysis accounting for known risk factors did not support a significant association between niacin and ischemic stroke risk. http://www.clinicaltrials.gov. Unique identifier: NCT00120289.

Ethnic differences in risk factors for ischemic stroke: a European case-control study.

PubMed

Hajat, Cother; Tilling, Kate; Stewart, Judy A; Lemic-Stojcevic, Nada; Wolfe, Charles D A

2004-07-01

The aim is to estimate the relative risk and population attributable risk (PAR) of risk factors for ischemic stroke by ethnic group. In this case-control study, cases of first ischemic stroke were taken from the South London Stroke Register and controls from a cross-sectional prevalence survey covering the same area. PAR was determined for each risk factor by ethnic group. Multivariable analysis was used to examine the association between risk factors and ischemic stroke across all ethnic groups. 664 cases and 716 controls aged 45 to 74 years were included, with ethnicity of white 78%:42%, black Caribbean 16%:43%, and black African 6%:15%, respectively. For the white group, high PAR was found for ischemic heart disease (IHD) on ECG (56% [95% CI, 49% to 62%]), obesity (49% [95% CI, 40% to 56%]), hypertension (HT) (38% [95% CI, 29% to 46%]), smoking (31% [95% CI, 19% to 41%]), transient ischemic attack (TIA) (23% [95% CI, 19% to 27%]), and atrial fibrillation (AF) (16% [95% CI, 10% to 21%]). In the black Caribbean compared with the white group, PAR was higher for HT (46% [95% CI, 21% to 63%]) and diabetes mellitus (DM) (29% [95% CI, 14% to 42%]), and lower for current smoking (18% [95% CI, 1% to 32%]) and AF (10% [95% CI, 0% to 18%]). In the black African group HT had a higher PAR (59% [95% CI, 91% to 82%]) than the other groups. PAR for AF (11% [95% CI, -11% to 29%]), obesity (30% [95% CI, -20% to 60%]), and DM (4% [95% CI, -25% to 26%]) was low compared with the other groups. In multivariable analysis, risk factors associated with ischemic stroke included TIA, AF, IHD on ECG, smoking, excess alcohol, obesity, HT, and DM. In the first European case-control study examining risk factors for ischemic stroke in black Caribbean and African populations, some differences were demonstrated in the impact of risk factors between these groups. It may be important to address such differences when developing stroke preventative strategies.

Detrimental role of the EP1 prostanoid receptor in blood-brain barrier damage following experimental ischemic stroke

PubMed Central

Frankowski, Jan C.; DeMars, Kelly M.; Ahmad, Abdullah S.; Hawkins, Kimberly E.; Yang, Changjun; Leclerc, Jenna L.; Doré, Sylvain; Candelario-Jalil, Eduardo

2015-01-01

Cyclooxygenase-2 (COX-2) is activated in response to ischemia and significantly contributes to the neuroinflammatory process. Accumulation of COX-2-derived prostaglandin E2 (PGE2) parallels the substantial increase in stroke-mediated blood-brain barrier (BBB) breakdown. Disruption of the BBB is a serious consequence of ischemic stroke, and is mainly mediated by matrix metalloproteinases (MMPs). This study aimed to investigate the role of PGE2 EP1 receptor in neurovascular injury in stroke. We hypothesized that pharmacological blockade or genetic deletion of EP1 protects against BBB damage and hemorrhagic transformation by decreasing the levels and activity of MMP-3 and MMP-9. We found that post-ischemic treatment with the EP1 antagonist, SC-51089, or EP1 genetic deletion results in a significant reduction in BBB disruption and reduced hemorrhagic transformation in an experimental model of transient focal cerebral ischemia. These neurovascular protective effects of EP1 inactivation are associated with a significant reduction in MMP-9/-3, less peripheral neutrophil infiltration, and a preservation of tight junction proteins (ZO-1 and occludin) composing the BBB. Our study identifies the EP1 signaling pathway as an important link between neuroinflammation and MMP-mediated BBB breakdown in ischemic stroke. Targeting the EP1 receptor could represent a novel approach to diminish the devastating consequences of stroke-induced neurovascular damage. PMID:26648273

[MELAS syndrome as a differential diagnosis of ischemic stroke].

PubMed

Finsterer, J

2009-01-01

Mitochondrial encephalomyopathy, lactacidosis and stroke-like episode (MELAS) syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder with a clinical onset between the first and third decade. The clinical hallmark is the stroke-like-episode, which mimicks ischemic stroke but is usually transient and non-disabling in nature. The morphological equivalent on MRI is a T2-hyperintensity, predominantly over the temporo-parieto-occipital region, not confined to a vascular territory, which is also hyperintense on diffusion weighted imaging and on apparent diffusion coefficient sequences (vasogenic edema, stroke-like lesion). Additional features include seizures, cognitive decline, psychosis, lactic acidosis, migraine, visual impairment, hearing loss, short stature, diabetes, or myopathy. Muscle biopsy typically shows ragged-red fibers, COX-negative fibers, SDH hyperreactivity, and abnormally shaped mitochondria with paracristalline inclusions. The diagnosis is confirmed by demonstration of a biochemical respiratory chain defect or one of the disease-causing mutations, of which 80 % affect the mitochondrial tRNALeu gene.

Cryptogenic embolic stroke in a girl with a trisomy 21 mosaic.

PubMed

Stöllberger, Claudia; Weiss, Simone; Zlabinger, Gerhard; Finsterer, Josef

2012-06-01

Stroke in trisomy 21 may be due to cardioembolism, atherosclerosis, vasculitis, moyamoya disease, sinus venous thrombosis, internal carotid hypoplasia or infections like endocarditis with septic emboli, meningitis or brain abscess. In rare cases, however, stroke etiology remains unexplained. We present a 19 year old Caucasian girl with trisomy 21 with a 47XX+21 karyotype who suffered at age 11 years from a transient ischemic attack with left hemiparesis, and at age 17 years from an ischemic stroke in the territory of the right cerebral medial artery. She suffered from arterial hypertension, obesity and hypercholesterolemia. Since blood coagulation studies, immunologic parameters, blood cultures, 24-h Holter monitoring, transthoracic and transesophageal echocardiography, magnetic resonance angiography of the extra- and intracranial vessels, thoracic and abdominal aorta and renal arteries did not provide any explanation for the stroke, implantation of a loop recorder is considered in order to detect episodes of clinically silent atrial fibrillation.

Why a polysomnogram should become part of the diagnostic evaluation of stroke and transient ischemic attack.

PubMed

Grigg-Damberger, Madeleine

2006-02-01

Neurologists need to recognize, diagnose, and treat obstructive sleep apnea (OSA) in patients with stroke or transient ischemic attack (TIA). Increasing medical evidence suggests that OSA is an independent risk factor for stroke and TIA. Stroke (or TIA) is more likely a cause, rather than a consequence, of OSA because PSG studies have shown: 1) apneas in stroke are typically obstructive, not central or Cheyne-Stokes in type; 2) apneas are just as frequent and severe in patients with either TIA or stroke; 3) OSA severity is not influenced by the acuteness or location of the stroke; 4) untreated OSA patients have more strokes, stroke morbidity, and mortality than those who are treated. OSA alone can induce hypertension, especially in younger men. A causal relationship has recently been demonstrated between OSA and hypertension. A distinctive feature of OSA-induced hypertension is loss of the normal nighttime fall in blood pressure ("nondippers"). Data from the Sleep Heart Health Study showed a dose-response association between OSA severity and the presence of hypertension 4 years later. Hypertension or ischemic heart disease usually develops in untreated patients with OSA over time without particular worsening of OSA. Studies have shown sleep itself is not a risk factor for stroke because most stroke and TIAs begin between 6 am and noon, while the individual is awake. However, OSA promptly be considered in stroke beginning during sleep because 88% of strokes that develop during sleep occur in "nondippers." Premature death in OSA patients is most often cardiovascular, but occurs while the patients are awake. The risk of myocardial infarction is increased 20-fold in untreated OSA. Treating OSA patients with continuous positive airway pressure can prevent or improve hypertension, reduce abnormal elevations of inflammatory cytokines and adhesion molecules, reduce excessive sympathetic tone, avoid increased vascular oxidative stress, reverse coagulation abnormalities, and reduce leptin levels. If all this can be achieved by a polysomnogram, then this test should become part of a neurologist's armamentarium for stroke and TIA.

Rationale and Study Design for a Single-Arm Phase IIa Study Investigating Feasibility of Preventing Ischemic Cerebrovascular Events in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning

PubMed Central

Liu, Shi-Meng; Zhao, Wen-Le; Song, Hai-Qing; Meng, Ran; Li, Si-Jie; Ren, Chang-Hong; Ovbiagele, Bruce; Ji, Xun-Ming; Feng, Wu-Wei

2018-01-01

Background: Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA. Methods: This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician's best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes. Conclusions: The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA. Trial Registration: ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820. PMID:29363651

Heart rate is a prognostic risk factor for myocardial infarction: a post hoc analysis in the PERFORM (Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack) study population.

PubMed

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

2013-10-09

Elevated resting heart rate is known to be detrimental to morbidity and mortality in cardiovascular disease, though its effect in patients with ischemic stroke is unclear. We analyzed the effect of baseline resting heart rate on myocardial infarction (MI) in patients with a recent noncardioembolic cerebral ischemic event participating in PERFORM. We compared fatal or nonfatal MI using adjusted Cox proportional hazards models for PERFORM patients with baseline heart rate <70 bpm (n=8178) or ≥70 bpm (n=10,802). In addition, heart rate was analyzed as a continuous variable. Other cerebrovascular and cardiovascular outcomes were also explored. Heart rate ≥70 bpm was associated with increased relative risk for fatal or nonfatal MI (HR 1.32, 95% CI 1.03-1.69, P=0.029). For every 5-bpm increase in heart rate, there was an increase in relative risk for fatal and nonfatal MI (11.3%, P=0.0002). Heart rate ≥70 bpm was also associated with increased relative risk for a composite of fatal or nonfatal ischemic stroke, fatal or nonfatal MI, or other vascular death (excluding hemorrhagic death) (P<0001); vascular death (P<0001); all-cause mortality (P<0001); and fatal or nonfatal stroke (P=0.04). For every 5-bpm increase in heart rate, there were increases in relative risk for fatal or nonfatal ischemic stroke, fatal or nonfatal MI, or other vascular death (4.7%, P<0.0001), vascular death (11.0%, P<0.0001), all-cause mortality (8.0%, P<0.0001), and fatal and nonfatal stroke (2.4%, P=0.057). Elevated heart rate ≥70 bpm places patients with a noncardioembolic cerebral ischemic event at increased risk for MI. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Guidelines for the Primary Prevention of Stroke

PubMed Central

Meschia, James F.; Bushnell, Cheryl; Boden-Albala, Bernadette; Braun, Lynne T.; Bravata, Dawn M.; Chaturvedi, Seemant; Creager, Mark A.; Eckel, Robert H.; Elkind, Mitchell S.V.; Fornage, Myriam; Goldstein, Larry B.; Greenberg, Steven M.; Horvath, Susanna E.; Iadecola, Costantino; Jauch, Edward C.; Moore, Wesley S.; Wilson, John A.

2016-01-01

The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of stroke among individuals who have not previously experienced a stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches to atherosclerotic disease of the cervicocephalic circulation, and antithrombotic treatments for preventing thrombotic and thromboembolic stroke. Further recommendations are provided for genetic and pharmacogenetic testing and for the prevention of stroke in a variety of other specific circumstances, including sickle cell disease and patent foramen ovale. PMID:25355838

Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists.

PubMed

Easton, J Donald; Saver, Jeffrey L; Albers, Gregory W; Alberts, Mark J; Chaturvedi, Seemant; Feldmann, Edward; Hatsukami, Thomas S; Higashida, Randall T; Johnston, S Claiborne; Kidwell, Chelsea S; Lutsep, Helmi L; Miller, Elaine; Sacco, Ralph L

2009-06-01

This scientific statement is intended for use by physicians and allied health personnel caring for patients with transient ischemic attacks. Formal evidence review included a structured literature search of Medline from 1990 to June 2007 and data synthesis employing evidence tables, meta-analyses, and pooled analysis of individual patient-level data. The review supported endorsement of the following, tissue-based definition of transient ischemic attack (TIA): a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. Patients with TIAs are at high risk of early stroke, and their risk may be stratified by clinical scale, vessel imaging, and diffusion magnetic resonance imaging. Diagnostic recommendations include: TIA patients should undergo neuroimaging evaluation within 24 hours of symptom onset, preferably with magnetic resonance imaging, including diffusion sequences; noninvasive imaging of the cervical vessels should be performed and noninvasive imaging of intracranial vessels is reasonable; electrocardiography should occur as soon as possible after TIA and prolonged cardiac monitoring and echocardiography are reasonable in patients in whom the vascular etiology is not yet identified; routine blood tests are reasonable; and it is reasonable to hospitalize patients with TIA if they present within 72 hours and have an ABCD(2) score >or=3, indicating high risk of early recurrence, or the evaluation cannot be rapidly completed on an outpatient basis.

Animal models of ischemic stroke and their application in clinical research.

PubMed

Fluri, Felix; Schuhmann, Michael K; Kleinschnitz, Christoph

2015-01-01

This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models.

Animal models of ischemic stroke and their application in clinical research

PubMed Central

Fluri, Felix; Schuhmann, Michael K; Kleinschnitz, Christoph

2015-01-01

This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models. PMID:26170628

Implication of left ventricular diastolic dysfunction in cryptogenic ischemic stroke.

PubMed

Seo, Jae-Young; Lee, Kyung Bok; Lee, Jung-Gon; Kim, Ji-Sun; Roh, Hakjae; Ahn, Moo-Young; Park, Byoung Won; Hyon, Min Su

2014-09-01

Left ventricular diastolic dysfunction (LVDD) is a predictor for atrial fibrillation (AF). This study was aimed to investigate whether LVDD in cryptogenic ischemic stroke (CS) could be a clue to stroke mechanism. The clinical and echocardiographic findings of 1589 consecutive patients with acute ischemic stroke or transient ischemic attack between 2004 and 2013 were reviewed. LVDDs among stroke subtypes were graded by transthoracic echocardiography into 4 groups by severity: normal, abnormal relaxation (grade I), pseudonormal (grade II), and restrictive diastolic filling (grade III), whereas severe LVDD was defined as grade III. We classified the lesion pattern of CS into cardioembolism-mimic or non-cardioembolism-mimic and determined whether cardioembolism-mimic lesions were associated with severe LVDD. The fraction of severe LVDD in CS was not different from that of stroke with AF (27.3% versus 37.1%; P=0.173) but was significantly higher than that of stroke without AF (27.3% versus 13.4%; P=0.008). Cardioembolism-mimic CS had more severe LVDD than non-cardioembolism-mimic CS (41.4% versus 11.5%; P=0.013). LVDD of grade II (odds ratio, 4.37; 95% confidence interval, 2.99-6.41) and grade III (odds ratio, 5.60; 95% confidence interval, 3.42-9.17) were independently related to stroke with AF after adjusting covariates. The severe LVDD could be a predictor of stroke with AF, and its frequency was similar between CS and stroke with AF. Cardioembolism-mimic CS had significantly more severe LVDD than non-cardioembolism-mimic CS. LVDD could be helpful to discriminate the stroke mechanism in the patients with acute CS. © 2014 American Heart Association, Inc.

ABCD² score may discriminate minor stroke from TIA on patient admission.

PubMed

Zhao, Hui; Li, Qingjie; Lu, Mengru; Shao, Yuan; Li, Jingwei; Xu, Yun

2014-02-01

With the advent of time-dependent thrombolytic therapy for ischemic stroke, it has become increasingly important to differentiate transient ischemic attack (TIA) from minor stroke patients after symptom onset quickly. This study investigated the difference between TIA and minor stroke based on age, blood pressure, clinical features, duration of TIA, presence of diabetes, ABCD² score, digital subtraction angiography (DSA) and blood lipids. One hundred seventy-one patients with clinical manifestations as transient neurological deficits in Nanjing Drum Tower Hospital were studied retrospectively. All patients were evaluated by ABCD² score, blood lipid test, fibrinogen, and Holter electrocardiograph and DSA on admission. Patients were categorized into TIA group or minor stroke group according to CT and MRI scan 24 h within symptom onset. The study suggested that minor stroke patients were more likely to have a higher ABCD² score (odds ratio (OR) 2.060; 95% confidence interval (CI) 1.293-3.264). Receiver-operating characteristic curves identified ABCD² score >4 as the optimal cut-off for minor stroke diagnosis. Total serum cholesterol seemed a better diagnostic indicator to discriminate minor stroke from TIA (OR 4.815; 95% CI 0.946-1.654) than other blood lipids in simple logistic regression, but not valuable for the differentiation between TIA and minor stroke in multivariate logistic regression. Higher severity of intracranial internal carotid stenosis, especially >90%, were more likely to have minor stroke, but was not a reliable diagnostic indicator (P > 0.05). ABCD² could help clinicians to differentiate possible TIA from minor stroke at hospital admission while blood lipid parameters and artery stenosis location offer limited help.

A comparison of risperidone and haloperidol for the risk of ischemic stroke in the elderly: a propensity score-matched cohort analysis.

PubMed

Shin, Ju-Young; Choi, Nam-Kyong; Lee, Joongyub; Park, Mi-Ju; Lee, Shin Haeng; Park, Byung-Joo

2015-08-01

With an increase in antipsychotic use in the elderly, the safety profile of antipsychotics has been emphasized. Strong concerns have been raised about whether the risk of ischemic stroke differs between risperidone and haloperidol. This study compared the risk of ischemic stroke between elderly patients taking risperidone and haloperidol. We conducted a retrospective cohort study using the Korea Health Insurance Review and Assessment Service database, applying a propensity-matched analysis. The cohort consisted of elderly patients who were newly prescribed haloperidol or risperidone between January 1, 2006 and December 31, 2009. Patients with prior cerebrovascular diseases (ICD-10, I60-I69), transient ischemic attack (ICD-10, G45), or cerebral tumors (ICD-10, C31) during 365 days prior to the initiation date were excluded. The study subjects were selected by propensity score matching. The outcome was defined as the first hospitalization for ischemic stroke (ICD-10, I63). Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for ischemic stroke with haloperidol compared with risperidone use. A total of 14,103 patients were included in the propensity-matched cohort for each drug. Overall, the incidence rate was higher for haloperidol users compared to the risperidone users (6.43 per 1000 person-years vs. 2.88 per 1000 person-years). A substantially increased risk was observed in haloperidol users (adjusted HR = 2.02, 95% CI, 1.12-3.62). The evidence showed that haloperidol should be prescribed in the elderly with caution. © The Author(s) 2015.

Noninvasive Ventilatory Correction in Patients With Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

PubMed

Tsivgoulis, Georgios; Alexandrov, Andrei V; Katsanos, Aristeidis H; Barlinn, Kristian; Mikulik, Robert; Lambadiari, Vaia; Bonakis, Anastasios; Alexandrov, Anne W

2017-08-01

Even though current guidelines suggest that noninvasive ventilatory correction (NIVC) could be considered for acute ischemic stroke patients with obstructive sleep apnea, available evidence is conflicting, with no adequately powered randomized clinical trial being available to date. We conducted a systematic review and meta-analysis of all available literature data evaluating the effect of NIVC on neurological improvement (based on decrease in National Institutes of Health Stroke Scale score), vascular events (recurrent stroke, transient ischemic attack, myocardial infarction and unstable angina), and mortality during the follow-up period. We identified 4 randomized clinical trials and 1 prospectively matched observational cohort, comprising a total of 389 patients (59.8% males, mean age: 64.4 years). The risk of both performance and detection bias was considered high in most of the included randomized clinical trials because of the lack of blinding in participants, personnel and/or outcome assessors. The mean decrease in National Institutes of Health Stroke Scale scores during the first (≤30) days of acute ischemic stroke was found to be greater in NIVC-treated patients in comparison to controls (standardized mean difference, 0.38; 95% confidence interval, 0.11-0.66; P =0.007). However, no significant differences were detected between NIVC-treated acute ischemic stroke patients and controls on both the risk of vascular events (risk ratio, 0.53; 95% confidence interval, 0.25-1.14; P =0.11) and mortality (risk ratio, 0.71; 95% confidence interval, 0.37-1.36; P =0.30). No evidence of heterogeneity ( I 2 =0%; P for Cochran Q>0.50) or publication bias were detected in all analyses. NIVC seems to be associated with greater short-term neurological improvement in acute ischemic stroke patients with obstructive sleep apnea. This finding deserves further investigation within the settings of an adequately powered, sham-control, randomized clinical trial. © 2017 American Heart Association, Inc.

Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults.

PubMed

Pezzini, Alessandro; Grassi, Mario; Lodigiani, Corrado; Patella, Rosalba; Gandolfo, Carlo; Zini, Andrea; Delodovici, Maria Luisa; Paciaroni, Maurizio; Del Sette, Massimo; Toriello, Antonella; Musolino, Rossella; Calabrò, Rocco Salvatore; Bovi, Paolo; Adami, Alessandro; Silvestrelli, Giorgio; Sessa, Maria; Cavallini, Anna; Marcheselli, Simona; Bonifati, Domenico Marco; Checcarelli, Nicoletta; Tancredi, Lucia; Chiti, Alberto; Del Zotto, Elisabetta; Spalloni, Alessandra; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Giacalone, Giacomo; Ferrazzi, Paola; Poli, Loris; Morotti, Andrea; Rasura, Maurizia; Simone, Anna Maria; Gamba, Massimo; Cerrato, Paolo; Micieli, Giuseppe; Melis, Maurizio; Massucco, Davide; De Giuli, Valeria; Iacoviello, Licia; Padovani, Alessandro

2014-04-22

Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited. We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th to 75th percentile, 53). The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval, 12.2%-17.9%) for primary end point, 14.0% (95% confidence interval, 11.4%-17.1%) for brain ischemia, and 0.7% (95% confidence interval, 0.4%-1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor were independent predictors of the composite end point in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their β-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0- to 5-year score was 0.66 (95% confidence interval, 0.61-0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65). Among patients with ischemic stroke aged 18 to 45 years, the long-term risk of recurrent thrombotic events is associated with modifiable, age-specific risk factors. The IPSYS score may serve as a simple tool for risk estimation.

GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.

PubMed

Fernández-Cadenas, Israel; Mendióroz, Maite; Giralt, Dolors; Nafria, Cristina; Garcia, Elena; Carrera, Caty; Gallego-Fabrega, Cristina; Domingues-Montanari, Sophie; Delgado, Pilar; Ribó, Marc; Castellanos, Mar; Martínez, Sergi; Freijo, Marimar; Jiménez-Conde, Jordi; Rubiera, Marta; Alvarez-Sabín, José; Molina, Carlos A; Font, Maria Angels; Grau Olivares, Marta; Palomeras, Ernest; Perez de la Ossa, Natalia; Martinez-Zabaleta, Maite; Masjuan, Jaime; Moniche, Francisco; Canovas, David; Piñana, Carlos; Purroy, Francisco; Cocho, Dolores; Navas, Inma; Tejero, Carlos; Aymerich, Nuria; Cullell, Natalia; Muiño, Elena; Serena, Joaquín; Rubio, Francisco; Davalos, Antoni; Roquer, Jaume; Arenillas, Juan Francisco; Martí-Fábregas, Joan; Keene, Keith; Chen, Wei-Min; Worrall, Bradford; Sale, Michele; Arboix, Adrià; Krupinski, Jerzy; Montaner, Joan

2017-05-01

Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS. We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method. The analyses revealed that rs1800801 in the MGP gene (hazard ratio, 1.33; P =9×10 - 03 ), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS ( P =3.2×10 - 09 ) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared with previous Stroke Prognosis Instrument-II score ( P =0.03). The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population. © 2017 American Heart Association, Inc.

Clopidogrel With Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) Trial: One-Year Outcomes.

PubMed

Wang, Yilong; Pan, Yuesong; Zhao, Xingquan; Li, Hao; Wang, David; Johnston, S Claiborne; Liu, Liping; Meng, Xia; Wang, Anxin; Wang, Chunxue; Wang, Yongjun

2015-07-07

The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial showed that the combined treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage in comparison with aspirin alone, but provided insufficient data to establish whether the benefit persisted over a longer period of time beyond the trial termination. We report the 1-year follow-up outcomes of this trial. The trial was a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China. We randomly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin therapy (loading dose of 300 mg of clopidogrel on day 1, followed by 75 mg of clopidogrel per day for 90 days, plus 75 mg of aspirin per day for the first 21 days) or to the aspirin-alone group (75 mg/d for 90 days). The primary outcome was stroke event (ischemic or hemorrhagic) during 1-year follow-up. Differences in outcomes between groups were assessed by using the Cox proportional hazards model. Stroke occurred in 275 (10.6%) patients in the clopidogrel-aspirin group, in comparison with 362 (14.0%) patients in the aspirin group (hazard ratio, 0.78; 95% confidence interval, 0.65-0.93; P=0.006). Moderate or severe hemorrhage occurred in 7 (0.3%) patients in the clopidogrel-aspirin group and in 9 (0.4%) patients in the aspirin group (P=0.44). The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted for the duration of 1-year of follow-up. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2015 American Heart Association, Inc.

Strokes after cardioversion of atrial fibrillation--The FibStroke study.

PubMed

Palomäki, Antti; Mustonen, Pirjo; Hartikainen, Juha E K; Nuotio, Ilpo; Kiviniemi, Tuomas; Ylitalo, Antti; Hartikainen, Päivi; Lehtola, Heidi; Luite, Riho; Airaksinen, K E Juhani

2016-01-15

Cardioversion of atrial fibrillation (AF) is associated with an increased risk for stroke. We identified all cardioversions during the 30 days preceding stroke or transient ischemic attack (TIA) in patients with a previously diagnosed AF, and sought to assess the characteristics of cardioversions leading to stroke or TIA. FibStroke is a cross-sectional observational multicenter registry that included AF patients with an ischemic stroke or intracranial bleed identified from a discharge registry of four Finnish hospitals. In total 3677 consecutive AF patients suffered 3252 strokes and 956 TIA episodes during 2003–2012. This pre-specified analysis focused on the 1644 events that occurred to patients with paroxysmal or persistent AF at the time of stroke/TIA. A total of 78 strokes and 22 TIA episodes were preceded by a cardioversion. Post-cardioversion strokes accounted for 6.4% of strokes in patients with paroxysmal/persistent AF. Of the 100 cardioversions leading to an ischemic event, 77 were acute and 23 were elective, 63 events occurred in patients not using anticoagulation, and 5 patients had periprocedural INR < 2. Importantly, 21 patients were in low risk of stroke, i.e. CHA2DS2-VASc score < 2. The median delay from cardioversion to event was 2 days. All nine patients who after an unsuccessful cardioversion developed a stroke had a spontaneous cardioversion prior to stroke. Every sixteenth stroke of patients with paroxysmal/persistent AF is preceded by a cardioversion. Most post-cardioversion strokes occur in patients not using oral anticoagulation before cardioversion of acute AF.

Brain Ischemia Induces Diversified Neuroantigen-Specific T-Cell Responses That Exacerbate Brain Injury.

PubMed

Jin, Wei-Na; Gonzales, Rayna; Feng, Yan; Wood, Kristofer; Chai, Zhi; Dong, Jing-Fei; La Cava, Antonio; Shi, Fu-Dong; Liu, Qiang

2018-06-01

Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury. Using a mouse strain that harbors a transgenic T-cell receptor to a central nervous system antigen, MOG 35-55 (myelin oligodendrocyte glycoprotein) epitope (2D2), we determined the anatomic location and involvement of antigen-presenting cells in the development of T-cell reactivity after brain ischemia and how T-cell reactivity impacts stroke outcome. Transient middle cerebral artery occlusion and photothrombotic stroke models were used in this study. We also quantified the presence and status of T cells from brain slices of ischemic patients. By coupling transfer of labeled MOG 35-55 -specific (2D2) T cells with tetramer tracking, we show an expansion in reactivity of 2D2 T cells to MOG 91-108 and MOG 103-125 in transient middle cerebral artery occlusion and photothrombotic stroke models. This reactivity and T-cell activation first occur locally in the brain after ischemia. Also, microglia act as antigen-presenting cells that effectively present MOG antigens, and depletion of microglia ablates expansion of 2D2 reactive T cells. Notably, the adoptive transfer of neuroantigen-experienced 2D2 T cells exacerbates Th1/Th17 responses and brain injury. Finally, T-cell activation and MOG-specific T cells are present in the brain of patients with ischemic stroke. Our findings suggest that brain ischemia activates and diversifies T-cell responses locally, which exacerbates ischemic brain injury. © 2018 The Authors.

Blood-Brain Barrier Alterations Provide Evidence of Subacute Diaschisis in an Ischemic Stroke Rat Model

PubMed Central

Garbuzova-Davis, Svitlana; Rodrigues, Maria C. O.; Hernandez-Ontiveros, Diana G.; Tajiri, Naoki; Frisina-Deyo, Aric; Boffeli, Sean M.; Abraham, Jerry V.; Pabon, Mibel; Wagner, Andrew; Ishikawa, Hiroto; Shinozuka, Kazutaka; Haller, Edward; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesario V.

2013-01-01

Background Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas. Methodology/Principal Findings In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO), significant BBB alterations characterized by large Evans Blue (EB) parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices. Conclusions/Significance These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke. PMID:23675488

Self-report of stroke, transient ischemic attack, or stroke symptoms and risk of future stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

PubMed Central

Judd, Suzanne E; Kleindorfer, Dawn O; McClure, Leslie A; Rhodes, J. David; Howard, George; Cushman, Mary; Howard, Virginia J.

2013-01-01

Background and Purpose History of stroke and Transient Ischemic Attack (TIA) are documented risk factors for subsequent stroke and all-cause mortality. Recent reports suggest increased risk among those reporting stroke symptoms absent stroke or TIA. However, the relative magnitude of increased stroke risk has not been described across the symptomatic spectrum: 1) asymptomatic (Asx), 2) stroke symptoms only (SS), 3) TIA, 4) stroke in the distant past (DS), and 5) recent stroke (RS). Methods Between 2003–2007 the REasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 black and white Americans aged 45+. DS and RS were defined as self-report of physician diagnosis of stroke >5 or <5 years before baseline, respectively. SS was defined as a history of any of six sudden onset stroke symptoms absent TIA/stroke diagnosis. Kaplan-Meier and proportional hazards analysis were used to contrast stroke risk differences. Results Over 5.0 ± 1.72 years of follow up, 737 strokes were validated. Compared to Asx persons, those with SS, TIA, DS and RS all had increased risk of future stroke. After adjustment for age, race, sex, income, education, alcohol intake, current smoking, and a history of diabetes, hypertension, myocardial infarction, atrial fibrillation, and dyslipidemia, there was 1.20-fold (not statistically significant) increased stroke risk for SS (95% CI 0.96, 1.51), 1.73-fold for TIA (95% CI 1.27, 2.36), 2.23-fold for DS (95% CI 1.61, 3.09) and 2.85-fold for RS (95% CI 2.16, 3.76). Discussion Results suggest a spectrum of risk from stroke symptoms to TIA, distant stroke, and recent stroke, and imply a need for establishing these categories in health screenings to manage risk for future stroke, reinforcing the clinical importance of stroke history including the presence of stroke symptoms. PMID:23233382

Periodontal Disease Associated with Aortic Arch Atheroma in Patients with Stroke or Transient Ischemic Attack.

PubMed

Sen, Souvik; Chung, Matthew; Duda, Viktoriya; Giamberardino, Lauren; Hinderliter, Alan; Offenbacher, Steven

2017-10-01

Periodontal disease (PD) is associated with recurrent vascular event in stroke or transient ischemic attack (TIA). In this study, we investigated whether PD is independently associated with aortic arch atheroma (AA). We also explored the relationship PD has with AA plaque thickness and other characteristics associated with atheroembolic risk among patients with stroke or TIA. Finally, we confirmed the association between AA and recurrent vascular event in patients with stroke or TIA. In this prospective longitudinal hospital-based cohort study, PD was assessed in patients with stroke and TIA. Patients with confirmed stroke and TIA (n = 106) were assessed by calibrated dental examiners to determine periodontal status and were followed over a median of 24 months for recurrent vascular events (stroke, myocardial infarction, and death). The extent of AA and other plaque characteristics was assessed by transesophageal echocardiography. Within our patient cohort, 27 of the 106 participants had recurrent vascular events (including 16 with stroke or TIA) over the median of 24-month follow-up. Severe PD was associated with increased AA plaque thickness and calcification. The results suggest that PD may be a risk factor for AA. In this cohort, we confirm the association of severe AA with recurrent vascular events. In patients with stroke or TIA, severe PD is associated with increased AA plaque thickness, a risk factor for recurrent events. Further studies are needed to confirm this finding and to determine whether treatment of PD can reduce the rate of AA plaque progression and recurrent vascular events. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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

Corkscrew angiopathy of intracranial vessels in a young stroke patient: a case report.

PubMed

Alurkar, Anand; Karanam, Lakshmi Sudha P; Oak, Sagar P

2012-10-23

We present a rare finding of a 'corkscrew appearance' of the distal cerebral vessels in a young Asian woman who presented with acute stroke. A 32-year-old Asian woman presented with a 3-month history of recurrent right-sided transient ischemic attacks. Her clinical workup and brain imaging results were normal. A digital subtraction angiogram revealed an abnormal corkscrew appearance of all intracranial distal vessels. She was discharged on a single antiplatelet drug. She had no further transient ischemic attacks on clinical follow-up. A digital subtraction angiogram performed 1 year later revealed no changes in the appearance of these vessels. To the best of our knowledge no similar previous reports exist in the literature. The present report describes a unique case of an unusual corkscrew appearance of the distal intracranial vessels. However, the underlying etiology in the present case remains unknown.

Corkscrew angiopathy of intracranial vessels in a young stroke patient: a case report

PubMed Central

2012-01-01

Introduction We present a rare finding of a ‘corkscrew appearance’ of the distal cerebral vessels in a young Asian woman who presented with acute stroke. Case presentation A 32-year-old Asian woman presented with a 3-month history of recurrent right-sided transient ischemic attacks. Her clinical workup and brain imaging results were normal. A digital subtraction angiogram revealed an abnormal corkscrew appearance of all intracranial distal vessels. She was discharged on a single antiplatelet drug. She had no further transient ischemic attacks on clinical follow-up. A digital subtraction angiogram performed 1 year later revealed no changes in the appearance of these vessels. Conclusion To the best of our knowledge no similar previous reports exist in the literature. The present report describes a unique case of an unusual corkscrew appearance of the distal intracranial vessels. However, the underlying etiology in the present case remains unknown. PMID:23092123

Enteric-coated aspirin versus other antiplatelet drugs in acute non-cardioembolic ischemic stroke: post-marketing study in Japan.

PubMed

Takahashi, Shunichi; Mizuno, Osamu; Sakaguchi, Toshiaki; Yamada, Takashi; Inuyama, Lyo

2014-01-01

Japanese guidelines recommend aspirin 160-300 mg/day, starting within 48 h, for patients with acute cerebral infarction. However, there are few reports evaluated in Japanese patients. Our objective was to examine the safety and efficacy of enteric-coated aspirin, compared with other oral antiplatelet drugs, in Japanese patients with acute ischemic stroke. We performed a prospective, non-randomized, observational and multicenter study between June 2005 and December 2007. Patients with symptomatic acute ischemic stroke, including transient ischemic attack (TIA), who started enteric-coated aspirin or other antiplatelet drugs within 7 days of hospitalization were registered. Outcome measures evaluated within 3 months were incidence of cerebral and non-cerebral hemorrhagic events, recurrence of ischemic stroke or TIA, non-cerebral ischemic events and death from any cause. Overall, 2,548 and 830 patients treated with enteric-coated aspirin (100-300 mg/day) or other antiplatelet drugs, respectively, were registered; approximately 60% were male, mean age was 70 years, 85% had pre-existing cardiovascular disease or other complications. Enteric-coated aspirin of 100 mg was mainly prescribed, and only approximately half of the patients were started on it within 48 h after onset of ischemic stroke. Safety and efficacy population excluded patients without follow-up data were 2,521 in enteric-coated aspirin and 807 in other antiplatelets. Hemorrhagic events occurred in 46 (1.8%) in the enteric-coated aspirin group and in 13 (1.6%) in the other antiplatelet drugs group, there was not significant. Recurrent ischemic stroke or TIA occurred in 39 (1.5%) of the enteric-coated aspirin and in 18 (2.2%) of other antiplatelet drugs, and there were any-cause death in 16 (0.6%) and 8 (1.0%). Incidences were slightly lower in the enteric-coated aspirin group compared with the other antiplatelet drugs group, but not statistically significant. It seems that these results showed the safety and efficacy of the enteric-coated aspirin in acute stroke care in Japanese patients. Incidence of hemorrhagic events was comparable between the enteric-coated aspirin group and the other antiplatelet drugs group.

Proton-sensitive cation channels and ion exchangers in ischemic brain injury: new therapeutic targets for stroke?

PubMed Central

Leng, Tiandong; Shi, Yejie; Xiong, Zhi-Gang; Sun, Dandan

2014-01-01

Ischemic brain injury results from complicated cellular mechanisms. The present therapy for acute ischemic stroke is limited to thrombolysis with the recombinant tissue plasminogen activator (rtPA) and mechanical recanalization. Therefore, a better understanding of ischemic brain injury is needed for the development of more effective therapies. Disruption of ionic homeostasis plays an important role in cell death following cerebral ischemia. Glutamate receptor-mediated ionic imbalance and neurotoxicity have been well established in cerebral ischemia after stroke. However, non-NMDA receptor-dependent mechanisms, involving acid-sensing ion channel 1a (ASIC1a), transient receptor potential melastatin 7 (TRPM7), and Na+/H+ exchanger isoform 1 (NHE1), have recently emerged as important players in the dysregulation of ionic homeostasis in the CNS under ischemic conditions. These H+-sensitive channels and/or exchangers are expressed in the majority of cell types of the neurovascular unit. Sustained activation of these proteins causes excessive influx of cations, such as Ca2+, Na+, and Zn2+, and leads to ischemic reperfusion brain injury. In this review, we summarize recent pre-clinical experimental research findings on how these channels/exchangers are regulated in both in vitro and in vivo models of cerebral ischemia. The blockade or transgenic knockdown of these proteins was shown to be neuroprotective in these ischemia models. Taken together, these non-NMDA receptor-dependent mechanisms may serve as novel therapeutic targets for stroke intervention. PMID:24467911

Self-report of stroke, transient ischemic attack, or stroke symptoms and risk of future stroke in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

PubMed

Judd, Suzanne E; Kleindorfer, Dawn O; McClure, Leslie A; Rhodes, J David; Howard, George; Cushman, Mary; Howard, Virginia J

2013-01-01

History of stroke and transient ischemic attack (TIA) are documented risk factors for subsequent stroke and all-cause mortality. Recent reports suggest increased risk among those reporting stroke symptoms absent stroke or TIA. However, the relative magnitude of increased stroke risk has not been described across the symptomatic spectrum: (1) asymptomatic, (2) stroke symptoms (SS) only, (3) TIA, (4) distant stroke (DS), and (5) recent stroke (RS). Between 2003 and 2007, the REasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30 239 black and white Americans ≥45 years of age. DS and RS were defined as self-report of physician diagnosis of stroke >5 or <5 years before baseline, respectively. SS was defined as a history of any of 6 sudden onset stroke symptoms absent TIA/stroke diagnosis. Kaplan-Meier and proportional hazards analysis were used to contrast stroke risk differences. Over 5.0±1.72 years of follow-up, 737 strokes were validated. Compared with asymptomatic persons, those with SS, TIA, DS, and RS all had increased risk of future stroke. After adjustment for age, race, sex, income, education, alcohol intake, current smoking, and a history of diabetes mellitus, hypertension, myocardial infarction, atrial fibrillation, and dyslipidemia, there was 1.20-fold (not statistically significant) increased stroke risk for SS (95% CI, 0.96-1.51), 1.73-fold for TIA (95% CI, 1.27-2.36), 2.23-fold for DS (95% CI, 1.61- 3.09), and 2.85-fold for RS (95% CI, 2.16-3.76). Results suggest a spectrum of risk from stroke symptoms to TIA, DS, and RS, and imply a need for establishing these categories in health screenings to manage risk for future stroke, reinforcing the clinical importance of stroke history including the presence of stroke symptoms.

Lipoprotein(a) Levels and Recurrent Vascular Events After First Ischemic Stroke.

PubMed

Lange, Kristin S; Nave, Alexander H; Liman, Thomas G; Grittner, Ulrike; Endres, Matthias; Ebinger, Martin

2017-01-01

The association of elevated lipoprotein(a) (Lp(a)) levels and the incidence of cardiovascular disease, especially coronary heart disease and ischemic stroke, is well established. However, evidence on the association between Lp(a) levels and residual vascular risk in stroke survivors is lacking. We aimed to elucidate the risk for recurrent cardiovascular and cerebrovascular events in the patients with first-ever ischemic stroke with elevated Lp(a). All patients with acute ischemic stroke who participated in the prospective Berlin C&S study (Cream & Sugar) between January 2009 and August 2014 with available 12-month follow-up data and stored blood samples were eligible for inclusion. Lp(a) levels were determined in serum samples using an isoform-insensitive nephelometry assay. We assessed the risk for the composite vascular end point of ischemic stroke, transient ischemic attack, myocardial infarction, nonelective coronary revascularization, and cardiovascular death with elevated Lp(a) defined as >30 mg/dL using Cox regression analyses. Of 465 C&S study participants, 250 patients were included into this substudy with a median National Institutes of Health Stroke Scale score of 2 (1-4). Twenty-six patients (10%) experienced a recurrent vascular event during follow-up. Among patients with normal Lp(a) levels, 11 of 157 subjects (7%) experienced an event at a median time of 161 days (interquartile range, 19-196 days), whereas in patients with elevated Lp(a) levels, 15 of 93 subjects (16%) experienced an event at a median time of 48 days (interquartile range, 9-194 days; P=0.026). The risk for a recurrent event was significantly higher in patients with elevated Lp(a) levels after adjustment for potential confounders (hazard ratio, 2.60; 95% confidence interval, 1.19-5.67; P=0.016). Elevated Lp(a) levels are associated with a higher risk for combined vascular event recurrence in patients with acute, first-ever ischemic stroke. This finding should be validated in larger, multicenter trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01378468. © 2016 American Heart Association, Inc.

Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142-TIPARP: Implications for cerebral ischemic stroke.

PubMed

Han, Bing; Zhang, Yuan; Zhang, Yanhong; Bai, Ying; Chen, Xufeng; Huang, Rongrong; Wu, Fangfang; Leng, Shuo; Chao, Jie; Zhang, John H; Hu, Gang; Yao, Honghong

2018-06-25

Circular RNAs (circRNAs) are highly expressed in the central nervous system and are involved in the regulation of physiological and pathophysiological processes. However, the potential role of circRNAs in stroke remains largely unknown. Here, using a circRNA microarray, we showed that circular RNA Hectd1 (circHectd1) levels were significantly increased in ischemic brain tissues in transient middle cerebral artery occlusion (tMCAO) mouse stroke models and further validated this finding in plasma samples from acute ischemic stroke (AIS) patients. Knockdown of circHectd1 expression significantly decreased infarct areas, attenuated neuronal deficits, and ameliorated astrocyte activation in tMCAO mice. Mechanistically, circHECTD1 functions as an endogenous MIR142 (microRNA 142) sponge to inhibit MIR142 activity, resulting in the inhibition of TIPARP (TCDD inducible poly[ADP-ribose] polymerase) expression with subsequent inhibition of astrocyte activation via macroautophagy/autophagy. Taken together, the results of our study indicate that circHECTD1 and its coupling mechanism are involved in cerebral ischemia, thus providing translational evidence that circHECTD1 can serve as a novel biomarker of and therapeutic target for stroke.

The synergetic effect of edaravone and borneol in the rat model of ischemic stroke.

PubMed

Wu, Hai-Yin; Tang, Ying; Gao, Li-Yan; Sun, Wei-Xiang; Hua, Yao; Yang, Shi-Bao; Zhang, Zheng-Ping; Liao, Gao-Yong; Zhou, Qi-Gang; Luo, Chun-Xia; Zhu, Dong-Ya

2014-10-05

Free radical production contributes to the early ischemic response and the neuroinflammatory response to injury initiates the second wave of cell death following ischemic stroke. Edaravone is a free radical scavenger, and borneol has shown anti-inflammatory effect. We investigated the synergistic effect of these two drugs in the rat model of transient cerebral ischemia. Edaravone scavenged OH, NO and ONOO─ concentration-dependently, and borneol inhibited ischemia/reperfusion-induced tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) expressions. In the rat model of transient cerebral ischemia and reperfusion, the combination of edaravone and borneol significantly ameliorated ischemic damage with an optimal proportion of 4:1. Emax (% inhibition) of edaravone, borneol and two drugs in combination was 55.7%, 65.8% and 74.3% respectively. ED50 of edaravone and borneol was 7.17 and 0.36 mg/kg respectively. When two drugs in combination, ED50 was 0.484 mg/kg, in which edaravone was 0.387 mg/kg (ineffective dose) and borneol was 0.097 mg/kg (ineffective dose). Combination index (CI)<1 among effects observed in experiments, suggesting a significant synergistic effect. Reduced levels of pro-inflammatory mediators and free radicals were probably associated with the synergistic effect of edaravone and borneol. The combination exhibited a therapeutic time window of 6h in ischemia/reperfusion model, and significantly ameliorated damages in permanent ischemia model. Moreover, two drugs in combination promoted long-term effect, including improved elemental vital signs, sensorimotor functions and spatial cognition. Our results suggest that the combination of edaravone and borneol have a synergistic effect for treating ischemic stroke. Copyright © 2014 Elsevier B.V. All rights reserved.

Accelerated recovery from acute brain injuries: clinical efficacy of neurotrophic treatment in stroke and traumatic brain injuries.

PubMed

Bornstein, N; Poon, W S

2012-04-01

Stroke is one of the most devastating vascular diseases in the world as it is responsible for almost five million deaths per year. Almost 90% of all strokes are ischemic and mainly due to atherosclerosis, cardiac embolism and small-vessel disease. Intracerebral or subarachnoid hemorrhage can lead to hemorrhagic stroke, which usually has the poorest prognosis. Cerebrolysin is a peptide preparation which mimics the action of a neurotrophic factor, protecting stroke-injured neurons and promoting neuroplasticity and neurogenesis. Cerebrolysin has been widely studied as a therapeutic tool for both ischemic and hemorrhagic stroke, as well as traumatic brain injury. In ischemic stroke, Cerebrolysin given as an adjuvant therapy to antiplatelet and rheologically active medication resulted in accelerated improvement in global, neurological and motor functions, cognitive performance and activities of daily living. Cerebrolysin was also safe and well tolerated when administered in patients suffering from hemorrhagic stroke. Traumatic brain injury leads to transient or chronic impairments in physical, cognitive, emotional and behavioral functions. This is associated with deficits in the recognition of basic emotions, the capacity to interpret the mental states of others, and executive functioning. Pilot clinical studies with adjuvant Cerebrolysin in the acute and postacute phases of the injury have shown faster recovery, which translates into an earlier onset of rehabilitation and shortened hospitalization time. Copyright 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

Synthesis and biological evaluation of pyrrolidine derivatives as novel and potent sodium channel blockers for the treatment of ischemic stroke.

PubMed

Seki, Maki; Tsuruta, Osamu; Tatsumi, Ryo; Soejima, Aki

2013-07-15

A novel series of pyrrolidine derivatives as Na(+) channel blockers was synthesized and evaluated for their inhibitory effects on neuronal Na(+) channels. Structure-activity relationship (SAR) studies of a pyrrolidine analogue 2 led to the discovery of 5e as a potent Na(+) channel blocker with a low inhibitory action against human ether-a-go-go-related gene (hERG) channels. Compound 5e showed remarkably neuroprotective activity in a rat transient middle cerebral artery occlusion (MCAO) model, suggesting that 5e would act as a neuroprotectant for ischemic stroke. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cortical myoclonus during IV thrombolysis for ischemic stroke

PubMed Central

Bentes, Carla; Peralta, Rita; Viana, Pedro; Morgado, Carlos; Melo, Teresa P.; Ferro, José M.

2014-01-01

We describe a patient with an acute middle cerebral artery ischemic stroke developing subtle involuntary movements of the paretic upper limb with cortical origin during rt-PA perfusion. Despite the multiple potential pathophysiological mechanisms for the relationship between thrombolysis and epileptic activity, seizures during this procedure are scarcely reported. Our hypothesis is that subtle and transient clinical seizures, like those described in our patient, may not be detected or are misdiagnosed as nonepileptic involuntary movements. We aimed to draw attention to the recognition challenge of this paroxysmal motor behavior, highlighting this clinical and neurophysiological identification using video recording and back-average analysis of the EEG. PMID:25667903

Dabigatran in Secondary Stroke Prevention: Clinical Experience with 106 Patients

PubMed Central

DeFelipe-Mimbrera, Alicia; Cánovas, Araceli Alonso; Guillán, Marta; Matute, Consuelo; Cruz, Antonio; Vera, Rocío; Masjuan, Jaime

2014-01-01

Introduction. Our aim was to analyze our clinical experience with dabigatran etexilate in secondary stroke prevention. Methods. We retrospectively included patients starting dabigatran etexilate for secondary stroke prevention from March 2010 to December 2012. Efficacy and safety variables were registered. Results. 106 patients were included, median follow-up of 12 months (range 1–31). Fifty-six females (52.8%), mean age 76.4 (range 50–95, SD 9.8), median CHADS2 4 (range 2–6), CHA2DS2-VASc 5 (range 2–9), and HAS-BLED 2 (range 1–5). Indication for dabigatran etexilate was ischemic stroke in 101 patients and acute cerebral hemorrhage (CH) due to warfarin in 5 (4.7%). Dabigatran etexilate 110 mg bid was prescribed in 71 cases (67%) and 150 mg bid was prescribed in the remaining. Seventeen patients (16%) suffered 20 complications during follow-up. Ischemic complications (10) were 6 transient ischemic attacks (TIA), 3 ischemic strokes, and 1 acute coronary syndrome. Hemorrhagic complications (10) were CH (1), gastrointestinal bleeding (6), mild hematuria (2), and mild metrorrhagia (1), leading to dabigatran etexilate discontinuation in 3 patients. Patients with previous CH remained uneventful. Three patients died (pneumonia, congestive heart failure, and acute cholecystitis) and 9 were lost during follow-up. Conclusions. Dabigatran etexilate was safe and effective in secondary stroke prevention in clinical practice, including a small number of patients with previous history of CH. PMID:25133166

Association of Progression of Carotid Artery Wall Volume and Recurrent Transient Ischemic Attack or Stroke: A Magnetic Resonance Imaging Study.

PubMed

Lu, Mingming; Peng, Peng; Cui, Yuanyuan; Qiao, Huiyu; Li, Dongye; Cai, Jianming; Zhao, Xihai

2018-03-01

This study aimed to investigate the association between carotid plaque progression and subsequent recurrent events using magnetic resonance imaging. Sixty-three symptomatic patients with ipsilateral carotid atherosclerotic stenosis (30%-69% stenosis) determined by ultrasound underwent first and second carotid artery magnetic resonance imaging for carotid artery at baseline and ≥6 months after the first scan, respectively. All the patients had clinical follow-up after the second magnetic resonance scan for ≤5 years until the onset of recurrent transient ischemic attack or stroke. Presence/absence of carotid plaque compositional features, particularly intraplaque hemorrhage and fibrous cap rupture was identified. The annual progression of carotid wall volume between 2 magnetic resonance scans was measured. Univariate and multivariate Cox regression was used to calculate the hazard ratio and corresponding 95% confidence interval of carotid plaque features in discriminating recurrent events. Receiver-operating-characteristic-curve analysis was conducted to determine the area-under-the-curve of carotid plaque features in predicting recurrent events. Sixty-three patients (mean age: 66.5±10.0 years old; 54 males) were eligible for final statistics analysis. During a mean follow-up duration of 55.1±13.6 months, 14.3% of patients (n=9) experienced ipsilateral recurrent transient ischemic attack/stroke. The annual progression of carotid wall volume was significantly associated with recurrent events before (hazard ratio, 1.14 per 10 mm 3 ; 95% confidence interval, 1.02-1.27; P =0.019) and after (hazard ratio, 1.19 per 10 mm3; 95% confidence interval, 1.03-1.37; P =0.022) adjusted for confounding factors. In discriminating the recurrence of transient ischemia attack/stroke, receiver-operator curve analysis indicated that combined with annual progression of wall volume, there was a significant incremental improvement in the area-under-the-curve of intraplaque hemorrhage (area-under-the-curve: 0.69-0.81) and fibrous cap rupture (area-under-the-curve: 0.73-0.84). The annual progression of carotid wall volume is independently associated with recurrent ischemic cerebrovascular events, and this measurement has added value for intraplaque hemorrhage and fibrous cap rupture in predicting future events. © 2018 American Heart Association, Inc.

Nitric Oxide Donors as Neuroprotective Agents after an Ischemic Stroke-Related Inflammatory Reaction

PubMed Central

Rojas-Mayorquín, Argelia E.; Ortuño-Sahagún, Daniel

2013-01-01

Cerebral ischemia initiates a cascade of detrimental events including glutamate-associated excitotoxicity, intracellular calcium accumulation, formation of Reactive oxygen species (ROS), membrane lipid degradation, and DNA damage, which lead to the disruption of cellular homeostasis and structural damage of ischemic brain tissue. Cerebral ischemia also triggers acute inflammation, which exacerbates primary brain damage. Therefore, reducing oxidative stress (OS) and downregulating the inflammatory response are options that merit consideration as potential therapeutic targets for ischemic stroke. Consequently, agents capable of modulating both elements will constitute promising therapeutic solutions because clinically effective neuroprotectants have not yet been discovered and no specific therapy for stroke is available to date. Because of their ability to modulate both oxidative stress and the inflammatory response, much attention has been focused on the role of nitric oxide donors (NOD) as neuroprotective agents in the pathophysiology of cerebral ischemia-reperfusion injury. Given their short therapeutic window, NOD appears to be appropriate for use during neurosurgical procedures involving transient arterial occlusions, or in very early treatment of acute ischemic stroke, and also possibly as complementary treatment for neurodegenerative diseases such as Parkinson or Alzheimer, where oxidative stress is an important promoter of damage. In the present paper, we focus on the role of NOD as possible neuroprotective therapeutic agents for ischemia/reperfusion treatment. PMID:23691263

Normobaric hyperoxia retards the evolution of ischemic brain tissue toward infarction in a rat model of transient focal cerebral ischemia.

PubMed

Xu, Ji; Zhang, Yuan; Liang, Zhouyuan; Wang, Ting; Li, Weiping; Ren, Lijie; Huang, Shaonong; Liu, Wenlan

2016-01-01

Oxygen therapy has been long considered a logical therapy for ischemic stroke. Our previous studies showed that normobaric hyperoxia (normobaric hyperoxia (NBO), 95% O2 with 5% CO2) treatment during ischemia reduced ischemic neuronal death and cerebromicrovascular injury in animal stroke models. In this study, we studied the effects of NBO on the evolution of ischemic brain tissue to infarction in a rat model of transient focal cerebral ischemia. Male Sprague-Dawley rats were given NBO (95% O2) or normoxia (21% O2) during 90-min filament occlusion of the middle cerebral artery (MCAO), followed by 3 or 22.5 h of reperfusion. 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to evaluate the longitudinal evolution of tissue infarction. Results： In normoxic rats, MCA-supplied cortical and striatal tissue was infarcted after 90-min MCAO with 22.5 h of reperfusion. NBO-treated rats showed a 61.4% reduction in infarct size and tissue infarction mainly occurred in the ischemic striatum. When infarction was assessed at an earlier time point, i.e. at 3 h of reperfusion, normoxic rats showed significantly smaller but mature infarction (no TTC staining, white color), with the infarction mainly occurring in the striatum. Unexpectedly, NBO-treated rats only showed immature lesion (partially stained by TTC, light white color) in the ischemic striatum, indicating that NBO treatment also retarded the process of neuronal death in the ischemic core. Of note, NBO-preserved striatal tissue underwent infarction after prolonged reperfusion. Conclusions： Our results demonstrate that NBO treatment given during cerebral ischemia retards the evolution of ischemic brain tissue toward infarction and NBO-preserved cortical tissue survives better than NBO-preserved striatal tissue during the phase of reperfusion.

Periodic Limb Movements and White Matter Hyperintensities in First-Ever Minor Stroke or High-Risk Transient Ischemic Attack.

PubMed

Boulos, Mark I; Murray, Brian J; Muir, Ryan T; Gao, Fuqiang; Szilagyi, Gregory M; Huroy, Menal; Kiss, Alexander; Walters, Arthur S; Black, Sandra E; Lim, Andrew S; Swartz, Richard H

2017-03-01

Emerging evidence suggests that periodic limb movements (PLMs) may contribute to the development of cerebrovascular disease. White matter hyperintensities (WMHs), a widely accepted biomarker for cerebral small vessel disease, are associated with incident stroke and death. We evaluated the association between increased PLM indices and WMH burden in patients presenting with stroke or transient ischemic attack (TIA), while controlling for vascular risk factors and stroke severity. Thirty patients presenting within 2 weeks of a first-ever minor stroke or high-risk TIA were prospectively recruited. PLM severity was measured with polysomnography. WMH burden was quantified using the Age Related White Matter Changes (ARWMC) scale based on neuroimaging. Partial Spearman's rank-order correlations and multiple linear regression models tested the association between WMH burden and PLM severity. Greater WMH burden was correlated with elevated PLM index and stroke volume. Partial Spearman's rank-order correlations demonstrated that the relationship between WMH burden and PLM index persisted despite controlling for vascular risk factors. Multivariate linear regression models revealed that PLM index was a significant predictor of an elevated ARWMC score while controlling for age, stroke volume, stroke severity, hypertension, and apnea-hypopnea index. The quantity of PLMs was associated with WMH burden in patients with first-ever minor stroke or TIA. PLMs may be a risk factor for or marker of WMH burden, even after considering vascular risk factors and stroke severity. These results invite further investigation of PLMs as a potentially useful target to reduce WMH and stroke burden. © Sleep Research Society (SRS) 2016. All rights reserved. For permissions, please email: journals.permissions@oup.com

Reduced expression of IA channels is associated with post-ischemic seizures.

PubMed

Lei, Zhigang; Zhang, Hui; Liang, Yanling; Xu, Zao C

2016-08-01

Post-stroke seizures are considered as a major cause of epilepsy in adults. The pathophysiologic mechanisms resulting in post-stroke seizures are not fully understood. The present study attempted to reveal a new mechanism underlying neuronal hyperexcitability responsible to the seizure development after ischemic stroke. Transient global ischemia was produced in adult Wistar rats using the 4-vessel occlusion (4-VO) method. The spontaneous behavioral seizures were defined by the Racine scale III-V. The neuronal death in the brain was determined by hematoxylin-eosin staining. The expression levels of A-type potassium channels were analyzed by immunohistochemical staining and western blotting. We found that the incidence of spontaneous behavioral seizures increased according to the severity of ischemia with 0% after 15-min ischemia and ∼50% after 25-min ischemia. All behavioral seizures occurred with 48h after ischemia. Morphological analysis indicated that brain damage was not correlated with behavioral seizures. Immunohistochemical staining showed that the expression levels of the A-type potassium channel subunit Kv4.2 was significantly reduced in ischemic brains with behavioral seizures, but not in ischemic brains without seizures. In addition, rats failing to develop spontaneous behavioral seizures within 2days after ischemia were more sensitive to bicuculline-induced seizures at 2 months after ischemia than control rats. Meanwhile, Kv4.2 expression was decreased in brain at 2 months after ischemia. Our results demonstrated the reduction of Kv4.2 expression might contribute to the development of post-ischemic seizures and long-term increased seizure susceptibility after ischemia. The mechanisms underlying post-stroke seizures and epilepsy is unknown so far. The down-regulation of IA channels may explained the abnormal neuronal hyperexcitability responsible for the seizure development after ischemic stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

Secondary stroke prevention with ximelagatran versus warfarin in patients with atrial fibrillation: pooled analysis of SPORTIF III and V clinical trials.

PubMed

Akins, Paul T; Feldman, Harvey A; Zoble, Robert G; Newman, David; Spitzer, Stefan G; Diener, Hans-Christoph; Albers, Gregory W

2007-03-01

Patients with nonvalvular atrial fibrillation and prior stroke or transient ischemic attack (TIA) are at high risk for recurrent stroke. We investigated whether ximelagatran was noninferior to warfarin in patients with prior stroke or TIA. We analyzed pooled data from the SPORTIF III and V trials in patients with prior stroke/TIA. The primary outcome was the composite annual rate of both ischemic and hemorrhagic strokes and systemic embolic events. Secondary analyses considered ischemic and hemorrhagic strokes separately, bleeding, and nonrandomized, concomitant therapy with aspirin < or =100 mg/d. Patients from SPORTIF III (n=3407) and SPORTIF V (n=3922) trials were categorized by prior stroke/TIA (21%) versus no prior stroke/TIA (79%) and by treatment group (ximelagatran vs warfarin). The primary event rate in patients with prior stroke/TIA was 2.83%/y with ximelagatran and 3.27%/y with warfarin (absolute difference, -0.44%; 95% CI, -1.88 to1.01; P=0.625). In those without prior stroke/TIA, the primary event rate was 1.31%/y with ximelagatran and 1.26%/y with warfarin (P=NS). Ischemic strokes outnumbered cerebral hemorrhages with both warfarin (31 of 36) and ximelagatran (30 of 32) treatment (difference between treatments was not significant). Combining aspirin with either anticoagulant was associated with higher rates of major bleeding (1.5%/y with warfarin and 4.95%/y with warfarin plus aspirin, P=0.004; 2.35%/y with ximelagatran and 5.09%/y with ximelagatran plus aspirin, P=0.046) but not lower rates of primary events. Ximelagatran was at least as effective as well-controlled warfarin for the secondary prevention of stroke. The nonrandomized, concomitant treatment with aspirin and anticoagulation was associated with increased bleeding without evidence of a reduction in primary outcome events.

Remote Ischemic Postconditioning for Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Zhao, Jing-Jing; Xiao, Hui; Zhao, Wen-Bo; Zhang, Xiao-Pei; Xiang, Yu; Ye, Zeng-Jie; Mo, Miao-Miao; Peng, Xue-Ting; Wei, Lin

2018-01-01

Background: Remote ischemic postconditioning (RIPostC) appears to protect distant organs from ischemia-reperfusion injury (IRI). However, cerebral protection results have remained inconclusive. In the present study, a meta-analysis was performed to compare stroke patients with and without RIPostC. Methods: CNKI, WanFang, VIP, CBM, PubMed, and Cochrane Library databases were searched up to July 2016. Data were analyzed using both fixed-effects and random-effects models by Review Manager. For each outcome, risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were calculated. Results: A total of 13 randomized controlled trials that enrolled a total of 794 study participants who suffered from or are at risk for brain IRI were selected. Compared with controls, RIPostC significantly reduced the recurrence of stroke or transient ischemic attacks (RR = 0.37; 95% CI: 0.26–0.55; P < 0.00001). Moreover, it can reduce the levels of the National Institutes of Health Stroke Scale score (MD: 1.96; 95% CI: 2.18–1.75; P < 0.00001), modified Rankin Scale score (MD: 0.73; 95% CI: 1.20–0.25; P = 0.00300), and high-sensitivity C-reactive protein (MD: 4.17; 95% CI: 4.71–3.62; P < 0.00001) between the two groups. There was no side effect of RIPostC using tourniquet cuff around the limb on ischemic stroke treating based on different intervention duration. Conclusion: The present meta-analysis suggests that RIPostC might offer cerebral protection for stroke patients suffering from or are at risk of brain IRI. PMID:29664057

Children with sickle cell anemia with normal transcranial Doppler ultrasounds and without silent infarcts have a low incidence of new strokes.

PubMed

Jordan, Lori C; Roberts Williams, Dionna O; Rodeghier, Mark J; Covert Greene, Brittany V; Ponisio, Maria R; Casella, James F; McKinstry, Robert C; Noetzel, Michael J; Kirkham, Fenella J; Meier, Emily R; Fuh, Beng; McNaull, Melissa; Sarnaik, Sharada; Majumdar, Suvankar; McCavit, Timothy L; DeBaun, Michael R

2018-06-01

In a prospective cohort study, we tested the hypothesis that children with sickle cell anemia (SCA) with normal transcranial Doppler ultrasound (TCD) velocities and without silent cerebral infarcts (SCIs) would have a lower incidence rate of new neurological events (strokes, seizures or transient ischemic attacks) compared to children with normal TCD measurements and SCIs, not receiving regular blood transfusions. Nonrandomized participants from the silent cerebral infarct transfusion (SIT) Trial who had screening magnetic resonance imaging (MRI) of the brain and normal TCD measurements were included. Follow-up ended at the time of first neurological event (stroke, seizure or transient ischemic attack), start of regular blood transfusion, or loss to follow-up, whichever came first. The primary endpoint was a new neurological event. Of 421 participants included, 68 had suspected SCIs. Mean follow-up was 3.6 years. Incidence rates of new neurological events in nontransfused participants with normal TCD values with SCIs and without SCIs were 1.71 and 0.47 neurological events per 100 patient-years, respectively, P = .065. The absence of SCI(s) at baseline was associated with a decreased risk of a new neurological event (hazard ratio 0.231, 95% CI 0.062-0.858; P = .029). Local pediatric neurologists examined 67 of 68 participants with suspected SCIs and identified 2 with overt strokes classified as SCIs by local hematologists; subsequently one had a seizure and the other an ischemic stroke. Children with SCA, without SCIs, and normal TCD measurements have a significantly lower rate of new neurological events when compared to those with SCIs and normal TCD measurements. Pediatric neurology assessment may assist risk stratification. © 2018 Wiley Periodicals, Inc.

Moderate sensitivity and high specificity of emergency department administrative data for transient ischemic attacks.

PubMed

Yu, Amy Y X; Quan, Hude; McRae, Andrew; Wagner, Gabrielle O; Hill, Michael D; Coutts, Shelagh B

2017-09-18

Validation of administrative data case definitions is key for accurate passive surveillance of disease. Transient ischemic attack (TIA) is a condition primarily managed in the emergency department. However, prior validation studies have focused on data after inpatient hospitalization. We aimed to determine the validity of the Canadian 10th International Classification of Diseases (ICD-10-CA) codes for TIA in the national ambulatory administrative database. We performed a diagnostic accuracy study of four ICD-10-CA case definition algorithms for TIA in the emergency department setting. The study population was obtained from two ongoing studies on the diagnosis of TIA and minor stroke versus stroke mimic using serum biomarkers and neuroimaging. Two reference standards were used 1) the emergency department clinical diagnosis determined by chart abstractors and 2) the 90-day final diagnosis, both obtained by stroke neurologists, to calculate the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the ICD-10-CA algorithms for TIA. Among 417 patients, emergency department adjudication showed 163 (39.1%) TIA, 155 (37.2%) ischemic strokes, and 99 (23.7%) stroke mimics. The most restrictive algorithm, defined as a TIA code in the main position had the lowest sensitivity (36.8%), but highest specificity (92.5%) and PPV (76.0%). The most inclusive algorithm, defined as a TIA code in any position with and without query prefix had the highest sensitivity (63.8%), but lowest specificity (81.5%) and PPV (68.9%). Sensitivity, specificity, PPV, and NPV were overall lower when using the 90-day diagnosis as reference standard. Emergency department administrative data reflect diagnosis of suspected TIA with high specificity, but underestimate the burden of disease. Future studies are necessary to understand the reasons for the low to moderate sensitivity.

Sleep modifications in acute transient global amnesia.

PubMed

Della Marca, Giacomo; Mazza, Marianna; Losurdo, Anna; Testani, Elisa; Broccolini, Aldobrando; Frisullo, Giovanni; Marano, Giuseppe; Morosetti, Roberta; Pilato, Fabio; Profice, Paolo; Vollono, Catello; Di Lazzaro, Vincenzo

2013-09-15

Transient global amnesia (TGA) is a temporary memory loss characterized by an abrupt onset of antero-grade and retrograde amnesia, totally reversible. Since sleep plays a major role in memory consolidation, and in the storage of memory-related traces into the brain cortex, the aims of the present study were: (1) to evaluate changes in sleep macro-structure in TGA; (2) to assess modifications in sleep micro-structure in TGA, with particular reference to the arousal EEG and to cyclic alternating pattern (CAP); (3) to compare sleep parameters in TGA patients with a control group of patients with acute ischemic events ("minor stroke" or transient ischemic attack [TIA]) clinically and neuroradiologically "similar" to the TGA. TGA GROUP: 17 patients, (8 men and 9 women, 60.2 ± 12.5 years). Stroke or TIA (SoT) group: 17 patients hospitalized in the Stroke Unit for recent onset of minor stroke or TIA with hemispheric localization; healthy controls (HC) group: 17 healthy volunteers, matched for age and sex. Patients and controls underwent full-night polysomnography. In the multivariate analysis (conditions TGA, SoT, and HC) a significant effect of the condition was observed for sleep efficiency index, number of awakenings longer 1 min, REM latency, CAP time, and CAP rate. TGA and SoT differed only for CAP time and CAP rate, which were lower in the TGA group. Microstructural modification associated with tga could be consequent to: (1) hippocampal dysfunction and memory impairment; (2) impairment of arousal-related structures (in particular, cholinergic pathways); (3) emotional distress.

Biomarkers and mortality after transient ischemic attack and minor ischemic stroke: population-based study.

PubMed

Greisenegger, Stefan; Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Rothwell, Peter M

2015-03-01

Premature death after transient ischemic attack or stroke is more often because of heart disease or cancer than stroke. Previous studies found blood biomarkers not usefully predictive of nonfatal stroke but possibly of all-cause death. This association might be explained by potentially treatable occult cardiac disease or cancer. We therefore aimed to validate the association of a panel of biomarkers with all-cause death, particularly cardiac death and cancer death, despite the absence of associations with risk of nonfatal vascular events. Fifteen biomarkers were measured in 929 consecutive patients in a population-based study (Oxford Vascular Study), recruited from 2002 and followed up to 2013. Associations were determined by Cox regression. Model discrimination was assessed by c-statistic and the integrated discrimination improvement. During 5560 patient-years of follow-up, none of the biomarkers predicted risk of nonfatal vascular events. However, soluble tumor necrosis factor α receptor-1, von Willebrand factor, heart-type fatty-acid-binding protein, and N-terminal pro-B-type natriuretic peptide were independently predictive of all-cause death (n=361; adjusted hazard ratio per SD, 95% confidence interval: heart-type fatty-acid-binding protein: 1.31, 1.12-1.56, P=0.002; N-terminal pro-B-type natriuretic peptide: 1.34, 1.11-1.62, P=0.002; soluble tumor necrosis factor α receptor-1: 1.45, 1.26-1.66, P=0.02; von Willebrand factor: 1.19, 1.04-1.36, P=0.01). The independent contribution of the four biomarkers taken together added prognostic information and improved model discrimination (integrated discrimination improvement=0.028, P=0.0001). N-terminal pro-B-type natriuretic peptide was most predictive of vascular death (adjusted hazard ratio=1.80, 95% confidence interval, 1.34-2.41, P<0.0001), whereas heart-type fatty-acid-binding protein predicted cancer deaths (1.64, 1.26-2.12, P=0.0002). Associations were strongest in patients without known prior cardiac disease or cancer. Several biomarkers predicted death of any cause after transient ischemic attack and minor stroke. N-terminal pro-B-type natriuretic peptide and heart-type fatty-acid-binding protein might improve patient selection for additional screening for occult cardiac disease or cancer, respectively. However, our results require validation in future studies. © 2015 American Heart Association, Inc.

Prevalence of Fabry Disease in Young Patients with Stroke in Argentina.

PubMed

Reisin, Ricardo C; Mazziotti, Julieta; Cejas, Luciana León; Zinnerman, Alberto; Bonardo, Pablo; Pardal, Manuel Fernández; Martínez, Alejandra; Riccio, Patricia; Ameriso, Sebastián; Bendersky, Eduardo; Nofal, Pedro; Cairola, Patricia; Jure, Lorena; Sotelo, Andrea; Rozenfeld, Paula; Ceci, Romina; Casas-Parera, Ignacio; Sánchez-Luceros, Analía

2018-03-01

Fabry disease (FD) is an underdiagnosed cause of stroke in young adults, but the frequency of this association is largely unknown. We estimated the prevalence of FD in a nationwide cohort of young adults who had stroke and transient ischemic attack (TIA) in Argentina. This was a prospective, multicenter study of stroke and FD in young adults (18-55 years) conducted in Argentina between 2011 and 2015. Patients were enrolled if they had had a TIA or an ischemic or hemorrhagic stroke within the previous 180 days. FD was diagnosed by measuring α-galactosidase A activity (males) and through genetic studies (females). We enrolled 311 patients (54% men, mean age: 41 years). Ischemic events occurred in 89% of patients (80% infarcts, 9% TIA) and hemorrhagic strokes in 11%. One female (.3% of the total group, 1% of the cryptogenic ischemic strokes) had the pathogenic mutation c.888G>A/p.Met296Ile /Exon 6 on the GAL gene. Her only other manifestation of FD was angiokeratoma. Eighteen females had nonpathogenic intronic variations: c.-10C>T, c.-12G>A, or both. Two patients had the nonpathogenic mutation D313Y, while a third had the likely benign mutation S126G. FD was identified in 1 patient (.3%) in this first Latin American study. The patient presented with a late-onset oligo-symptomatic form of the disease. A large number of nonpathogenic mutations were present in our cohort, and it is essential that they not be mistaken for pathogenic mutations to avoid unnecessary enzyme replacement treatment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Self-reported transient ischemic attack and stroke symptoms: methods and baseline prevalence. The ARIC Study, 1987-1989.

PubMed

Toole, J F; Lefkowitz, D S; Chambless, L E; Wijnberg, L; Paton, C C; Heiss, G

1996-11-01

As part of the Atherosclerosis Risk in Communities (ARIC) Study assessment of the etiology and sequelae of atherosclerosis, a standardized questionnaire on transient ischemic attack (TIA) and nonfatal stroke and a computerized diagnostic algorithm simulating clinical reasoning were developed and tested at the four ARIC field centers: Forsyth County, North Carolina; Minneapolis, Minnesota; Jackson, Mississippi; and Washington County, Maryland. The diagnostic algorithm used participant responses to a series of questions about six neurologic trigger symptoms to identify symptoms of TIA or stroke and their vascular distribution. Among 12,205 ARIO participants reporting their lifetime occurrence of one or more symptoms probably due to cerebrovascular causes, nearly half (47%) reported the sudden onset of at least one symptom sometime prior to their ARIC examination. Of those with at least one symptom, only 12.9% were classified by the computer algorithm as having symptoms of TIA or stroke. Dizziness/loss of balance was the most frequently reported symptom (36%); 1.2% of these persons were classified by the algorithm as having a TIA/stroke event. Positive symptoms of speech dysfunction were classified most often (77.%) as being symptoms of TIA or stroke. Symptoms suggesting TIA were reported more frequently than symptoms suggesting stroke by both sexes. TIA or stroke-like phenomena were more frequent (p < 0.001) in females (7%) than in males (5%) and increased with age in both sexes (p = 0.13 for females; p = 0.02 for males). In Forsyth County, TIA and stroke symptoms were greater in African Americans than in Caucasians (p = 0.05, controlling for sex). The association of algorithmically defined symptoms of TIA or stroke with traditional cerebrovascular risk factors is the subject of a companion paper.

Effect of peer education on stroke prevention: the prevent recurrence of all inner-city strokes through education randomized controlled trial.

PubMed

Kronish, Ian M; Goldfinger, Judith Z; Negron, Rennie; Fei, Kezhen; Tuhrim, Stanley; Arniella, Guedy; Horowitz, Carol R

2014-11-01

Efforts to reduce disparities in recurrent stroke among Black and Latino stroke survivors have met with limited success. We aimed to determine the effect of peer education on secondary stroke prevention among predominantly minority stroke survivors. Between 2009 and 2012, we enrolled 600 stroke or transient ischemic attack survivors from diverse, low-income communities in New York City into a 2-arm randomized clinical trial that compared a 6 week (1 session/week), peer-led, community-based, stroke prevention self-management group workshop (N=301) to a wait-list control group (N=299). The primary outcome was the proportion with a composite of controlled blood pressure (<140/90 mm Hg), low-density lipoprotein cholesterol <100 mg/dL, and use of antithrombotic medications at 6 months. Secondary outcomes included control of the individual stroke risk factors. All analyses were by intent-to-treat. There was no difference in the proportion of intervention and control group participants achieving the composite outcome (34% versus 34%; P=0.98). The proportion with controlled blood pressure at 6 months was greater in the intervention group than in the control group (76% versus 67%; P=0.02). This corresponded to a greater change in systolic blood pressure in the intervention versus control group (-3.63 SD, 19.81 mm Hg versus +0.34 SD, 23.76 mm Hg; P=0.04). There were no group differences in the control of cholesterol or use of antithrombotics. A low-cost peer education self-management workshop modestly improved blood pressure, but not low-density lipoprotein cholesterol or antithrombotic use, among stroke and transient ischemic attack survivors from vulnerable, predominantly minority urban communities. http://www.clinicaltrials.gov/show/NCT0102727. Unique identifier: NCT01027273. © 2014 American Heart Association, Inc.

Association of Osteopontin, Neopterin, and Myeloperoxidase With Stroke Risk in Patients With Prior Stroke or Transient Ischemic Attacks: Results of an Analysis of 13 Biomarkers From the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trial.

PubMed

Ganz, Peter; Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik; Bao, Weihang; Preston, Gregory M; Welch, K Michael A

2017-12-01

Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic attack and no known coronary heart disease. This analysis explored the relationships between 13 plasma biomarkers assessed at trial enrollment and the occurrence of outcome strokes. We conducted a case-cohort study of 2176 participants; 562 had outcome strokes and 1614 were selected randomly from those without outcome strokes. Time to stroke was evaluated by Cox proportional hazards models. There was no association between time to stroke and lipoprotein-associated phospholipase A 2 , monocyte chemoattractant protein-1, resistin, matrix metalloproteinase-9, N-terminal fragment of pro-B-type natriuretic peptide, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, or soluble CD40 ligand. In adjusted analyses, osteopontin (hazard ratio per SD change, 1.362; P <0.0001), neopterin (hazard ratio, 1.137; P =0.0107), myeloperoxidase (hazard ratio, 1.177; P =0.0022), and adiponectin (hazard ratio, 1.207; P =0.0013) were independently associated with outcome strokes. After adjustment for the Stroke Prognostic Instrument-II and treatment, osteopontin, neopterin, and myeloperoxidase remained independently associated with outcome strokes. The addition of these 3 biomarkers to Stroke Prognostic Instrument-II increased the area under the receiver operating characteristic curve by 0.023 ( P =0.015) and yielded a continuous net reclassification improvement (29.1%; P <0.0001) and an integrated discrimination improvement (42.3%; P <0.0001). Osteopontin, neopterin, and myeloperoxidase were independently associated with the risk of recurrent stroke and improved risk classification when added to a clinical risk algorithm. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00147602. © 2017 American Heart Association, Inc.

Late night activity regarding stroke codes: LuNAR strokes.

PubMed

Tafreshi, Gilda; Raman, Rema; Ernstrom, Karin; Rapp, Karen; Meyer, Brett C

2012-08-01

There is diurnal variation for cardiac arrest and sudden cardiac death. Stroke may show a similar pattern. We assessed whether strokes presenting during a particular time of day or night are more likely of vascular etiology. To compare emergency department stroke codes arriving between 22:00 and 8:00 hours (LuNAR strokes) vs. others (n-LuNAR strokes). The purpose was to determine if late night strokes are more likely to be true strokes or warrant acute tissue plasminogen activator evaluations. We reviewed prospectively collected cases in the University of California, San Diego Stroke Team database gathered over a four-year period. Stroke codes at six emergency departments were classified based on arrival time. Those arriving between 22:00 and 8:00 hours were classified as LuNAR stroke codes, the remainder were classified as 'n-LuNAR'. Patients were further classified as intracerebral hemorrhage, acute ischemic stroke not receiving tissue plasminogen activator, acute ischemic stroke receiving tissue plasminogen activator, transient ischemic attack, and nonstroke. Categorical outcomes were compared using Fisher's Exact test. Continuous outcomes were compared using Wilcoxon's Rank-sum test. A total of 1607 patients were included in our study, of which, 299 (19%) were LuNAR code strokes. The overall median NIHSS was five, higher in the LuNAR group (n-LuNAR 5, LuNAR 7; P=0·022). There was no overall differences in patient diagnoses between LuNAR and n-LuNAR strokes (P=0·169) or diagnosis of acute ischemic stroke receiving tissue plasminogen activator (n-LuNAR 191 (14·6%), LuNAR 42 (14·0%); P=0·86). Mean arrival to computed tomography scan time was longer during LuNAR hours (n-LuNAR 54·9±76·3 min, LuNAR 62·5±87·7 min; P=0·027). There was no significant difference in 90-day mortality (n-LuNAR 15·0%, LuNAR 13·2%; P=0·45). Our stroke center experience showed no difference in diagnosis of acute ischemic stroke between day and night stroke codes. This similarity was further supported in similar rates of tissue plasminogen activator administration. Late night strokes may warrant a more rapid stroke specialist evaluation due to the longer time elapsed from symptom onset and the longer time to computed tomography scan. © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.

Systemic risk score evaluation in ischemic stroke patients (SCALA): a prospective cross sectional study in 85 German stroke units.

PubMed

Weimar, Christian; Goertler, Michael; Röther, Joachim; Ringelstein, E Bernd; Darius, Harald; Nabavi, Darius Günther; Kim, In-Ha; Theobald, Karlheinz; Diener, Han-Christoph

2007-11-01

Stratification of patients with transient ischemic attack (TIA) or ischemic stroke (IS) by risk of recurrent stroke can contribute to optimized secondary prevention. We therefore aimed to assess cardiovascular risk factor profiles of consecutive patients hospitalized with TIA/IS to stratify the risk of recurrent stroke according to the Essen Stroke Risk Score (ESRS) and of future cardiovascular events according to the ankle brachial index (ABI) as a marker of generalized atherosclerosis In this cross-sectional observational study, 85 neurological stroke units throughout Germany documented cardiovascular risk factor profiles of 10 consecutive TIA/IS patients on standardized questionnaires. Screening for PAD was done with Doppler ultrasonography to calculate the ABI. A total of 852 patients (57% men) with a mean age of 67+/-12.4 years were included of whom 82.9 % had IS. The median National Institutes of Health stroke sum score was 4 (TIA: 1). Arterial hypertension was reported in 71%, diabetes mellitus in 26%, clinical PAD in 10%, and an ABI < or = 0.9 in 51%. An ESRS > or = 3 was observed in 58%, which in two previous retrospective analyses corresponded to a recurrent stroke risk of > or = 4%/year. The correlation between the ESRS and the ABI was low (r = 0.21). A high proportion of patients had asymptomatic atherosclerotic disease and a considerable risk of recurrent stroke according to the ABI and ESRS category. The prognostic accuracy as well as the potential benefit of various risk stratification scores in secondary stroke prevention require validation in a larger prospective study.

The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

PubMed

Ramos-Araque, Maria E; Rodriguez, Cristina; Vecino, Rebeca; Cortijo Garcia, Elisa; de Lera Alfonso, Mercedes; Sanchez Barba, Mercedes; Colàs-Campàs, Laura; Purroy, Francisco; Arenillas, Juan F; Almeida, Angeles; Delgado-Esteban, Maria

2018-04-23

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.

High prevalence of stroke symptoms among persons without a diagnosis of stroke or transient ischemic attack in a general population: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

PubMed

Howard, Virginia J; McClure, Leslie A; Meschia, James F; Pulley, Leavonne; Orr, Sean C; Friday, Gary H

2006-10-09

A substantial portion of the general population has clinically silent stroke on brain imaging. These lesions may cause symptoms. This study assessed the prevalence of stroke symptoms in a stroke- and transient ischemic attack (TIA)-free population and the association of symptoms with risk factors indexed by the Framingham Stroke Risk Score. We performed a cross-sectional analysis from a randomly sampled national cohort enrolled from January 25, 2003, through November 30, 2005, with oversampling from the southeastern stroke belt and African American populations. The main outcome measure was stroke symptoms assessed by validated questionnaire. The study included 18 462 (41% African American; 51% female; mean age, 65.8 years) participants who reported no stroke or TIA. The prevalence of stroke symptoms was 5.8% for sudden painless hemibody weakness, 8.5% for sudden hemibody numbness, 4.6% for sudden painless loss of vision in one or both eyes, 3.1% for sudden hemifield visual loss, 2.7% for sudden inability to understand speech, and 3.8% for sudden inability of linguistic expression. The prevalence of 1 or more symptoms was 17.8%. Relative to the first quartile of the Framingham Stroke Risk Score, the adjusted odds ratio for 1 or more stroke symptoms increased from 1.0 (95% confidence interval [CI], 0.90-1.2) in the second quartile to 1.2 (95% CI, 1.1-1.5) and 1.5 (95% CI, 1.3-1.6) in successive quartiles. Symptoms were more prevalent among African American compared with white participants and among those with lower income, lower educational level, and fair to poor perceived health status. The general population without prior diagnosed stroke or TIA has a high prevalence of stroke symptoms. The relationship between symptoms and risk factors suggests that some symptomatic individuals may have had clinically undetected cerebrovascular events and may benefit from aggressive stroke prophylaxis.

Annual Research Progress Report. Fiscal Year 2003. Volume’s 1 and 2

DTIC Science & Technology

2003-01-01

transient ischemic attack, amaurosis fugax or stroke in the cerebral distribution of the operated side, 3) the occurrence of criteria for reoperation...Functional Severity and Recovery of Motor Limbs in Acute Brain Injury KEYWORDS: Stroke /Diagnostic assessment. PRINCIPAL INVESTIGATOR: LTC...A Randomized Trial. (1/16/2001) 02-86002 655Knapik, Joseph, PhD DAC. Injury Control and Running Footwear. (3/12/2002) CHPPM 02-98001E

Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials.

PubMed

1994-07-11

Atrial fibrillation is associated with an increased risk of ischemic stroke. Data on individual patients were pooled from five recently completed randomized trials comparing warfarin (all studies) or aspirin (the Atrial Fibrillation, Aspirin, Anticoagulation Study and the Stroke Prevention in Atrial Fibrillation Study) with control in patients with atrial fibrillation. The purpose of the analysis was to (1) identify patient features predictive of a high or low risk of stroke, (2) assess the efficacy of antithrombotic therapy in major patient subgroups (eg, women), and (3) obtain the most precise estimate of the efficacy and risks of antithrombotic therapy in atrial fibrillation. For the warfarin-control comparison there were 1889 patient-years receiving warfarin and 1802 in the control group. For the aspirin-placebo comparison there were 1132 patient-years receiving aspirin and 1133 receiving placebo. The daily dose of aspirin was 75 mg in the Atrial Fibrillation, Aspirin, Anticoagulation Study and 325 mg in the Stroke Prevention in Atrial Fibrillation Study. To monitor warfarin dosage, three studies used prothrombin time ratios and two used international normalized ratios. The lowest target intensity was a prothrombin time ratio of 1.2 to 1.5 and the highest target intensity was an international normalized ratio of 2.8 to 4.2. The primary end points were ischemic stroke and major hemorrhage, as assessed by each study. At the time of randomization the mean age was 69 years and the mean blood pressure was 142/82 mm Hg. Forty-six percent of the patients had a history of hypertension, 6% had a previous transient ischemic attack or stroke, and 14% had diabetes. Risk factors that predicted stroke on multivariate analyses in control patients were increasing age, history of hypertension, previous transient ischemic attack or stroke, and diabetes. Patients younger than 65 years who had none of the other predictive factors (15% of all patients) had an annual rate of stroke of 1.0%, 95% confidence interval (CI) 0.3% to 3.0%. The annual rate of stroke was 4.5% for the control group and 1.4% for the warfarin group (risk reduction, 68%; 95% CI, 50% to 79%). The efficacy of warfarin was consistent across all studies and subgroups of patients. In women, warfarin decreased the risk of stroke by 84% (95% CI, 55% to 95%) compared with 60% (95% CI, 35% to 76%) in men. The efficacy of aspirin was not as consistent. The risk reduction with 75 mg of aspirin in the Atrial Fibrillation, Aspirin, Anticoagulation Study was 18% (95% CI, 60% to 58%), and with 325 mg of aspirin in the Stroke Prevention in Atrial Fibrillation Study the risk reduction was 44% (95% CI, 7% to 66%). When both studies were combined the risk reduction was 36% (95% CI, 4% to 57%). The annual rate of major hemorrhage (intracranial bleeding or a bleed requiring hospitalization or 2 units of blood) was 1.0% for the control group, 1.0% for the aspirin group, and 1.3% for the warfarin group. In these five randomized trials warfarin consistently decreased the risk of stroke in patients with atrial fibrillation (a 68% reduction in risk) with virtually no increase in the frequency of major bleeding. Patients with atrial fibrillation younger than 65 years without a history of hypertension, previous stroke or transient ischemic attack, or diabetes were at very low risk of stroke even when not treated. The efficacy of aspirin was less consistent. Further studies are needed to clarify the role of aspirin in atrial fibrillation.

[Actual review of diagnostics and endovascular therapy of intracranial arterial stenoses].

PubMed

Gizewski, E R; Weber, R; Forsting, M

2011-02-01

Approximately 6 - 50% of all ischemic strokes are caused by intracranial arterial stenosis (IAS). Despite medical prevention, patients with symptomatic IAS have a high annual risk for recurrent ischemic stroke of about 12%, and up to 19% in the case of high-grade IAS (≥ 70%). Digital subtraction angiography remains the gold standard for the diagnosis and grading of IAS. However, noninvasive imaging techniques including CT angiography, MR angiography, or transcranial Doppler and duplex ultrasound examinations are used in the clinical routine to provide additional information about the brain structure and hemodynamic. However, for technical reasons, the grading of stenoses is sometimes difficult and inaccurate. To date, aspirin is recommended as the treatment of choice in the prevention of recurrent ischemic stroke in patients with IAS. IAS patients who suffer a recurrent ischemic stroke or transient ischemic attack while taking aspirin can be treated with endovascular stenting or angioplasty in specialized centers. The periprocedural complication rate of these endovascular techniques is about 2 - 7% at experienced neuro-interventional centers. The rate of re-stenosis is reported between 10 and 40% depending on patient age and stenosis location. Further randomized studies comparing medical secondary prevention and endovascular therapy are currently being performed. With regard to the improvement of endovascular methods and lower complication rates, the indication for endovascular therapy in IAS could be broadened especially for stenosis in the posterior circulation. © Georg Thieme Verlag KG Stuttgart · New York.

Impact of living and socioeconomic characteristics on cardiovascular risk in ischemic stroke patients.

PubMed

Amarenco, Pierre; Abboud, Halim; Labreuche, Julien; Arauz, Antonio; Bryer, Alan; Lavados, Pablo M; Massaro, Ayrton; Munoz Collazos, Mario; Steg, Philippe Gabriel; Yamout, Bassem I; Vicaut, Eric

2014-12-01

We aimed to stratify the risk of vascular event recurrence in patients with cerebral infarction according to living and socioeconomic characteristics and geographic region. The Outcomes in Patients with TIA and Cerebrovascular Disease (OPTIC) study is an international prospective study of patients aged 45 years or older who required secondary prevention of stroke [following either an acute transient ischemic attack, minor ischemic strokes, or recent (less than six-months previous), stable, first-ever, nondisabling ischemic stroke]. A total 3635 patients from 245 centers in 17 countries in four regions (Latin America, Middle East, North Africa, South Africa) were enrolled between 2007 and 2008. The outcome measure was the two-year rate of a composite of major vascular events (vascular death, myocardial infarction and stroke). During the two-year follow-up period, 516 patients experienced at least one major cardiovascular event, resulting in an event rate of 15·6% (95% confidence interval 14·4-16·9%). Event rates varied across geographical region (P < 0·001), ranging from 13·0% in Latin America to 20·7% in North Africa. Unemployment status, living in a rural area, not living in fully serviced accommodation (i.e., house or apartment with its own electricity, toilet and water supply), no health insurance coverage, and low educational level (less than two-years of schooling) were predictors of major vascular events. Major vascular event rates steeply increased with the number of low-quality living/socioeconomic conditions (from 13·4% to 47·9%, adjusted P value for trend <0·001). Vascular risk in stroke patients in low- and middle-income countries varies not only with the number of arterial beds involved but also with socioeconomic variables. © 2014 World Stroke Organization.

Symptomatic carotid stenosis and stroke risk in patients with transient ischemic attack according to the tissue-based definition.

PubMed

Al-Khaled, Mohamed; Scheef, Björn

2016-10-01

Symptomatic carotid stenosis (sCS), a common cause of transient ischemic attack (TIA), is correlated with higher stroke risk. We investigated the frequency and associated factors of sCS in patients with TIA and the association between sCS and stroke risk following TIA. Over a three-year period (2011-2013), 861 consecutive patients with TIA, who were admitted to the Department of Neurology at the University of Lübeck, Germany, were included in a monocenter study and prospectively evaluated. Diagnosis of TIA was in accordance with the tissue-based definition (transient neurological symptoms without evidence of infarction by brain imaging). Of 827 patients (mean age, 70 ± 13.2 years; 49.7% women), 64 patients (7.7%; 95% confidence interval [CI], 5.9%-9.7%) exhibited sCS and 3 patients (0.3%) showed an occlusion of the corresponding internal carotid artery. Logistic regression revealed that sCS was associated with male sex (odds ratio [OR], 2.7; 95% CI, 1.2-3.6; p = 0.012), amaurosis fugax (OR, 8.1; 95% CI, 3.4-19-4; p < 0.001), unilateral weakness (OR, 3.4; 95% CI, 1.9-6.1; p < 0.001), symptom duration less than 1 h (OR, 2.0; 95% CI, 1.1-3.4; p = 0.019) and previous stroke (OR, 2.7; 95% CI, 1.5-4.7; p = 0.001). During hospitalization (mean, 6.6 days), five patients (0.6%; 95% CI, 0.1%-1.2%) suffered from stroke. The stroke risk was higher in patients with sCS than in those without sCS (6.3% vs. 0.1%; p < 0.001), whereas the recurrent TIA risk (2.6%) did not differ between the groups (4.7% vs. 2.5%; p = 0.29). SCS appears to be associated with a higher risk of stroke in patients with TIA defined according to the tissue-based definition.

Family History in Young Patients With Stroke.

PubMed

Thijs, Vincent; Grittner, Ulrike; Dichgans, Martin; Enzinger, Christian; Fazekas, Franz; Giese, Anne-Katrin; Kessler, Christof; Kolodny, Edwin; Kropp, Peter; Martus, Peter; Norrving, Bo; Ringelstein, Erich Bernd; Rothwell, Peter M; Schmidt, Reinhold; Tanislav, Christian; Tatlisumak, Turgut; von Sarnowski, Bettina; Rolfs, Arndt

2015-07-01

Family history of stroke is an established risk factor for stroke. We evaluated whether family history of stroke predisposed to certain stroke subtypes and whether it differed by sex in young patients with stroke. We used data from the Stroke in Fabry Patients study, a large prospective, hospital-based, screening study for Fabry disease in young patients (aged <55 years) with stroke in whom cardiovascular risk factors and family history of stroke were obtained and detailed stroke subtyping was performed. A family history of stroke was present in 1578 of 4232 transient ischemic attack and ischemic stroke patients (37.3%). Female patients more often had a history of stroke in the maternal lineage (P=0.027) than in the paternal lineage. There was no association with stroke subtype according to Trial of Org 10172 in Acute Stroke Treatment nor with the presence of white matter disease on brain imaging. Patients with dissection less frequently reported a family history of stroke (30.4% versus 36.3%; P=0.018). Patients with a parental history of stroke more commonly had siblings with stroke (3.6% versus 2.6%; P=0.047). Although present in about a third of patients, a family history of stroke is not specifically related to stroke pathogenic subtypes in patients with young stroke. Young women with stroke more often report stroke in the maternal lineage. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2015 American Heart Association, Inc.

High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke.

PubMed

Carpenter, Randall S; Iwuchukwu, Ifeanyi; Hinkson, Cyrus L; Reitz, Sydney; Lee, Wonhee; Kukino, Ayaka; Zhang, An; Pike, Martin M; Ardelt, Agnieszka A

2016-05-15

Estrogens have previously been shown to protect the brain against acute ischemic insults, by potentially augmenting cerebrovascular function after ischemic stroke. The current study hypothesized that treatment with sustained release of high-dose 17β-estradiol (E2) at the time of reperfusion from middle cerebral artery occlusion (MCAO) in rats would attenuate reperfusion injury, augment post-stroke angiogenesis and cerebral blood flow, and attenuate lesion volume. Female Wistar rats underwent ovariectomy, followed two weeks later by transient, two-hour right MCAO (tMCAO) and treatment with E2 (n=13) or placebo (P; n=12) pellets starting at reperfusion. E2 treatment resulted in significantly smaller total lesion volume, smaller lesions within striatal and cortical brain regions, and less atrophy of the ipsilateral hemisphere after six weeks of recovery. E2-treated animals exhibited accelerated recovery of contralateral forelimb sensorimotor function in the cylinder test. Magnetic resonance imaging (MRI) showed that E2 treatment reduced the formation of lesion cysts, decreased lesion volume, and increased lesional cerebral blood flow (CBF). K(trans), a measure of vascular permeability, was increased in the lesions. This finding, which represents lesion neovascularization, was not altered by E2 treatment. Ischemic stroke-related angiogenesis and vessel formation was confirmed with immunolabeling of brain tissue and was not altered with E2 treatment. In summary, E2 treatment administered immediately following reperfusion significantly reduced lesion size, cyst formation, and brain atrophy while improving lesional CBF and accelerating recovery of functional deficits in a rat model of ischemic stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

Ischemic Strokes (Clots)

MedlinePlus

... Month Infographic Stroke Hero F.A.S.T. Quiz Ischemic Strokes (Clots) Updated:May 21,2018 Ischemic stroke accounts for about 87 percent of all cases. View a detailed animation of ischemic stroke . Ischemic strokes occur as a result of an ...

Risk factors for ischemic stroke and its subtypes in Chinese vs. Caucasians: Systematic review and meta-analysis.

PubMed

Tsai, Chung-Fen; Anderson, Niall; Thomas, Brenda; Sudlow, Cathie L M

2015-06-01

Chinese populations are reported to have a different distribution of ischemic stroke subtypes compared with Caucasians. To understand this better, we aimed to evaluate the differences in prevalence of risk factors in ischemic stroke and their distributions among ischemic stroke subtypes in Chinese vs. Caucasians. We systematically sought studies conducted since 1990 with data on frequency of risk factors among ischemic stroke subtypes in Chinese or Caucasians. For each risk factor, we calculated study-specific and random effects pooled estimates in Chinese and Caucasians separately for: prevalence among ischemic stroke; odds ratios, comparing prevalence for each ischemic stroke subtype vs. all others. We included seven studies among 16,199 Chinese, and eleven among 16,189 Caucasian ischemic stroke patients. Risk factors studied were hypertension, diabetes, atrial fibrillation, ischemic heart disease, hypercholesterolemia, smoking and alcohol. Chinese ischemic stroke patients had younger onset of stroke than Caucasians, similar prevalence of hypertension, diabetes, smoking and alcohol, and significantly lower prevalence of atrial fibrillation, ischemic heart disease and hypercholesterolemia. Risk factor associations with ischemic stroke subtypes were mostly similar among Chinese and Caucasian ischemic stroke patients. Compared with all other ischemic subtypes, diabetes was more common in large artery stroke, atrial fibrillation and ischemic heart disease in cardioembolic stroke, and hypertension and diabetes in lacunar stroke. Our study showed a lower prevalence of atrial fibrillation, ischemic heart disease and hypercholesterolemia in Chinese, and mostly similar risk factor associations in Chinese and Caucasian ischemic stroke patients. Further analyses of individual patient data to allow adjustment for confounders are needed to confirm and extend these findings. © 2015 World Stroke Organization.

Inpatient versus Outpatient Management of TIA or Minor Stroke: Clinical Outcome.

PubMed

Majidi, Shahram; Leon Guerrero, Christopher R; Burger, Kathleen M; Rothrock, John F

2017-06-01

The management of patients with acute transient ischemic attack (TIA) or minor stroke is highly variable. Whether hospitalization of such patients significantly improves short-term clinical outcome is unknown. We assessed the short-term clinical outcome associated with inpatient versus outpatient management of patients with TIA or minor stroke. We evaluated a consecutive series of patients with acute TIA or minor ischemic stroke (NIH Stroke Scale score ≤ 3) presenting to a single emergency department (ED). We randomized patients to either hospital-based or outpatient-based management. All patients underwent interview and examination 7-10 days following the index event. This study included 100 patients, 41 with TIA and 59 with minor stroke. Nineteen (46%) of the TIA patients and 29 (49%) of the minor stroke patients randomized to hospital management, and the remaining 22 TIA patients and 30 minor stroke patients randomized to outpatient-based management. In the patients with a minor stroke, neurologic worsening occurred in 6 out of 29 (21%) in the inpatient arm compared with 3 out of 30 (10%) in the outpatient arm ( p = 0.3). In none of these cases was acute interventional therapy or need for urgent admission considered medically appropriate. In the patients with a TIA, recurrence of a TIA occurred in 2 out of 19 (11%) in the inpatient arm compared with 2 out of 22 (9%) in the outpatient arm ( p = 1). None of the patients with a TIA randomized to the inpatient arm experienced a stroke compared with 1 out of 22 in the outpatient arm ( p = 1). There were no deaths in either group. Routine hospitalization of all patients with TIA or minor ischemic stroke may not positively affect short-term clinical outcome.

Inpatient versus Outpatient Management of TIA or Minor Stroke: Clinical Outcome

PubMed Central

Majidi, Shahram; Leon Guerrero, Christopher R.; Burger, Kathleen M.; Rothrock, John F.

2017-01-01

Background The management of patients with acute transient ischemic attack (TIA) or minor stroke is highly variable. Whether hospitalization of such patients significantly improves short-term clinical outcome is unknown. We assessed the short-term clinical outcome associated with inpatient versus outpatient management of patients with TIA or minor stroke. Methods We evaluated a consecutive series of patients with acute TIA or minor ischemic stroke (NIH Stroke Scale score ≤ 3) presenting to a single emergency department (ED). We randomized patients to either hospital-based or outpatient-based management. All patients underwent interview and examination 7–10 days following the index event. Results This study included 100 patients, 41 with TIA and 59 with minor stroke. Nineteen (46%) of the TIA patients and 29 (49%) of the minor stroke patients randomized to hospital management, and the remaining 22 TIA patients and 30 minor stroke patients randomized to outpatient-based management. In the patients with a minor stroke, neurologic worsening occurred in 6 out of 29 (21%) in the inpatient arm compared with 3 out of 30 (10%) in the outpatient arm (p = 0.3). In none of these cases was acute interventional therapy or need for urgent admission considered medically appropriate. In the patients with a TIA, recurrence of a TIA occurred in 2 out of 19 (11%) in the inpatient arm compared with 2 out of 22 (9%) in the outpatient arm (p = 1). None of the patients with a TIA randomized to the inpatient arm experienced a stroke compared with 1 out of 22 in the outpatient arm (p = 1). There were no deaths in either group. Conclusion Routine hospitalization of all patients with TIA or minor ischemic stroke may not positively affect short-term clinical outcome. PMID:28702120

Contribution of EEG in transient neurological deficits.

PubMed

Lozeron, Pierre; Tcheumeni, Nadine Carole; Turki, Sahar; Amiel, Hélène; Meppiel, Elodie; Masmoudi, Sana; Roos, Caroline; Crassard, Isabelle; Plaisance, Patrick; Benbetka, Houria; Guichard, Jean-Pierre; Houdart, Emmanuel; Baudoin, Hélène; Kubis, Nathalie

2018-01-01

Identification of stroke mimics and 'chameleons' among transient neurological deficits (TND) is critical. Diagnostic workup consists of a brain imaging study, for a vascular disease or a brain tumour and EEG, for epileptiform discharges. The precise role of EEG in this diagnostic workup has, however, never been clearly delineated. However, this could be crucial in cases of atypical or incomplete presentation with consequences on disease management and treatment. We analysed the EEG patterns on 95 consecutive patients referred for an EEG within 7 days of a TND with diagnostic uncertainty. Patients were classified at the discharge or the 3-month follow-up visit as: 'ischemic origin', 'migraine aura', 'focal seizure', and 'other'. All patients had a brain imaging study. EEG characteristics were correlated to the TND symptoms, imaging study, and final diagnosis. Sixty four (67%) were of acute onset. Median symptom duration was 45 min. Thirty two % were 'ischemic', 14% 'migraine aura', 19% 'focal seizure', and 36% 'other' cause. EEGs were recorded with a median delay of 1.6 day after symptoms onset. Forty EEGs (42%) were abnormal. Focal slow waves were the most common finding (43%), also in the ischemic group (43%), whether patients had a typical presentation or not. Epileptiform discharges were found in three patients, one with focal seizure and two with migraine aura. Non-specific EEG focal slowing is commonly found in TND, and may last several days. We found no difference in EEG presentation between stroke mimics and stroke chameleons, and between other diagnoses.

Coadministration of the Human Umbilical Cord Matrix-Derived Mesenchymal Cells and Aspirin Alters Postischemic Brain Injury in Rats.

PubMed

Shams ara, Ali; Sheibani, Vahid; Esmaeilpour, Khadije; Eslaminejad, Touba; Nematollahi-Mahani, Seyed N

2015-09-01

Ischemic stroke is an acute brain insult that induces dramatic changes in the neurons. Treatment of brain stroke is one of the main therapeutic targets of neuroprotective therapies. The aim of this study was to evaluate the protective potential of implanted human umbilical cord mesenchymal stem (hUCMs) cells with/without aspirin (ASA) against focal cerebral ischemia. We assessed the migration and distribution of PKH26-labeled cells after transplantation. After day 10 of transient occlusion, we evaluated the effect of ASA and hUCMs on the recovery of learning and memory in rats by Morris water maze. Afterward, animals were sacrificed, and the infarct area in the brain was evaluated using 2, 3, 5-triphenyltetrazolium chloride staining and also by hematoxylin and eosin. The recovery of learning and memory in ischemic animals that received ASA and hUCM cells improved significantly compared with the untreated ischemic animals. Coadministration of ASA and hUCM cells did not improve the outcome at a comparable rate with ASA and hUCM cells alone. PKH26-labeled cells were detectable in the ischemic area of the brain tissue sections. 2,3,5-Triphenyltetrazolium chloride staining and histologic examinations showed that treatment with ASA and hUCM cells could significantly alter the ischemic area. The results of the present study suggest that ASA and hUCM cells can withstand degenerative changes induced by artificial stroke in the rat. Also the learning and memory disturbance in the ASA and cell-treated animals is less pronounced than ischemic animals. Coadministration of ASA and hUCM cells did not raise the outcome higher than administration of ASA and hUCM cells alone. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Novel antiepileptic drug lacosamide exerts neuroprotective effects by decreasing glial activation in the hippocampus of a gerbil model of ischemic stroke.

PubMed

Ahn, Ji Yun; Yan, Bing Chun; Park, Joon Ha; Ahn, Ji Hyeon; Lee, Dae Hwan; Kim, In Hye; Cho, Jeong-Hwi; Chen, Bai Hui; Lee, Jae-Chul; Cho, Young Shin; Shin, Myoung Chul; Cho, Jun Hwi; Hong, Seongkweon; Won, Moo-Ho; Kim, Sung Koo

2015-12-01

Lacosamide, which is a novel antiepileptic drug, has been reported to exert various additional therapeutic effects. The present study investigated the neuroprotective effects of lacosamide against transient cerebral ischemia-induced neuronal cell damage in the hippocampal cornu ammonis (CA)-1 region of a gerbil model. Neuronal Nuclei immunohistochemistry demonstrated that pre- and post-surgical treatment (5 min ischemia) with 25 mg/kg lacosamide protected CA1 pyramidal neurons in the lacosamide-treated-ischemia-operated group from ischemic injury 5 days post-ischemia, as compared with gerbils in the vehicle-treated-ischemia-operated group. Furthermore, treatment with 25 mg/kg lacosamide markedly attenuated the activation of astrocytes and microglia in the ischemic CA1 region at 5 days post-ischemia. The results of the present study suggested that pre- and post-surgical treatment of the gerbils with lacosamide was able to protect against transient cerebral ischemic injury-induced CA1 pyramidal neuronal cell death in the hippocampus. In addition, the neuroprotective effects of lacosamide may be associated with decreased activation of glial cells in the ischemic CA1 region.

Dynamic change of collateral flow varying with distribution of regional blood flow in acute ischemic rat cortex

NASA Astrophysics Data System (ADS)

Wang, Zhen; Luo, Weihua; Zhou, Fangyuan; Li, Pengcheng; Luo, Qingming

2012-12-01

Cerebral blood flow (CBF) is critical for the maintenance of cerebral function by guaranteed constant oxygen and glucose supply to brain. Collateral channels (CCs) are recruited to provide alternatives to CBF to ischemic regions once the primary vessel is occluded during ischemic stroke. However, the knowledge of the relationship between dynamic evolution of collateral flow and the distribution of regional blood flow remains limited. In this study, laser speckle imaging was used to assess dynamic changes of CCs and regional blood flow in a rat cortex with permanent middle cerebral artery occlusion (MCAo). We found that CCs immediately provided blood flow to ischemic territories after MCAo. More importantly, there were three kinds of dynamic changes of CCs during acute stroke: persistent CC, impermanent CC, and transient CC, respectively, related to different distributions of regional blood flow. Although there was the possible occurrence of peri-infarct depolarization (PID) during ischemia, there was no obvious significance about the onset time and duration of CCs between rats with and without PID. These results suggest that the initial arising of CCs does not ensure their persistence, and that collateral flow could be varied with distribution of regional blood flow in acute ischemic stroke, which may facilitate the understanding of collateral recruitment and promote the development of collateral therapeutics in the future.

Dynamic change of collateral flow varying with distribution of regional blood flow in acute ischemic rat cortex.

PubMed

Wang, Zhen; Luo, Weihua; Zhou, Fangyuan; Li, Pengcheng; Luo, Qingming

2012-12-01

Cerebral blood flow (CBF) is critical for the maintenance of cerebral function by guaranteed constant oxygen and glucose supply to brain. Collateral channels (CCs) are recruited to provide alternatives to CBF to ischemic regions once the primary vessel is occluded during ischemic stroke. However, the knowledge of the relationship between dynamic evolution of collateral flow and the distribution of regional blood flow remains limited. In this study, laser speckle imaging was used to assess dynamic changes of CCs and regional blood flow in a rat cortex with permanent middle cerebral artery occlusion (MCAo). We found that CCs immediately provided blood flow to ischemic territories after MCAo. More importantly, there were three kinds of dynamic changes of CCs during acute stroke: persistent CC, impermanent CC, and transient CC, respectively, related to different distributions of regional blood flow. Although there was the possible occurrence of peri-infarct depolarization (PID) during ischemia, there was no obvious significance about the onset time and duration of CCs between rats with and without PID. These results suggest that the initial arising of CCs does not ensure their persistence, and that collateral flow could be varied with distribution of regional blood flow in acute ischemic stroke, which may facilitate the understanding of collateral recruitment and promote the development of collateral therapeutics in the future.

Endothelial dysfunction and arterial stiffness in ischemic stroke: the role of sleep-disordered breathing.

PubMed

Cereda, Carlo W; Tamisier, Renaud; Manconi, Mauro; Andreotti, Jennifer; Frangi, Jane; Pifferini, Valeria; Bassetti, Claudio L

2013-04-01

Sleep-disordered breathing (SDB) represents a risk factor for cardiovascular morbidity after a cerebral ischemic event (acute ischemic event, ischemic stroke, or transient ischemic attack). In the present study, endothelial function and arterial stiffness were analyzed in patients who experienced a postacute ischemic event with relation to SDB, sleep disruption, and nocturnal oxygenation parameters. SDB was assessed by full polysomnography in patients with acute ischemic event 3 months after the admission at our stroke unit. Moderate-severe SDB was defined according to the apnea-hypopnea index as apnea-hypopnea index ≥ 20. Endothelial function and arterial stiffness were assessed by peripheral arterial tonometry using Endo-PAT 2000. Thirty-seven patients were included. The augmentation index was significantly different between patients with apnea-hypopnea index <20 and apnea-hypopnea index ≥ 20 (22.4 ± 15.6% versus 34.6 ± 21.6%; P=0.042), whereas reactive hyperemia index level was not (2.02 ± 0.65 versus 2.31 ± 0.61; P=0.127). Patients with apnea-hypopnea index ≥ 20 showed an increased risk for arterial stiffness (odds ratio, 5.98 [95% CI, 1.11-41.72]) even when controlling for age, sex, body mass index, hypertension, and diabetes mellitus. The augmentation index was correlated with the arousal index (P=0.010) and with mean O2 saturation (P = 0.043). Poststroke patients with moderate-severe SDB were more prone to have increased arterial stiffness, although we did not find significant differences in endothelial function. Arterial stiffness also correlated with sleep disruption (arousal index) and mean O2 saturation.

The European Stroke Organisation Guidelines: a standard operating procedure.

PubMed

Ntaios, George; Bornstein, Natan M; Caso, Valeria; Christensen, Hanne; De Keyser, Jacques; Diener, Hans-Christoph; Diez-Tejedor, Exuperio; Ferro, Jose M; Ford, Gary A; Grau, Armin; Keller, Emanuella; Leys, Didier; Russell, David; Toni, Danilo; Turc, Guillaume; Van der Worp, Bart; Wahlgren, Nils; Steiner, Thorsten

2015-10-01

In 2008, the recently founded European Stroke Organisation published its guidelines for the management of ischemic stroke and transient ischemic attack. This highly cited document was translated in several languages and was updated in 2009. Since then, the European Stroke Organisation has published guidelines for the management of intracranial aneurysms and subarachnoidal hemorrhage, for the establishment of stroke units and stroke centers, and recently for the management of intracerebral hemorrhage. In recent years, the methodology for the development of guidelines has evolved significantly. To keep pace with this progress and driven by the strong determination of the European Stroke Organisation to further promote stroke management, education, and research, the European Stroke Organisation decided to delineate a detailed standard operating procedure for its guidelines. There are two important cornerstones in this standard operating procedure: The first is the implementation of the Grading of Recommendations Assessment, Development, and Evaluation methodology for the development of its Guideline Documents. The second one is the decision of the European Stroke Organisation to move from the classical model of a single Guideline Document about a major topic (e.g. management of ischemic stroke) to focused modules (i.e. subdivisions of a major topic). This will enable the European Stroke Organisation to react faster when new developments in a specific stroke field occur and update its recommendations on the related module rather swiftly; with the previous approach of a single large Guideline Document, its entire revision had to be completed before an updated publication, delaying the production of up-to-date guidelines. After discussion within the European Stroke Organisation Guidelines Committee and significant input from European Stroke Organisation members as well as methodologists and analysts, this document presents the official standard operating procedure for the development of the Guideline Documents of the European Stroke Organisation. © 2015 World Stroke Organization.

Cost‐Effectiveness of Clopidogrel‐Aspirin Versus Aspirin Alone for Acute Transient Ischemic Attack and Minor Stroke

PubMed Central

Pan, Yuesong; Wang, Anxin; Liu, Gaifen; Zhao, Xingquan; Meng, Xia; Zhao, Kun; Liu, Liping; Wang, Chunxue; Johnston, S. Claiborne; Wang, Yilong; Wang, Yongjun

2014-01-01

Background Treatment with the combination of clopidogrel and aspirin taken soon after a transient ischemic attack (TIA) or minor stroke was shown to reduce the 90‐day risk of stroke in a large trial in China, but the cost‐effectiveness is unknown. This study sought to estimate the cost‐effectiveness of the clopidogrel‐aspirin regimen for acute TIA or minor stroke. Methods and Results A Markov model was created to determine the cost‐effectiveness of treatment of acute TIA or minor stroke patients with clopidogrel‐aspirin compared with aspirin alone. Inputs for the model were obtained from clinical trial data, claims databases, and the published literature. The main outcome measure was cost per quality‐adjusted life‐years (QALYs) gained. One‐way and multivariable probabilistic sensitivity analyses were performed to test the robustness of the findings. Compared with aspirin alone, clopidogrel‐aspirin resulted in a lifetime gain of 0.037 QALYs at an additional cost of CNY 1250 (US$ 192), yielding an incremental cost‐effectiveness ratio of CNY 33 800 (US$ 5200) per QALY gained. Probabilistic sensitivity analysis showed that clopidogrel‐aspirin therapy was more cost‐effective in 95.7% of the simulations at a willingness‐to‐pay threshold recommended by the World Health Organization of CNY 105 000 (US$ 16 200) per QALY. Conclusions Early 90‐day clopidogrel‐aspirin regimen for acute TIA or minor stroke is highly cost‐effective in China. Although clopidogrel is generic, Plavix is brand in China. If Plavix were generic, treatment with clopidogrel‐aspirin would have been cost saving. PMID:24904018

Dolichoectasia in vertebrobasilar arteries presented as transient ischemic attacks: A case report.

PubMed

Najafi, Mohammad Reza; Toghianifar, Nafiseh; Abdar Esfahani, Morteza; Najafi, Mohammad Amin; Mollakouchakian, Mohammad Javad

2016-01-01

Vertebrobasilar dolichoectasia (VBD) is a rare vasculopathy. The etiology of this disease is unknown. Transient ischemic attacks (TIAs) of vertebrobasilar system refer to a transient (< 24 hours) lowering of blood flow in the posterior circulation of the brain. We present a case of dolichoectasia in the vertebrobasilar artery that presented with TIAs. A hypertensive 54-year-old man with true vertigo, nausea, imbalance, dysarthria, dysmetria, horizontal nystagmus, and gait ataxia was referred to Alzahra Hospital, Isfahan, Iran. The symptoms improved in the 1st day, but recurred in the 2nd day, lasting for 6-7 hours. According to clinical manifestations, a diagnosis of TIAs in the vertebrobasilar circulation was made. Imaging studies showed vascular anomaly. The vascular anomaly was considered as the cause of the patient's symptoms. A medical management was started using antiplatelet and antihypertensive drugs. The patient was referred for a more evaluation for other vascular anomalies. Dolichoectasia usually affects vertebral and basilar arteries and simultaneous involvement of carotid arteries is rare seen in only 0.5% of these patients. The usual symptom of dolichoectasia is ischemia and rarely hemorrhages. The most common type of ischemic stroke is lacunar type. Ischemia evolves from embolic that originate from thrombi or plaques in the walls of the ectatic artery. While hemodynamic effects are the most common cause of the presenting signs and symptoms of the anomaly. We report a case of dolichoectasia that presented with TIAs of the verterbrobasilar artery. VBD is a distinct arteriopathy known as stroke risk.

Atrial ectopic activity in cryptogenic ischemic stroke and TIA: a risk factor for recurrence.

PubMed

Pinho, João; Braga, Carlos Galvão; Rocha, Sofia; Santos, Ana Filipa; Gomes, André; Cabreiro, Ana; Magalhães, Sónia; Ferreira, Carla

2015-02-01

To characterize atrial ectopic activity in patients with cryptogenic ischemic stroke (CIS) or transient ischemic attack (TIA) and determine its prognostic significance. Retrospective cohort study, in which 184 patients with CIS or TIA who had performed 24-hour Holter electrocardiogram were included. The median follow-up was 27.5 months. Baseline clinical and imagiologic characteristics, etiologic investigation results, and ischemic stroke and TIA recurrences information were collected. Number of atrial premature complexes (APCs) per hour was categorized as less than 10 APCs/hour, 10-30 APCs/hour, and more than 30 APCs/hour. Most of the patients had less than 10 APCs/hour (82.6%), 8.2% had 10-30 APCs/hour, and 9.2% had more than 30 APCs/hour. Patients with more than 30 APCs/hour had a greater median left atrium diameter than patients with 30 APCs/hour or less (42 mm vs. 38 mm; 95% confidence interval [CI], .50-7.00; P = .003). Annual recurrence rate of CIS or TIA was 2.9% in patients with less than 10 APCs/hour, 11.0% in 10-30 APCs/hour, and 22.6% in more than 30 APCs/hour (P = .001). More than 30 APCs/hour were independently associated with recurrence risk in multivariate survival analysis (hazard ratio, 3.40; 95% CI, 1.12-10.32; P = .030). In patients with CIS or TIA, frequent atrial ectopic activity (>30 APCs/h) was independently associated with increased risk of stroke or TIA recurrence. Further studies need to validate frequent atrial ectopic activity as a risk factor for recurrence in cryptogenic stroke and confirm its role as a predictor of occult atrial fibrillation. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of percutaneous left atrial appendage closure to prevent thromboembolic events in atrial fibrillation patients with high stroke and bleeding risk.

PubMed

Seeger, Julia; Bothner, Carlo; Dahme, Tillman; Gonska, Birgid; Scharnbeck, Dominik; Markovic, Sinisa; Rottbauer, Wolfgang; Wöhrle, Jochen

2016-03-01

The randomized PROTECT AF trial demonstrated non-inferiority of left atrial appendage (LAA) closure to oral anticoagulation with warfarin. Current guidelines give a class IIb recommendation for LAA closure. We evaluated the efficacy and safety of LAA closure in a consecutive series of non-valvular atrial fibrillation patients with contraindications to long-term oral anticoagulation or at high bleeding risk. 101 consecutive non-valvular atrial fibrillation patients (age 74.7 ± 7.5 years) at high risk for stroke (CHA2DS2-VASc Score 4.4 ± 1.6) and high bleeding risk (HAS-BLED Score 4.2 ± 1.3) received LAA closure with either the Watchman closure device (n = 38) or the Amplatzer cardiac plug (n = 63). Dual antiplatelet therapy with aspirin and clopidogrel was recommended for 3-6 months after device implantation, followed by long-term antiplatelet therapy with aspirin. No anticoagulation was given after device implantation. Mean follow-up was 400 days. One patient (1 %) experienced a transient ischemic attack, and two patients (2 %) suffered from ischemic stroke. While on recommended antiplatelet therapy, bleeding occurred in 12/101 patients (12 %). Bleeding was significantly reduced with 3 compared with 6 months dual antiplatelet therapy (3.0 vs. 16.2 %, p < 0.05) while ischemic or thrombotic events were similar. Left atrial appendage closure in patients with non-valvular atrial fibrillation and high risk for stroke and bleeding events effectively prevented stroke and reduced cerebral ischemic events compared to expected stroke rate according to CHA2DS2-VASc Score. Dual antiplatelet therapy for 3 months reduced the rate of bleeding events compared to 6 months therapy with no increase of thrombotic events.

Short‐term Changes in Ambient Particulate Matter and Risk of Stroke: A Systematic Review and Meta‐analysis

PubMed Central

Wang, Yi; Eliot, Melissa N.; Wellenius, Gregory A.

2014-01-01

Background Stroke is a leading cause of death and long‐term disability in the United States. There is a well‐documented association between ambient particulate matter air pollution (PM) and cardiovascular disease morbidity and mortality. Given the pathophysiologic mechanisms of these effects, short‐term elevations in PM may also increase the risk of ischemic and/or hemorrhagic stroke morbidity and mortality, but the evidence has not been systematically reviewed. Methods and Results We provide a comprehensive review of all observational human studies (January 1966 to January 2014) on the association between short‐term changes in ambient PM levels and cerebrovascular events. We also performed meta‐analyses to evaluate the evidence for an association between each PM size fraction (PM2.5, PM10, PM2.5‐10) and each outcome (total cerebrovascular disease, ischemic stroke/transient ischemic attack, hemorrhagic stroke) separately for mortality and hospital admission. We used a random‐effects model to estimate the summary percent change in relative risk of the outcome per 10‐μg/m3 increase in PM. Conclusions We found that PM2.5 and PM10 are associated with a 1.4% (95% CI 0.9% to 1.9%) and 0.5% (95% CI 0.3% to 0.7%) higher total cerebrovascular disease mortality, respectively, with evidence of inconsistent, nonsignificant associations for hospital admission for total cerebrovascular disease or ischemic or hemorrhagic stroke. Current limited evidence does not suggest an association between PM2.5‐10 and cerebrovascular mortality or morbidity. We discuss the potential sources of variability in results across studies, highlight some observations, and identify gaps in literature and make recommendations for future studies. PMID:25103204

Effects of long-term post-ischemic treadmill exercise on gliosis in the aged gerbil hippocampus induced by transient cerebral ischemia

PubMed Central

Ahn, Ji Hyeon; Shin, Myoung Cheol; Park, Joon Ha; Kim, In Hye; Cho, Jeong-Hwi; Lee, Tae-Kyeong; Lee, Jae-Chul; Chen, Bai Hui; Shin, Bich Na; Tae, Hyun-Jin; Park, Jinseu; Choi, Soo Young; Lee, Yun Lyul; Kim, Dae Won; Kim, Yang Hee; Won, Moo-Ho; Cho, Jun Hwi

2017-01-01

Therapeutic exercise is an integral component of the rehabilitation of patients who have suffered a stroke. The objective of the present study was to use immunohistochemistry to investigate the effects of post-ischemic exercise on neuronal damage or death and gliosis in the aged gerbil hippocampus following transient cerebral ischemia. Aged gerbils (male; age, 22–24 months) underwent ischemia and were subjected to treadmill exercise for 1 or 4 weeks. Neuronal death was detected in the stratum pyramidale of the hippocampal CA1 region and in the polymorphic layer of the dentate gyrus using cresyl violet and Fluoro-Jade B histofluorescence staining. No significant difference in neuronal death was identified following 1 or 4 weeks of post-ischemic treadmill exercise. However, post-ischemic treadmill exercise affected gliosis (the activation of astrocytes and microglia). Glial fibrillary acidic protein-immunoreactive astrocytes and ionized calcium binding adaptor molecule 1-immunoreactive microglia were activated in the CA1 and polymorphic layer of the dentate gyrus of the group without treadmill exercise. Conversely, 4 weeks of treadmill exercise significantly alleviated ischemia-induced astrocyte and microglial activation; however, 1 week of treadmill exercise did not alleviate gliosis. These findings suggest that long-term post-ischemic treadmill exercise following transient cerebral ischemia does not influence neuronal protection; however, it may effectively alleviate transient cerebral ischemia-induced astrocyte and microglial activation in the aged hippocampus. PMID:28440411

Living within stories: Exploring the experiences of people with transient ischemic attack.

PubMed

Crowfoot, Gary Mitchell; van der Riet, Pamela Jane; Maguire, Jane Margaret

2016-03-01

A transient ischemic attack (TIA) significantly increases a person's risk of ischemic stroke. However, little is known about the experiences of these people or what influences their decision to access care. This article explores the stories of three people who experienced a TIA. All participants were interviewed after receiving a diagnosis of TIA by a specialist neurologist. By utilizing a framework of narrative inquiry, several storylines were revealed across temporal, social, and geographical landscapes. The main storylines include: bodily disruption, time stasis, altered temporal perceptions, the roles of others, and help-seeking behavior. The primary author also reflects upon his own origin and explores how this inquiry has influenced his perceptions, career, and nursing practice. This inquiry may assist healthcare workers to gain insight into the experiences of people with TIA and suggests how involvement of significant others is beneficial when educating people at risk of TIA. © 2015 Wiley Publishing Asia Pty Ltd.

Multiple biomarkers and risk of clinical and subclinical vascular brain injury: the framingham offspring study

USDA-ARS?s Scientific Manuscript database

Several biomarkers have been individually associated with vascular brain injury, but no prior study has explored the simultaneous association of a biologically plausible panel of biomarkers with the incidence of stroke/transient ischemic attack and the prevalence of subclinical brain injury. In 3127...

Patient-Centred Innovations for Persons With Multimorbidity - Quebec

ClinicalTrials.gov

2017-12-13

Hypertension; Depression; Anxiety; Musculoskeletal Pain; Arthritis; Rheumatoid Arthritis; Osteoporosis; Chronic Obstructive Pulmonary Disease (COPD); Asthma; Chronic Bronchitis; Cardiovascular Disease; Heart Failure; Stroke; Transient Ischemic Attacks; Ulcer; Gastroesophageal Reflux; Irritable Bowel; Crohn's Disease; Ulcerative Colitis; Diverticulosis; Chronic Hepatitis; Diabetes; Thyroid Disorder; Cancer; Kidney Disease; Urinary Tract Problem; Dementia; Alzheimer's Disease; Hyperlipidemia; HIV

Aspirin Versus Aspirin Plus Clopidogrel as Antithrombotic Treatment Following Transcatheter Aortic Valve Replacement With a Balloon-Expandable Valve: The ARTE (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation) Randomized Clinical Trial.

PubMed

Rodés-Cabau, Josep; Masson, Jean-Bernard; Welsh, Robert C; Garcia Del Blanco, Bruno; Pelletier, Marc; Webb, John G; Al-Qoofi, Faisal; Généreux, Philippe; Maluenda, Gabriel; Thoenes, Martin; Paradis, Jean-Michel; Chamandi, Chekrallah; Serra, Vicenç; Dumont, Eric; Côté, Mélanie

2017-07-10

The aim of this study was to compare aspirin plus clopidogrel with aspirin alone as antithrombotic treatment following transcatheter aortic valve replacement (TAVR) for the prevention of ischemic events, bleeding events, and death. Few data exist on the optimal antithrombotic therapy following TAVR. This was a randomized controlled trial comparing aspirin (80 to 100 mg/day) plus clopidogrel (75 mg/day) (dual antiplatelet therapy [DAPT]) versus aspirin alone (single-antiplatelet therapy [SAPT]) in patients undergoing TAVR with a balloon-expandable valve. The primary endpoint was the occurrence of death, myocardial infarction (MI), stroke or transient ischemic attack, or major or life-threatening bleeding (according to Valve Academic Research Consortium 2 definitions) within the 3 months following the procedure. The trial was prematurely stopped after the inclusion of 74% of the planned study population. A total of 222 patients were included, 111 allocated to DAPT and 111 to SAPT. The composite of death, MI, stroke or transient ischemic attack, or major or life-threatening bleeding tended to occur more frequently in the DAPT group (15.3% vs. 7.2%, p = 0.065). There were no differences between groups in the occurrence of death (DAPT, 6.3%; SAPT, 3.6%; p = 0.37), MI (DAPT, 3.6%; SAT, 0.9%; p = 0.18), or stroke or transient ischemic attack (DAPT, 2.7%; SAPT, 0.9%; p = 0.31) at 3 months. DAPT was associated with a higher rate of major or life-threatening bleeding events (10.8% vs. 3.6% in the SAPT group, p = 0.038). There were no differences between groups in valve hemodynamic status post-TAVR. This small trial showed that SAPT (vs. DAPT) tended to reduce the occurrence of major adverse events following TAVR. SAPT reduced the risk for major or life-threatening events while not increasing the risk for MI or stroke. Larger studies are needed to confirm these results. (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation: The ARTE Trial [ARTE], NCT01559298; Aspirin Versus Aspirin+Clopidogrel as Antithrombotic Treatment Following TAVI [ARTE], NCT02640794). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Dabigatran Etexilate Reduces Thrombin-Induced Inflammation and Thrombus Formation in Experimental Ischemic Stroke.

PubMed

Dittmeier, Melanie; Wassmuth, Kathrin; Schuhmann, Michael K; Kraft, Peter; Kleinschnitz, Christoph; Fluri, Felix

2016-01-01

Dabigatran etexilate (DE), a direct-acting, oral inhibitor of thrombin, significantly reduces the risk of stroke compared with traditional anticoagulants, without increasing the risk of major bleeding. However, studies on the fate of cerebral tissue after ischemic stroke in patients receiving DE are sparse and the role of dabigatran-mediated reduction of thrombin in this context has not yet been investigated. Here, we investigated whether pretreatment with DE reduces thrombin-mediated pro-inflammatory mechanisms and leakage of the blood-brain barrier (BBB) following ischemic stroke in rats. Male Wistar rats received DE (15 mg/kg) or a vehicle solution 1 hour before transient middle cerebral artery occlusion (tMCAO) for 90 minutes. Infarct volume, neurologic outcome and intracranial hemorrhage (ICH) were determined after tMCAO. Thrombin generation was indirectly assessed by measuring thrombin/antithrombin III complex. Microvascular patency was evaluated histologically. Cytokine expression and immunoreactivity of cluster of differentiation (CD) 68 were examined to characterize inflammatory processes after pretreatment with DE. BBB integrity was examined by quantifying brain edema. Rats given DE revealed a significant reduction in infarct size without an increase in ICH and significant recovery of neurologic deficits compared to controls. Administration of DE decreased thrombin generation and thrombus formation, dampened the CD68-immunoreactivity and attenuated pro-inflammatory cytokine expression in the cerebral parenchyma ipsilateral to the ischemic lesion. BBB permeability was unaltered following treatment with DE. In summary, prophylactic anticoagulation with DE improves stroke outcome by reducing thrombin-induced inflammation and thrombus formation without increasing the rate of ICH.

Dietary Intake of α-Linolenic Acid Is Not Appreciably Associated with Risk of Ischemic Stroke among Middle-Aged Danish Men and Women.

PubMed

Bork, Christian S; Venø, Stine K; Lundbye-Christensen, Søren; Jakobsen, Marianne U; Tjønneland, Anne; Schmidt, Erik B; Overvad, Kim

2018-06-01

Intake of the plant-derived omega-3 (n-3) fatty acid α-linolenic acid (ALA) may reduce the risk of ischemic stroke. We have investigated the associations between dietary intake of ALA and the risk of ischemic stroke and ischemic stroke subtypes. This was a follow-up study. A total of 57,053 participants aged 50-64 y were enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Intake of ALA was assessed by a validated semiquantitative food frequency questionnaire. Potential incident cases of ischemic stroke were identified in the Danish National Patient Register, validated, and classified into subtypes based on assumed etiology. Statistical analyses were performed via Cox proportional hazard regression with adjustment for established ischemic stroke risk factors. A total of 1859 ischemic stroke cases were identified during a median of 13.5 y of follow-up. In multivariable analyses using restricted cubic splines adjusting for traditional risk factors for ischemic stroke, we observed no clear associations between dietary intake of ALA and the risk of total ischemic stroke or any of its subtypes including ischemic stroke due to large artery atherosclerosis, ischemic stroke due to small-vessel occlusion, and ischemic stroke due to cardio-embolism. Dietary intake of ALA was neither consistently nor appreciably associated with the risk of ischemic stroke or ischemic stroke subtypes among middle-aged Danish men and women. This study was registered at clinicaltrials.gov as NCT03258983.

Dipyridamole for preventing recurrent ischemic stroke and other vascular events: a meta-analysis of individual patient data from randomized controlled trials.

PubMed

Leonardi-Bee, Jo; Bath, Philip M W; Bousser, Marie-Germaine; Davalos, Antoni; Diener, Hans-Christoph; Guiraud-Chaumeil, Bernard; Sivenius, Juhani; Yatsu, Frank; Dewey, Michael E

2005-01-01

Results from randomized controlled trials of dipyridamole, given with or without aspirin, for secondary prevention after ischemic stroke or transient ischemic attack (TIA) have given conflicting results. We performed a meta-analysis using individual patient data from relevant randomized controlled trials. Randomized controlled trials involving dipyridamole in patients with previous ischemic stroke or TIA were sought from searches of the Cochrane Library, other electronic databases, references lists, earlier reviews, and contact with the manufacturer of dipyridamole. Individual patient data were merged from 5 of 7 relevant trials involving 11 459 patients. Results were adjusted for age, gender, qualifying event, and history of previous hypertension. Recurrent stroke was reduced by dipyridamole as compared with control (OR, 0.82; 95% CI, 0.68 to 1.00), and by combined aspirin and dipyridamole versus aspirin alone (OR, 0.78; 95% CI, 0.65 to 0.93), dipyridamole alone (OR, 0.74; 95% CI, 0.60 to 0.90), or control (OR, 0.61; 95% CI, 0.51 to 0.71). The point estimates obtained for the comparisons of aspirin and dipyridamole versus control (OR, 0.63; significant) or versus aspirin (OR, 0.88; nonsignificant) were similar if the data from the largest trial, ESPS II (which provided 57% of data), were excluded. Similar findings were observed for nonfatal stroke. The combination of aspirin and dipyridamole also significantly reduced the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone (OR, 0.84; 95% CI, 0.72 to 0.97), dipyridamole alone (OR, 0.76; 95% CI, 0.64 to 0.90), or control (OR, 0.66; 95% CI, 0.57 to 0.75). Vascular death was not altered in any group. Dipyridamole, given alone or with aspirin, reduces stroke recurrence in patients with previous ischemic cerebrovascular disease. The combination of aspirin and dipyridamole also reduces the composite of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone.

Phosphorylated recombinant HSP27 protects the brain and attenuates blood-brain barrier disruption following stroke in mice receiving intravenous tissue-plasminogen activator.

PubMed

Shimada, Yoshiaki; Shimura, Hideki; Tanaka, Ryota; Yamashiro, Kazuo; Koike, Masato; Uchiyama, Yasuo; Urabe, Takao; Hattori, Nobutaka

2018-01-01

Loss of integrity of the blood-brain barrier (BBB) in ischemic stroke victims initiates a devastating cascade of events causing brain damage. Maintaining the BBB is important to preserve brain function in ischemic stroke. Unfortunately, recombinant tissue plasminogen activator (tPA), the only effective fibrinolytic treatment at the acute stage of ischemic stroke, also injures the BBB and increases the risk of brain edema and secondary hemorrhagic transformation. Thus, it is important to identify compounds that maintain BBB integrity in the face of ischemic injury in patients with stroke. We previously demonstrated that intravenously injected phosphorylated recombinant heat shock protein 27 (prHSP27) protects the brains of mice with transient middle cerebral artery occlusion (tMCAO), an animal stroke-model. Here, we determined whether prHSP27, in addition to attenuating brain injury, also decreases BBB damage in hyperglycemic tMCAO mice that had received tPA. After induction of hyperglycemia and tMCAO, we examined 4 treatment groups: 1) bovine serum albumin (BSA), 2) prHSP27, 3) tPA, 4) tPA plus prHSP27. We examined the effects of prHSP27 by comparing the BSA and prHSP27 groups and the tPA and tPA plus prHSP27 groups. Twenty-four hours after injection, prHSP27 reduced infarct volume, brain swelling, neurological deficits, the loss of microvessel proteins and endothelial cell walls, and mortality. It also reduced the rates of hemorrhagic transformation, extravasation of endogenous IgG, and MMP-9 activity, signs of BBB damage. Therefore, prHSP27 injection attenuated brain damage and preserved the BBB in tPA-injected, hyperglycemic tMCAO experimental stroke-model mice, in which the BBB is even more severely damaged than in simple tMCAO mice. The attenuation of brain damage and BBB disruption in the presence of tPA suggests the effectiveness of prHSP27 and tPA as a combination therapy. prHSP27 may be a novel therapeutic agent for ischemic stroke patients whose BBBs are injured following tPA injections.

One-Year Incidence, Time Trends, and Predictors of Recurrent Ischemic Stroke in Sweden From 1998 to 2010: An Observational Study.

PubMed

Bergström, Lisa; Irewall, Anna-Lotta; Söderström, Lars; Ögren, Joachim; Laurell, Katarina; Mooe, Thomas

2017-08-01

Recent data on the incidence, time trends, and predictors of recurrent ischemic stroke are limited for unselected patient populations. Data for ischemic stroke patients were obtained from The Swedish Stroke Register (Riksstroke) between 1998 and 2009 and merged with The Swedish National Inpatient Register. A reference group of patients was created by Statistics Sweden. The ischemic stroke patient cohort was divided into 4 time periods. Recurrent ischemic stroke within 1 year was recorded until 2010. Kaplan-Meier and Cox regression analyses were performed to study time trends and predictors of ischemic stroke recurrence. Of 196 765 patients with ischemic stroke, 11.3% had a recurrent ischemic stroke within 1 year. The Kaplan-Meier estimates of the 1-year cumulative incidence of recurrent ischemic stroke decreased from 15.0% in 1998 to 2001 to 12.0% in 2007 to 2010 in the stroke patient cohort while the cumulative incidence of ischemic stroke decreased from 0.7% to 0.4% in the reference population. Age >75 years, prior ischemic stroke or myocardial infarction, atrial fibrillation without warfarin treatment, diabetes mellitus, and treatment with β-blockers or diuretics were associated with a higher risk while warfarin treatment for atrial fibrillation, lipid-lowering medication, and antithrombotic treatment (acetylsalicylic acid, dipyridamole) were associated with a reduced risk of recurrent ischemic stroke. The risk of recurrent ischemic stroke decreased from 1998 to 2010. Well-known risk factors for stroke were associated with a higher risk of ischemic stroke recurrence; whereas, secondary preventive medication was associated with a reduced risk, emphasizing the importance of secondary preventive treatment. © 2017 American Heart Association, Inc.

Intracerebral hemorrhage and deep microbleeds associated with cnm-positive Streptococcus mutans; a hospital cohort study

PubMed Central

Tonomura, Shuichi; Ihara, Masafumi; Kawano, Tomohiro; Tanaka, Tomotaka; Okuno, Yoshinori; Saito, Satoshi; Friedland, Robert P.; Kuriyama, Nagato; Nomura, Ryota; Watanabe, Yoshiyuki; Nakano, Kazuhiko; Toyoda, Kazunori; Nagatsuka, Kazuyuki

2016-01-01

Oral infectious diseases are epidemiologically associated with stroke. We previously showed that oral Streptococcus mutans with the cnm gene encoding a collagen-binding Cnm protein induced intracerebral hemorrhage (ICH) experimentally and was also associated with cerebral microbleeds (CMBs) in our population-based cohort study. We therefore investigated the roles of cnm-positive Streptococcus mutans in this single hospital-based, observational study that enrolled 100 acute stroke subjects. The cnm gene in Streptococcus mutans isolated from saliva was screened using PCR techniques and its collagen-binding activities examined. CMBs were evaluated on T2* gradient-recalled echo MRI. One subject withdrew informed consent and 99 subjects (63 males) were analyzed, consisting of 67 subjects with ischemic stroke, 5 with transient ischemic attack, and 27 with ICH. Eleven cases showed Streptococcus mutans strains positive for cnm. The presence of cnm-positive Streptococcus mutans was significantly associated with ICH [OR vs. ischemic stroke, 4.5; 95% CI, 1.17–19.1] and increased number of deep CMBs [median (IQR), 3 (2–9) vs. 0 (0–1), p = 0.0002]. In subjects positive for Streptococcus mutans, collagen binding activity was positively correlated with the number of deep CMBs (R2 = 0.405; p < 0.0001). These results provide further evidence for the key role of oral health in stroke. PMID:26847666

Intracerebral hemorrhage and deep microbleeds associated with cnm-positive Streptococcus mutans; a hospital cohort study.

PubMed

Tonomura, Shuichi; Ihara, Masafumi; Kawano, Tomohiro; Tanaka, Tomotaka; Okuno, Yoshinori; Saito, Satoshi; Friedland, Robert P; Kuriyama, Nagato; Nomura, Ryota; Watanabe, Yoshiyuki; Nakano, Kazuhiko; Toyoda, Kazunori; Nagatsuka, Kazuyuki

2016-02-05

Oral infectious diseases are epidemiologically associated with stroke. We previously showed that oral Streptococcus mutans with the cnm gene encoding a collagen-binding Cnm protein induced intracerebral hemorrhage (ICH) experimentally and was also associated with cerebral microbleeds (CMBs) in our population-based cohort study. We therefore investigated the roles of cnm-positive Streptococcus mutans in this single hospital-based, observational study that enrolled 100 acute stroke subjects. The cnm gene in Streptococcus mutans isolated from saliva was screened using PCR techniques and its collagen-binding activities examined. CMBs were evaluated on T2* gradient-recalled echo MRI. One subject withdrew informed consent and 99 subjects (63 males) were analyzed, consisting of 67 subjects with ischemic stroke, 5 with transient ischemic attack, and 27 with ICH. Eleven cases showed Streptococcus mutans strains positive for cnm. The presence of cnm-positive Streptococcus mutans was significantly associated with ICH [OR vs. ischemic stroke, 4.5; 95% CI, 1.17-19.1] and increased number of deep CMBs [median (IQR), 3 (2-9) vs. 0 (0-1), p = 0.0002]. In subjects positive for Streptococcus mutans, collagen binding activity was positively correlated with the number of deep CMBs (R(2) = 0.405; p < 0.0001). These results provide further evidence for the key role of oral health in stroke.

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

PubMed

Beretta, Simone; Versace, Alessandro; Carone, Davide; Riva, Matteo; Dell'Era, Valentina; Cuccione, Elisa; Cai, Ruiyao; Monza, Laura; Pirovano, Silvia; Padovano, Giada; Stiro, Fabio; Presotto, Luca; Paternò, Giovanni; Rossi, Emanuela; Giussani, Carlo; Sganzerla, Erik P; Ferrarese, Carlo

2017-10-01

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p < 0.001) and higher chance of good functional outcome (OR 4.58, p < 0.001). Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p < 0.001) and lateral (+19.2%; p = 0.016) MCA territory compared to pretreatment during MCA occlusion. Safety indicators were treatment-related mortality and cardiorespiratory effects. The highest efficacy and safety profile was observed for HDT. Our findings suggest that acute modulation of cerebral collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

Cerebral microbleeds are not associated with long-term cognitive outcome in patients with transient ischemic attack or minor stroke.

PubMed

Brundel, Manon; Kwa, Vincent I H; Bouvy, Willem H; Algra, Ale; Kappelle, L Jaap; Biessels, Geert Jan

2014-01-01

Cerebral microbleeds have been related to cerebrovascular disease and dementia. They occur more frequently in patients with ischemic stroke than in the general population, but their relation to cognition in these patients is uncertain, particularly in the long run. We examined the relationship between microbleeds in patients with a transient ischemic attack (TIA) or minor ischemic stroke, and cognitive performance 4 years later. Participants were recruited from a prospective multicenter cohort of patients with a TIA or minor ischemic stroke (n=397). They underwent magnetic resonance imaging (MRI), including a T2*-weighted sequence, within 3 months after their ischemic event. Microbleeds, atrophy, lacunae and white matter hyperintensities (WMH) were rated visually. Cognitive status was examined in 94% of all patients who were still alive after a mean interval of 3.8 years by the Dutch version of the Telephone Interview for Cognitive Status (TICS; n=280) or by an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) obtained from a close relative if a TICS could not be obtained (n=48). The relationship between presence of microbleeds and TICS or IQCODE score was assessed with linear regression analyses adjusted for age, sex, educational level and time interval between MRI and cognitive evaluation. The mean age was 65±12 years at inclusion. The vascular event at inclusion was a TIA in 170 patients (52%) and a minor ischemic stroke in 155 patients (47%). Microbleeds were present in 11.6% of the patients. Patients with microbleeds were significantly older than patients without microbleeds (70±9 vs. 64±12 years), more often had hypertension, and had more cerebral atrophy, WMH and lacunae on MRI (all p<0.05). The mean TICS score was 35.3±5.9 for patients with microbleeds (n=29) and 34.6±5.2 for patients without microbleeds (n=251); the adjusted mean difference (95% CI) was 1.69 (-0.01 to 3.38). The total IQCODE score was 66.0±10.8 for patients with microbleeds (n=9) and 63.1±12.9 for patients without microbleeds (n=39); the adjusted mean difference was 2.43 (-7.55 to 12.41). The relative risk (adjusted for age) for abnormal cognitive performance when having microbleeds was 1.19 (95% CI: 0.63-2.26). Subcortical atrophy was associated with lower TICS score [standardized regression coefficient β: -0.12 (-0.23 to 0.00); p=0.04] and with lower IQCODE score [0.51 (0.19-0.83); p=0.00]. The adjusted mean difference of IQCODE scores between patients with and those without a lacunar infarct was 0.39 (0.12-0.65; p=0.01). In this sample of patients with a recent TIA or minor ischemic stroke, microbleeds were not associated with cognitive performance 4 years later. Apparently, this association is different from other markers of small vessel disease. © 2014 S. Karger AG, Basel.

Quality of Life Is Poorer for Patients With Stroke Who Require an Interpreter: An Observational Australian Registry Study.

PubMed

Kilkenny, Monique F; Lannin, Natasha A; Anderson, Craig S; Dewey, Helen M; Kim, Joosup; Barclay-Moss, Karen; Levi, Chris; Faux, Steven; Hill, Kelvin; Grabsch, Brenda; Middleton, Sandy; Thrift, Amanda G; Grimley, Rohan; Donnan, Geoffrey; Cadilhac, Dominique A

2018-03-01

In multicultural Australia, some patients with stroke cannot fully understand, or speak, English. Language barriers may reduce quality of care and consequent outcomes after stroke, yet little has been reported empirically. An observational study of patients with stroke or transient ischemic attack (2010-2015) captured from 45 hospitals participating in the Australian Stroke Clinical Registry. The use of interpreters in hospitals, which is routinely documented, was used as a proxy for severe language barriers. Health-Related Quality of Life was assessed using the EuroQoL-5 dimension-3 level measured 90 to 180 days after stroke. Logistic regression was undertaken to assess the association between domains of EuroQoL-5 dimension and interpreter status. Among 34 562 registrants, 1461 (4.2%) required an interpreter. Compared with patients without interpreters, patients requiring an interpreter were more often women (53% versus 46%; P <0.001), aged ≥75 years (68% versus 51%; P <0.001), and had greater access to stroke unit care (85% versus 78%; P <0.001). After accounting for patient characteristics and stroke severity, patients requiring interpreters had comparable discharge outcomes (eg, mortality, discharged to rehabilitation) to patients not needing interpreters. However, these patients reported poorer Health-Related Quality of Life (visual analogue scale coefficient, -9; 95% CI, -12.38, -5.62), including more problems with self-care (odds ratio: 2.22; 95% CI, 1.82, 2.72), pain (odds ratio: 1.84; 95% CI, 1.52, 2.34), anxiety or depression (odds ratio: 1.60; 95% CI, 1.33, 1.93), and usual activities (odds ratio: 1.62; 95% CI, 1.32, 2.00). Patients requiring interpreters reported poorer Health Related Quality of Life after stroke/transient ischemic attack despite greater access to stroke units. These findings should be interpreted with caution because we are unable to account for prestroke Health Related Quality of Life. Further research is needed. © 2018 American Heart Association, Inc.

Inhibition of transient receptor potential vanilloid-1 confers neuroprotection, reduces tumor necrosis factor-alpha, and increases IL-10 in a rat stroke model.

PubMed

Hakimizadeh, Elham; Shamsizadeh, Ali; Roohbakhsh, Ali; Arababadi, Mohammad Kazemi; Hajizadeh, Mohammad R; Shariati, Mehdi; Rahmani, Mohammad R; Allahtavakoli, Mohammad

2017-08-01

Stroke is a major cause of mortality and long-term disability in adults. Transient receptor potential vanilloid-1 (TRPV1) plays a crucial role in neuroinflammation. In this study, the effects of TRPV1 agonist (capsaicin) and antagonist (AMG9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and neurological deficits were evaluated 1, 3, and 7 days after stroke. Then, infarct volume, brain edema, body temperature, mRNA expression of TRPV1, and serum concentrations of tumor necrosis factor-alpha (TNF-α) and IL-10 were measured. Compared to the vehicle group, AMG9810 significantly decreased the infarct volume (P < 0.01). Latency for the removal of sticky labels from the forepaw and the hanging time were significantly decreased and increased, respectively, following administration of AMG9810 (P < 0.01 and P < 0.001 vs. vehicle) 3 and 7 days after stroke. Compared to the sham group, the mRNA expression of TRPV1 was significantly increased in vehicle group (P < 0.01). Administration of AMG9810 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P < 0.05). Moreover, our results indicate that AMG9810 might a promising candidate for the hypothermic treatment of stroke. The findings also suggest a key role for AMG9810 in reducing inflammation after stroke and imply that TRPV1 could be a potential target for the treatment of ischemic stroke. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Is Transient Ischemic Attack a Medical Emergency? An Evidence-Based Analysis

PubMed Central

Sehatzadeh, S

2015-01-01

Background Transient ischemic attack (TIA) is a brief episode of dysfunction in a confined area of the brain. The risk of stroke following TIA is approximately 4% within the first 2 days and 9% within the first month. Therefore, early diagnosis and treatment is critical to reduce mortality and risk of stroke in patients who have experienced a TIA. Objectives This systematic review aimed to investigate the impact of the urgent evaluation and initiation of treatment of patients with TIA on the risk of subsequent stroke and death. Data Sources A literature search was performed for studies published from January 1, 2007, until December 21, 2012. The search was updated monthly to April 1, 2013. Results All identified studies showed that urgent assessment and initiation of treatment of TIA is an effective strategy in reducing the incidence of stroke. Among these, a large observational study found a large effect in that the risk of stroke was reduced by 80%, and a Canadian study found that providing urgent care significantly reduced the rate of stroke in high-risk patients. Another Canadian study reported a significant reduction in the rate of death among patients referred to stroke prevention clinics, compared to patients not referred to such services. One study showed that patients discharged from an emergency department with standard care had significantly higher rates of stroke and subsequent TIA in the first month, compared to those who were hospitalized. However, another study showed that for patients at low to moderate risk, rate of stroke was similar between inpatients and those managed in a TIA clinic. Limitations Our analysis was restricted to the effect of the combined interventions. The magnitude of benefit of each individual component of the intervention cannot be determined through this review. Conclusions The results of this systematic review have important clinical and health system implications. Urgent management of TIA patients in specialized TIA clinics rather than regular practice results in a lower rate of stroke and disability. PMID:26355823

Impact of General Practitioner Transient Ischemic Attack Training on 90-Day Stroke Outcomes: Secondary Analysis of a Cluster Randomized Controlled Trial.

PubMed

Ranta, Annemarei; Dovey, Susan; Gommans, John; Tilyard, Murray; Weatherall, Mark

2018-07-01

Many patients with transient ischemic attack (TIA) receive initial assessments by general practitioners (GPs) who may lack TIA management experience. In a randomized controlled trial (RCT), we showed that electronic decision support for GPs improves patient outcomes and guideline adherence. Some stroke services prefer to improve referrer expertise through TIA/stroke education sessions instead of promoting TIA decision aids or triaging tools. This is a secondary analysis of whether a GP education session influenced TIA management and outcomes. Post hoc analysis of a multicenter, single blind, parallel group, cluster RCT comparing TIA/stroke electronic decision support guided GP management with usual care to assess whether a pretrial TIA/stroke education session also affected RCT outcomes. Of 181 participating GPs, 79 (43.7%) attended an education session and 140 of 291 (48.1%) trial patients were managed by these GPs. There were fewer 90-day stroke events and 90-day vascular events or deaths in patients treated by GPs who attended education; 2 of 140 (1.4%) and 10 of 140 (7.1%) respectively, compared with those who did not; 5 of 151 (3.3%), and 14 of 151 (9.3%), respectively. Logistic regression for association between 90-day stroke and 90-day vascular events or death and education, however, was nonsignificant (odds ratio [OR] .42 (.08 to 2.22), P = .29 and .59 (95% confidence interval [CI] .27 to 1.29), P = .18 respectively. Guideline adherence was not improved by the education session: OR .84 (95% CI .49 to 1.45), P = .54. In the described setting, a GP TIA/stroke education session did not significantly enhance guideline adherence or reduce 90-day stroke or vascular events following TIA. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Characterizing Strokes and Stroke Mimics Transported by Helicopter Emergency Medical Services.

PubMed

Sequeira, Denisse; Martin-Gill, Christian; Kesinger, Matthew R; Thompson, Laura R; Jovin, Tudor G; Massaro, Lori M; Guyette, Francis X

2016-01-01

Stroke is the leading cause of disability in the United States with most of these patients being transported by emergency medical services. These providers are the first medical point of contact and must be able to rapidly and accurately identify stroke and transport these patients to the appropriate facilities for treatment. There are many conditions that have similar presentations to stroke and can be mistakenly identified as potential strokes, thereby affecting the initial prehospital triage. A retrospective observational study examined patients with suspected strokes transported to a single comprehensive stroke center (CSC) by a helicopter emergency medical service (HEMS) agency from 2007 through 2013. Final diagnosis was extracted from the Get with the Guidelines (GWTG) database and hospital discharge diagnosis for those not included in the database. Frequencies of discharge diagnosis were calculated and then stratified into interfacility vs. scene transfers. In this study 6,243 patients were transported: 3,376 patients were screened as potential strokes, of which 2,527 had a final diagnosis of stroke (2,242 ischemic stroke and 285 transient ischemic attack), 166 had intracranial hemorrhage, and 655 were stroke mimics. Stroke mimics were more common among scene transfers (223, 32%) than among interfacility transfers (432, 16%). In our study approximately 20% of potential stroke patients transported via HEMS were mimics. Identifying the need for CSC resources can be an important factor in creating a prehospital triage tool to facilitate patient transport to an appropriate health care facility.

Association of alpha-thalassemia, TNF-alpha (-308G>A) and VCAM-1 (c.1238G>C) gene polymorphisms with cerebrovascular disease in a newborn cohort of 411 children with sickle cell anemia.

PubMed

Belisário, André Rolim; Nogueira, Frederico Lisboa; Rodrigues, Rahyssa Sales; Toledo, Nayara Evelin; Cattabriga, Ana Luiza Moreira; Velloso-Rodrigues, Cibele; Duarte, Filipe Otávio Chaves; Silva, Célia Maria; Viana, Marcos Borato

2015-01-01

Cerebrovascular disease (CVD) is a severe complication associated with sickle cell anemia. Abnormal transcranial Doppler (TCD) identifies some children at high risk, but other markers would be helpful. This cohort study was aimed at evaluating the effects of genetic biomarkers on the risk of developing CVD in children from Minas Gerais, Brazil. Clinical and hematological data were retrieved from children's records. Outcomes studied were overt ischemic stroke and CVD (overt ischemic stroke, transient ischemic attack, abnormal TCD, or abnormal cerebral angiography). Out of 411 children, 386 (93.9%) had SS genotype, 23 (5.6%) had Sβ(0)-thal and two had severe Sβ(+)-thal (0.5%). Frequency of CVD was lower in Sβ-thal group (p=0.05). No effect of VCAM-1 polymorphism on stroke or CVD risks was detected. Cumulative incidence of stroke was significantly higher for children with TNF-α A allele (p=0.02) and lower for children with HBA deletion (p=0.02). However, no association between CVD and TNF-α -308G>A was found. CVD cumulative incidence was significantly lower for children with HBA deletion (p=0.004). This study found no association between VCAM1 c.1238G>C and stroke. An association between stroke and TNF-α -308A allele has been suggested. Our results have confirmed the protective role of HBA deletion against stroke and CVD. Copyright © 2014 Elsevier Inc. All rights reserved.

The Japan Statin Treatment Against Recurrent Stroke (J-STARS): A Multicenter, Randomized, Open-label, Parallel-group Study.

PubMed

Hosomi, Naohisa; Nagai, Yoji; Kohriyama, Tatsuo; Ohtsuki, Toshiho; Aoki, Shiro; Nezu, Tomohisa; Maruyama, Hirofumi; Sunami, Norio; Yokota, Chiaki; Kitagawa, Kazuo; Terayama, Yasuo; Takagi, Makoto; Ibayashi, Setsuro; Nakamura, Masakazu; Origasa, Hideki; Fukushima, Masanori; Mori, Etsuro; Minematsu, Kazuo; Uchiyama, Shinichiro; Shinohara, Yukito; Yamaguchi, Takenori; Matsumoto, Masayasu

2015-09-01

Although statin therapy is beneficial for the prevention of initial stroke, the benefit for recurrent stroke and its subtypes remains to be determined in Asian, in whom stroke profiles are different from Caucasian. This study examined whether treatment with low-dose pravastatin prevents stroke recurrence in ischemic stroke patients. This is a multicenter, randomized, open-label, blinded-endpoint, parallel-group study of patients who experienced non-cardioembolic ischemic stroke. All patients had a total cholesterol level between 4.65 and 6.21 mmol/L at enrollment, without the use of statins. The pravastatin group patients received 10 mg of pravastatin/day; the control group patients received no statins. The primary endpoint was the occurrence of stroke and transient ischemic attack (TIA), with the onset of each stroke subtype set to be one of the secondary endpoints. Although 3000 patients were targeted, 1578 patients (491 female, age 66.2 years) were recruited and randomly assigned to pravastatin group or control group. During the follow-up of 4.9 ± 1.4 years, although total stroke and TIA similarly occurred in both groups (2.56 vs. 2.65%/year), onset of atherothrombotic infarction was less frequent in pravastatin group (0.21 vs. 0.64%/year, p = 0.0047, adjusted hazard ratio 0.33 [95%CI 0.15 to 0.74]). No significant intergroup difference was found for the onset of other stroke subtypes, and for the occurrence of adverse events. Although whether low-dose pravastatin prevents recurrence of total stroke or TIA still needs to be examined in Asian, this study has generated a hypothesis that it may reduce occurrence of stroke due to larger artery atherosclerosis. This study was initially supported by a grant from the Ministry of Health, Labour and Welfare, Japan. After the governmental support expired, it was conducted in collaboration between Hiroshima University and the Foundation for Biomedical Research and Innovation.

Risk of ischemic stroke after atrial fibrillation diagnosis: A national sample cohort

PubMed Central

Son, Mi Kyoung; Lim, Nam-Kyoo; Kim, Hyung Woo

2017-01-01

Atrial fibrillation (AF) is a major risk factor for ischemic stroke and associated with a 5-fold higher risk of stroke. In this retrospective cohort study, the incidence of and risk factors for ischemic stroke in patients with AF were identified. All patients (≥30 years old) without previous stroke who were diagnosed with AF in 2007–2013 were selected from the National Health Insurance Service-National Sample Cohort. To identify factors that influenced ischemic stroke risk, Cox proportional hazard regression analysis was conducted. During a mean follow-up duration of 3.2 years, 1022 (9.6%) patients were diagnosed with ischemic stroke. The overall incidence rate of ischemic stroke was 30.8/1000 person-years. Of all the ischemic stroke that occurred during the follow-up period, 61.0% occurred within 1-year after AF diagnosis. Of the patients with CHA2DS2-VASc score of ≥2, only 13.6% were receiving warfarin therapy within 30 days after AF diagnosis. Relative to no antithrombotic therapy, warfarin treatment for >90 days before the index event (ischemic stroke in stroke patients and death/study end in non-stroke patients) associated with decreased ischemic stroke risk (Hazard Ratio = 0.41, 95%confidence intervals = 0.32–0.53). Heart failure, hypertension, and diabetes mellitus associated with greater ischemic stroke risk. AF patients in Korea had a higher ischemic stroke incidence rate than patients in other countries and ischemic stroke commonly occurred at early phase after AF diagnosis. Long-term (>90 days) continuous warfarin treatment may be beneficial for AF patients. However, warfarin treatment rates were very low. To prevent stroke, programs that actively detect AF and provide anticoagulation therapy are needed. PMID:28636620

Cohort Study of ECG Left Ventricular Hypertrophy Trajectories: Ethnic Disparities, Associations With Cardiovascular Outcomes, and Clinical Utility.

PubMed

Iribarren, Carlos; Round, Alfred D; Lu, Meng; Okin, Peter M; McNulty, Edward J

2017-10-05

ECG left ventricular hypertrophy (LVH) is a well-known predictor of cardiovascular disease. However, no prior study has characterized patterns of presence/absence of ECG LVH ("ECG LVH trajectories") across the adult lifespan in both sexes and across ethnicities. We examined: (1) correlates of ECG LVH trajectories; (2) the association of ECG LVH trajectories with incident coronary heart disease, transient ischemic attack, ischemic stroke, hemorrhagic stroke, and heart failure; and (3) reclassification of cardiovascular disease risk using ECG LVH trajectories. We performed a cohort study among 75 412 men and 107 954 women in the Northern California Kaiser Permanente Medical Care Program who had available longitudinal exposures of ECG LVH and covariates, followed for a median of 4.8 (range <1-9.3) years. ECG LVH was measured by Cornell voltage-duration product. Adverse trajectories of ECG LVH (persistent, new development, or variable pattern) were more common among blacks and Native American men and were independently related to incident cardiovascular disease with hazard ratios ranging from 1.2 for ECG LVH variable pattern and transient ischemic attack in women to 2.8 for persistent ECG LVH and heart failure in men. ECG LVH trajectories reclassified 4% and 7% of men and women with intermediate coronary heart disease risk, respectively. ECG LVH trajectories were significant indicators of coronary heart disease, stroke, and heart failure risk, independently of level and change in cardiovascular disease risk factors, and may have clinical utility. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Patient-Centred Innovations for Persons With Multimorbidity - Ontario

ClinicalTrials.gov

2017-12-14

Hypertension; Depression; Anxiety; Musculoskeletal Pain; Arthritis; Rheumatoid Arthritis; Osteoporosis; Chronic Obstructive Pulmonary Disease (COPD); Asthma; Chronic Bronchitis; Cardiovascular Disease; Heart Failure; Stroke; Transient Ischemic Attacks; Ulcer; Gastroesophageal Reflux; Irritable Bowel; Crohn's Disease; Ulcerative Colitis; Diverticulosis; Chronic Hepatitis; Diabetes; Thyroid Disorder; Cancer; Kidney Disease; Urinary Tract Problem; Dementia; Alzheimer's Disease; Hyperlipidemia; HIV; Multimorbidity

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.

εPKC confers acute tolerance to cerebral ischemic reperfusion injury

PubMed Central

Bright, Rachel; Sun, Guo-Hua; Yenari, Midori A.; Steinberg, Gary K.; Mochly-Rosen, Daria

2008-01-01

In response to mild ischemic stress, the brain elicits endogenous survival mechanisms to protect cells against a subsequent lethal ischemic stress, referred to as ischemic tolerance. The molecular signals that mediate this protection are thought to involve the expression and activation of multiple kinases, including protein kinase C (PKC). Here we demonstrate that εPKC mediates cerebral ischemic tolerance in vivo. Systemic delivery of ψεRACK, an εPKC-selective peptide activator, confers neuroprotection against a subsequent cerebral ischemic event when delivered immediately prior to stroke. In addition, activation of εPKC by ψεRACK treatment decreases vascular tone in vivo, as demonstrated by a reduction in microvascular cerebral blood flow. Here we demonstrate the role of acute and transient εPKC in early cerebral tolerance in vivo and suggest that extra-parenchymal mechanisms, such as vasoconstriction, may contribute to the conferred protection. PMID:18586397

Glyburide is associated with attenuated vasogenic edema in stroke patients.

PubMed

Kimberly, W Taylor; Battey, Thomas W K; Pham, Ly; Wu, Ona; Yoo, Albert J; Furie, Karen L; Singhal, Aneesh B; Elm, Jordan J; Stern, Barney J; Sheth, Kevin N

2014-04-01

Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known. Using a case-control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the glyburide advantage in malignant edema and stroke-pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 (MMP-9) plasma level in large hemispheric stroke. We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level. Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial.

Processes of care associated with acute stroke outcomes.

PubMed

Bravata, Dawn M; Wells, Carolyn K; Lo, Albert C; Nadeau, Steven E; Melillo, Jean; Chodkowski, Diane; Struve, Frederick; Williams, Linda S; Peixoto, Aldo J; Gorman, Mark; Goel, Punit; Acompora, Gregory; McClain, Vincent; Ranjbar, Noshene; Tabereaux, Paul B; Boice, John L; Jacewicz, Michael; Concato, John

2010-05-10

Many processes of care have been proposed as metrics to evaluate stroke care. We sought to identify processes of stroke care that are associated with improved patient outcomes after adjustment for both patient characteristics and other process measures. This retrospective cohort study included patients 18 years or older with an ischemic stroke or transient ischemic attack (TIA) onset no more than 2 days before admission and a neurologic deficit on admission. Patients were excluded if they resided in a skilled nursing facility, were already admitted to the hospital at stroke onset, or were transferred from another acute-care facility. The combined outcome included in-hospital mortality, discharge to hospice, or discharge to a skilled nursing facility. Seven processes of stroke care were evaluated: fever management, hypoxia management, blood pressure management, neurologic evaluation, swallowing evaluation, deep vein thrombosis (DVT) prophylaxis, and early mobilization. Risk adjustment included age, comorbidity (medical history), concomitant medical illness present at admission, preadmission symptom course, prestroke functional status, code status, stroke severity, nonneurologic status, modified APACHE (Acute Physiology and Chronic Health Evaluation) III score, and admission brain imaging findings. Among 1487 patients, the outcome was observed in 239 (16%). Three processes of care were independently associated with an improvement in the outcome after adjustment: swallowing evaluation (adjusted odds ratio [OR], 0.64; 95% confidence interval [CI], 0.43-0.94); DVT prophylaxis (adjusted OR, 0.60; 95% CI, 0.37-0.96); and treating all episodes of hypoxia with supplemental oxygen (adjusted OR, 0.26; 95% CI, 0.09-0.73). Outcomes among patients with ischemic stroke or TIA can be improved by attention to swallowing function, DVT prophylaxis, and treatment of hypoxia.

Baseline feature of a randomized trial assessing the effects of disease management programs for the prevention of recurrent ischemic stroke.

PubMed

Fukuoka, Yasuko; Hosomi, Naohisa; Hyakuta, Takeshi; Omori, Toyonori; Ito, Yasuhiro; Uemura, Jyunichi; Kimura, Kazumi; Matsumoto, Masayasu; Moriyama, Michiko

2015-03-01

Comprehensive and long-term patient education programs designed to improve self-management can help patients better manage their medical condition. Using disease management programs (DMPs) that were created for each of the risk factor according to clinical practice guidelines, we evaluate their influence on the prevention of stroke recurrence. This is a randomized study conducted with ischemic stroke patients within 1 year from their onset. Subjects in the intervention group received a 6-month DMPs that included self-management education provided by a nurse along with support in collaboration with the primary care physician. Those in the usual care group received ordinary outpatient care. The primary end points are stroke recurrence and stroke death. Patients were enrolled for 2 years with plans for a 2-year follow-up after the 6-month education period (total of 30 months). A total of 321 eligible subjects (average age, 67.3 years; females, 96 [29.9%]), including 21 subjects (6.5%) with transient ischemic attack, were enrolled in this study. Regarding risk factors for stroke, 260 subjects (81.0%) had hypertension, 249 subjects (77.6%) had dyslipidemia, 102 subjects (31.8%) had diabetes mellitus, 47 subjects (14.6%) had atrial fibrillation, and 98 subjects (30.5%) had chronic kidney disease. There were no significant differences between the 2 groups with respect to subject characteristics. This article describes the rationale, design, and baseline features of a randomized controlled trial that aimed to assess the effects of DMPs for the secondary prevention of stroke. Subject follow-up is in progress and will end in 2015. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Association of multiple ischemic strokes with mortality in incident hemodialysis patients: an application of multistate model to determine transition probabilities in a retrospective observational cohort.

PubMed

Wetmore, James B; Mahnken, Jonathan D; Phadnis, Milind A

2016-09-21

Little is known about the effect of multiple, or subsequent, ischemic strokes in patients receiving hemodialysis. We undertook a retrospective cohort study of incident hemodialysis patients with Medicare coverage who had experienced a first ischemic stroke. Factors associated with either a subsequent ischemic stroke or death following a first new stroke were modeled. A multistate model with Cox proportional hazards was used to predict transition probabilities from first ischemic stroke to either subsequent stroke or to death, and the demographic and clinical factors associated with the respective transition probabilities were determined. Effect of a subsequent ischemic stroke on survival was quantified. Overall, 12,054 individuals (mean age 69.7 years, 41.3 % male, 53.0 % Caucasian and 34.0 % African-American) experienced a first new ischemic stroke. Female sex was associated with an increased risk of having a subsequent ischemic stroke (adjusted hazard ratio 1.37, 95 % confidence intervals 1.20 - 1.56, P < 0.0001); African-Americans, as compared to Caucasians, had lower likelihood of dying after a first new ischemic stroke (0.81, 0.77 - 0.85, P < 0.0001). A subsequent stroke trended towards having a higher likelihood of transitioning to death compared to a first new ischemic stroke on dialysis (1.72, 0.96 - 3.09, P = 0.071). When a subsequent ischemic stroke occurs at 24 months, probability of survival dropped >15 %, in absolute terms, from 0.254 to 0.096, with substantial drops observed at subsequent time points such that the probability of survival was more than halved. Likelihood of subsequent ischemic stroke and of survival in hemodialysis patients appears to vary by sex and race: females are more likely than males to experience a subsequent ischemic stroke, and Caucasians are more likely than African-Americans to die after a first new ischemic stroke. The risk of a transitioning to a subsequent stroke (after having had a first) increases until about 1 year, then decreases. Subsequent strokes are associated with decreased probability of survival, an effect which increases as time since first stroke elapses. This information may be of assistance to clinicians when counseling hemodialysis patients about the implications of recurrent ischemic stroke.

[Risk factors in cerebrovascular disease. Do transient ischemic attacks lead to changes in lifestyle?].

PubMed

Sánchez, F; Aguilar, M; Porta, R; Urbano, F; Martínez, I; Bonaventura, I; Ribó, J M

1994-01-01

A minor stroke does not cause sufficient alarm in patients to change their lifestyles. 46 patients who suffered strokes in the previous 2 years were contacted by telephone, recording rehabilitation programs, medical therapy and modification of dietary habits. It was discovered that only 50% of those requiring motor rehabilitation actually received such treatment; and only one of twenty carried on speech exercises. Subsequent ischemic events were reported by 22 patients: 12 of whom had strokes, 8 ischemic myocardial attacks and two patients suffered both conditions. The majority of patients followed the prescribed medical treatment and advice badly. Of the 46 patients reviewed, 31 were hypertensive and only 16 follow recommended diets. Out of 15 smokers only, 6 gave up, and from 21 with dislypemia only 10 modified their diets. Of all patients only the most severely affected complied satisfactorily to medical treatments; a possible explanation for this would be that the contact between patients and physician (neurologist and family doctors) was discontinued immediately after the patients discharge from hospital. It is recommended therefore that steps be taken to insure better communication between neurologist, general practitioner and patient; thereby improving prognosis.

Sensitivity and Specificity of an Adult Stroke Screening Tool in Childhood Ischemic Stroke.

PubMed

Neville, Kerri; Lo, Warren

2016-05-01

There are frequent delays in the diagnosis of acute pediatric ischemic stroke. A screening tool that could increase the suspicion of acute ischemic stroke could aid early recognition and might improve initial care. An earlier study reported that children with acute ischemic stroke have signs that can be recognized with two adult stroke scales. We tested the hypothesis that an adult stroke scale could distinguish children with acute ischemic stroke from children with acute focal neurological deficits not due to stroke. We retrospectively applied an adult stroke scale to the recorded examinations of 53 children with acute symptomatic acute ischemic stroke and 53 age-matched control subjects who presented with focal neurological deficits. We examined the sensitivity and specificity of the stroke scale and the occurrence of acute seizures as predictors of stroke status. The total stroke scale did not differentiate children with acute ischemic stroke from those who had acute deficits from nonstroke causes; however, the presence of arm weakness was significantly associated with stroke cases. Acute seizures were significantly associated with stroke cases. An adult stroke scale is not sensitive or specific to distinguish children with acute ischemic stroke from those with nonstroke focal neurological deficits. The development of a pediatric acute ischemic stroke screening tool should include arm weakness and perhaps acute seizures as core elements. Such a scale must account for the limitations of language in young or intellectually disabled children. Copyright © 2016 Elsevier Inc. All rights reserved.

Antithrombotic and Thrombolytic Therapy for Ischemic Stroke

PubMed Central

Lansberg, Maarten G.; O’Donnell, Martin J.; Khatri, Pooja; Lang, Eddy S.; Nguyen-Huynh, Mai N.; Schwartz, Neil E.; Sonnenberg, Frank A.; Schulman, Sam; Vandvik, Per Olav; Spencer, Frederick A.; Alonso-Coello, Pablo; Guyatt, Gordon H.

2012-01-01

Objectives: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA). Methods: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence. Results: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B). Conclusions: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. PMID:22315273

The Effects of Statins on Infections after Stroke or Transient Ischemic Attack: A Meta-Analysis

PubMed Central

Lin, Shao-Peng; Long, You-Ming; Chen, Xiao-Hui

2015-01-01

Background Previous studies have reported that statins can prevent infections, and these findings were ascribed to the anti-inflammatory and immunomodulatory properties of statins. However, the effects of statins on the risk of infection after stroke or transient ischemic attack (TIA) remain controversial. The aim of this study was to evaluate the relationship between statins and the risk of infection after stroke or TIA by means of a meta-analysis. Methodology and Findings Studies were found by searching major electronic databases using key terms and restricting the results to studies published in English language and human studies. Pooled odds ratio (OR) for the association between infection and statins were analyzed using Stata software. A total of five studies that included 8,791 stroke or TIA patients (3,269 patients in the statin use group and 5,522 in the placebo group) were eligible and abstracted. Pooled analysis demonstrated that statins did not significantly affect the incidence of infection after stroke or TIA compared with a placebo (OR 0.819, 95% CI 0.582–1.151, I2 = 64.2%, p= 0.025). Sensitivity analyses showed that the removal of any single study did not significantly affect the pooled OR. Cumulative meta-analysis showed that the incidence of infection did not vary by publication year. No statistical evidence of publication bias was found among the studies selected, based on the results of Egger’s (p = 1.000) and Begg’s (p = 0.762) tests. Conclusions This meta-analysis does not support the hypothesis that statins reduce the risk of infections in stroke or TIA patients. PMID:26158560

Cost-effectiveness of clopidogrel-aspirin versus aspirin alone for acute transient ischemic attack and minor stroke.

PubMed

Pan, Yuesong; Wang, Anxin; Liu, Gaifen; Zhao, Xingquan; Meng, Xia; Zhao, Kun; Liu, Liping; Wang, Chunxue; Johnston, S Claiborne; Wang, Yilong; Wang, Yongjun

2014-06-05

Treatment with the combination of clopidogrel and aspirin taken soon after a transient ischemic attack (TIA) or minor stroke was shown to reduce the 90-day risk of stroke in a large trial in China, but the cost-effectiveness is unknown. This study sought to estimate the cost-effectiveness of the clopidogrel-aspirin regimen for acute TIA or minor stroke. A Markov model was created to determine the cost-effectiveness of treatment of acute TIA or minor stroke patients with clopidogrel-aspirin compared with aspirin alone. Inputs for the model were obtained from clinical trial data, claims databases, and the published literature. The main outcome measure was cost per quality-adjusted life-years (QALYs) gained. One-way and multivariable probabilistic sensitivity analyses were performed to test the robustness of the findings. Compared with aspirin alone, clopidogrel-aspirin resulted in a lifetime gain of 0.037 QALYs at an additional cost of CNY 1250 (US$ 192), yielding an incremental cost-effectiveness ratio of CNY 33 800 (US$ 5200) per QALY gained. Probabilistic sensitivity analysis showed that clopidogrel-aspirin therapy was more cost-effective in 95.7% of the simulations at a willingness-to-pay threshold recommended by the World Health Organization of CNY 105 000 (US$ 16 200) per QALY. Early 90-day clopidogrel-aspirin regimen for acute TIA or minor stroke is highly cost-effective in China. Although clopidogrel is generic, Plavix is brand in China. If Plavix were generic, treatment with clopidogrel-aspirin would have been cost saving. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Novel antiepileptic drug lacosamide exerts neuroprotective effects by decreasing glial activation in the hippocampus of a gerbil model of ischemic stroke

PubMed Central

AHN, JI YUN; YAN, BING CHUN; PARK, JOON HA; AHN, JI HYEON; LEE, DAE HWAN; KIM, IN HYE; CHO, JEONG-HWI; CHEN, BAI HUI; LEE, JAE-CHUL; CHO, YOUNG SHIN; SHIN, MYOUNG CHUL; CHO, JUN HWI; HONG, SEONGKWEON; WON, MOO-HO; KIM, SUNG KOO

2015-01-01

Lacosamide, which is a novel antiepileptic drug, has been reported to exert various additional therapeutic effects. The present study investigated the neuroprotective effects of lacosamide against transient cerebral ischemia-induced neuronal cell damage in the hippocampal cornu ammonis (CA)-1 region of a gerbil model. Neuronal Nuclei immunohistochemistry demonstrated that pre- and post-surgical treatment (5 min ischemia) with 25 mg/kg lacosamide protected CA1 pyramidal neurons in the lacosamide-treated-ischemia-operated group from ischemic injury 5 days post-ischemia, as compared with gerbils in the vehicle-treated-ischemia-operated group. Furthermore, treatment with 25 mg/kg lacosamide markedly attenuated the activation of astrocytes and microglia in the ischemic CA1 region at 5 days post-ischemia. The results of the present study suggested that pre- and post-surgical treatment of the gerbils with lacosamide was able to protect against transient cerebral ischemic injury-induced CA1 pyramidal neuronal cell death in the hippocampus. In addition, the neuroprotective effects of lacosamide may be associated with decreased activation of glial cells in the ischemic CA1 region. PMID:26668588

Web-based tool for dynamic functional outcome after acute ischemic stroke and comparison with existing models.

PubMed

Ji, Ruijun; Du, Wanliang; Shen, Haipeng; Pan, Yuesong; Wang, Penglian; Liu, Gaifen; Wang, Yilong; Li, Hao; Zhao, Xingquan; Wang, Yongjun

2014-11-25

Acute ischemic stroke (AIS) is one of the leading causes of death and adult disability worldwide. In the present study, we aimed to develop a web-based risk model for predicting dynamic functional status at discharge, 3-month, 6-month, and 1-year after acute ischemic stroke (Dynamic Functional Status after Acute Ischemic Stroke, DFS-AIS). The DFS-AIS was developed based on the China National Stroke Registry (CNSR), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Good functional outcome was defined as modified Rankin Scale (mRS) score ≤ 2 at discharge, 3-month, 6-month, and 1-year after AIS, respectively. Independent predictors of each outcome measure were obtained using multivariable logistic regression. The area under the receiver operating characteristic curve (AUROC) and plot of observed and predicted risk were used to assess model discrimination and calibration. A total of 12,026 patients were included and the median age was 67 (interquartile range: 57-75). The proportion of patients with good functional outcome at discharge, 3-month, 6-month, and 1-year after AIS was 67.9%, 66.5%, 66.9% and 66.9%, respectively. Age, gender, medical history of diabetes mellitus, stroke or transient ischemic attack, current smoking and atrial fibrillation, pre-stroke dependence, pre-stroke statins using, admission National Institutes of Health Stroke Scale score, admission blood glucose were identified as independent predictors of functional outcome at different time points after AIS. The DFS-AIS was developed from sets of predictors of mRS ≤ 2 at different time points following AIS. The DFS-AIS demonstrated good discrimination in the derivation and validation cohorts (AUROC range: 0.837-0.845). Plots of observed versus predicted likelihood showed excellent calibration in the derivation and validation cohorts (all r = 0.99, P < 0.001). When compared to 8 existing models, the DFS-AIS showed significantly better discrimination for good functional outcome and mortality at discharge, 3-month, 6-month, and 1-year after AIS (all P < 0.0001). The DFS-AIS is a valid risk model to predict functional outcome at discharge, 3-month, 6-month, and 1-year after AIS.

Sex differences in cryptogenic stroke with patent foramen ovale.

PubMed

Nedeltchev, Krassen; Wiedmer, Sebastian; Schwerzmann, Markus; Windecker, Stephan; Haefeli, Tobias; Meier, Bernhard; Mattle, Heinrich P; Arnold, Marcel

2008-09-01

Sex differences in patients with patent foramen ovale (PFO) and cryptogenic stroke have not been systematically analyzed. We aimed to determine sex influences on demographics, vascular risk factors, clinical manifestations, stroke location, and clinical outcome. One thousand two hundred eighty-eight consecutive patients with ischemic stroke or transient ischemic attack (TIA) were admitted to a single stroke center. All patients underwent a complete stroke workup including clinical examination, standard blood tests, cerebral and vascular imaging, transesophageal echocardiography, and 24-hour electrocardiography. In 500 patients, no definite etiology could be established (cryptogenic stroke/TIA). Of them, 167 patients (107 men and 60 women, mean age 52 +/- 13 years) had an PFO. The prevalence of PFO in patients with cryptogenic stroke or TIA was higher in men than in women (38% vs 28%, P = .014). Stroke severity and the prevalence of risk factors did not differ between the 2 sexes. There was an independent association between male sex and stroke location in the posterior cerebral circulation (OR 3.0, 95% CI 1.4-6.5, P = .006). Men and women did not differ in respect to PFO grade, prevalence of right-to-left shunt at rest, or coexistence of atrial septal aneurysm. Clinical outcome at 3 months was similar in both sexes. Patent foramen ovale was more prevalent in men than in women with cryptogenic stroke. There were no sex influences on age, risk factors, echocardiographic characteristics of PFO, or clinical outcome. Male sex was independently associated with stroke in the posterior cerebral circulation.

Carotid intima media thickness and plaques can predict the occurrence of ischemic cerebrovascular events.

PubMed

Prati, Patrizio; Tosetto, Alberto; Vanuzzo, Diego; Bader, Giovanni; Casaroli, Marco; Canciani, Luigi; Castellani, Sergio; Touboul, Pierre-Jean

2008-09-01

The clinical usefulness of noninvasive measurement of carotid intima media thickness and plaque visualization in the general population is still uncertain. We evaluated the age-specific incidence rates of cerebrovascular events in a cohort of 1348 subjects randomly taken from the census list of San Daniele Township and followed for a mean period of 12.7 years. The association among common carotid intima media thickness, measured at baseline, arterial risk factors, and incidence of ischemic cerebrovascular events was modeled using Poisson regression. The predictive ability of common carotid intima media thickness over arterial risk factors (summarized in the Framingham Stroke Risk Score) was evaluated by receiver operating characteristic curve analysis. During the follow-up, 115 subjects developed nonfatal ischemic stroke, transient ischemic attack, or vascular death, which were the predefined study end points. After adjustment for age and sex, hypertension, diabetes, common carotid intima media thickness above 1 mm, and carotid plaques were all independent risk factors for development of vascular events. Inclusion of carotid findings (presence of common carotid intima media thickness above 1 mm or carotid plaques) resulted in a predictive power higher than Framingham Stroke Risk Score alone only on for those subjects with a Framingham Stroke Risk Score over 20%. Although common carotid intima media thickness and presence of carotid plaques are known to be risk factors for the development of vascular events and to be independent from the conventional risk factors summarized in the Framingham Stroke Risk Score, their contribution to individual risk prediction is limited. Further studies will be required to address the role of carotid ultrasonography in the primary prevention of high-risk subjects.

Stroke as the First Clinical Manifestation of Takayasu's Arteritis.

PubMed

Pereira, Vanessa Caldeira; de Freitas, Carlos Clayton Macedo; Luvizutto, Gustavo José; Sobreira, Marcone Lima; Peixoto, Daniel Escobar Bueno; Magalhães, Inaldo do Nascimento; Bazan, Rodrigo; Braga, Gabriel Pereira

2014-09-01

Takayasu's arteritis is a chronic inflammatory disease, and neurological symptoms occur in 50% of cases, most commonly including headache, dizziness, visual disturbances, convulsive crisis, transient ischemic attack, stroke and posterior reversible encephalopathy syndrome. The aim of this study was to report the case of a young Brazilian female with a focal neurological deficit. She presented with asymmetry of brachial and radial pulses, aphasia, dysarthria and right hemiplegia. Stroke was investigated extensively in this young patient. Only nonspecific inflammatory markers such as velocity of hemosedimentation and C-reactive protein were elevated. During hospitalization, clinical treatment was performed with pulse therapy showing improvement in neurological recuperation on subsequent days. In the chronic phase, the patient was submitted to medicated angioplasty of the brachiocephalic trunk with paclitaxel, with significant improvement of the stenosis. At the 6-month follow-up, the neurological exam presented mild dysarthria, faciobrachial predominant disproportionate hemiparesis, an NIHSS score of 4 and a modified Rankin Scale score of 3 (moderate incapacity). In conclusion, Takayasu's arteritis must be recognized as a potential cause of ischemic stroke in young females.

Comparison of cardiovascular risk factors and survival in patients with ischemic or hemorrhagic stroke.

PubMed

Henriksson, Karin M; Farahmand, Bahman; Åsberg, Signild; Edvardsson, Nils; Terént, Andreas

2012-06-01

Differences in risk factor profiles between patients with ischemic and hemorrhagic stroke may have an impact on subsequent mortality. To explore cardiovascular disease risk factors, including the CHADS(2) score, with survival after ischemic or hemorrhagic stroke. Between 2001 and 2005, 87 111 (83%) ischemic stroke, 12 497 (12%) hemorrhagic stroke, and 5435 (5%) patients with unspecified stroke were identified in the Swedish Stroke Register. Data on gender, age, and cardiovascular disease risk factors were linked to the Swedish Hospital Discharge and Cause of Death Registers. Adjusted odds and hazard ratios and 95% confidence interval were calculated using logistic and Cox proportional hazard regression models. Hemorrhagic stroke patients were younger than ischemic stroke patients. All cardiovascular disease risk factors studied, alone or combined in the CHADS(2) score, were associated with higher odds ratios for ischemic stroke vs. hemorrhagic stroke. Higher CHADS(2) scores and all studied risk factors except hypertension were associated with higher odds ratio for death by ischemic stroke than hemorrhagic stroke. Ischemic stroke was associated with lower early mortality (within 30 days) vs. hemorrhagic stroke (hazard ratio = 0·28, confidence interval 0·27 to 0·29). Patients with hemorrhagic stroke had a higher risk of dying within the first 30 days after stroke, but the risk of death was similar in the two groups after one-month. Hypertension was the only cardiovascular disease risk factor associated with an increased mortality rate for hemorrhagic stroke as compared to ischemic stroke. © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.

Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration.

PubMed

Jolly, Sanjit S; James, Stefan; Džavík, Vladimír; Cairns, John A; Mahmoud, Karim D; Zijlstra, Felix; Yusuf, Salim; Olivecrona, Goran K; Renlund, Henrik; Gao, Peggy; Lagerqvist, Bo; Alazzoni, Ashraf; Kedev, Sasko; Stankovic, Goran; Meeks, Brandi; Frøbert, Ole

2017-01-10

Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST-segment-elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with ST-segment-elevation myocardial infarction. Included were large (n≥1000), randomized, controlled trials comparing manual thrombectomy and PCI alone in patients with ST-segment-elevation myocardial infarction. Individual patient data were provided by the leadership of each trial. The prespecified primary efficacy outcome was cardiovascular mortality within 30 days, and the primary safety outcome was stroke or transient ischemic attack within 30 days. The 3 eligible randomized trials (TAPAS [Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction], TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia], and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) enrolled 19 047 patients, of whom 18 306 underwent PCI and were included in the primary analysis. Cardiovascular death at 30 days occurred in 221 of 9155 patients (2.4%) randomized to thrombus aspiration and 262 of 9151 (2.9%) randomized to PCI alone (hazard ratio, 0.84; 95% confidence interval, 0.70-1.01; P=0.06). Stroke or transient ischemic attack occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio, 1.43; 95% confidence interval, 0.98-2.10; P=0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure, or target vessel revascularization. In the subgroup with high thrombus burden (TIMI [Thrombolysis in Myocardial Infarction] thrombus grade ≥3), thrombus aspiration was associated with fewer cardiovascular deaths (170 [2.5%] versus 205 [3.1%]; hazard ratio, 0.80; 95% confidence interval, 0.65-0.98; P=0.03) and with more strokes or transient ischemic attacks (55 [0.9%] versus 34 [0.5%]; odds ratio, 1.56; 95% confidence interval, 1.02-2.42, P=0.04). However, the interaction P values were 0.32 and 0.34, respectively. Routine thrombus aspiration during PCI for ST-segment-elevation myocardial infarction did not improve clinical outcomes. In the high thrombus burden group, the trends toward reduced cardiovascular death and increased stroke or transient ischemic attack provide a rationale for future trials of improved thrombus aspiration technologies in this high-risk subgroup. URLs: http://www.ClinicalTrials.gov http://www.crd.york.ac.uk/prospero/. Unique identifiers: NCT02552407 and CRD42015025936. © 2016 American Heart Association, Inc.

Protective effects of angiopoietin-like 4 on the blood-brain barrier in acute ischemic stroke treated with thrombolysis in mice.

PubMed

Zhang, Bin; Xu, Xiaofeng; Chu, Xiuli; Yu, Xiaoyang; Zhao, Yuwu

2017-04-03

Given the risk of blood-brain barrier damage (BBB) caused by ischemic and tissue plasminogen activator thrombolysis, the preservation of vascular integrity is important. Angiopoietin-like 4 (ANGPTL4), a protein secreted in hypoxia, is involved in the regulation of vascular permeability. We hypothesized that Angptl4 might exert a protective effect in thrombolysis through stabilizing blood-brain barrier and inhibit hyper-permeability. We investigated the role of Angptl4 in stroke using a transient focal cerebral ischemia mouse model. The treated mice were administered Angptl4 1h after the ischemic event upon reperfusion. Our results showed that Angptl4 combined with thrombolysis greatly reduced the infarct volume and consequent neurological deficit. Western blot analyses and gelatin zymography revealed that Angptl4 protected the integrity of the endothelium damaged by thrombolysis. Angptl4 inhibited the up-regulation of vascular endothelial growth factor (VEGF) in the vascular endothelium after stroke, which was suppressed by counteracting VEGFR signaling and diminishing downstream Src signaling, and led to the increased stability of junctions and improved endothelial cell barrier integrity. These findings demonstrated that Angptl4 protects the permeability of the BBB damaged by ischemic and thrombolysis. Suggested that Angptl4 might be a promising target molecule in therapies for vasoprotection after thrombolysis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice

PubMed Central

Jin, Rong; Zhu, Xiaolei; Liu, Lin; Nanda, Anil; Granger, D Neil; Li, Guohong

2013-01-01

Background and Purpose Statins are widely used in the primary and secondary prevention of ischemic stroke, but their effects on stroke-induced immunodeppression and post-stroke infections are elusive. We investigated effects of simvastatin treatment on stroke-induced splenic atrophy and lung susceptibility to bacterial infection in acute experimental stroke in mice. Methods Ischemic stroke was induced by transient occlusion of middle cerebral artery (MCAO) followed by reperfusion. In some experiments, splenectomies were performed 2 weeks prior to MCAO. Animals were randomly assigned to sham and MCAO groups treated subcutaneously with vehicle or simvastatin (20 mg/kg/day). Brain infarction, neurological function, brain interferon-γ expression, splenic atrophy and apoptosis, and lung infection were examined. Results Simvastatin reduced stroke-induced spleen atrophy and splenic apoptosis via increased mitochrondrial anti-apoptotic Bcl-2 expression and decreased pro-apoptotic Bax translocation from cytosol into mitochondria. Splenectomy reduced brain interferon-γ (3d) and infarct size (5d) after stroke and these effects were reversed by adoptive transfer of splenocytes. Simvastatin inhibited brain interferon-γ (3d) and reduced infarct volume and neurological deficits (5d) after stroke, and these protective effects were observed not only in naïve stroke mice but also in splenectomied stroke mice adoptively transferred with splenocytes. Simvastatin also decreased the stroke-associated lung susceptibility to spontaneous bacterial infection. Conclusions Results provide the first direct experimental evidence that simvastatin ameliorates stroke-induced peripheral immunodepression by attenuating spleen atrophy and lung bacterial infection. These findings contribute to a better understanding of beneficial effects of statins in the treatment of stroke. PMID:23391769

Diagnostic work-up for detection of paroxysmal atrial fibrillation after acute ischemic stroke: cross-sectional survey on German stroke units.

PubMed

Rizos, Timolaos; Quilitzsch, Anika; Busse, Otto; Haeusler, Karl Georg; Endres, Matthias; Heuschmann, Peter; Veltkamp, Roland

2015-06-01

Multiple methods to detect paroxysmal atrial fibrillation (pAF) in patients with acute stroke are available. However, it is unknown which approaches are currently used in clinical routine and guidelines remain vague to the extent of cardiac monitoring. We characterize diagnostic efforts for pAF detection on German stroke units (SU). A standardized anonymous questionnaire was sent to all clinical leads of certified SUs in Germany. The questionnaire focused on basic characteristics of SUs, procedures to detect AF, and estimates on AF detection. One hundred seventy-nine SU leads participated (response rate 71.6%). All patients undergo continuous bedside ECG monitoring. A percentage of 77.6 SUs initiate additional 24-hour Holter ECG in >50% of patients without known AF. Patients with transient ischemic attack are monitored significantly shorter than patients with ischemic stroke. Independent of SU type or size, 67.6% of leads assumed to fail detecting pAF in 5% to 20% of patients. In cryptogenic stroke, additional ECG monitoring is recommended by 90.2% but only 13.8% of SUs perform routine ECG follow-up visits. The use of implanted event recorders is low (1-10 patients/y by 60.7% of SUs; 28.1%: no use). A percentage of 83.9 do not use external event recorders. Our survey demonstrates substantial heterogeneity among German SUs on diagnostic work-up for pAF. Future prospective multicenter studies should systematically evaluate the impact of different methods to uncover pAF. © 2015 American Heart Association, Inc.

Warfarin versus aspirin in patients with reduced cardiac ejection fraction (WARCEF): rationale, objectives, and design.

PubMed

Pullicino, Patrick; Thompson, John L P; Barton, Bruce; Levin, Bruce; Graham, Susan; Freudenberger, Ronald S

2006-02-01

Warfarin is widely prescribed for patients with heart failure without level 1 evidence, and an adequately powered randomized study is needed. The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction study is a National Institutes of Health-funded, randomized, double-blind clinical trial with a target enrollment of 2860 patients. It is designed to test with 90% power the 2-sided primary null hypothesis of no difference between warfarin (International Normalized Ratio 2.5-3) and aspirin (325 mg) in 3- to 5-year event-free survival for the composite endpoint of death, or stroke (ischemic or hemorrhagic) among patients with cardiac ejection fraction < or =35% who do not have atrial fibrillation or mechanical prosthetic heart valves. Secondary analyses will compare warfarin and aspirin for reduction of all-cause mortality, ischemic stroke, and myocardial infarction (MI), balanced against the risk of intracerebral hemorrhage, among women and African Americans; and compare warfarin and aspirin for prevention of stroke alone. Randomization is stratified by site, New York Heart Association (NYHA) heart class (I vs II-IV), and stroke or transient ischemic attack (TIA) within 1 year before randomization versus no stroke or TIA in that period. NYHA class I patients will not exceed 20%, and the study has a target of 20% (or more) patients with stroke or TIA within 12 months. Randomized patients receive active warfarin plus placebo or active aspirin plus placebo, double-blind. The results should help guide the selection of optimum antithrombotic therapy for patients with left ventricular dysfunction.

Isolated transient vertigo: posterior circulation ischemia or benign origin?

PubMed

Blasberg, Tobias F; Wolf, Lea; Henke, Christian; Lorenz, Matthias W

2017-06-14

Isolated transient vertigo can be the only symptom of posterior circulation ischemia. Thus, it is important to differentiate isolated vertigo of a cerebrovascular origin from that of more benign origins, as patients with cerebral ischemia have a much higher risk for future stroke than do those with 'peripheral' vertigo. The current study aims to identify risk factors for cerebrovascular origin of isolated transient vertigo, and for future cerebrovascular events. From the files of 339 outpatients with isolated transient vertigo we extracted history, clinical and technical findings, diagnosis, and follow-up information on subsequent stroke or transient ischemic attack (TIA). Risk factors were analyzed using multivariate regression models (logistic or Cox) and reconfirmed in univariate analyses. On first presentation, 48 (14.2%) patients received the diagnosis 'probable or definite cerebrovascular vertigo'. During follow-up, 41 patients suffered stroke or TIA (event rate 7.9 per 100 person years, 95% confidence interval (CI) 5.5-10.4), 26 in the posterior circulation (event rate 4.8 per 100 person years, 95% CI 3.0-6.7). The diagnosis was not associated with follow-up cerebrovascular events. In multivariate models testing multiple potential determinants, only the presentation mode was consistently associated with the diagnosis and stroke risk: patients who presented because of vertigo (rather than reporting vertigo when they presented for other reasons) had a significantly higher risk for future stroke or TIA (p = 0.028, event rate 13.4 vs. 5.4 per 100 person years) and for future posterior circulation stroke or TIA (p = 0.044, event rate 7.8 vs. 3.5 per 100 person years). We here report for the first time follow-up stroke rates in patients with transient isolated vertigo. In such patients, the identification of those with cerebrovascular origin remains difficult, and presentation mode was found to be the only consistent risk factor. Confirmation in an independent prospective sample is needed.

Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus.

PubMed

Young, Lawrence H; Viscoli, Catherine M; Curtis, Jeptha P; Inzucchi, Silvio E; Schwartz, Gregory G; Lovejoy, Anne M; Furie, Karen L; Gorman, Mark J; Conwit, Robin; Abbott, J Dawn; Jacoby, Daniel L; Kolansky, Daniel M; Pfau, Steven E; Ling, Frederick S; Kernan, Walter N

2017-05-16

Insulin resistance is highly prevalent among patients with atherosclerosis and is associated with an increased risk for myocardial infarction (MI) and stroke. The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone decreased the composite risk for fatal or nonfatal stroke and MI in patients with insulin resistance without diabetes mellitus, after a recent ischemic stroke or transient ischemic attack. The type and severity of cardiac events in this population and the impact of pioglitazone on these events have not been described. We performed a secondary analysis of the effects of pioglitazone, in comparison with placebo, on acute coronary syndromes (MI and unstable angina) among IRIS participants. All potential acute coronary syndrome episodes were adjudicated in a blinded fashion by an independent clinical events committee. The study cohort was composed of 3876 IRIS participants, mean age 63 years, 65% male, 89% white race, and 12% with a history of coronary artery disease. Over a median follow-up of 4.8 years, there were 225 acute coronary syndrome events, including 141 MIs and 84 episodes of unstable angina. The MIs included 28 (19%) with ST-segment elevation. The majority of MIs were type 1 (94, 65%), followed by type 2 (45, 32%). Serum troponin was 10× to 100× upper limit of normal in 49 (35%) and >100× upper limit of normal in 39 (28%). Pioglitazone reduced the risk of acute coronary syndrome (hazard ratio, 0.71; 95% confidence interval, 0.54-0.94; P =0.02). Pioglitazone also reduced the risk of type 1 MI (hazard ratio, 0.62; 95% confidence interval, 0.40-0.96; log-rank P =0.03), but not type 2 MI (hazard ratio, 1.05; 95% confidence interval, 0.58-1.91; P =0.87). Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100× upper limit of normal (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87; P =0.02), but not smaller MIs. Among patients with insulin resistance without diabetes mellitus, pioglitazone reduced the risk for acute coronary syndromes after a recent cerebrovascular event. Pioglitazone appeared to have its most prominent effect in preventing spontaneous type 1 MIs. URL: http://clinicaltrials.gov. Unique identifier: NCT00091949. © 2017 American Heart Association, Inc.

Clinical and Demographic Characteristics Associated With Suboptimal Primary Stroke and Transient Ischemic Attack Prevention: Retrospective Analysis.

PubMed

Turner, Grace M; Calvert, Melanie; Feltham, Max G; Ryan, Ronan; Finnikin, Samuel; Marshall, Tom

2018-03-01

Primary prevention of stroke and transient ischemic attack (TIA) is important to reduce the burden of these conditions; however, prescribing of prevention drugs is suboptimal. We aimed to identify individual clinical and demographic characteristics associated with potential missed opportunities for prevention therapy with lipid-lowering, anticoagulant, or antihypertensive drugs before stroke/TIA. We analyzed anonymized electronic primary care records from a UK primary care database that covers 561 family practices. Patients with first-ever stroke/TIA, ≥18 years, with diagnosis between January 1, 2009, and December 31, 2013, were included. Missed opportunities for prevention were defined as people with clinical indications for lipid-lowering, anticoagulant, or antihypertensive drugs but not prescribed these drugs before their stroke/TIA. Mixed-effect logistic regression models evaluated the relationship between missed opportunities and individual clinical/demographic characteristics. The inclusion criteria were met by 29 043 people with stroke/TIA. Patients with coronary heart disease, chronic kidney disease, peripheral arterial disease, or diabetes mellitus were at less risk of a missed opportunity for prescription of lipid-lowering and antihypertensive drugs. However, patients with a 10-year cardiovascular disease risk ≥20% but without these diagnoses had increased risk of having a missed opportunity for prescription of lipid-lowering drugs or antihypertensive drugs. Women were less likely to be prescribed anticoagulants but more likely to be prescribed antihypertensive drugs. The elderly (≥85 years of age) were less likely to be prescribed all 3 prevention drugs, compared with people aged 75 to 79 years. Knowing the patient characteristics predictive of missed opportunities for stroke prevention may help primary care identify and appropriately manage these patients. Improving the management of these groups may reduce their risk and potentially prevent large number of future strokes and TIAs in the population. © 2018 American Heart Association, Inc.

Prevalence, Incidence, Prognosis, Early Stroke Risk, and Stroke-Related Prognostic Factors of Definite or Probable Transient Ischemic Attacks in China, 2013

PubMed Central

Jiang, Bin; Sun, Haixin; Ru, Xiaojuan; Sun, Dongling; Chen, Zhenghong; Liu, Hongmei; Li, Yichong; Zhang, Mei; Wang, Limin; Wang, Linhong; Wu, Shengping; Wang, Wenzhi

2017-01-01

The epidemiological characteristics of transient ischemic attacks (TIAs) in China are unclear. In 2013, we conducted a nationally representative, door-to-door epidemiological survey on TIA in China using a complex, multistage, probability sampling design. Results showed that the weighted prevalence of TIA in China was 103.3 [95% confidence interval (CI): 83.9–127.2] per 100,000 in the population, 92.4 (75.0–113.8) per 100,000 among men, and 114.7 (87.2–151.0) per 100,000 among women. The weighted incidence of TIA was 23.9 (17.8–32.0) per 100,000 in the population, 21.3 (14.3–31.5) per 100,000 among men, and 26.6 (17.0–41.7) per 100,000 among women. No difference in average prognosis was found between TIA and stroke in the population. Weighted risk of stroke among TIA patients was 9.7% (6.5–14.3%), 11.1% (7.5–16.1%), and 12.3% (8.4–17.7%) at 2, 30, and 90 days, respectively. The risk of stroke was higher among male patients with a history of TIA than among female patients with a history of TIA (OR: 2.469; 95% CI: 1.172–5.201; P = 0.018), and higher among TIA patients with hypertension than among TIA patients without hypertension (OR: 2.671; 1.547–4.613; P < 0.001). It can be concluded that there are an estimated 1.35 million TIA patients nationwide, with 0.31 million new cases of TIA annually in China. TIA patients were not better managed prior to a stroke event. Early risk of stroke among TIA patients is high. Sex and hypertension may be stroke-associated prognostic factors among TIA patients. TIA clinics and surveillance should be integrated into the national health-care system. PMID:28713329

Long-term outcome of vertebral artery origin stenosis in patients with acute ischemic stroke

PubMed Central

2013-01-01

Background Vertebral artery origin (VAO) stenosis is occasionally observed in patients who have acute ischemic stroke. We investigated the long-term outcomes and clinical significance of VAO stenosis in patients with acute ischemic stroke. Methods We performed a prospective observational study using a single stroke center registry to investigate the risk of recurrent stroke and vascular outcomes in patients with acute ischemic stroke and VAO stenosis. To relate the clinical significance of VAO stenosis to the vascular territory of the index stroke, patients were classified into an asymptomatic VAO stenosis group and a symptomatic VAO stenosis group. Results Of the 774 patients who had acute ischemic stroke, 149 (19.3%) of them had more than 50% stenosis of the VAO. During 309 patient-years of follow-up (mean, 2.3 years), there were 7 ischemic strokes, 6 hemorrhagic strokes, and 2 unknown strokes. The annual event rates were 0.97% for posterior circulation ischemic stroke, 4.86% for all stroke, and 6.80% for the composite cardiovascular outcome. The annual event rate for ischemic stroke in the posterior circulation was significantly higher in patients who had symptomatic VAO stenosis than in patients who had asymptomatic stenosis (1.88% vs. 0%, p = 0.046). In a multivariate analysis, the hazard ratio, per one point increase of the Essen Stroke Risk Score (ESRS) for the composite cardiovascular outcome, was 1.46 (95% CI, 1.02-2.08, p = 0.036). Conclusions Long-term outcomes of more than 50% stenosis of the VAO in patients with acute ischemic stroke were generally favorable. Additionally, ESRS was a predictor for the composite cardiovascular outcome. Asymptomatic VAO stenosis may not be a specific risk factor for recurrent ischemic stroke in the posterior circulation. However, VAO stenosis may require more clinical attention as a potential source of recurrent stroke when VAO stenosis is observed in patients who have concurrent ischemic stroke in the posterior circulation. PMID:24215371

Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED).

PubMed

Towfighi, Amytis; Cheng, Eric M; Ayala-Rivera, Monica; McCreath, Heather; Sanossian, Nerses; Dutta, Tara; Mehta, Bijal; Bryg, Robert; Rao, Neal; Song, Shlee; Razmara, Ali; Ramirez, Magaly; Sivers-Teixeira, Theresa; Tran, Jamie; Mojarro-Huang, Elizabeth; Montoya, Ana; Corrales, Marilyn; Martinez, Beatrice; Willis, Phyllis; Macias, Mireya; Ibrahim, Nancy; Wu, Shinyi; Wacksman, Jeremy; Haber, Hilary; Richards, Adam; Barry, Frances; Hill, Valerie; Mittman, Brian; Cunningham, William; Liu, Honghu; Ganz, David A; Factor, Diane; Vickrey, Barbara G

2017-02-06

Recurrent strokes are preventable through awareness and control of risk factors such as hypertension, and through lifestyle changes such as healthier diets, greater physical activity, and smoking cessation. However, vascular risk factor control is frequently poor among stroke survivors, particularly among socio-economically disadvantaged blacks, Latinos and other people of color. The Chronic Care Model (CCM) is an effective framework for multi-component interventions aimed at improving care processes and outcomes for individuals with chronic disease. In addition, community health workers (CHWs) have played an integral role in reducing health disparities; however, their effectiveness in reducing vascular risk among stroke survivors remains unknown. Our objectives are to develop, test, and assess the economic value of a CCM-based intervention using an Advanced Practice Clinician (APC)-CHW team to improve risk factor control after stroke in an under-resourced, racially/ethnically diverse population. In this single-blind randomized controlled trial, 516 adults (≥40 years) with an ischemic stroke, transient ischemic attack or intracerebral hemorrhage within the prior 90 days are being enrolled at five sites within the Los Angeles County safety-net setting and randomized 1:1 to intervention vs usual care. Participants are excluded if they do not speak English, Spanish, Cantonese, Mandarin, or Korean or if they are unable to consent. The intervention includes a minimum of three clinic visits in the healthcare setting, three home visits, and Chronic Disease Self-Management Program group workshops in community venues. The primary outcome is blood pressure (BP) control (systolic BP <130 mmHg) at 1 year. Secondary outcomes include: (1) mean change in systolic BP; (2) control of other vascular risk factors including lipids and hemoglobin A1c, (3) inflammation (C reactive protein [CRP]), (4) medication adherence, (5) lifestyle factors (smoking, diet, and physical activity), (6) estimated relative reduction in risk for recurrent stroke or myocardial infarction (MI), and (7) cost-effectiveness of the intervention versus usual care. If this multi-component interdisciplinary intervention is shown to be effective in improving risk factor control after stroke, it may serve as a model that can be used internationally to reduce race/ethnic and socioeconomic disparities in stroke in resource-constrained settings. ClinicalTrials.gov Identifier NCT01763203 .

How Does Cardiovascular Disease First Present in Women and Men? Incidence of 12 Cardiovascular Diseases in a Contemporary Cohort of 1,937,360 People.

PubMed

George, Julie; Rapsomaniki, Eleni; Pujades-Rodriguez, Mar; Shah, Anoop Dinesh; Denaxas, Spiros; Herrett, Emily; Smeeth, Liam; Timmis, Adam; Hemingway, Harry

2015-10-06

Given the recent declines in heart attack and stroke incidence, it is unclear how women and men differ in first lifetime presentations of cardiovascular diseases (CVDs). We compared the incidence of 12 cardiac, cerebrovascular, and peripheral vascular diseases in women and men at different ages. We studied 1 937 360 people, aged ≥ 30 years and free from diagnosed CVD at baseline (51% women), using linked electronic health records covering primary care, hospital admissions, acute coronary syndrome registry, and mortality (Cardiovascular Research Using LInked Bespoke Studies and Electronic Records [CALIBER] research platform). During 6 years median follow-up between 1997 and 2010, 114 859 people experienced an incident cardiovascular diagnosis, the majority (66%) of which were neither myocardial infarction nor ischemic stroke. Associations of male sex with initial diagnoses of CVD, however, varied from strong (age-adjusted hazard ratios, 3.6-5.0) for abdominal aortic aneurysm, myocardial infarction, and unheralded coronary death (particularly >60 years), through modest (hazard ratio, 1.5-2.0) for stable angina, ischemic stroke, peripheral arterial disease, heart failure, and cardiac arrest, to weak (hazard ratio <1.5) for transient ischemic attack, intracerebral hemorrhage, and unstable angina, and inverse (0.69) for subarachnoid hemorrhage (all P<0.001). The majority of initial presentations of CVD are neither myocardial infarction nor ischemic stroke, yet most primary prevention studies focus on these presentations. Sex has differing associations with different CVDs, with implications for risk prediction and management strategies. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01164371. © 2015 The Authors.

The design, rationale, and baseline characteristics of a nationwide cohort registry in China: blood pressure and clinical outcome in TIA or ischemic stroke.

PubMed

Xu, Jie; Liu, Yi; Tao, Yongli; Xie, Xuewei; Gu, Hongqiu; Pan, Yuesong; Zhao, Xingquan; Wang, Yongjun; Yan, Aoshuang; Wang, Yilong

2016-01-01

The relationship between poststroke blood pressure (BP) and clinical outcomes in ischemic stroke (IS) is still controversial. However, there is no large BP database for IS or transient ischemic attack (TIA) in China. This study aims to describe the rationale, study design, and baseline characteristics of a nationwide BP database in IS or TIA patients in China. The BOSS (blood pressure and clinical outcome in TIA or ischemic stroke) study was a hospital-based, prospective cohort study aiming to assess BP parameters and clinical outcome in IS/TIA patients. BP parameters were based on office BP, ambulatory BP, and home BP. Clinical outcomes included stroke recurrence, combined vascular events, and disability. Electronic case-report forms were used to record baseline and follow-up data. The patients were followed up for clinical outcomes at 3 months through face-to-face interview and at 12 months by telephone. Between October 2012 and February 2014, the BOSS registry recruited 2,608 patients from 61 hospitals, with a mean age of 62.5 years, 32.4% of whom were female, 88.9% with an entry diagnosis of IS, and 86% diagnosed with hypertension. The rates of patients lost-to-follow-up were 3.1% at 3 months and 5.1% at 1 year; 93% of patients completed ambulatory BP monitoring during hospitalization and 94.7% finished a 3-month BP diary. The BOSS registry will provide important evidence about BP management in the acute phase and secondary prevention for IS/TIA patients.

[Economic evaluation of dabigatran for stroke prevention in patients with non-valvular atrial fibrillation].

PubMed

Silva Miguel, Luís; Rocha, Evangelista; Ferreira, Jorge

2013-01-01

To estimate the cost-effectiveness and cost-utility of dabigatran in the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation in Portugal. A Markov model was used to simulate patients' clinical course, estimating the occurrence of ischemic and hemorrhagic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and intra- and extracranial hemorrhage. The clinical parameters are based on the results of the RE-LY trial, which compared dabigatran with warfarin, and on a meta-analysis that estimated the risk of each event in patients treated with aspirin or with no antithrombotic therapy. Dabigatran provides an increase of 0.331 life years and 0.354 quality-adjusted life years for each patient. From a societal perspective, these clinical gains entail an additional expenditure of 2978 euros. Thus, the incremental cost is 9006 euros per life year gained and 8409 euros per quality-adjusted life year. The results show that dabigatran reduces the number of events, especially the most severe such as ischemic and hemorrhagic stroke, as well as their long-term sequelae. The expense of dabigatran is partially offset by lower event-related costs and by the fact that INR monitoring is unnecessary. It can thus be concluded that the use of dabigatran in clinical practice in Portugal is cost-effective. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Out-of-range INR values and outcomes among new warfarin patients with non-valvular atrial fibrillation.

PubMed

Nelson, Winnie W; Wang, Li; Baser, Onur; Damaraju, Chandrasekharrao V; Schein, Jeffrey R

2015-02-01

Although efficacious in stroke prevention in non-valvular atrial fibrillation, many warfarin patients are sub-optimally managed. To evaluate the association of international normalized ratio control and clinical outcomes among new warfarin patients with non-valvular atrial fibrillation. Adult non-valvular atrial fibrillation patients (≥18 years) initiating warfarin treatment were selected from the US Veterans Health Administration dataset between 10/2007 and 9/2012. Valid international normalized ratio values were examined from the warfarin initiation date through the earlier of the first clinical outcome, end of warfarin exposure or death. Each patient contributed multiple in-range and out-of-range time periods. The relative risk ratios of clinical outcomes associated with international normalized ratio control were estimated. 34,346 patients were included for analysis. During the warfarin exposure period, the incidence of events per 100 person-years was highest when patients had international normalized ratio <2:13.66 for acute coronary syndrome; 10.30 for ischemic stroke; 2.93 for transient ischemic attack; 1.81 for systemic embolism; and 4.55 for major bleeding. Poisson regression confirmed that during periods with international normalized ratio <2, patients were at increased risk of developing acute coronary syndrome (relative risk ratio: 7.9; 95 % confidence interval 6.9-9.1), ischemic stroke (relative risk ratio: 7.6; 95 % confidence interval 6.5-8.9), transient ischemic attack (relative risk ratio: 8.2; 95 % confidence interval 6.1-11.2), systemic embolism (relative risk ratio: 6.3; 95 % confidence interval 4.4-8.9) and major bleeding (relative risk ratio: 2.6; 95 % confidence interval 2.2-3.0). During time periods with international normalized ratio >3, patients had significantly increased risk of major bleeding (relative risk ratio: 1.5; 95 % confidence interval 1.2-2.0). In a Veterans Health Administration non-valvular atrial fibrillation population, exposure to out-of-range international normalized ratio values was associated with significantly increased risk of adverse clinical outcomes.

Predictors of long-term survival among first-ever ischemic and hemorrhagic stroke in a Brazilian stroke cohort.

PubMed

Goulart, Alessandra C; Fernandes, Tiotrefis G; Santos, Itamar S; Alencar, Airlane P; Bensenor, Isabela M; Lotufo, Paulo A

2013-05-24

Few studies have examined both ischemic and hemorrhagic stroke to identify prognostic factors associated to long-term stroke survival. We investigated long-term survival and predictors that could adversely influence ischemic and hemorrhagic first-ever stroke prognosis. We prospectively ascertained 665 consecutive first-ever ischemic and hemorrhagic stroke cases from "The Study of Stroke Mortality and Morbidity" (The EMMA Study) in a community hospital in São Paulo, Brazil. We evaluated cardiovascular risk factors and sociodemographic characteristics (age, gender, race and educational level). We found a lower survival rate among hemorrhagic cases compared to ischemic stroke cases at the end of 4 years of follow-up (52% vs. 44%, p = 0.04). The risk of death was two times higher among people with ischemic stroke without formal education. Also, we found consistently higher risk of death for diabetics with ischemic stroke (HR = 1.45; 95% CI = 1.07-1.97) compared to no diabetics. As expected, age equally influenced on the high risk of poor survival, regardless of stroke subtype. For ischemic stroke, the lack of formal education and diabetes were significant independent predictors of poor long-term survival.

Peripheral Frequency of CD4+ CD28− Cells in Acute Ischemic Stroke

PubMed Central

Tuttolomondo, Antonino; Pecoraro, Rosaria; Casuccio, Alessandra; Di Raimondo, Domenico; Buttà, Carmelo; Clemente, Giuseppe; Corte, Vittoriano della; Guggino, Giuliana; Arnao, Valentina; Maida, Carlo; Simonetta, Irene; Maugeri, Rosario; Squatrito, Rosario; Pinto, Antonio

2015-01-01

Abstract CD4+ CD28− T cells also called CD28 null cells have been reported as increased in the clinical setting of acute coronary syndrome. Only 2 studies previously analyzed peripheral frequency of CD28 null cells in subjects with acute ischemic stroke but, to our knowledge, peripheral frequency of CD28 null cells in each TOAST subtype of ischemic stroke has never been evaluated. We hypothesized that CD4+ cells and, in particular, the CD28 null cell subset could show a different degree of peripheral percentage in subjects with acute ischemic stroke in relation to clinical subtype and severity of ischemic stroke. The aim of our study was to analyze peripheral frequency of CD28 null cells in subjects with acute ischemic stroke in relation to TOAST diagnostic subtype, and to evaluate their relationship with scores of clinical severity of acute ischemic stroke, and their predictive role in the diagnosis of acute ischemic stroke and diagnostic subtype We enrolled 98 consecutive subjects admitted to our recruitment wards with a diagnosis of ischemic stroke. As controls we enrolled 66 hospitalized patients without a diagnosis of acute ischemic stroke. Peripheral frequency of CD4+ and CD28 null cells has been evaluated with a FACS Calibur flow cytometer. Subjects with acute ischemic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to control subjects without acute ischemic stroke. Subjects with cardioembolic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to subjects with other TOAST subtypes. We observed a significant relationship between CD28 null cells peripheral percentage and Scandinavian Stroke Scale and NIHSS scores. ROC curve analysis showed that CD28 null cell percentage may be useful to differentiate between stroke subtypes. These findings seem suggest a possible role for a T-cell component also in acute ischemic stroke clinical setting showing a different peripheral frequency of CD28 null cells in relation of each TOAST subtype of stroke. PMID:25997053

Self-perceived psychological stress and ischemic stroke: a case-control study

PubMed Central

Jood, Katarina; Redfors, Petra; Rosengren, Annika; Blomstrand, Christian; Jern, Christina

2009-01-01

Background A growing body of evidence suggests that psychological stress contributes to coronary artery disease. However, associations between stress and stroke are less clear. In this study, we investigated the possible association between ischemic stroke and self-perceived psychological stress, as measured by a single-item questionnaire, previously reported to be associated with myocardial infarction. Methods In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), 600 consecutive patients with acute ischemic stroke (aged 18 to 69 years) and 600 age-matched and sex-matched population controls were recruited. Ischemic stroke subtype was determined according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Self-perceived psychological stress preceding stroke was assessed retrospectively using a single-item questionnaire. Results Permanent self-perceived psychological stress during the last year or longer was independently associated with overall ischemic stroke (multivariate adjusted odds ratio (OR) 3.49, 95% confidence interval (CI) 2.06 to 5.93). Analyses by stroke subtype showed that this association was present for large vessel disease (OR 3.91, 95% CI 1.58 to 9.67), small vessel disease (OR 3.20, 95% CI 1.64 to 6.24), and cryptogenic stroke (OR 4.03, 95% CI 2.34 to 6.95), but not for cardioembolic stroke (OR 1.48, 95% CI 0.64 to 3.39). Conclusion In this case-control study, we found an independent association between self-perceived psychological stress and ischemic stroke. A novel finding was that this association differed by ischemic stroke subtype. Our results emphasize the need for further prospective studies addressing the potential role for psychological stress as a risk factor for ischemic stroke. In such studies ischemic stroke subtypes should be taken into consideration. PMID:19796376

Ischemic Stroke

MedlinePlus

A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...

Characteristics, treatment, and outcomes of periprocedural cerebrovascular accidents during electrophysiologic procedures.

PubMed

Harb, Serge C; Thomas, George; Saliba, Walid I; Nakhoul, Georges N; Hussein, Ayman A; Duarte, Valeria E; Bhargava, Mandeep; Baranowski, Bryan; Tchou, Patrick; Dresing, Thomas; Callahan, Thomas; Kanj, Mohamed; Natale, Andrea; Lindsay, Bruce D; Wazni, Oussama M

2013-06-01

We sought to identify the characteristics, treatment, and outcomes of periprocedural cerebrovascular accident (PCVA) during electrophysiologic (EP) procedures. Periprocedural cerebrovascular accident is one of the most feared complications during EP procedures with very few data regarding its characteristics, management, and outcomes. Between January 1998 and December 2008, we reviewed 30,032 invasive EP procedures for PCVA occurrence and characteristics. Management and outcomes were also determined. Thirty-eight CVAs were identified. Twenty (53 %) were intraprocedural and 18 (47 %) postprocedural. Thirty-two (84 %) were classified as strokes and six (16 %) as transient ischemic attacks. All CVAs except one (37, 97 %) were ischemic and the vast majority occurred during ablation procedures (36, 95 %). Among the 31 patients with ischemic stroke, 11 (35 %) were treated with reperfusion (eight catheter-based therapy and three intravenous t-PA) of whom five (46 %) had complete recovery, three (27 %) had partial recovery, and three (27 %) had no recovery. No hemorrhagic transformations occurred. Periprocedural cerebrovascular accident during EP procedures is rare and is almost always ischemic. It occurs more frequently during ablation procedures. Reperfusion therapy is feasible and safe.

Greater Cincinnati/Northern Kentucky Stroke Study: volume of first-ever ischemic stroke among blacks in a population-based study.

PubMed

Kissela, B; Broderick, J; Woo, D; Kothari, R; Miller, R; Khoury, J; Brott, T; Pancioli, A; Jauch, E; Gebel, J; Shukla, R; Alwell, K; Tomsick, T

2001-06-01

The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm(3). The volume of first-ever ischemic stroke in the population is not known. The first phase of the population-based Greater Cincinnati/Northern Kentucky Stroke Study identified all ischemic strokes occurring in blacks in the greater Cincinnati region between January and June of 1993. The patients in this phase of the study who had a first-ever ischemic clinical stroke were identified, and the volume of ischemic stroke was measured. There were 257 verified clinical cases of ischemic stroke, of which 181 had a first-ever ischemic infarct. Imaging was available for 150 of these patients, and 79 had an infarct on the CT or MRI study that was definitely or possibly related to the clinical symptoms. For these patients, volumetric measurements were performed by means of the modified ellipsoid method. The median volume of first-ever ischemic stroke for the 79 patients was 2.5 cm(3) (interquartile range, 0.5 to 8.8 cm(3)). There was a significant relation between location of lesion and infarct size (P<0.001) and between volume and mechanism of stroke (P=0.001). The volume of first-ever ischemic stroke among blacks in our population-based study is smaller than has been previously reported in acute stroke therapy trials. The large proportion of small, mild strokes in blacks may be an important reason for the low percentage of patients who meet the inclusion criteria for tissue plasminogen activator. Further study is necessary to see if these results are generalizable to a multiracial population.

Ten-year risk of stroke in patients with previous cerebral infarction and the impact of carotid surgery in the Asymptomatic Carotid Surgery Trial.

PubMed

Streifler, Jonathan Y; den Hartog, Anne G; Pan, Samuel; Pan, Hongchao; Bulbulia, Richard; Thomas, Dafydd J; Brown, Martin M; Halliday, Alison

2016-12-01

Silent brain infarcts are common in patients at increased risk of stroke and are associated with a poor prognosis. In patients with asymptomatic carotid stenosis, similar adverse associations were claimed, but the impact of previous infarction or symptoms on the beneficial effects of carotid endarterectomy is not clear. Our aim was to evaluate the impact of prior cerebral infarction in patients enrolled in the Asymptomatic Carotid Surgery Trial, a large trial with 10-year follow-up in which participants whose carotid stenosis had not caused symptoms for at least six months were randomly allocated either immediate or deferred carotid endarterectomy. The first Asymptomatic Carotid Surgery Trial included 3120 patients. Of these, 2333 patients with baseline brain imaging were identified and divided into two groups irrespective of treatment assignment, 1331 with evidence of previous cerebral infarction, defined as a history of ischemic stroke or transient ischemic attack > 6 months prior to randomization or radiological evidence of an asymptomatic infarct (group 1) and 1002 with normal imaging and no prior stroke or transient ischemic attack (group 2). Stroke and vascular deaths were compared during follow-up, and the impact of carotid endarterectomy was observed in both groups. Baseline characteristics of patients with and without baseline brain imaging were broadly similar. Of those included in the present report, male gender and hypertension were more common in group 1, while mean ipsilateral stenosis was slightly greater in group 2. At 10 years follow-up, stroke was more common among participants with cerebral infarction before randomization (absolute risk increase 5.8% (1.8-9.8), p = 0.004), and the risk of stroke and vascular death was also higher in this group (absolute risk increase 6.9% (1.9-12.0), p = 0.007). On multivariate analysis, prior cerebral infarction was associated with a greater risk of stroke (hazard ratio = 1.51, 95% confidence interval: 1.17-1.95, p = 0.002) and of stroke or other vascular death (hazard ratio = 1.30, 95% confidence interval: 1.11-1.52, p = 0.001). At 10 years, greater absolute benefits from immediate carotid endarterectomy were seen in those patients with prior cerebral infarction (6.7% strokes immediate carotid endarterectomy vs. 14.7% delayed carotid endarterectomy; hazard ratio 0.47 (0.34-0.65), p = 0.003), compared to those lower risk patients without prior cerebral infarction (6.0% vs. 9.9%, respectively; hazard ratio 0.61 (0.39-0.94), p = 0.005), though it must be emphasized that the first Asymptomatic Carotid Surgery Trial was not designed to test this retrospective and non-randomized comparison. Asymptomatic carotid stenosis patients with prior cerebral infarction have a higher stroke risk during long-term follow-up than those without prior cerebral infarction. Evidence of prior ischemic events might help identify patients in whom carotid intervention is particularly beneficial. © 2016 World Stroke Organization.

[Stroke. are there any difference between patients with or without patent foramen ovale in left atrial appendage systolic function?].

PubMed

Contreras, Alejandro E; Perrote, Federico; Concari, Ignacio; Brenna, Eduardo J; Lucero, Cecilia

2012-01-01

The aim of this study was to evaluate the systolic function of the left atrial appendage (LAA) in a group with and without patent foramen ovale (PFO) who suffered ischemic cerebrovascular events. Between September 2010 and October 2011, 17 patients were referred for transesophageal echocardiography (TEE) after suffering a stroke. PFO was defined as the passage of at least one bubble through atrial septum with bubble test. We compared systolic velocity in the appendage between patients with and without PFO and a control group. Were 8 women and 9 men, mean age 54.1 ± 19.5 years and 8 patients were under 55 years of age. All patients had suffered a ischemic cerebrovascular events, 41.2% had stroke, 52.9% transient ischemic attack and amaurosis fugax 5.9%. In the assessment of TEE, 11.8% had atrial septal aneurysm and 35.3% PFO. Mean LAA systolic velocity was 66.3 ± 20.3 cm / sec. There was no difference in systolic velocity of the LAA between patients with and without PFO (67.5 ± 11.8 cm / sec vs 65.7 ± 24.3 cm / sec respectively, p = 0.87). The control group of 8 patients, 5 women and 3 men, mean age 39.5 ± 18 years, had a LAA systolic velocity of 77.6 ± 28.9 cm / sec, no significant differences with ischemic patients. There were no differences in systolic function of the LAA between patients with and without PFO with ischemic cerebrovascular event.

Remote pre-procedural ischemic stroke as the greatest risk in carotid‑stenting‑associated stroke and death: a single center's experience.

PubMed

Rašiová, Mária; Špak, Ľubomír; Farkašová, Ľudmila; Pataky, Štefan; Koščo, Martin; Hudák, Marek; Moščovič, Matej; Leško, Norbert

2017-08-01

The goal of carotid artery stenting (CAS) is to decrease the stroke risk in patients with carotid stenosis. This procedure carries an immediate risk of stroke and death and many patients do not benefit from it, especially asymptomatic patients. It is crucial to accurately select the patients who would benefit from carotid procedure, and to rule out those for whom the procedure might be hazardous. Remote ischemic stroke is a known risk factor for stroke recurrence during surgery. The aim of our study was to determine the periprocedural complication risk (within 30 days after CAS) associated with carotid stenting (stroke, death) in patients with and without remote pre-procedural ischemic stroke, to analyze periprocedural risk in other specific patient subgroups treated with CAS, and to determine the impact of observed variables on all-cause mortality during long-term follow-up. We conducted a retrospective review of prospectively collected data from all patients treated with protected CAS between June 20, 2008 and December 31, 2015. Patient age, gender, type of carotid stenosis (symptomatic versus asymptomatic), side of stenosis (right or left carotid artery), type of cerebral protection (proximal versus distal), presence of comorbidities (remote ischemic pre-procedural ischemic stroke, coronary artery disease, diabetes mellitus, peripheral artery disease), previous ipsilateral carotid endarterectomy (CEA), contralateral carotid occlusion (CCO) and previous contralateral CAS/CEA were analyzed to identify higher CAS risk and to determine the impact of these variables on all-cause mortality during follow-up. Survival data were obtained from the Health Care Surveillance Authority registry. Mean follow-up was 1054 days (interquartile range 547.3; 1454.8). Remote pre-procedural ischemic stroke was defined as any-territory ischemic stroke >6 months prior to CAS. Primary periprocedural endpoint incidence (stroke/death) in 502 patients was 3.8% (N.=19) of all patients, 5.4% (N.=10) of symptomatic patients and 2.8% (N.=9) of asymptomatic patients. The risk of periprocedural stroke/death was 3.4 times higher in patients with (N.=198) compared to patients without remote ischemic stroke (N.=304) (6.6% versus 2.0% of patients without remote ischemic stroke; P=0.008). Periprocedural stroke/death in symptomatic patients (N.=186) was non-significantly higher in patients with remote ischemic stroke (N.=76) compared with patients without remote ischemic stroke (N.=110) (7.9% versus 3.6%; P=0.206). Asymptomatic patients with remote ischemic stroke (N.=122) had a 5.6-time-higher periprocedural risk of stroke/death compared with asymptomatic patients without remote ischemic stroke (N.=194) (5.7% versus 1.0%; P=0.014). Patients ≥75 years (N.=83) had a 3.0-time-higher periprocedural risk of stroke/death compared with younger patients (N.=419) (8.4% versus 2.9%; P=0.015); a non-significant increase of periprocedural stroke/death was found in both symptomatic (N.=35) and asymptomatic (N.=48) elderly patients (11.4% versus 4.0%, P=0.078; and 6.3% versus 2.4%, P=0.124, respectively). Increased periprocedural risk of stroke/death was not documented in other analyzed patient subgroups. During long-term follow-up, a 1.5-time-higher mortality risk was found in patients with remote ischemic stroke compared with patients without remote ischemic stroke in multivariable analysis; other patient subgroups (except older versus younger patients) did not differ in long-term mortality following carotid stenting. In our experience, all patients with remote pre-procedural any-territory ischemic stroke belong to risky subgroup for periprocedural stroke death after CAS. All asymptomatic patients with remote ischemic stroke should not be treated with CAS. Remote ischemic stroke increases all-cause mortality in long-term follow-up after carotid stenting. Patients aged ≥75 years also have increased risk of periprocedural stroke and death after CAS. These factors should help us to be more selective when planning carotid procedures.

Is It Acute Stroke or Not - A Prospective Observational Study from a Multidisciplinary Emergency Department.

PubMed

Wolf, Marc E; Chatzikonstantinou, Anastasios; Grüttner, Joachim; Ebert, Anne D; Walter, Thomas; Hennerici, Michael G; Fatar, Marc

2016-01-01

Acute stroke is a medical emergency with various clinical presentations. Since the introduction of systemic thrombolytic treatment, stroke diagnosis has been made quickly and with great caution, and the trend of rapid presentation at hospitals has increased. In our multidisciplinary Emergency Department, we prospectively collected and analysed data of consecutive patients presenting with suspected acute stroke (SAS) or transient ischemic attack (TIA). Four hundred ten patients (200 men, mean age 68 ± 16, range 17-93 years) with SAS were admitted of which 105 were prehospitally announced as within the time-window for thrombolytic treatment (TW). Diagnosis of acute stroke/TIA was retained in 147 (35.9%). The initially reported TW <4.5 h was wrong in 35.3%. Thrombolysis was performed in 27 patients (23.5% of ischemic stroke patients; 6.6% of all SAS). Diagnosis of another neurologic disease was made in 62 (15.1%). Major differential diagnoses came from the field of internal medicine, psychiatry or otorhinolaryngology. One hundred fifty patients (36.6%) were rapidly discharged. About half the number of our patients admitted for SAS did not suffer from an acute neurologic disease. Residual symptoms post-stroke might be partly responsible for initial misinterpretation. The crucial difference between symptom onset and symptom recognition needs to be emphasized to improve the prehospital assessment of the TW. © 2016 S. Karger AG, Basel.

Glyburide is associated with attenuated vasogenic edema in stroke patients

PubMed Central

Kimberly, W. Taylor; Battey, Thomas W. K.; Pham, Ly; Wu, Ona; Yoo, Albert J.; Furie, Karen L.; Singhal, Aneesh B.; Elm, Jordan J.; Stern, Barney J.; Sheth, Kevin N.

2016-01-01

Background and Purpose Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 (SUR1) and transient receptor potential cation channel subfamily M member 4 (TRPM4). However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known. Methods Using a case control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the Glyburide Advantage in Malignant Edema and Stroke-Pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 plasma level in large hemispheric stroke. Results We report that IV glyburide was associated with attenuated T2 fluid attenuated inversion recovery (FLAIR) signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood matrix metalloproteinase-9 (MMP-9) level. Conclusions Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial. PMID:24072459

Automated Software System to Promote Anticoagulation and Reduce Stroke Risk: Cluster-Randomized Controlled Trial.

PubMed

Holt, Tim A; Dalton, Andrew; Marshall, Tom; Fay, Matthew; Qureshi, Nadeem; Kirkpatrick, Susan; Hislop, Jenny; Lasserson, Daniel; Kearley, Karen; Mollison, Jill; Yu, Ly-Mee; Hobbs, F D Richard; Fitzmaurice, David

2017-03-01

Oral anticoagulants (OAC) substantially reduce risk of stroke in atrial fibrillation, but uptake is suboptimal. Electronic health records enable automated identification of people at risk but not receiving treatment. We investigated the effectiveness of a software tool (AURAS-AF [Automated Risk Assessment for Stroke in Atrial Fibrillation]) designed to identify such individuals during routine care through a cluster-randomized trial. Screen reminders appeared each time the electronic health records of an eligible patient was accessed until a decision had been taken over OAC treatment. Where OAC was not started, clinicians were prompted to indicate a reason. Control practices continued usual care. The primary outcome was the proportion of eligible individuals receiving OAC at 6 months. Secondary outcomes included rates of cardiovascular events and reports of adverse effects of the software on clinical decision-making. Forty-seven practices were randomized. The mean proportion-prescribed OAC at 6 months was 66.3% (SD=9.3) in the intervention arm and 63.9% (9.5) in the control arm (adjusted difference 1.21% [95% confidence interval -0.72 to 3.13]). Incidence of recorded transient ischemic attack was higher in the intervention practices (median 10.0 versus 2.3 per 1000 patients with atrial fibrillation; P =0.027), but at 12 months, we found a lower incidence of both all cause stroke ( P =0.06) and hemorrhage ( P =0.054). No adverse effects of the software were reported. No significant change in OAC prescribing occurred. A greater rate of diagnosis of transient ischemic attack (possibly because of improved detection or overdiagnosis) was associated with a reduction (of borderline significance) in stroke and hemorrhage over 12 months. URL: http://www.isrctn.com. Unique Identifier: ISRCTN55722437. © 2017 American Heart Association, Inc.

Magnetic resonance imaging-based cerebral tissue classification reveals distinct spatiotemporal patterns of changes after stroke in non-human primates.

PubMed

Bouts, Mark J R J; Westmoreland, Susan V; de Crespigny, Alex J; Liu, Yutong; Vangel, Mark; Dijkhuizen, Rick M; Wu, Ona; D'Arceuil, Helen E

2015-12-15

Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combining quantitative T2 and diffusion MRI indices into MRI 'tissue signatures', (2) to evaluate temporal differences in these signatures between transient (n = 2) and permanent (n = 2) middle cerebral artery occlusion, and (3) to correlate histopathology findings in the chronic stroke period to the acute and subacute MRI derived tissue signatures. An improved iterative self-organizing data analysis algorithm was used to combine T2, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps across seven successive timepoints (1, 2, 3, 24, 72, 144, 240 h) which revealed five temporal MRI signatures, that were different from the normal tissue pattern (P < 0.001). The distribution of signatures between brains with permanent and transient occlusions varied significantly between groups (P < 0.001). Qualitative comparisons with histopathology revealed that these signatures represented regions with different histopathology. Two signatures identified areas of progressive injury marked by severe necrosis and the presence of gitter cells. Another signature identified less severe but pronounced neuronal and axonal degeneration, while the other signatures depicted tissue remodeling with vascular proliferation and astrogliosis. These exploratory results demonstrate the potential of temporally and spatially combined voxel-based methods to generate tissue signatures that may correlate with distinct histopathological features. The identification of distinct ischemic MRI signatures associated with specific tissue fates may further aid in assessing and monitoring the efficacy of novel pharmaceutical treatments for stroke in a pre-clinical and clinical setting.

Race/ethnic Differences in Post-stroke Depression (PSD): Findings from the Stroke Warning Information and Faster Treatment (SWIFT) Study.

PubMed

Goldmann, Emily; Roberts, Eric T; Parikh, Nina S; Lord, Aaron S; Boden-Albala, Bernadette

2016-01-21

Post-stroke depression (PSD) is common and associated with poor stroke outcomes, but few studies have examined race/ethnic disparities in PSD. Given the paucity of work and inconsistent findings in this important area of research, our study aimed to examine race/ethnic differences in depression in a multi-ethnic cohort of stroke patients. Longitudinal. Prospective trial of a post-stroke educational intervention. 1,193 mild/moderate ischemic stroke/transient ischemic attack (TIA) patients. We used the Center for Epidemiologic Studies Depression (CES-D) Scale to assess subthreshold (CES-D score 8-15) and full (CES-D score ≥ 16) depression at one month ("early") and 12 months ("late") following stroke. Multinomial logistic regression analyses examined the association between race/ethnicity and early and late PSD separately. The prevalence of subthreshold and full PSD was 22.5% and 32.6% in the early period and 22.0% and 27.4% in the late period, respectively. Hispanics had 60% lower odds of early full PSD compared with non-Hispanic Whites after adjusting for other covariates (OR=.4, 95% CI: .2, .8). Race/ethnicity was not significantly associated with late PSD. Hispanic stroke patients had half the odds of PSD in early period compared with Whites, but no difference was found in the later period. Further studies comparing trajectories of PSD between race/ethnic groups may further our understanding of race/ethnic disparities in PSD and help identify effective interventions.

Disparities in stroke type and vascular risk factors between 2 Hispanic populations in Miami and Mexico city.

PubMed

Romano, Jose G; Arauz, Antonio; Koch, Sebastian; Dong, Chuanhui; Marquez, Juan M; Artigas, Carol; Merlos, Marlon; Hernandez, Bernardo; Roa, Luis F; Rundek, Tatjana; Sacco, Ralph L

2013-08-01

The heterogeneous nature and determinants of stroke among different Hispanic groups was examined by comparing hospitalized Hispanic stroke patients in Miami, where the Hispanic population is largely of Caribbean origin, to a Mestizo population in Mexico City. Consecutive Hispanic patients who were admitted with stroke or transient ischemic attack (TIA) and included in the prospective stroke registries of 2 tertiary care teaching hospitals were studied. Demographic factors, stroke subtypes, vascular risk factors, stroke severity, and outcomes were compared. Vascular risk factor definitions were standardized. A total of 928 patients (520 Mexicans and 408 Miami Hispanics) were analyzed. Mexicans were younger, with a greater proportion of women. More cerebral venous thromboses (CVTs) were admitted in Mexico, while TIA and stroke mimics were more commonly admitted in Miami; cardioembolic strokes were more commonly ascertained in Miami, and more cryptogenic strokes in Mexico. Stroke severity was similar for intracerebral hemorrhages, but more severe ischemic strokes and CVTs were included in the Mexican registry. Outcome at 1 and 3 months was similar in both registries after adjusting for age and baseline stroke severity. After adjusting for age and sex, hypertension, dyslipidemia, and atrial fibrillation were more frequent, and diabetes mellitus was less frequent, among Miami Hispanics compared to Mexicans. We found significant differences in the frequency of hypertension, diabetes, dyslipidemia, and atrial fibrillation in Miami Hispanics and Mexican stroke patients, highlighting the heterogeneity of the Hispanic ethnic group. Future studies are needed to clarify the relative contribution of genetic and environmental disparities amongst Mexican and Caribbean Hispanic stroke patients. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Stroke or transient ischemic attack in patients with transvenous pacemaker or defibrillator and echocardiographically detected patent foramen ovale.

PubMed

DeSimone, Christopher V; Friedman, Paul A; Noheria, Amit; Patel, Nikhil A; DeSimone, Daniel C; Bdeir, Sami; Aakre, Christopher A; Vaidya, Vaibhav R; Slusser, Joshua P; Hodge, David O; Ackerman, Michael J; Rabinstein, Alejandro A; Asirvatham, Samuel J

2013-09-24

A patent foramen ovale (PFO) may permit arterial embolization of thrombi that accumulate on the leads of cardiac implantable electronic devices in the right-sided cardiac chambers. We sought to determine whether a PFO increases the risk of stroke/transient ischemic attack (TIA) in patients with endocardial leads. We retrospectively evaluated all patients who had endocardial leads implanted between January 1, 2000, and October 25, 2010, at Mayo Clinic Rochester. Echocardiography was used to establish definite PFO and non-PFO cohorts. The primary end point of stroke/TIA consistent with a cardioembolic etiology and the secondary end point of mortality during postimplantation follow-up were compared in PFO versus non-PFO patients with the use of Cox proportional hazards models. We analyzed 6075 patients (364 with PFO) followed for a mean 4.7 ± 3.1 years. The primary end point of stroke/TIA was met in 30/364 (8.2%) PFO versus 117/5711 (2.0%) non-PFO patients (hazard ratio, 3.49; 95% confidence interval, 2.33-5.25; P<0.0001). The association of PFO with stroke/TIA remained significant after multivariable adjustment for age, sex, history of stroke/TIA, atrial fibrillation, and baseline aspirin/warfarin use (hazard ratio, 3.30; 95% confidence interval, 2.19-4.96; P<0.0001). There was no significant difference in all-cause mortality between PFO and non-PFO patients (hazard ratio, 0.91; 95% confidence interval, 0.77-1.07; P=0.25). In patients with endocardial leads, the presence of a PFO on routine echocardiography is associated with a substantially increased risk of embolic stroke/TIA. This finding suggests a role of screening for PFOs in patients who require cardiac implantable electronic devices; if a PFO is detected, PFO closure, anticoagulation, or nonvascular lead placement may be considered.

Association of ALOX5AP with ischemic stroke: a population-based case-control study.

PubMed

Kaushal, Ritesh; Pal, Prodipto; Alwell, Kathleen; Haverbusch, Mary; Flaherty, Matthew; Moomaw, Charles; Sekar, Padmini; Kissela, Brett; Kleindorfer, Dawn; Chakraborty, Ranajit; Broderick, Joseph; Deka, Ranjan; Woo, Daniel

2007-06-01

Arachidonate 5-lipoxygenase activating protein (ALOX5AP) has been reported to demonstrate linkage and association with ischemic stroke and myocardial infarction. However, replication studies have been conflicting and to date, a significant proportion of blacks have not been studied. We prospectively recruited cases of ischemic stroke from all 16 hospitals in the Greater Cincinnati/Northern Kentucky region and demographically matched them to stroke-free population-based controls. Single nucleotide polymorphisms (SNPs) were selected based on association with ischemic stroke in prior studies. Allelic, genotypic and haplotypic association testing was performed using HAPLOVIEW. Multiple logistic regression was used to control for the presence of traditional risk factors including hypertension, diabetes, hypercholesterolemia and smoking. A total of 357 cases and 482 controls were genotyped. The SNPs, rs9579646 and rs4769874 were found to be significantly associated at both allelic (P=0.019 and P<10(-4), respectively) and genotypic level with ischemic stroke among whites after correction for multiple testing. Haplotype association was identified with ischemic stroke as well as ischemic stroke subtypes among whites. Although an overall haplotype association with ischemic stroke was identified among blacks no evidence of association among individual haplotypes, alleles or genotypes were observed. Allele frequencies for the SNPs examined were markedly different among whites and blacks. In conclusion, we report significant association of variants of ALOX5AP with ischemic stroke and ischemic stroke subtypes among whites. No significant association was identified among blacks.

Prognostic Significance of Blood Pressure Variability on Beat-to-Beat Monitoring After Transient Ischemic Attack and Stroke.

PubMed

Webb, Alastair J S; Mazzucco, Sara; Li, Linxin; Rothwell, Peter M

2018-01-01

Visit-to-visit and day-to-day blood pressure (BP) variability (BPV) predict an increased risk of cardiovascular events but only reflect 1 form of BPV. Beat-to-beat BPV can be rapidly assessed and might also be predictive. In consecutive patients within 6 weeks of transient ischemic attack or nondisabling stroke (Oxford Vascular Study), BPV (coefficient of variation) was measured beat-to-beat for 5 minutes (Finometer), day-to-day for 1 week on home monitoring (3 readings, 3× daily), and on awake ambulatory BP monitoring. BPV after 1-month standard treatment was related (Cox proportional hazards) to recurrent stroke and cardiovascular events for 2 to 5 years, adjusted for mean systolic BP. Among 520 patients, 26 had inadequate beat-to-beat recordings, and 22 patients were in atrial fibrillation. Four hundred five patients had all forms of monitoring. Beat-to-beat BPV predicted recurrent stroke and cardiovascular events independently of mean systolic BP (hazard ratio per group SD, stroke: 1.47 [1.12-1.91]; P =0.005; cardiovascular events: 1.41 [1.08-1.83]; P =0.01), including after adjustment for age and sex (stroke: 1.47 [1.12-1.92]; P =0.005) and all risk factors (1.40 [1.00-1.94]; P =0.047). Day-to-day BPV was less strongly associated with stroke (adjusted hazard ratio, 1.29 [0.97-1.71]; P =0.08) but similarly with cardiovascular events (1.41 [1.09-1.83]; P =0.009). BPV on awake ambulatory BP monitoring was nonpredictive (stroke: 0.89 [0.59-1.35]; P =0.59; cardiovascular events: 1.08 [0.77-1.52]; P =0.65). Despite a weak correlation ( r =0.119; P =0.02), beat-to-beat BPV was associated with risk of recurrent stroke independently of day-to-day BPV (1.41 [1.05-1.90]; P =0.02). Beat-to-beat BPV predicted recurrent stroke and cardiovascular events, independently of mean systolic BP and risk factors but short-term BPV on ambulatory BP monitoring did not. Beat-to-beat BPV may be a useful additional marker of cardiovascular risk. © 2017 The Authors.

Risk factors in various subtypes of ischemic stroke according to TOAST criteria.

PubMed

Aquil, Nadia; Begum, Imtiaz; Ahmed, Arshia; Vohra, Ejaz Ahmed; Soomro, Bashir Ahmed

2011-05-01

To identify the frequency of risk factors in various subtypes of acute ischemic stroke according to TOAST criteria. Cross-sectional, observational study. Ziauddin Hospital, Karachi, from January to December 2007. Patients with acute ischemic stroke were enrolled. Studied variables included demographic profile, history of risk factors, physical and neurological examination, and investigations relevant with the objectives of the study. Findings were described as frequency percentages. Proportions of risk factors against subtypes was compared using chi-square test with significance at p < 0.05. Out of the 100 patients with acute ischemic stroke, mean age at presentation was 63.5 years. Risk factor distribution was hypertension in 85%, Diabetes mellitus in 49%, ischemic heart disease in 30%, dyslipedemia in 22%, smoking in 9%, atrial fibrillation in 5%, and previous history of stroke in 29%. The various subtypes of acute ischemic stroke were lacunar infarct in 43%, large artery atherosclerosis in 31%, cardioembolic type in 8%, stroke of other determined etiology in 1% and stroke of undetermined etiology in 18%. Hypertension and Diabetes were the most important risk factors in both large and small artery atherosclerosis. In patients with cardio-embolic stroke significant association was found with ischemic heart disease (p=0.01). Importance and relevance of risk factors evaluated for subtypes rather than ischemic stroke as a whole should be reflected in preventive efforts against the burden of ischemic stroke.

Contemporary medical therapies of atherosclerotic carotid artery disease.

PubMed

Cheng, Suk F; Brown, Martin M

2017-03-01

Contemporary medical therapy consists of identification and treatment of all patient-modifiable vascular risk factors. Specific atherosclerotic disease therapies are designed to reduce the risk of thrombosis, and the disease progression in order to reduce the risk of future cardiovascular events. Contemporary medical management emphasizes the need to support the patient in achieving lifestyle modifications and to adjust medication to achieve individualized target values for specific quantifiable risk factors. Antiplatelet therapy in the form of aspirin or clopidogrel is routinely used for the prevention of ischemic stroke in patients who have had a transient ischemic attack or stroke. There is evidence from a recent trial that the use of combination antiplatelet therapy with aspirin and clopidogrel started within 24 hours of minor stroke or transient ischemic attack reduces the risk of recurrent stroke compared to the use of aspirin alone, and therefore we use aspirin plus clopidogrel in recently symptomatic patients with carotid stenosis pending carotid revascularization. Anticoagulation with heparins or vitamin K antagonist is not recommended except in patients at risk for cardio-embolic events. Lowering blood pressure to target levels has been shown to slow down the progression of carotid artery stenosis and reduces the intima-media thickness of the carotid plaque, while lowering lipid levels with statins has become an essential element in the medical therapy of carotid artery stenosis. Diabetes management should be optimized. Lifestyle choices, including tobacco smoking, physical inactivity, unhealthy diet, obesity, and excessive alcohol intake, are all important modifiable vascular risk factors. The combination of dietary modification, physical exercise, and use of aspirin, a statin, and an antihypertensive agent can be expected to give a cumulative relative stroke risk reduction of 80%. The evidence suggests that intensive medical therapy is so effective that carotid revascularization may no longer be necessary in many of the patients in whom carotid surgery or stenting is currently performed. Two large ongoing trials are therefore comparing the risks and benefits of carotid revascularization versus intensive medical therapy alone. Copyright © 2017 Elsevier Inc. All rights reserved.

The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice

PubMed Central

Gelderblom, Mathias; Leypoldt, Frank; Lewerenz, Jan; Birkenmayer, Gabriel; Orozco, Denise; Ludewig, Peter; Thundyil, John; Arumugam, Thiruma V; Gerloff, Christian; Tolosa, Eva; Maher, Pamela; Magnus, Tim

2012-01-01

The development of the brain tissue damage in ischemic stroke is composed of an immediate component followed by an inflammatory response with secondary tissue damage after reperfusion. Fisetin, a flavonoid, has multiple biological effects, including neuroprotective and antiinflammatory properties. We analyzed the effects of fisetin on infarct size and the inflammatory response in a mouse model of stroke, temporary middle cerebral artery occlusion, and on the activation of immune cells, murine primary and N9 microglial and Raw264.7 macrophage cells and human macrophages, in an in vitro model of inflammatory immune cell activation by lipopolysaccharide (LPS). Fisetin not only protected brain tissue against ischemic reperfusion injury when given before ischemia but also when applied 3 hours after ischemia. Fisetin also prominently inhibited the infiltration of macrophages and dendritic cells into the ischemic hemisphere and suppressed the intracerebral immune cell activation as measured by intracellular tumor necrosis factor α (TNFα) production. Fisetin also inhibited LPS-induced TNFα production and neurotoxicity of macrophages and microglia in vitro by suppressing nuclear factor κB activation and JNK/Jun phosphorylation. Our findings strongly suggest that the fisetin-mediated inhibition of the inflammatory response after stroke is part of the mechanism through which fisetin is neuroprotective in cerebral ischemia. PMID:22234339

Huge Free-Floating Thrombus in the Internal Carotid Artery.

PubMed

Tanriverdi, Uygur; Kizilkilic, Osman; Ince, Birsen

2017-12-01

Free-floating thrombus in the carotid artery is extremely rare. A 70-year-old male patient with pre-existing Crohn's disease admitted to our clinic with recurrent transient ischemic attacks. Angiography showed a huge thrombus in internal carotid artery. He responded to anticoagulation treatment and delayed endovascular intervention. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Transient Beneficial Effects of Excitatory Theta Burst Stimulation in a Patient with Phonological Agraphia after Left Supramarginal Gyrus Infarction

ERIC Educational Resources Information Center

Nardone, Raffaele; De Blasi, Pierpaolo; Zuccoli, Giulio; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen

2012-01-01

We report a patient showing isolated phonological agraphia after an ischemic stroke involving the left supramarginal gyrus (SMG). In this patient, we investigated the effects of focal repetitive transcranial magnetic stimulation (rTMS) given as theta burst stimulation (TBS) over the left SMG, corresponding to the Brodmann area (BA) 40. The patient…

Hospital costs of ischemic stroke and TIA in the Netherlands.

PubMed

Buisman, Leander R; Tan, Siok Swan; Nederkoorn, Paul J; Koudstaal, Peter J; Redekop, William K

2015-06-02

There have been no ischemic stroke costing studies since major improvements were implemented in stroke care. We therefore determined hospital resource use and costs of ischemic stroke and TIA in the Netherlands for 2012. We conducted a retrospective cost analysis using individual patient data from a national diagnosis-related group registry. We analyzed 4 subgroups: inpatient ischemic stroke, inpatient TIA, outpatient ischemic stroke, and outpatient TIA. Costs of carotid endarterectomy and costs of an extra follow-up visit were also estimated. Unit costs were based on reference prices from the Dutch Healthcare Insurance Board and tariffs provided by the Dutch Healthcare Authority. Linear regression analysis was used to examine the association between hospital costs and various patient and hospital characteristics. A total of 35,903 ischemic stroke and 21,653 TIA patients were included. Inpatient costs were €5,328 ($6,845) for ischemic stroke and €2,470 ($3,173) for TIA. Outpatient costs were €495 ($636) for ischemic stroke and €587 ($754) for TIA. Costs of carotid endarterectomy were €6,836 ($8,783). Costs of inpatient days were the largest contributor to hospital costs. Age, hospital type, and region were strongly associated with hospital costs. Hospital costs are higher for inpatients and ischemic strokes compared with outpatients and TIAs, with length of stay (LOS) the most important contributor. LOS and hospital costs have substantially declined over the last 10 years, possibly due to improved hospital stroke care and efficient integrated stroke services. © 2015 American Academy of Neurology.

Cumulative Lifetime Marijuana Use and Incident Cardiovascular Disease in Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

PubMed

Reis, Jared P; Auer, Reto; Bancks, Michael P; Goff, David C; Lewis, Cora E; Pletcher, Mark J; Rana, Jamal S; Shikany, James M; Sidney, Stephen

2017-04-01

To investigate the effects of marijuana in the development of incident cardiovascular and cerebrovascular outcomes. Participants were 5113 adults aged 18 to 30 years at baseline (1985-1986) from the Coronary Artery Risk Development in Young Adults study, who were followed for more than 25 years. We estimated cumulative lifetime exposure to marijuana using repeated assessments collected at examinations every 2 to 5 years. The primary outcome was incident cardiovascular disease (CVD) through 2013. A total of 84% (n = 4286) reported a history of marijuana use. During a median 26.9 years (131 990 person-years), we identified 215 CVD events, including 62 strokes or transient ischemic attacks, 104 cases of coronary heart disease, and 50 CVD deaths. Compared with no marijuana use, cumulative lifetime and recent marijuana use showed no association with incident CVD, stroke or transient ischemic attacks, coronary heart disease, or CVD mortality. Marijuana use was not associated with CVD when stratified by age, gender, race, or family history of CVD. Neither cumulative lifetime nor recent use of marijuana is associated with the incidence of CVD in middle age.

In Potential Stroke Patients on Warfarin, the International Normalized Ratio Predicts Ischemia.

PubMed

Cao, Cathy; Martinelli, Ashley; Spoelhof, Brian; Llinas, Rafael H; Marsh, Elisabeth B

2017-01-01

Stroke can occur in patients on warfarin despite anticoagulation. Patients with a low international normalized ratio (INR) should theoretically be at greater risk for ischemia than those who are therapeutic. Therefore, INR may be able to indicate whether new neurological deficits are more likely strokes or stroke mimics in patients on warfarin. This study evaluates the association and predictive value of INR in determining the likelihood of ischemia. Patients were identified using the acute stroke registry at a Primary Stroke Center from January 2013 through December 2014. All adult patients undergoing evaluation for acute stroke with prior documented use of warfarin and an INR level at presentation were included. Data were collected regarding patient demographics, medical comorbidities, stroke severity, reason for anticoagulation, and laboratory studies including INR. Student t tests and χ2 analysis were used to evaluate factors associated with increased likelihood of ischemia (stroke or transient ischemic attack) versus mimic. Significant results were entered into a multivariable regression analysis. Sensitivity and specificity analyses were conducted to determine the predictive value of INR for ischemic risk. 116 patients were included; 46 were diagnosed with ischemia, 70 were diagnosed as mimics. 75% of patients were on warfarin for atrial fibrillation versus 25% for venous thrombosis. A statistically significant difference in mean INR for patients with ischemia (n = 46) versus mimics (n = 70) was observed (1.7 vs. 2.8; p < 0.001). In multivariable analysis, both sub-therapeutic INR (p < 0.001) and atrial fibrillation (p = 0.014) were predictors of ischemia. In patients with an INR ≥2, the predictive value of having a non-ischemic etiology was 79%. No patient with an INR of ≥3.6 was found to have ischemia. Sub-therapeutic INR and atrial fibrillation are strongly associated with ischemia in patients on warfarin presenting with acute neurologic symptoms. Ischemia is far less likely in patients with an INR of ≥2 and rare in those with an INR ≥3.6. This study shows that the INR value of a patient on warfarin can help stratify patients' risk for acute ischemic stroke and guide further neurologic imaging and workup. © 2017 The Author(s). Published by S. Karger AG, Basel.

One-year atherothrombotic vascular events rates in outpatients with recent non-cardioembolic ischemic stroke: the EVEREST (Effective Vascular Event REduction after STroke) registry.

PubMed

Suzuki, Norihiro; Sato, Motoki; Houkin, Kiyohiro; Terayama, Yasuo; Uchiyama, Shinichiro; Daida, Hiroyuki; Shigematsu, Hiroshi; Goto, Shinya; Tanaka, Kortaro; Origasa, Hideki; Miyamoto, Susumu; Minematsu, Kazuo; Matsumoto, Masayasu; Okada, Yasushi

2012-05-01

Patients with recent ischemic stroke may have higher risk of atherothrombosis than stable patients with established vascular events. Our aims were to investigate 1-year atherothrombotic vascular event rates and to assess the risk factors for recurrent ischemic stroke in this population. This prospective cohort study was conducted between January 2007 and July 2009 at 313 hospitals in Japan. Outpatients who were at least 45 years of age and who had received oral antiplatelet therapy were enrolled within 2 weeks to 6 months from the last onset of noncardioembolic ischemic stroke. At 12 ± 3 months after enrollment, data on presence/absence of atherothrombotic vascular events were collected. The primary endpoint was the occurrence of fatal or nonfatal ischemic stroke. A total of 3452 patients were enrolled, and 3411 patients who had baseline data were included in the analysis. The 1-year event rate was 3.81% (95% confidence interval 3.15-4.48%) for fatal or nonfatal ischemic stroke and 0.84% (95% confidence interval 0.52-1.15%) for all-cause mortality. The annual rate of recurrent ischemic stroke was significantly higher in patients who had ischemic stroke at least twice than in patients who had first-ever ischemic stroke (5.02% vs 3.59%; P = .0313). In the multivariable Cox regression analysis, recurrent ischemic stroke was significantly associated with age (P = .0033), the presence of diabetes (P = .0129), and waist circumference ≥80 cm (P = .0056). Patients with recent ischemic stroke have a higher risk of stroke recurrence than stable patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry even though they received antiplatelet therapy. The rigorous management of risk factors is needed. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Ischemic stroke subtype incidence among whites, blacks, and Hispanics: the Northern Manhattan Study.

PubMed

White, Halina; Boden-Albala, Bernadette; Wang, Cuiling; Elkind, Mitchell S V; Rundek, Tanja; Wright, Clinton B; Sacco, Ralph L

2005-03-15

Stroke incidence is greater in blacks than in whites; data on Hispanics are limited. Comparing subtype-specific ischemic stroke incidence rates may help to explain race-ethnic differences in stroke risk. The aim of this population-based study was to determine ischemic stroke subtype incidence rates for whites, blacks, and Hispanics living in one community. A comprehensive stroke surveillance system incorporating multiple overlapping strategies was used to identify all cases of first ischemic stroke occurring between July 1, 1993, and June 30, 1997, in northern Manhattan. Ischemic stroke subtypes were determined according to a modified NINDS scheme, and age-adjusted, race-specific incidence rates calculated. The annual age-adjusted incidence of first ischemic stroke per 100,000 was 88 (95% CI, 75 to 101) in whites, 149 (95% CI, 132 to 165) in Hispanics, and 191 (95% CI, 160 to 221) in blacks. Among blacks compared with whites, the relative rate of intracranial atherosclerotic stroke was 5.85 (95% CI, 1.82 to 18.73); extracranial atherosclerotic stroke, 3.18 (95% CI, 1.42 to 7.13); lacunar stroke, 3.09 (95% CI, 1.86 to 5.11); and cardioembolic stroke, 1.58 (95% CI, 0.99 to 2.52). Among Hispanics compared with whites, the relative rate of intracranial atherosclerotic stroke was 5.00 (95% CI, 1.69 to 14.76); extracranial atherosclerotic stroke, 1.71 (95% CI, 0.80 to 3.63); lacunar stroke, 2.32 (95% CI, 1.48 to 3.63); and cardioembolic stroke, 1.42 (95% CI, 0.97 to 2.09). The high ischemic stroke incidence among blacks and Hispanics compared with whites is due to higher rates of all ischemic stroke subtypes.

Magnetic resonance imaging of blood-brain barrier permeability in ischemic stroke using diffusion-weighted arterial spin labeling in rats.

PubMed

Tiwari, Yash V; Lu, Jianfei; Shen, Qiang; Cerqueira, Bianca; Duong, Timothy Q

2017-08-01

Diffusion-weighted arterial spin labeling magnetic resonance imaging has recently been proposed to quantify the rate of water exchange (K w ) across the blood-brain barrier in humans. This study aimed to evaluate the blood-brain barrier disruption in transient (60 min) ischemic stroke using K w magnetic resonance imaging with cross-validation by dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology in the same rats. The major findings were: (i) at 90 min after stroke (30 min after reperfusion), group K w magnetic resonance imaging data showed no significant blood-brain barrier permeability changes, although a few animals showed slightly abnormal K w . Dynamic contrast-enhanced magnetic resonance imaging confirmed this finding in the same animals. (ii) At two days after stroke, K w magnetic resonance imaging revealed significant blood-brain barrier disruption. Regions with abnormal K w showed substantial overlap with regions of hyperintense T 2 (vasogenic edema) and hyperperfusion. Dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology confirmed these findings in the same animals. The K w values in the normal contralesional hemisphere and the ipsilesional ischemic core two days after stroke were: 363 ± 17 and 261 ± 18 min -1 , respectively (P < 0.05, n = 9). K w magnetic resonance imaging is sensitive to blood-brain barrier permeability changes in stroke, consistent with dynamic contrast-enhanced magnetic resonance imaging and Evans blue extravasation. K w magnetic resonance imaging offers advantages over existing techniques because contrast agent is not needed and repeated measurements can be made for longitudinal monitoring or averaging.

Omega-3 polyunsaturated fatty acids ameliorate neuroinflammation and mitigate ischemic stroke damage through interactions with astrocytes and microglia.

PubMed

Zendedel, Adib; Habib, Pardes; Dang, Jon; Lammerding, Leoni; Hoffmann, Stefanie; Beyer, Cordian; Slowik, Alexander

2015-01-15

Omega-3 polyunsaturated fatty acids (PUFA n3) provide neuroprotection due to their anti-inflammatory and anti-apoptotic properties as well as their regulatory function on growth factors and neuronal plasticity. These qualities enable PUFA n3 to ameliorate stroke outcome and limit neuronal damage. Young adult male rats received transient middle cerebral artery occlusion (tMCAO). PUFA n3 were intravenously administered into the jugular vein immediately after stroke and 12h later. We analyzed stroke volume and behavioral performance as well as the regulation of functionally-relevant genes in the penumbra. The extent of ischemic damage was reduced and behavioral performance improved subject to applied PUFA n3. Expression of Tau and growth-associated protein-43 genes were likewise restored. Ischemia-induced increase of cytokine mRNA levels was abated by PUFA n3. Using an in vitro approach, we demonstrate that cultured astroglial and microglia directly respond to PUFA n3 administration by preventing ischemia-induced increase of cyclooxygenase 2, hypoxia-inducible factor 1alpha, inducible nitric oxide synthase, and interleukin 1beta. Cultured cortical neurons also appeared as direct targets, since PUFA n3 shifted the Bcl-2-like protein 4 (Bax)/B-cell lymphoma 2 (Bcl 2) ratio towards an anti-apoptotic constellation. Thus, PUFA n3 reveal a high neuroprotective and anti-inflammatory potential in an acute ischemic stroke model by targeting astroglial and microglial function as well as improving neuronal survival strategies. Our findings signify the potential clinical feasibility of PUFA n3 therapeutic treatment in stroke and other acute neurological diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Variation in Organization of Transient Ischemic Attack Care in The Netherlands. A Nationwide Survey Study.

PubMed

Muller, Fenna Floortje; de Beer, Frank; Visser, Marieke Christine

2017-09-01

Previous research has shown the importance of urgent initiation of antiplatelet therapy after transient ischemic attack (TIA) to reduce the risk of stroke. Many hospitals in the Netherlands have therefore implemented rapid pathways for assessment of patients with TIA. Dutch stroke guidelines lack clear directives for organization of TIA assessment and thus allow for variation. The aim of this study was to investigate variation in organization of TIA assessment in Dutch hospitals. One neurologist per hospital (of 88 Dutch hospitals) with special interest in stroke was invited to participate in a web-based survey addressing the organization, content, and timing of TIA assessment. Seventy (80%) neurologists completed the survey, all of whom reported performing TIA assessment in their hospital. There was considerable variation in the method of application and the location of assessment. In 10% of the hospitals, patients with TIA are always admitted to the ward. The content of diagnostics is fairly similar, but hospitals vary in the extent of cardiological workup. Almost all hospitals aim for a swift start of assessment as directed by guidelines, but access time differs. Eighty-six percent of respondents reported that antiplatelet therapy is usually initiated before assessment, based on history. This study showed variation in organization of TIA assessment in Dutch hospitals, especially regarding location within the hospital, time to assessment after announcement, and cardiological workup. Further research is needed to investigate implications of this variation for quality of care. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A novel animal model of dysphagia following stroke.

PubMed

Sugiyama, Naoto; Nishiyama, Eiji; Nishikawa, Yukitoshi; Sasamura, Takashi; Nakade, Shinji; Okawa, Katsumasa; Nagasawa, Tadashi; Yuki, Akane

2014-02-01

Patients who have an ischemic stroke are at high risk of swallowing disorders. Aspiration due to swallowing disorders, specifically delayed trigger of the pharyngeal stage of swallowing, predisposes such patients to pneumonia. In the present study, we evaluated swallowing reflex in a rat model of transient middle cerebral artery occlusion (tMCAO), which is one of the most common experimental animal models of cerebral ischemia, in order to develop a novel animal model of dysphagia following ischemic stroke. A swallowing reflex was elicited by a 10-s infusion of distilled water (DW) to the pharyngolaryngeal region in the tMCAO rat model. Swallowing reflex was estimated using the electromyographic activity of the mylohyoid muscle from 1 to 3 weeks after surgery. Two weeks after tMCAO, the number of swallows significantly decreased and the onset latency of the first swallow was prolonged compared with that of the sham group. The number of swallows in rats significantly increased by infusions of 10 mM citric acid and 0.6 μM capsaicin to the pharyngolaryngeal region compared with the number from infusion of DW. It has been reported that sensory stimulation of the pharyngolaryngeal region with citric acid, capsaicin, and L-menthol ameliorates hypofunction of pharyngeal-stage swallowing in dysphagia patients. Therefore, the tMCAO rat model may show some of the symptoms of pharyngeal-stage swallowing disorders, similar to those in patients with ischemic stroke. This rat tMCAO model has the potential to become a novel animal model of dysphagia following stroke that is useful for development of therapeutic methods and drugs.

Angiographic Features, Collaterals, and Infarct Topography of Symptomatic Occlusive Radiation Vasculopathy

PubMed Central

Zou, Winnie X.Y.; Leung, Thomas W.; Yu, Simon C.H.; Wong, Edward H.C.; Leung, S.F.; Soo, Yannie O.Y.; Ip, Vincent H.L.; Chan, Anne Y.Y.; Lam, Wynnie W.M.; Siu, Deyond Y.W.; Abrigo, Jill; Lee, Kwok Tung; Liebeskind, David S.; Wong, Ka Sing

2014-01-01

Background and Purpose Occlusive radiation vasculopathy (ORV) predisposes head-and-neck cancer survivors to ischemic strokes. Methods We analyzed the digital subtraction angiography acquired in 96 patients who had first-ever transient ischemic attack or ischemic strokes attributed to ORV. Another age-matched 115 patients who had no radiotherapy but symptomatic high-grade (>70%) carotid stenoses were enrolled as referent subjects. Digital subtraction angiography was performed within 2 months from stroke onset and delineated carotid and vertebrobasilar circulations from aortic arch up to intracranial branches. Two reviewers blinded to group assignment recorded all vascular lesions, collateral status, and infarct pattern. Results ORV patients had less atherosclerotic risk factors at presentation. In referent patients, high-grade stenoses were mostly focal at the proximal internal carotid artery. In contrast, high-grade ORV lesions diffusely involved the common carotid artery and internal carotid artery and were more frequently bilateral (54% versus 22%), tandem (23% versus 10%), associated with complete occlusion in one or both carotid arteries (30% versus 9%), vertebral artery (VA) steno-occlusions (28% versus 16%), and external carotid artery stenosis (19% versus 5%) (all P<0.05). With comparable rates of vascular anomaly, ORV patients showed more established collateral circulations through leptomeningeal arteries, anterior communicating artery, posterior communicating artery, suboccipital/costocervical artery, and retrograde flow in ophthalmic artery. In terms of infarct topography, the frequencies of cortical or subcortical watershed infarcts were similar in both groups. Conclusions ORV angiographic features and corresponding collaterals are distinct from atherosclerotic patterns at initial stroke presentation. Clinical decompensation, despite more extensive collateralization, may precipitate stroke in ORV. PMID:23306321

Change in platelet endothelial cell adhesion molecule-1 immunoreactivity in the dentate gyrus in gerbils fed a folate-deficient diet.

PubMed

Yoo, Ki-Yeon; Hwang, In Koo; Kim, Young Sup; Kwon, Dae Young; Won, Moo Ho

2008-02-01

Folate deficiency increases stroke risk. We examined whether folate deficiency affects platelet endothelial cell adhesion molecule-1 (PECAM-1), which is an immunoglobulin-associated cell adhesion molecule and mediates the final common pathway of neutrophil transendothelial migration, in blood vessels in the gerbil dentate gyrus after transient forebrain ischemia. Gerbils were exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to common carotid artery occlusion for 5 min. In the control diet (CD)- and FAD-treated sham-operated groups, weak PECAM-1 immunoreactivity was detected in the blood vessels located in the dentate gyrus. PECAM-1 immunoreactivity in both groups was increased by 4 days after ischemic insult. PECAM-1 immunoreactivity in the FAD-treated group was twice as high that in the CD-treated-sham-operated group 4 days after ischemic insult. Western blot analyses showed that the change patterns in PECAM-1 protein levels in the dentate gyrus in both groups after ischemic insult were similar to changes in PECAM-1 immunohistochemistry in the ischemic dentate gyrus. Our results suggest that folate deficiency enhances PECAM-1 in the dentate gyrus induced by transient ischemia.

Hyperglycemia and diabetes have different impacts on outcome of ischemic and hemorrhagic stroke.

PubMed

Snarska, Katarzyna K; Bachórzewska-Gajewska, Hanna; Kapica-Topczewska, Katarzyna; Drozdowski, Wiesław; Chorąży, Monika; Kułakowska, Alina; Małyszko, Jolanta

2017-02-01

Stroke is the second leading cause of long-term disability and death worldwide. Diabetes and hyperglycemia may impact the outcome of stroke. We examined the impact of hyperglycemia and diabetes on in-hospital death among ischemic and hemorrhagic stroke patients. Data from 766 consecutive patients with ischemic (83.15%) and hemorrhagic stroke were analyzed. Patients were classified into four groups: ischemic and diabetic; ischemic and non-diabetic; hemorrhagic and diabetic; and hemorrhagic and non-diabetic. Serum glucose was measured on admission at the emergency department together with biochemical and clinical parameters. Mean admission glucose in ischemic stroke patients with diabetes was higher than in non-diabetic ones ( p < 0.001) and in hemorrhagic stroke patients with diabetes than in those without diabetes ( p < 0.05). Mean admission glucose in all patients who died was significantly higher than in patients who survived. In multivariate analysis, the risk factors for outcome in patients with ischemic stroke and without diabetes were age, admission glucose level and estimated glomerular filtration rate (eGFR), while in diabetics they were female gender, admission glucose level, and eGFR; in patients with hemorrhagic stroke and without diabetes they were age and admission glucose levels. The cut-off value in predicting death in patients with ischemic stroke and without diabetes was above 113.5 mg/dl, while in diabetics it was above 210.5 mg/dl. Hyperglycemia on admission is associated with worsened clinical outcome and increased risk of in-hospital death in ischemic and hemorrhagic stroke patients. Diabetes increased the risk of in-hospital death in hemorrhagic stroke patients, but not in ischemic ones.

Ischemic stroke and select adipose-derived and sex hormones: a review.

PubMed

Meadows, Kristy L

2018-06-06

Ischemic stroke is the fifth leading cause of death in the USA and is the leading cause of serious, long-term disability worldwide. The principle sex hormones (estrogen, progesterone, and testosterone), both endogenous and exogenous, have profound effects on various stroke outcomes and have become the focus of a number of studies evaluating risk factors and treatment options for ischemic stroke. In addition, the expression of other hormones that may influence stroke outcome, including select adipose-derived hormones (adiponectin, leptin, and ghrelin), can be regulated by sex hormones and are also the focus of several ischemic stroke studies. This review aims to summarize some of the preclinical and clinical studies investigating the principle sex hormones, as well as select adipose-derived hormones, as risk factors or potential treatments for ischemic stroke. In addition, the potential for relaxin, a lesser studied sex hormone, as a novel treatment option for ischemic stroke is explored.

Genetics of ischemic stroke: future clinical applications.

PubMed

Wang, Michael M

2006-11-01

Ischemic stroke has long been thought to have a genetic component that is independent of conventional vascular risk factors. It has been estimated that over one half of stroke risk is determined by inherited genes. However, until recently, strong evidence of genetic influence on ischemic stroke has been subject to criticism because the risk factors for stroke are also inherited and because previous studies suffered from limitations imposed by this highly heterogeneous neurological disorder. Recent advances in molecular genetics have led to the identification of specific genetic loci that impart susceptibility to ischemic stroke. We review the studies of these genes and discuss the future potential applications of genetic markers on the management of ischemic stroke patients.

Impact of atrial fibrillation on stroke-related healthcare costs.

PubMed

Sussman, Matthew; Menzin, Joseph; Lin, Iris; Kwong, Winghan J; Munsell, Michael; Friedman, Mark; Selim, Magdy

2013-11-25

Limited data exist on the economic implications of stroke among patients with atrial fibrillation (AF). This study assesses the impact of AF on healthcare costs associated with ischemic stroke (IS), hemorrhagic stroke (HS), or transient ischemic attack (TIA). A retrospective analysis of MarketScan claims data (2005-2011) for AF patients ≥18 years old with ≥1 inpatient claim for stroke, or ≥1 ED or inpatient claim for TIA as identified by ICD-9-CM codes who had ≥12 months continuous enrollment prior to initial stroke. Initial event- and stroke-related costs 12 months post-index were compared among patients with AF and without AF. Adjusted costs were estimated, controlling for demographics, comorbidities, anticoagulant use, and baseline resource use. Data from 23,807 AF patients and 136,649 patients without AF were analyzed. Unadjusted mean cost of the index event was $20,933 for IS, $59,054 for HS, $8616 for TIA hospitalization, and $3395 for TIA ED visit. After controlling for potential confounders, adjusted mean incremental costs (index plus 12-month post-index) for AF patients were higher than those for non-AF patients by: $4726, $7824, and $1890 for index IS, HS, TIA (identified by hospitalization), respectively, and $1700 for TIA (identified by ED) (all P<0.01). In multivariate regression analysis, AF was associated with a 20% (IS), 13% (HS), and 18% (TIA) increase in total stroke-related costs. Stroke-related care for IS, HS, and TIA is costly, especially among individuals with AF. Reducing the risk of AF-related stroke is important from both clinical and economic standpoints.

Carotid Artery Stent Placement and Carotid Endarterectomy: A Challenge for Urgent Treatment after Stroke-Early and 12-Month Outcomes in a Comprehensive Stroke Center.

PubMed

Rocco, Alessandro; Sallustio, Fabrizio; Toschi, Nicola; Rizzato, Barbara; Legramante, Jacopo; Ippoliti, Arnaldo; Marchetti, Andrea Ascoli; Pampana, Enrico; Gandini, Roberto; Diomedi, Marina

2018-06-20

To compare feasibility, 12-month outcome, and periprocedural and postprocedural risks between carotid artery stent (CAS) placement and carotid endarterectomy (CEA) performed within 1 week after transient ischemic attack (TIA) or mild to severe stroke onset in a single comprehensive stroke center. Retrospective analysis of prospective data collected from 1,148 patients with ischemic stroke admitted to a single stroke unit between January 2013 and July 2015 was conducted. Among 130 consecutive patients with symptomatic carotid stenosis, 110 (10 with TIA, 100 with stroke) with a National Institutes of Health Stroke Scale (NIHSS) score < 20 and a prestroke modified Rankin Scale (mRS) score < 2 were eligible for CAS placement or CEA and treated according to the preference of the patient or a surrogate. Periprocedural (< 48 h) and postprocedural complications, functional outcome, stroke, and death rate up to 12 months were analyzed. Sixty-two patients were treated with CAS placement and 48 were treated with CEA. Several patients presented with moderate or major stroke (45.8% CEA, 64.5% CAS). NIHSS scores indicated slightly greater severity at onset in patients treated with a CAS vs CEA (6.6 ± 5.7 vs 4.2 ± 3.4; P = .08). Complication rates were similar between groups. mRS scores showed a significant improvement over time and a significant interaction with age in both groups. Similar incidences of death or stroke were shown on survival analysis. A subanalysis in patients with NIHSS scores ≥ 4 showed no differences in complication rate and outcome. CAS placement and CEA seem to offer early safe and feasible secondary stroke prevention treatments in experienced centers, even after major atherosclerotic stroke. Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.

Microbubble signal and trial of org in acute stroke treatment (TOAST) classification in ischemic stroke.

PubMed

Lee, Chan-Hyuk; Kang, Hyun Goo; Lee, Ji Sung; Ryu, Han Uk; Jeong, Seul-Ki

2018-07-15

Right-to-left shunt (RLS) through a patent foramen ovale (PFO) is likely associated with ischemic stroke. Many studies have attempted to demonstrate the association between RLS and ischemic stroke. However, information on the association between the degree of RLS and the subtypes of ischemic stroke categorized by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification is lacking. This was a retrospective study involving 508 patients with ischemic stroke who underwent a transcranial Doppler (TCD) microbubble test between 2013 and 2015. The degree of RLS was divided into 4 grades according to the microbubble signal (MBS) as follows: no MBS, grade 1; MBS < 20, grade 2; MBS > 20, grade 3; curtain sign, grade 4. The degree of RLS and the type of ischemic stroke as classified by TOAST were analyzed and compared with other clinical information and laboratory findings. The higher RLS grade was associated with the cardioembolism (CE) and stroke of undetermined etiology (SUE), and the microbubble signals were inversely related with small vessel disease (SVD). An MBS higher than grade 3 showed a 2.95-fold higher association with SUE than large artery atherosclerosis (LAA), while grade 4 MBS revealed an approximately 8-fold higher association with SUE than LAA. RLS identified by the TCD microbubble test was significantly and independently associated with cryptogenic ischemic stroke (negative evaluation). Subsequent studies are needed to determine the biologic relationship between RLS and ischemic stroke, particularly the cryptogenic subtype of ischemic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathway.

PubMed

Liu, Chao; Wu, Jiliang; Xu, Kui; Cai, Fei; Gu, Jun; Ma, Liqun; Chen, Jianguo

2010-03-01

Recently more evidences support baicalein (Bai) is neuroprotective in models of ischemic stroke. This study was conducted to determine the molecular mechanisms involved in this effect. Either permanent or transient (2 h) middle cerebral artery occlusion (MCAO) was induced in rats in this study. Permanent MCAO led to larger infarct volumes in contrast to transient MCAO. Only in transient MCAO, Bai administration significantly reduced infarct size. Baicalein also markedly reduced apoptosis in the penumbra of transient MCAO rats. Additionally, oxygen and glucose deprivation (OGD) was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular reactive oxygen species level and nitrotyrosine formation induced by OGD was counteracted by Bai, which is parallel with attenuated cell injury. The reduction of phosphorylation Akt and glycogen synthase kinase-3beta (GSK3beta) induced by OGD was restored by Bai, which was associated with preserved levels of phosphorylation of PTEN, the phophatase that negatively regulates Akt. As a consequence, Bcl-2/Bcl-xL-associated death protein phosphorylation was increased and the protein level of Bcl-2 in motochondria was maintained, which subsequently antagonize cytochrome c released in cytosol. LY294002 blocked the increase in phospho-AKT evoked by Bai and abolished the associated protective effect. Together, these findings provide evidence that Bai protects neurons against ischemia injury and this neuroprotective effect involves PI3K/Akt and PTEN pathway.

Association between atherogenic dyslipidemia and recurrent stroke risk in patients with different subtypes of ischemic stroke.

PubMed

Zhao, Lu; Wang, Ruihao; Song, Bo; Tan, Song; Gao, Yuan; Fang, Hui; Lu, Jie; Xu, Yuming

2015-07-01

The association between atherogenic dyslipidemia and stroke recurrence remains unclear, and may be influenced by different subtypes of ischemic stroke. We aimed to investigate whether atherogenic dyslipidemia contributed to stroke recurrence in ischemic stroke patients and in those with certain subtypes of ischemic stroke. We conducted a prospective hospital-based study enrolling patients with acute ischemic stroke. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol <40 mg/dl and triglycerides ≥200 mg/dl. Ischemic stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The patients were followed up at 3, 6, 12 and 24 months after stroke onset. The association between atherogenic dyslipidemia and stroke recurrence was analyzed by using multivariable Cox regression model. In the 510 ischemic stroke patients, 64 patients (12·5%) had atherogenic dyslipidemia, and 66 patients (12·9%) experienced stroke recurrence events within 24 months. Kaplan-Meier analysis revealed that stroke recurrence rate was significantly higher in patients with atherogenic dyslipidemia than those without in all the stroke patients (20·3% vs. 11·9%; P = 0·048), and more evident in those of large-artery atherosclerosis subtype (31·0% vs. 14·1%; P = 0·014), but not in the other subtypes. Multivariable Cox regression analysis revealed that atherogenic dyslipidemia was associated with higher stroke recurrence risk among stroke patients of large-artery atherosclerosis subtype (hazard ratio, 2·79; 95% confidence interval, 1·24-6·28), but not significant in all the stroke patients (hazard ratio, 1·69; 95% confidence interval, 0·85-3·37). Atherogenic dyslipidemia is associated with higher risk of stroke recurrence in ischemic stroke patients. Such association might be more pronounced in large-artery atherosclerosis subtype and needs further investigation to establish such relationship. © 2015 World Stroke Organization.

Percutaneous patent foramen ovale closure: the Paradoxical Cerebral Embolism Prevention Registry.

PubMed

Paiva, Luís; Dinis, Paulo; Providência, Rui; Costa, Marco; Margalho, Susana; Goncalves, Lino

2015-03-01

The natural history and therapeutic interventions for secondary prevention after a cerebrovascular event in patients with patent foramen ovale (PFO) are not yet established. This study aims to assess the safety and efficacy of percutaneous PFO closure in a population of patients with ischemic cerebrovascular disease of unknown etiology. This prospective observational study included patients with a history of cryptogenic transient ischemic attack (TIA) or stroke who underwent percutaneous PFO closure. The effectiveness of the device for the secondary prevention of TIA or stroke was assessed by comparing observed events in the sample with expected events for this clinical setting. The sample included 193 cases of percutaneous PFO closure (age 46.4 ± 13.1 years, 62.2% female) with a mean follow-up of 4.3 ± 2.2 years, corresponding to a total exposure to ischemic events of 542 patient-years. The high-risk characteristics of the PFO were assessed prior to device implantation. There were seven primary endpoint events during follow-up (1.3 per 100 patient-years), corresponding to a relative risk reduction of 68.2% in recurrent TIA or stroke compared to medical therapy alone. The procedure was associated with a low rate of device- or intervention-related complications (1.5%). In this long-term registry, percutaneous PFO closure was shown to be a safe and effective therapy for the secondary prevention of cryptogenic stroke or TIA. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Methylene Blue Ameliorates Ischemia/Reperfusion-Induced Cerebral Edema: An MRI and Transmission Electron Microscope Study.

PubMed

Fang, Qing; Yan, Xu; Li, Shaowu; Sun, Yilin; Xu, Lixin; Shi, Zhongfang; Wu, Min; Lu, Yi; Dong, Liping; Liu, Ran; Yuan, Fang; Yang, Shao-Hua

2016-01-01

The neuroprotective effect of methylene blue (MB) has been identified against various brain disorders, including ischemic stroke. In the present study, we evaluated the effects of MB on postischemic brain edema using magnetic resonance imaging (MRI) and transmission electron microscopy (TEM). Adult male rats were subjected to transient focal cerebral ischemia induced by 1 h middle cerebral artery occlusion (MCAO), followed by reperfusion. MB was infused intravenously immediately after reperfusion (3 mg/kg) and again at 3 h post-occlusion (1.5 mg/kg). Normal saline was administered as vehicle control. Sequential MRIs, including apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI), were obtained at 0.5, 2.5, and 48 h after the onset of stroke. Separated groups of animals were sacrificed at 2.5 and 48 h after stroke for ultrastructural analysis by TEM. In addition, final lesion volumes were analyzed by triphenyltetrazolium chloride (TTC) staining at 48 h after stroke. Ischemic stroke induced ADC lesion volume at 0.5 h during MCAOs that were temporally recovered at 1.5 h after reperfusion. No significant difference in ADC-defined lesion was observed between vehicle and MB treatment groups. At 48 h after stroke, MB significantly reduced ADC lesion and T2WI lesion volume and attenuated cerebral swelling. Consistently, MB treatment significantly decreased TTC-defined lesion volume at 48 h after stroke. TEM revealed remarkable swollen astrocytes, astrocytic perivascular end-feet, and concurrent shrunken neurons in the penumbra at 2.5 and 48 h after MCAO. MB treatment attenuated astrocyte swelling, the perivascular astrocytic foot process, and endothelium and also alleviated neuron degeneration. This study demonstrated that MB could decrease postischemic brain edema and provided additional evidence that future clinical investigation of MB for the treatment of ischemic stroke is warrented.

Identification of ischemic regions in a rat model of stroke.

PubMed

Popp, Anke; Jaenisch, Nadine; Witte, Otto W; Frahm, Christiane

2009-01-01

Investigations following stroke first of all require information about the spatio-temporal dimension of the ischemic core as well as of perilesional and remote affected tissue. Here we systematically evaluated regions differently impaired by focal ischemia. Wistar rats underwent a transient 30 or 120 min suture-occlusion of the middle cerebral artery (MCAO) followed by various reperfusion times (2 h, 1 d, 7 d, 30 d) or a permanent MCAO (1 d survival). Brains were characterized by TTC, thionine, and immunohistochemistry using MAP2, HSP72, and HSP27. TTC staining reliably identifies the infarct core at 1 d of reperfusion after 30 min MCAO and at all investigated times following 120 min and permanent MCAO. Nissl histology denotes the infarct core from 2 h up to 30 d after transient as well as permanent MCAO. Absent and attenuated MAP2 staining clearly identifies the infarct core and perilesional affected regions at all investigated times, respectively. HSP72 denotes perilesional areas in a limited post-ischemic time (1 d). HSP27 detects perilesional and remote impaired tissue from post-ischemic day 1 on. Furthermore a simultaneous expression of HSP72 and HSP27 in perilesional neurons was revealed. TTC and Nissl staining can be applied to designate the infarct core. MAP2, HSP72, and HSP27 are excellent markers not only to identify perilesional and remote areas but also to discriminate affected neuronal and glial populations. Moreover markers vary in their confinement to different reperfusion times. The extent and consistency of infarcts increase with prolonged occlusion of the MCA. Therefore interindividual infarct dimension should be precisely assessed by the combined use of different markers as described in this study.

Identification of Ischemic Regions in a Rat Model of Stroke

PubMed Central

Popp, Anke; Jaenisch, Nadine; Witte, Otto W.; Frahm, Christiane

2009-01-01

Background Investigations following stroke first of all require information about the spatio-temporal dimension of the ischemic core as well as of perilesional and remote affected tissue. Here we systematically evaluated regions differently impaired by focal ischemia. Methodology/Principal Findings Wistar rats underwent a transient 30 or 120 min suture-occlusion of the middle cerebral artery (MCAO) followed by various reperfusion times (2 h, 1 d, 7 d, 30 d) or a permanent MCAO (1 d survival). Brains were characterized by TTC, thionine, and immunohistochemistry using MAP2, HSP72, and HSP27. TTC staining reliably identifies the infarct core at 1 d of reperfusion after 30 min MCAO and at all investigated times following 120 min and permanent MCAO. Nissl histology denotes the infarct core from 2 h up to 30 d after transient as well as permanent MCAO. Absent and attenuated MAP2 staining clearly identifies the infarct core and perilesional affected regions at all investigated times, respectively. HSP72 denotes perilesional areas in a limited post-ischemic time (1 d). HSP27 detects perilesional and remote impaired tissue from post-ischemic day 1 on. Furthermore a simultaneous expression of HSP72 and HSP27 in perilesional neurons was revealed. Conclusions/Significance TTC and Nissl staining can be applied to designate the infarct core. MAP2, HSP72, and HSP27 are excellent markers not only to identify perilesional and remote areas but also to discriminate affected neuronal and glial populations. Moreover markers vary in their confinement to different reperfusion times. The extent and consistency of infarcts increase with prolonged occlusion of the MCA. Therefore interindividual infarct dimension should be precisely assessed by the combined use of different markers as described in this study. PMID:19274095

TIA model is attainable in Wistar rats by intraluminal occlusion of the MCA for 10min or shorter.

PubMed

Durukan Tolvanen, A; Tatlisumak, E; Pedrono, E; Abo-Ramadan, U; Tatlisumak, T

2017-05-15

Transient ischemic attack (TIA) has received only little attention in the experimental research field. Recently, we introduced a TIA model for mice, and here we set similar principles for simulating this human condition in Wistar rats. In the model: 1) transient nature of the event is ensured, and 2) 24h after the event animals are free from any sensorimotor deficit and from any detectable lesion by magnetic resonance imaging (MRI). Animals experienced varying durations of ischemia (5, 10, 12.5, 15, 25, and 30min, n=6-8pergroup) by intraluminal middle cerebral artery occlusion (MCAO). Ischemia severity and reperfusion rates were controlled by cerebral blood flow measurements. Sensorimotor neurological evaluations and MRI at 24h differentiated between TIA and ischemic stroke. Hematoxylin and eosin staining and apoptotic cell counts revealed pathological correlates of the event. We found that already 12.5min of ischemia was long enough to induce ischemic stroke in Wistar rats. Ten min or shorter durations induced neither gross neurological deficits nor infarcts visible on MRI, but histologically caused selective neuronal necrosis. A separate group of animals with 10min of ischemia followed up to 1week after reperfusion remained free of infarction and any MRI signal change. Thus, 10min or shorter focal cerebral ischemia induced by intraluminal MCAO in Wistar rats provides a clinically relevant TIA the rat. This model is useful for studying molecular correlates of TIA. Copyright © 2017 Elsevier B.V. All rights reserved.

Nurse-Led Intervention to Improve Knowledge of Medications in Survivors of Stroke or Transient Ischemic Attack: A Cluster Randomized Controlled Trial.

PubMed

Olaiya, Muideen T; Cadilhac, Dominique A; Kim, Joosup; Ung, David; Nelson, Mark R; Srikanth, Velandai K; Bladin, Christopher F; Gerraty, Richard P; Fitzgerald, Sharyn M; Phan, Thanh G; Frayne, Judith; Thrift, Amanda G

2016-01-01

Limited evidence exists on effective interventions to improve knowledge of preventive medications in patients with chronic diseases, such as stroke. We investigated the effectiveness of a nurse-led intervention, where a component was to improve knowledge of prevention medications, in patients with stroke or transient ischemic attack (TIA). Prospective sub-study of the Shared Team Approach between Nurses and Doctors for Improved Risk Factor Management, a randomized controlled trial of risk factor management. We recruited patients aged ≥18 years and hospitalized for stroke/TIA. The intervention comprised an individualized management program, involving nurse-led education, and management plan with medical specialist oversight. The outcome, participants' knowledge of secondary prevention medications at 12 months, was assessed using questionnaires. A score of ≥5 was considered as good knowledge. Effectiveness of the intervention on knowledge of medications was determined using logistic regression. Between May 2014 and January 2015, 142 consecutive participants from the main trial were included in this sub-study, 64 to usual care and 78 to the intervention (median age 68.9 years, 68% males, and 79% ischemic stroke). In multivariable analyses, we found no significant difference between intervention groups in knowledge of medications. Factors independently associated with good knowledge (score ≥5) at 12 months included higher socioeconomic position (OR 4.79, 95% CI 1.76, 13.07), greater functional ability (OR 1.69, 95% CI 1.17, 2.45), being married/living with a partner (OR 3.12, 95% CI 1.10, 8.87), and using instructions on pill bottle/package as an administration aid (OR 4.82, 95% CI 1.76, 13.22). Being aged ≥65 years was associated with poorer knowledge of medications (OR 0.24, 95% CI 0.08, 0.71), while knowledge was worse among those taking three medications (OR 0.15, 95% CI 0.03, 0.66) or ≥4 medications (OR 0.09, 95% CI 0.02, 0.44), when compared to participants taking fewer (≤2) prevention medications. There was no evidence that the nurse-led intervention was effective for improving knowledge of secondary prevention medications in patients with stroke/TIA at 12 months. However, older patients and those taking more medications should be particularly targeted for more intensive education. Australian New Zealand Clinical Trials Registry (ACTRN12688000166370).

Flavanone Intake Is Inversely Associated with Risk of Incident Ischemic Stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study1234

PubMed Central

Goetz, Margarethe E; Judd, Suzanne E; Hartman, Terryl J; McClellan, William; Anderson, Aaron; Vaccarino, Viola

2016-01-01

Background: Flavonoids may have beneficial cerebrovascular effects, but evidence from racially and geographically representative cohorts in comprehensive flavonoid databases is lacking. Given racial and geographic disparities in stroke incidence, representative cohort studies are needed. Objectives: We evaluated the association between flavonoid intake and incident ischemic stroke in a biracial, national cohort using updated flavonoid composition tables and assessed differences in flavonoid intake by sex, race, and region of residence. Methods: We evaluated 20,024 participants in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a biracial prospective study. Participants with stroke history or missing dietary data were excluded. Flavonoid intake was estimated by using a Block98 food frequency questionnaire and the USDA’s Provisional Flavonoid Addendum and Proanthocyanidin Database. Associations between quintiles of flavonoid intake and incident ischemic stroke were evaluated by using Cox proportional hazards models, adjusting for confounders. Results: Over 6.5 y, 524 acute ischemic strokes occurred. Flavanone intake was lower in the Southeastern United States but higher in blacks than in whites. After multivariable adjustment, flavanone intake was inversely associated with incident ischemic stroke (HR: 0.72; 95% CI: 0.55, 0.95; P-trend = 0.03). Consumption of citrus fruits and juices was inversely associated with incident ischemic stroke (HR: 0.69; 95% CI: 0.53, 0.91; P-trend = 0.02). Total flavonoids and other flavonoid subclasses were not associated with incident ischemic stroke. There was no statistical interaction with sex, race, or region for any flavonoid measure. Conclusions: Greater consumption of flavanones, but not total or other flavonoid subclasses, was inversely associated with incident ischemic stroke. Associations did not differ by sex, race, or region for the association; however, regional differences in flavanone intake may contribute to regional disparities in ischemic stroke incidence. Higher flavanone intake in blacks suggests that flavanone intake is not implicated in racial disparities in ischemic stroke incidence. PMID:27655760

Flavanone Intake Is Inversely Associated with Risk of Incident Ischemic Stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

PubMed

Goetz, Margarethe E; Judd, Suzanne E; Hartman, Terryl J; McClellan, William; Anderson, Aaron; Vaccarino, Viola

2016-11-01

Flavonoids may have beneficial cerebrovascular effects, but evidence from racially and geographically representative cohorts in comprehensive flavonoid databases is lacking. Given racial and geographic disparities in stroke incidence, representative cohort studies are needed. We evaluated the association between flavonoid intake and incident ischemic stroke in a biracial, national cohort using updated flavonoid composition tables and assessed differences in flavonoid intake by sex, race, and region of residence. We evaluated 20,024 participants in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a biracial prospective study. Participants with stroke history or missing dietary data were excluded. Flavonoid intake was estimated by using a Block98 food frequency questionnaire and the USDA's Provisional Flavonoid Addendum and Proanthocyanidin Database. Associations between quintiles of flavonoid intake and incident ischemic stroke were evaluated by using Cox proportional hazards models, adjusting for confounders. Over 6.5 y, 524 acute ischemic strokes occurred. Flavanone intake was lower in the Southeastern United States but higher in blacks than in whites. After multivariable adjustment, flavanone intake was inversely associated with incident ischemic stroke (HR: 0.72; 95% CI: 0.55, 0.95; P-trend = 0.03). Consumption of citrus fruits and juices was inversely associated with incident ischemic stroke (HR: 0.69; 95% CI: 0.53, 0.91; P-trend = 0.02). Total flavonoids and other flavonoid subclasses were not associated with incident ischemic stroke. There was no statistical interaction with sex, race, or region for any flavonoid measure. Greater consumption of flavanones, but not total or other flavonoid subclasses, was inversely associated with incident ischemic stroke. Associations did not differ by sex, race, or region for the association; however, regional differences in flavanone intake may contribute to regional disparities in ischemic stroke incidence. Higher flavanone intake in blacks suggests that flavanone intake is not implicated in racial disparities in ischemic stroke incidence. © 2016 American Society for Nutrition.

Use of a Diagnostic Score to Prioritize Computed Tomographic (CT) Imaging for Patients Suspected of Ischemic Stroke Who May Benefit from Thrombolytic Therapy

PubMed Central

Bots, Michiel L.; Selvarajah, Sharmini; Kappelle, L. Jaap; Abdul Aziz, Zariah; Sidek, Norsima Nazifah; Vaartjes, Ilonca

2016-01-01

Background A shortage of computed tomographic (CT) machines in low and middle income countries often results in delayed CT imaging for patients suspected of a stroke. Yet, time constraint is one of the most important aspects for patients with an ischemic stroke to benefit from thrombolytic therapy. We set out to assess whether application of the Siriraj Stroke Score is able to assist physicians in prioritizing patients with a high probability of having an ischemic stroke for urgent CT imaging. Methods From the Malaysian National Neurology Registry, we selected patients aged 18 years and over with clinical features suggesting of a stroke, who arrived in the hospital 4.5 hours or less from ictus. The prioritization of receiving CT imaging was left to the discretion of the treating physician. We applied the Siriraj Stroke Score to all patients, refitted the score and defined a cut-off value to best distinguish an ischemic stroke from a hemorrhagic stroke. Results Of the 2176 patients included, 73% had an ischemic stroke. Only 33% of the ischemic stroke patients had CT imaging within 4.5 hours. The median door-to-scan time for these patients was 4 hours (IQR: 1;16). With the recalibrated score, it would have been possible to prioritize 95% (95% CI: 94%–96%) of patients with an ischemic stroke for urgent CT imaging. Conclusions In settings where CT imaging capacity is limited, we propose the use of the Siriraj Stroke Score to prioritize patients with a probable ischemic stroke for urgent CT imaging. PMID:27768752

Incidence, recurrence, and long-term survival of ischemic stroke subtypes: A population-based study in the Middle East.

PubMed

Saber, Hamidreza; Thrift, Amanda G; Kapral, Moira K; Shoamanesh, Ashkan; Amiri, Amin; Farzadfard, Mohammad T; Behrouz, Réza; Azarpazhooh, Mahmoud Reza

2017-10-01

Background Incidence, risk factors, case fatality and survival rates of ischemic stroke subtypes are unknown in the Middle East due to the lack of community-based incidence stroke studies in this region. Aim To characterize ischemic stroke subtypes in a Middle Eastern population. Methods The Mashad Stroke Incidence Study is a community-based study that prospectively ascertained all cases of stroke among the 450,229 inhabitants of Mashhad, Iran between 2006 and 2007. We identified 512 cases of first-ever ischemic stroke [264 men (mean age 65.5 ± 14.4) and 248 women (mean age 64.14 ± 14.5)]. Subtypes of ischemic stroke were classified according to the TOAST criteria. Incidence rates were age standardized to the WHO and European populations. Results The proportion of stroke subtypes was distributed as follows: 14.1% large artery disease, 15% cardioembolic, 22.5% small artery disease, 43.9% undetermined and 4.5% other. The greatest overall incidence rates were attributed to undetermined infarction (49.97/100,000) followed by small artery disease (25.54/100,000). Prevalence of hypertension, diabetes and atrial fibrillation differed among ischemic stroke subtypes. Overall, there were 268 (52.34%) deaths and 73 (14.25%) recurrent strokes at five years after incident ischemic stroke, with the greatest risk of recurrence seen in the large artery disease (35.6%) and cardioembolic (35.5%) subgroups. Survival was similar in men and women for each stroke subtype. Conclusions We observed markedly greater incidence rates of ischemic stroke subtypes than in other countries within the Mashad Stroke Incidence Study after age standardization. Our findings should be considered when planning prevention and stroke care services in this region.

Variation in mortality of ischemic and hemorrhagic strokes in relation to high temperature.

PubMed

Lim, Youn-Hee; Kim, Ho; Hong, Yun-Chul

2013-01-01

Outdoor temperature has been reported to have a significant influence on the seasonal variations of stroke mortality, but few studies have investigated the effect of high temperature on the mortality of ischemic and hemorrhagic strokes. The main study goal was to examine the effect of temperature, particularly high temperature, on ischemic and hemorrhagic strokes. We investigated the association between outdoor temperature and stroke mortality in four metropolitan cities in Korea during 1992-2007. We used time series analysis of the age-adjusted mortality rate for ischemic and hemorrhagic stroke deaths by using generalized additive and generalized linear models, and estimated the percentage change of mortality rate associated with a 1°C increase of mean temperature. The temperature-responses for the hemorrhagic and ischemic stroke mortality differed, particularly in the range of high temperature. The estimated percentage change of ischemic stroke mortality above a threshold temperature was 5.4 % (95 % CI, 3.9-6.9 %) in Seoul, 4.1 % (95 % CI, 1.6-6.6 %) in Incheon, 2.3 % (-0.2 to 5.0 %) in Daegu and 3.6 % (0.7-6.6 %) in Busan, after controlling for daily mean humidity, mean air pressure, day of the week, season, and year. Additional adjustment of air pollution concentrations in the model did not change the effects. Hemorrhagic stroke mortality risk significantly decreased with increasing temperature without a threshold in the four cities after adjusting for confounders. These findings suggest that the mortality of hemorrhagic and ischemic strokes show different patterns in relation to outdoor temperature. High temperature was harmful for ischemic stroke but not for hemorrhagic stroke. The risk of high temperature to ischemic stroke did not differ by age or gender.

Variation in mortality of ischemic and hemorrhagic strokes in relation to high temperature

NASA Astrophysics Data System (ADS)

Lim, Youn-Hee; Kim, Ho; Hong, Yun-Chul

2013-01-01

Outdoor temperature has been reported to have a significant influence on the seasonal variations of stroke mortality, but few studies have investigated the effect of high temperature on the mortality of ischemic and hemorrhagic strokes. The main study goal was to examine the effect of temperature, particularly high temperature, on ischemic and hemorrhagic strokes. We investigated the association between outdoor temperature and stroke mortality in four metropolitan cities in Korea during 1992-2007. We used time series analysis of the age-adjusted mortality rate for ischemic and hemorrhagic stroke deaths by using generalized additive and generalized linear models, and estimated the percentage change of mortality rate associated with a 1°C increase of mean temperature. The temperature-responses for the hemorrhagic and ischemic stroke mortality differed, particularly in the range of high temperature. The estimated percentage change of ischemic stroke mortality above a threshold temperature was 5.4 % (95 % CI, 3.9-6.9 %) in Seoul, 4.1 % (95 % CI, 1.6-6.6 %) in Incheon, 2.3 % (-0.2 to 5.0 %) in Daegu and 3.6 % (0.7-6.6 %) in Busan, after controlling for daily mean humidity, mean air pressure, day of the week, season, and year. Additional adjustment of air pollution concentrations in the model did not change the effects. Hemorrhagic stroke mortality risk significantly decreased with increasing temperature without a threshold in the four cities after adjusting for confounders. These findings suggest that the mortality of hemorrhagic and ischemic strokes show different patterns in relation to outdoor temperature. High temperature was harmful for ischemic stroke but not for hemorrhagic stroke. The risk of high temperature to ischemic stroke did not differ by age or gender.

Low density lipoprotein receptor related protein-1 and 6 gene variants and ischemic stroke risk

PubMed Central

Harriott, Andrea M.; Heckman, Michael G.; Rayaprolu, Sruti; Soto-Ortolaza, Alexandra I.; Diehl, Nancy N.; Kanekiyo, Takahisa; Liu, Chia-Chen; Bu, Guojun; Malik, Rainer; Cole, John W.; Meschia, James F.; Ross, Owen A.

2015-01-01

Background Low density lipoprotein receptor related proteins-1 and 6 have been implicated in cerebral ischemia. In addition, genetic variation in LRP1 and LRP6 has been linked with various factors that are related to risk of ischemic stroke. The aim of this study was to examine the association of LRP1 and LRP6 gene variants with risk of ischemic stroke as part of the Ischemic Stroke Genetics Study (ISGS). Methods We included a Caucasian series (434 stroke patients, 319 controls) and an African American series (161 stroke patients, 116 controls). Fourteen LRP6 variants and 3 LRP1 variants were genotyped and assessed for association with ischemic stroke. Results In the Caucasian series, significant associations with ischemic stroke were observed for LRP6 rs2075241 (OR:0.42, P=0.023), rs2302685 (OR:0.44, P=0.049), rs7975614 (OR: 0.07, P=0.017), rs10492120 (OR: 0.62, P=0.036), and rs10743980 (OR: 0.66, P=0.037). Risk of ischemic stroke was significantly lower for carriers of any of these five protective LRP6 variants (24.0% of subjects) compared to non-carriers (OR:0.57, P=0.003). The protective association for LRP6 rs2075241 was observed at a similar magnitude across ischemic stroke subtypes, while the effects of rs23022685, rs10492120, and rs10743980 were most apparent for cardioembolic and large vessel stroke. In the African American series, LRP1 rs11172113 was associated with an increased risk of stroke (OR:1.89, P=0.006). Conclusions The results of our preliminary study provide evidence that LRP6 and LRP1 variants may be associated with risk of ischemic stroke. Validation in larger studies is warranted. PMID:26031789

A Novel Imaging Technique (X-Map) to Identify Acute Ischemic Lesions Using Noncontrast Dual-Energy Computed Tomography.

PubMed

Noguchi, Kyo; Itoh, Toshihide; Naruto, Norihito; Takashima, Shutaro; Tanaka, Kortaro; Kuroda, Satoshi

2017-01-01

We evaluated whether X-map, a novel imaging technique, can visualize ischemic lesions within 20 hours after the onset in patients with acute ischemic stroke, using noncontrast dual-energy computed tomography (DECT). Six patients with acute ischemic stroke were included in this study. Noncontrast head DECT scans were acquired with 2 X-ray tubes operated at 80 kV and Sn150 kV between 32 minutes and 20 hours after the onset. Using these DECT scans, the X-map was reconstructed based on 3-material decomposition and compared with a simulated standard (120 kV) computed tomography (CT) and diffusion-weighted imaging (DWI). The X-map showed more sensitivity to identify the lesions as an area of lower attenuation value than a simulated standard CT in all 6 patients. The lesions on the X-map correlated well with those on DWI. In 3 of 6 patients, the X-map detected a transient decrease in the attenuation value in the peri-infarct area within 1 day after the onset. The X-map is a powerful tool to supplement a simulated standard CT and characterize acute ischemic lesions. However, the X-map cannot replace a simulated standard CT to diagnose acute cerebral infarction. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Combined effects of family history of CVD and heart rate on ischemic stroke incidence among Inner Mongolians in China.

PubMed

Zhou, Yipeng; Tian, Yunfan; Zhong, Chongke; Batu, Buren; Xu, Tian; Li, Hongmei; Zhang, Mingzhi; Wang, Aili; Zhang, Yonghong

2016-05-01

This study aimed to evaluate the combined effects of family history of cardiovascular diseases (FHCVD) and heart rate on ischemic stroke incidence among Inner Mongolians in China. A prospective cohort study was conducted among 2589 participants aged 20 years and older from Inner Mongolia, China. The participants were divided into four groups according to status of FHCVD and heart rate and followed up from June 2002 to July 2012. Cox proportional hazards models were used to evaluate the combined effects of FHCVD and heart rate on the incidence of ischemic stroke. A total of 76 ischemic stroke occurred during the follow-up period. The observed ischemic stroke cases tended to be older and male, and had higher prevalence of smoking, drinking, hypertension and FHCVD as well as higher systolic and diastolic blood pressures at baseline compared with those who did not experience ischemic stroke. Age- and gender-adjusted hazard ratio (95% confidence interval) of ischemic stroke in the participants with both FHCVD and heart rate ≥ 80 were 2.89 (1.51-5.53), compared with those without FHCVD and heart rate < 80. After multiple adjustment, the association between ischemic stroke risk and both FHCVD and heart rate ≥ 80 remained statistically significant (hazard ratio, 2.47; 95% confidence interval: 1.22-5.01). Our main finding that participants with both FHCVD and faster heart rate have the highest risk of ischemic stroke suggests that faster heart rate may increase the risk of ischemic stroke among people with FHCVD.

Whole Grain Consumption and Risk of Ischemic Stroke: Results From 2 Prospective Cohort Studies.

PubMed

Juan, Juan; Liu, Gang; Willett, Walter C; Hu, Frank B; Rexrode, Kathryn M; Sun, Qi

2017-12-01

Higher intake of whole grains may exert cardiometabolic benefits, although findings on stroke risk are inconclusive. The potentially differential effects of individual whole grain foods on ischemic stroke have not been examined. We analyzed whole grain consumption in relation to ischemic stroke among 71 750 women from the Nurses' Health Study and 42 823 men from the Health Professionals Follow-up Study who were free of cardiovascular disease, diabetes mellitus, and cancer at baseline (1984 and 1986, respectively) through 2010 using a Cox proportional hazards model. Validated semiquantitative food frequency questionnaires were used to assess consumption of whole grain intake, including whole grain cold breakfast cereal, dark bread, oatmeal, brown rice, popcorn, bran, and germ. Self-reported incident cases of ischemic stroke were confirmed through medical record review. During 2 820 128 person-years of follow-up in the 2 cohorts, 2458 cases of ischemic stroke were identified and confirmed. Intake of total whole grains was not associated with risk of ischemic stroke after adjustment for covariates: the pooled hazard ratio (95% confidence interval) comparing extreme intake levels was 1.04 (0.91-1.19). However, intake of whole grain cold breakfast cereal and total bran was inversely associated with ischemic stroke after multivariate adjustment: the pooled hazard ratios (95% confidence intervals) were 0.88 (0.80-0.96; P trend =0.008) and 0.89 (0.79-1.00; P trend =0.004), respectively. Other whole grain foods were not associated with a lower risk of ischemic stroke. Although overall consumption of whole grains was not associated with lower risk of ischemic stroke, greater consumption of whole grain cold breakfast cereal and bran was significantly associated with a lower risk of ischemic stroke. More studies are needed to replicate these associations between individual whole grain foods and risk of ischemic stroke among other populations. © 2017 American Heart Association, Inc.

Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke: The Framingham Study.

PubMed

Saber, Hamidreza; Himali, Jayandra J; Beiser, Alexa S; Shoamanesh, Ashkan; Pikula, Aleksandra; Roubenoff, Ronenn; Romero, Jose R; Kase, Carlos S; Vasan, Ramachandran S; Seshadri, Sudha

2017-07-01

Low insulin-like growth factor 1 (IGF-1) has been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders. During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex, and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke, with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% confidence interval, 1.09-5.06; P =0.03) as compared with those in the top quintile. We observed an effect modification by diabetes mellitus and waist-hip ratio for the association between IGF-1 and ischemic stroke ( P <0.1). In subgroup analyses, the effects were restricted to subjects with diabetics and those in top waist-hip ratio quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P =0.007) and 41% (hazard ratio, 0.59; 95% confidence interval, 0.37-0.95; P =0.031) lower risk of incident ischemic stroke, respectively. IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance. © 2017 American Heart Association, Inc.

Increased pulse wave velocity in patients with acute lacunar infarction doubled the risk of future ischemic stroke.

PubMed

Saji, Naoki; Murotani, Kenta; Shimizu, Hirotaka; Uehara, Toshiyuki; Kita, Yasushi; Toba, Kenji; Sakurai, Takashi

2017-04-01

The aim of this study was to determine whether pulse wave velocity (PWV), a marker of vascular endothelial impairment and arteriosclerosis, predicts future ischemic stroke in patients who developed acute lacunar infarction. Patients with a first-ever ischemic stroke due to acute lacunar infarction were enrolled in this study. An oscillometric device (Form PWV/ABI; Omron Colin, Tokyo, Japan) was used to measure brachial-ankle PWV 1 week after stroke onset. Patients were followed for at least 5 years. The main end point of the study was recurrent ischemic stroke. Event-free survival was analyzed using Kaplan-Meier plots and log-rank tests. The risk of recurrent ischemic stroke was estimated using the Cox proportional-hazards model. Of the 156 patients (61% male, mean age: 69.2±11.3 years) assessed in this study, 29 developed recurrent ischemic stroke. The median brachial-ankle PWV value was 20.4 m s -1 . Patients with high PWV values had a greater risk of recurrent ischemic stroke than patients with low PWV values (28% vs. 15%, P=0.08). Kaplan-Meier curve analysis showed that patients with high PWV values had a less favorable (that is, free of recurrent ischemic stroke) survival time (P=0.015). A multivariate Cox proportional-hazards model identified high PWV as an independent predictor of recurrent ischemic stroke after adjusting for age, sex and blood pressure (hazard ratio 2.35, 95% confidence interval, 1.02-5.70, P=0.044). In patients with acute lacunar infarction, a high PWV predicts a twofold greater risk of future ischemic stroke, independent of patient age, sex and blood pressure levels.

Sleep Modifications in Acute Transient Global Amnesia

PubMed Central

Della Marca, Giacomo; Mazza, Marianna; Losurdo, Anna; Testani, Elisa; Broccolini, Aldobrando; Frisullo, Giovanni; Marano, Giuseppe; Morosetti, Roberta; Pilato, Fabio; Profice, Paolo; Vollono, Catello; Di Lazzaro, Vincenzo

2013-01-01

Study Objective: Transient global amnesia (TGA) is a temporary memory loss characterized by an abrupt onset of antero-grade and retrograde amnesia, totally reversible. Since sleep plays a major role in memory consolidation, and in the storage of memory-related traces into the brain cortex, the aims of the present study were: (1) to evaluate changes in sleep macro-structure in TGA; (2) to assess modifications in sleep micro-structure in TGA, with particular reference to the arousal EEG and to cyclic alternating pattern (CAP); (3) to compare sleep parameters in TGA patients with a control group of patients with acute ischemic events (“minor stroke” or transient ischemic attack [TIA]) clinically and neuroradiologically “similar” to the TGA. Methods: TGA group: 17 patients, (8 men and 9 women, 60.2 ± 12.5 years). Stroke or TIA (SoT) group: 17 patients hospitalized in the Stroke Unit for recent onset of minor stroke or TIA with hemispheric localization; healthy controls (HC) group: 17 healthy volunteers, matched for age and sex. Patients and controls underwent full-night polysomnography. Results: In the multivariate analysis (conditions TGA, SoT, and HC) a significant effect of the condition was observed for sleep efficiency index, number of awakenings longer 1 min, REM latency, CAP time, and CAP rate. TGA and SoT differed only for CAP time and CAP rate, which were lower in the TGA group. Conclusions: Microstructural modification associated with TGA could be consequent to: (1) hippocampal dysfunction and memory impairment; (2) impairment of arousal-related structures (in particular, cholinergic pathways); (3) emotional distress. Citation: Della Marca G; Mazza M; Losurdo A; Testani E; Broccolini A; Frisullo G; Marano G; Morosetti R; Pilato F; Profice P; Vollono C; Di Lazzaro V. Sleep modifications in acute transient global amnesia. J Clin Sleep Med 2013;9(9):921-927. PMID:23997704

Limb remote ischemic post-conditioning mitigates brain recovery in a mouse model of ischemic stroke by regulating reactive astrocytic plasticity.

PubMed

Cheng, Xue; Zhao, Haiping; Yan, Feng; Tao, Zhen; Wang, Rongliang; Han, Ziping; Li, Guangwen; Luo, Yumin; Ji, Xunming

2018-05-01

Maladaptive alterations of astrocytic plasticity may cause brain edema in the acute stage of stroke and glial scar formation in the recovery stage. The present study was designed to investigate the potential regulation of limb remote ischemic post-conditioning (RIPC) on astrocytic plasticity in experimental cerebral ischemia-reperfusion injury. Cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO) for 1 h in C57BL/6 mice, who were treated with RIPC immediately after reperfusion. The results showed that RIPC decreased hemispheric swelling, infarct volume and brain atrophy, and increased neurological function recovery and survival rates of ischemic mice at 3 and 14 d after cerebral ischemia-reperfusion, respectively. Moreover, the proportion of astrocyte subtypes was adjusted by RIPC treatment, demonstrated by decreased expression of the fibrous type (glial fibrillary acidic protein, GFAP) and increased expression of the protoplasmic type (glutamine synthetase, GS) in the ipsilateral side of the mouse brain at 14 d after cerebral ischemia-reperfusion. RIPC treatment adjusted the proportion of GFAP subtypes by downregulating the protein level of GFAPα, as well as upregulating the GFAPδ/GFAPα ratio in the ipsilateral side at 3 and 14 d after reperfusion. Notably, RIPC inhibited the phosphorylation of signal transducer and activators of transcriptions 3 (p-STAT3) in the ipsilateral side at 3 and 14 d after cerebral ischemia-reperfusion. Taken together, the results show that RIPC treatment could regulate reactive astrocytic plasticity and inhibition of STAT3 phosphorylation to promote neurological function recovery following ischemic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Discrimination of acute ischemic stroke from nonischemic vertigo in patients presenting with only imbalance.

PubMed

Honda, Shoji; Inatomi, Yuichiro; Yonehara, Toshiro; Hashimoto, Yoichiro; Hirano, Teruyuki; Ando, Yukio; Uchino, Makoto

2014-01-01

Some patients who present with an acute feeling of imbalance are experiencing an ischemic stroke that is not evident on computed tomography (CT) scans. The aim of this study was to compare ischemic stroke and nonischemic vertigo patient groups and to investigate independent factors associated with ischemic stroke. We examined 332 consecutive patients with an acute feeling of imbalance who showed no neurologic findings or responsible lesions on CT scan at the hyperacute phase. We examined their clinical backgrounds, physical findings, and laboratory examinations, with ischemic stroke diagnosed by later CT and/or magnetic resonance imaging (MRI). We identified 41 (12.3%) ischemic stroke patients. Atrial fibrillation (odds ratio 4.1; 95% confidence interval 1.4-11.5), white blood cell count (10(3)/μL, 1.4; 1.2-1.6), head and/or neck pain (4.6; 2.1-10.3), first attack of imbalance feeling (3.3; 1.1-12.2), and dizziness (3.7; 1.7-8.3) were significant and independent factors associated with ischemic stroke among patients with an acute feeling of imbalance. We used these factors to calculate an "imbalance score"; 1 point was given for the presence of each factor and a score of 3-5 points was independently associated with ischemic stroke. An awareness of these factors may indicate that further examinations including MRI are necessary to rule out ischemic stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation: 1-Year follow-up outcome data of the EWOLUTION trial.

PubMed

Boersma, Lucas V; Ince, Hueseyin; Kische, Stephan; Pokushalov, Evgeny; Schmitz, Thomas; Schmidt, Boris; Gori, Tommaso; Meincke, Felix; Protopopov, Alexey Vladimir; Betts, Timothy; Foley, David; Sievert, Horst; Mazzone, Patrizio; De Potter, Tom; Vireca, Elisa; Stein, Kenneth; Bergmann, Martin W

2017-09-01

Left atrial appendage (LAA) occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials. EWOLUTION was designed to provide data in routine practice from a prospective multicenter registry. A total of 1025 patients scheduled for a WATCHMAN implant were prospectively and sequentially enrolled at 47 centers. Indication for LAA closure was based on European Society of Cardiology guidelines. Follow-up and transesophageal echocardiography (TEE) were performed per local practice. The baseline CHA 2 DS 2 -VASc score was 4.5 ± 1.6; the mean age was 73.4 ± 9 years; previous transient ischemic attack/ischemic stroke was present in 312 (30.5%), 155 (15.1%) had previous hemorrhagic stroke, and 320 (31.3%) had a history of major bleeding; and 750 (73%) were deemed unsuitable for oral anticoagulation therapy. WATCHMAN implant succeeded in 1005 (98.5%) of patients, without leaks >5 mm in 1002 (99.7%) with at least 1 TEE follow-up in 875 patients (87%). Antiplatelet therapy was used in 784 (83%), while vitamin K antagonists were used in only 75 (8%). At 1 year, mortality was 98 (9.8%), reflecting the advanced age and comorbidities in this population. Device thrombus was observed in 28 patients at routine TEE (3.7%) and was not correlated with the drug regimen (P = .14). Ischemic stroke rate was 1.1% (relative risk 84% vs estimated historical data); the major bleeding rate was 2.6% and was predominantly (2.3%) nonprocedure/device related. LAA closure with the WATCHMAN device has a high implant and sealing success. This method of stroke risk reduction appears to be safe and effective with an ischemic stroke rate as low as 1.1%, even though 73% of patients had a contraindication to and were not using oral anticoagulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Ischemic stroke risk factors during Greek economic crisis.

PubMed

Katsanos, Aristeidis H; Fiolaki, Aidonio; Markou, Sofia; Markoula, Sofia; Kosmidou, Maria; Kyritsis, Athanassios P; Giannopoulos, Sotirios

2016-02-01

The impact of Greece's economic crisis on healthcare is of great concern. The aim of the present study was to assess the impact of economic crisis on the prevention of cerebral ischemic events. Retrospective analysis of patients with ischemic stroke (IS) or transient ischemic attack (TIA) admitted to a tertiary neurological department in northwestern Greece during the period 2008-2014. Using 2011 as the transitional year IS/TIA patients were dichotomized according to their admission date in two subgroups: the "before economic crisis" subgroup and the "after economic crisis" subgroup. Logistic regression analyses were performed to identify predictor variables of statin/antihypertensive pretreatment. Patients admitted after the economic crisis outbreak (mean age: 57.6 ± 13.5 years) were found to have lower waist periphery measurements (p = 0.001), lower incidence of diabetes (p = 0.028), hyperlipidemia (p = 0.002) and metabolic syndrome(p < 0.001), at stroke onset with lower rates of antilipidemic treatment prescription prior to stroke onset compared to those patients with cerebral ischemia that were hospitalized before the financial crisis (mean age: 59.6 ± 11.1 years). However, between the two subgroups were no significant differences in the rates of untreated patients with hyperlipidemia (p = 0.189) and/or hypertension (p = 0.313). Even though statin pretreatment prior to stroke onset was found to be reduced during economic crisis compared to the period before the crisis, (OR = 0.58, 95%CI: 0.34-0.95, p = 0.032), this association did not retain statistical significance in the multivariate logistic regression analysis (OR = 1.69, 95%CI = 0.83-3.42, p = 0.143). Our study supports that at present financial crisis has not significantly affected the prevention of cerebrovascular events in the citizens of a provincial city area. Data from other regions and time-periods are needed for the final verdict. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R(2)CHADS(2) index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) study cohorts.

PubMed

Piccini, Jonathan P; Stevens, Susanna R; Chang, YuChiao; Singer, Daniel E; Lokhnygina, Yuliya; Go, Alan S; Patel, Manesh R; Mahaffey, Kenneth W; Halperin, Jonathan L; Breithardt, Günter; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Fox, Keith A A; Califf, Robert M

2013-01-15

We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial. In ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), 14 264 patients with nonvalvular AF and creatinine clearance ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non-central nervous system embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation), an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 patients (4.0%) experienced primary end-point events. Reduced creatinine clearance was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack. Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, as well as vascular disease of the heart and limbs (C-index 0.635). A model that included creatinine clearance (R(2)CHADS(2)) improved net reclassification index by 6.2% compared with CHA(2)DS(2)VASc (C statistic=0.578) and by 8.2% compared with CHADS(2) (C statistic=0.575). The inclusion of creatinine clearance <60 mL/min and prior stroke or transient ischemic attack in a model with no other covariates led to a C statistic of 0.590.Validation of R(2)CHADS(2) in an external, separate population improved net reclassification index by 17.4% (95% confidence interval, 12.1%-22.5%) relative to CHADS(2). In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00403767.

Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.

PubMed

Kilarski, Laura L; Achterberg, Sefanja; Devan, William J; Traylor, Matthew; Malik, Rainer; Lindgren, Arne; Pare, Guillame; Sharma, Pankaj; Slowik, Agniesczka; Thijs, Vincent; Walters, Matthew; Worrall, Bradford B; Sale, Michele M; Algra, Ale; Kappelle, L Jaap; Wijmenga, Cisca; Norrving, Bo; Sandling, Johanna K; Rönnblom, Lars; Goris, An; Franke, Andre; Sudlow, Cathie; Rothwell, Peter M; Levi, Christopher; Holliday, Elizabeth G; Fornage, Myriam; Psaty, Bruce; Gretarsdottir, Solveig; Thorsteinsdottir, Unnar; Seshadri, Sudha; Mitchell, Braxton D; Kittner, Steven; Clarke, Robert; Hopewell, Jemma C; Bis, Joshua C; Boncoraglio, Giorgio B; Meschia, James; Ikram, M Arfan; Hansen, Bjorn M; Montaner, Joan; Thorleifsson, Gudmar; Stefanson, Kari; Rosand, Jonathan; de Bakker, Paul I W; Farrall, Martin; Dichgans, Martin; Markus, Hugh S; Bevan, Steve

2014-08-19

To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases. Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls. In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p = 7.12 × 10(-11)) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p = 0.695). Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage. © 2014 American Academy of Neurology.

Hydroxychloroquine Use Is Associated With Decreased Incident Cardiovascular Events in Rheumatoid Arthritis Patients.

PubMed

Sharma, Tarun S; Wasko, Mary Chester M; Tang, Xiaoqin; Vedamurthy, Deepak; Yan, Xiaowei; Cote, Jonida; Bili, Androniki

2016-01-04

Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA) patients. This study is the first to report the association of hydroxychloroquine (an antirheumatic medication that has been associated with decreased risk of diabetes, a less atherogenic lipid profile, and antithrombotic properties) with CVD in RA. A retrospective incident RA cohort from January 1, 2001, to October 31, 2013, excluding patients with CVD prior to RA diagnosis, was constructed. Patients were categorized as hydroxychloroquine users versus nonusers and were allowed to contribute time to either group according to hydroxychloroquine exposure. The primary outcome was adjudicated incident CVD defined as a composite of coronary artery disease, stroke, transient ischemic attack, sudden cardiac death, and peripheral artery disease with arterial revascularization procedure. The secondary outcome was a composite of incident coronary artery disease, stroke, and transient ischemic attack. Cox time-varying regression models were used to estimate the association between hydroxychloroquine exposure and development of CVD, after adjusting for propensity score and relevant confounders, including demographics, CVD-related comorbidities, RA severity, and activity indicators and medications. We included 1266 RA patients, 547 hydroxychloroquine users, and 719 nonusers. During the observation period, 102 CVD events occurred, 3 in hydroxychloroquine users and 99 in nonusers. The fully adjusted Cox model showed a hazard ratio of 0.28 (95% CI 0.12-0.63, P=0.002) for incident CVD and 0.30 (95% CI 0.13-0.68, P=0.004) for incident composite coronary artery disease, stroke, and transient ischemic attack for hydroxychloroquine users versus nonusers, respectively. In this hypothesis-generating study, hydroxychloroquine use was associated with a 72% decrease in the risk of incident CVD in RA patients. If these preliminary results are confirmed in larger studies, our findings may be used as a rationale for a randomized study of hydroxychloroquine use for primary prevention of CVD in RA or nonrheumatic high-risk patients. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

[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.

Safety of Intravenous Thrombolysis within 4.5 h of symptom onset in patients with negative post-treatment stroke imaging for cerebral infarction.

PubMed

Giraldo, Elias A; Khalid, Aisha; Zand, Ramin

2011-08-01

Patients with stroke symptoms but negative diffusion-weighted imaging (DWI) might have transient ischemic attacks (TIA) or stroke mimics. Brain DWI is important for the diagnosis of cerebral infarction but it is not available before thrombolysis for most patients to avoid treatment delay. This study aimed to evaluate the safety of IV thrombolysis in patients with a negative post-treatment DWI for cerebral infarction. We conducted a retrospective study of 89 patients treated with IV recombinant tissue plasminogen activator (rt-PA) within 4.5 h after stroke symptom onset. The patients were identified in our acute stroke registry from January 2009 to September 2010. Information on patients' demographics, clinical characteristics, neuroimaging, treatment complications, and outcomes was obtained and analyzed. Out of 89 patients, 23 patients (26%) had a negative DWI on follow-up stroke imaging. Fourteen patients had a TIA and nine patients had a stroke mimic, including Todd's paralysis, complicated migraine, and somatoform disorder. We found significant differences between patients with a positive and a negative DWI in mean age (62 years vs. 52 years; P < 0.01) and median admission NIH stroke scale score (11 points versus 6 points; P < 0.001). Among patients with a positive DWI, four patients had a symptomatic intracerebral hemorrhage (ICH). No patients with a negative DWI had symptomatic or asymptomatic ICH. Our results suggest that the administration of IV rt-PA within the first 4.5 h of symptom onset in patients with suspected ischemic stroke is safe even when post-treatment DWI does not demonstrate cerebral infarction.

An International Standard Set of Patient-Centered Outcome Measures After Stroke.

PubMed

Salinas, Joel; Sprinkhuizen, Sara M; Ackerson, Teri; Bernhardt, Julie; Davie, Charlie; George, Mary G; Gething, Stephanie; Kelly, Adam G; Lindsay, Patrice; Liu, Liping; Martins, Sheila C O; Morgan, Louise; Norrving, Bo; Ribbers, Gerard M; Silver, Frank L; Smith, Eric E; Williams, Linda S; Schwamm, Lee H

2016-01-01

Value-based health care aims to bring together patients and health systems to maximize the ratio of quality over cost. To enable assessment of healthcare value in stroke management, an international standard set of patient-centered stroke outcome measures was defined for use in a variety of healthcare settings. A modified Delphi process was implemented with an international expert panel representing patients, advocates, and clinical specialists in stroke outcomes, stroke registers, global health, epidemiology, and rehabilitation to reach consensus on the preferred outcome measures, included populations, and baseline risk adjustment variables. Patients presenting to a hospital with ischemic stroke or intracerebral hemorrhage were selected as the target population for these recommendations, with the inclusion of transient ischemic attacks optional. Outcome categories recommended for assessment were survival and disease control, acute complications, and patient-reported outcomes. Patient-reported outcomes proposed for assessment at 90 days were pain, mood, feeding, selfcare, mobility, communication, cognitive functioning, social participation, ability to return to usual activities, and health-related quality of life, with mobility, feeding, selfcare, and communication also collected at discharge. One instrument was able to collect most patient-reported subdomains (9/16, 56%). Minimum data collection for risk adjustment included patient demographics, premorbid functioning, stroke type and severity, vascular and systemic risk factors, and specific treatment/care-related factors. A consensus stroke measure Standard Set was developed as a simple, pragmatic method to increase the value of stroke care. The set should be validated in practice when used for monitoring and comparisons across different care settings. © 2015 The Authors.

Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies.

PubMed

Hart, R G; Pearce, L A; Miller, V T; Anderson, D C; Rothrock, J F; Albers, G W; Nasco, E

2000-01-01

While atrial fibrillation (AF) increases the risk of cardioembolic stroke, some ischemic strokes in AF patients are noncardioembolic. To assess ischemic stroke mechanisms in AF and to compare their responses to antithrombotic therapies. On-therapy analyses of ischemic strokes occurring in 3,950 participants in the Stroke Prevention in Atrial Fibrillation I-III clinical trials. Strokes were classified by presumed mechanism according to specified neurologic features by neurologists unaware of antithrombotic therapy. Of 217 ischemic strokes, 52% were classified as probably cardioembolic, 24% as noncardioembolic, and 24% as of uncertain cause (i.e., 68% of classifiable infarcts were deemed cardioembolic). Compared to those receiving placebo or no antithrombotic therapy, the proportion of cardioembolic stroke was lower in patients taking adjusted-dose warfarin (p = 0.02), while the proportion of noncardioembolic stroke was lower in those taking aspirin (p = 0.06). Most (56%) ischemic strokes occurring in AF patients taking adjusted-dose warfarin were noncardioembolic vs. 16% of strokes in those taking aspirin. Adjusted-dose warfarin reduced cardioembolic strokes by 83% (p < 0.001) relative to aspirin. Cardioembolic strokes were particularly disabling (p = 0.05). Most ischemic strokes in AF patients are probably cardioembolic, and these are sharply reduced by adjusted-dose warfarin. Aspirin in AF patients appears to primarily reduce noncardioembolic strokes. AF patients at highest risk for stroke have the highest rates of cardioembolic stroke and have the greatest reduction in stroke by warfarin. Copyright 2000 S. Karger AG, Basel

Challenges in assessing hospital-level stroke mortality as a quality measure: comparison of ischemic, intracerebral hemorrhage, and total stroke mortality rates.

PubMed

Xian, Ying; Holloway, Robert G; Pan, Wenqin; Peterson, Eric D

2012-06-01

Public reporting efforts currently profile hospitals based on overall stroke mortality rates, yet the "mix" of hemorrhagic and ischemic stroke cases may impact this rate. Using the 2005 to 2006 New York state data, we examined the degree to which hospital stroke mortality rankings varied regarding ischemic versus hemorrhagic versus total stroke. Observed/expected ratio was calculated using the Agency for Healthcare Research and Quality Inpatient Quality Indicator software. The observed/expected ratio and outlier status based on stroke types across hospitals were examined using Pearson correlation coefficients (r) and weighted κ. Overall 30-day stroke mortality rates were 15.2% and varied from 11.3% for ischemic stroke and 37.3% for intracerebral hemorrhage. Hospital risk-adjusted ischemic stroke observed/expected ratio was weakly correlated with its own intracerebral hemorrhage observed/expected ratio (r=0.38). When examining hospital performance group (mortality better, worse, or no different than average), disagreement was observed in 35 of 81 hospitals (κ=0.23). Total stroke mortality observed/expected ratio and rankings were correlated with intracerebral hemorrhage (r=0.61 and κ=0.36) and ischemic stroke (r=0.94 and κ=0.71), but many hospitals still switched classification depending on mortality metrics. However, hospitals treating a higher percent of hemorrhagic stroke did not have a statistically significant higher total stroke mortality rate relative to those treating fewer hemorrhagic strokes. Hospital stroke mortality ratings varied considerably depending on whether ischemic, hemorrhagic, or total stroke mortality rates were used. Public reporting of stroke mortality measures should consider providing risk-adjusted outcome on separate stroke types.

Determinants of Emergency Medical Services Utilization Among Acute Ischemic Stroke Patients in Hubei Province in China.

PubMed

Yin, Xiaoxv; Yang, Tingting; Gong, Yanhong; Zhou, Yanfeng; Li, Wenzhen; Song, Xingyue; Wang, Mengdie; Hu, Bo; Lu, Zuxun

2016-03-01

Emergency medical services (EMS) can effectively shorten the prehospital delay for patients with acute ischemic stroke. This study aimed to investigate EMS utilization and its associated factors in patients with acute ischemic stroke in China. A cross-sectional study was conducted from October 1, 2014, to January 31, 2015, which included 2096 patients admitted for acute ischemic stroke from 66 hospitals in Hubei province in China. A multivariable stepwise logistic regression model was undertaken to identify the factors associated with EMS utilization. Of the 2096 participants, only 323 cases (15.4%) used EMS. Those acute ischemic stroke patients who previously used EMS (odds ratio [OR] =9.8), whose National Institutes of Health Stroke Scale score was ≥10 (OR=3.7), who lived in urban communities (OR=2.5), who had sudden onset of symptoms (OR=2.4), who experienced their first stroke (OR=1.8), and who recognized initial symptom as stroke (OR=1.4) were more likely to use EMS. Additionally, when acute ischemic stroke patients' stroke symptom were noticed first by others (OR=2.1), rather than by the patients, EMS was more likely to be used. A very low proportion of patients with acute ischemic stroke used the EMS in Hubei province in China. Considerable education programs are required regarding knowledge of potential symptoms and the importance of EMS for stroke. © 2016 American Heart Association, Inc.

Limb-shaking transient ischemic attack masquerading as lumbar radiculopathy from pericallosal artery stenosis treated successfully with intracranial angioplasty and stenting.

PubMed

Kalia, Junaid; Wolfe, Thomas; Zaidat, Osama O

2010-03-01

The pericallosal artery is rarely associated with intracranial atherosclerotic disease and, until recently, was usually not amenable to endovascular therapy with balloon angioplasty and stenting. We present an elderly patient with postural left leg-shaking episodes secondary to pericallosal artery stenosis, which was treated initially with primary intracranial balloon angioplasty, and subsequently, angioplasty and stenting as a result of recurrent stenosis. Both procedures were preformed without complications, and the patient remained free of symptoms on 6-month follow-up. This case demonstrates unique clinical and neuroendovascular aspects; the isolated postural leg-shaking transient ischemic attacks, initially mistaken for radiculopathy and local joint etiology, were found later to be cerebrovascular ischemic in origin. Moreover, the correlation between the findings of computed tomography perfusion and angiography localized the lesion into the medial frontal lobe and pericallosal artery territory. In addition, the technical aspect provides insight into the current state of neuroendovascular techniques, addressing the difficulty of access into very small and distal intracranial arteries affected by stenosis. Copyright 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Neuroprotective Mechanisms of Taurine against Ischemic Stroke.

PubMed

Menzie, Janet; Prentice, Howard; Wu, Jang-Yen

2013-06-03

Ischemic stroke exhibits a multiplicity of pathophysiological mechanisms. To address the diverse pathophysiological mechanisms observed in ischemic stroke investigators seek to find therapeutic strategies that are multifaceted in their action by either investigating multipotential compounds or by using a combination of compounds. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions. It exhibits antioxidative properties, stabilizes membrane, functions as an osmoregulator, modulates ionic movements, reduces the level of pro-inflammators, regulates intracellular calcium concentration; all of which contributes to its neuroprotective effect. Data are accumulating that show the neuroprotective mechanisms of taurine against stroke pathophysiology. In this review, we describe the neuroprotective mechanisms employed by taurine against ischemic stroke and its use in clinical trial for ischemic stroke.

The Use of Major Risk Factors for Computer-Based Distinction of Diabetic Patients with Ischemic Stroke and Without Stroke

DTIC Science & Technology

2001-10-25

THE USE of MAJOR RISK FACTORS for COMPUTER-BASED DISTINCTION of DIABETIC PATIENTS with ISCHEMIC STROKE and WITHOUT STROKE Sibel Oge Merey1...highlighting the major risk factors of diabetic patients with non-embolic stroke and without stroke by performing dependency analysis and decision making...of Major Risk Factors for Computer-Based Distinction of Diabetic Patients with Ischemic Stroke and Without Stroke Contract Number Grant Number

Usefulness of cardiometabolic index for the estimation of ischemic stroke risk among general population in rural China.

PubMed

Wang, Haoyu; Chen, Yintao; Guo, Xiaofan; Chang, Ye; Sun, Yingxian

2017-11-01

Cardiometabolic index (CMI) has been recognized as a novel and practical marker for the assessment of cardiometabolic risk as it is independently related to diabetes and atherosclerotic progression. This study tested the hypothesis that CMI represents a risk of ischemic stroke in a general population of rural China. From July 2012 to August 2013, we examined data from a large cross-sectional study of 11,345 participants (mean age 53.8 years; 60.8% females) who underwent biochemical determinations and anthropometric measurements in rural areas of northeast China. Ischemic stroke was documented as a history of cerebrovascular events and verified by medical record review. The prevalence of ischemic stroke was given to 3.1% of females and 3.2% of males. The cardio-metabolic profile was notably more adverse in ischemic stroke groups, irrespective of gender. A dose-response manner was detected for the prevalence of ischemic stroke, exhibiting a significant increase from the lowest to the highest quartiles of CMI (1.2% to 6.4% in females, P for trend<0.001; 2.3% to 4.3% in males, P for trend = 0.017). In multivariable analysis, for every 1 SD increment in CMI, the probability of ischemic stroke increased by 18% in females and 14% in males, respectively. The odds ratios for ischemic stroke comparing the top versus bottom quartiles of CMI were 2.047 (95%CI: 1.168-3.587) for females and 1.722 (95%CI: 1.019-2.910) for males. According to the area under receiver operating characteristic (AUC), the discrimination power of CMI in predicting ischemic stroke was relatively higher for females (AUC: 0.685) than males (AUC: 0.573). The strong and independent association of CMI with ischemic stroke in females, in comparison with the much lesser degree in males, provides further insight to better stratify by sex in investigations of ischemic stroke and solidly corroborates the potential role of ischemic stroke prevention targeted at CMI.

Emerging Roles of microRNAs in Ischemic Stroke: As Possible Therapeutic Agents

PubMed Central

Khoshnam, Seyed Esmaeil; Winlow, William; Farbood, Yaghoob; Moghaddam, Hadi Fathi; Farzaneh, Maryam

2017-01-01

Stroke is one of the leading causes of death and physical disability worldwide. The consequences of stroke injuries are profound and persistent, causing in considerable burden to both the individual patient and society. Current treatments for ischemic stroke injuries have proved inadequate, partly owing to an incomplete understanding of the cellular and molecular changes that occur following ischemic stroke. MicroRNAs (miRNA) are endogenously expressed RNA molecules that function to inhibit mRNA translation and have key roles in the pathophysiological processes contributing to ischemic stroke injuries. Potential therapeutic areas to compensate these pathogenic processes include promoting angiogenesis, neurogenesis and neuroprotection. Several miRNAs, and their target genes, are recognized to be involved in these recoveries and repair mechanisms. The capacity of miRNAs to simultaneously regulate several target genes underlies their unique importance in ischemic stroke therapeutics. In this Review, we focus on the role of miRNAs as potential diagnostic and prognostic biomarkers, as well as promising therapeutic agents in cerebral ischemic stroke. PMID:28480877

Clinical and Economic Implications of Apixaban Versus Aspirin in the Low-Risk Nonvalvular Atrial Fibrillation Patients.

PubMed

Lip, Gregory Y H; Lanitis, Tereza; Mardekian, Jack; Kongnakorn, Thitima; Phatak, Hemant; Dorian, Paul

2015-10-01

Although recommended by guidelines, the benefits of treating patients with atrial fibrillation with a low-stroke risk score, with aspirin or anticoagulants, have not been clearly established. With advent of safer non-vitamin K antagonist oral anticoagulant, we assessed the clinical and economic implications of 5 mg BID of apixaban versus aspirin among patients with a relative low risk of stroke as assessed using the CHADS2 (congestive heart failure, hypertension, age>75, diabetes mellitus, stroke/transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke/transient ischemic attack, vascular disease) stroke risk classification. A previously developed and validated Markov model was adapted. A secondary analysis of the Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study was conducted to estimate event rates in different low-risk cohorts by treatment. Three cohorts (n=1000) with a CHADS2 score of 1, CHA2DS2-VASc score of 1, and CHA2DS2-VASc of score 2 to 4 were simulated to assess the number of clinical events avoided in terms of strokes and major bleeds, as well as life years gained, quality-adjusted life years gained, costs, and incremental costs per quality-adjusted life year gained. Apixaban was associated with fewer strokes and systemic embolism versus aspirin across all subgroups; however, it caused more major bleeding events. The reduction in systemic embolism offset the increase in major bleeding events leading to increased life expectancy and quality-adjusted life year gains, achieved at an increased cost that was lower than the UK threshold of $44,400 (ie, £30,000) per quality-adjusted life year gained across the 3 cohorts examined. Anticoagulant treatment with apixaban versus aspirin in low-risk patients, as identified using CHADS2 or CHA2DS2-VASc, is projected to increase life expectancy and provide clinical benefits that are cost effective. © 2015 American Heart Association, Inc.

Short-Term Exposure to Fine Particulate Matter and Risk of Ischemic Stroke.

PubMed

Matsuo, Ryu; Michikawa, Takehiro; Ueda, Kayo; Ago, Tetsuro; Nitta, Hiroshi; Kitazono, Takanari; Kamouchi, Masahiro

2016-12-01

There is a strong association between ambient concentrations of particulate matter (PM) and cardiovascular disease. However, it remains unclear whether acute exposure to fine PM (PM 2.5 ) triggers ischemic stroke events and whether the timing of exposure is associated with stroke risk. We, therefore, examined the association between ambient PM 2.5 and occurrence of ischemic stroke. We analyzed data for 6885 ischemic stroke patients from a multicenter hospital-based stroke registry in Japan who were previously independent and hospitalized within 24 hours of stroke onset. Time of symptom onset was confirmed, and the association between PM (suspended PM and PM 2.5 ) and occurrence of ischemic stroke was analyzed by time-stratified case-crossover analysis. Ambient PM 2.5 and suspended PM at lag days 0 to 1 were associated with subsequent occurrence of ischemic stroke (ambient temperature-adjusted odds ratio [95% confidence interval] per 10 μg/m 3 : suspended PM, 1.02 [1.00-1.05]; PM 2.5 , 1.03 [1.00-1.06]). In contrast, ambient suspended PM and PM 2.5 at lag days 2 to 3 or 4 to 6 showed no significant association with stroke occurrence. The association between PM 2.5 at lag days 0 to 1 and ischemic stroke was maintained after adjusting for other air pollutants (nitrogen dioxide, photochemical oxidants, or sulfur dioxide) or influenza epidemics and was evident in the cold season. These findings suggest that short-term exposure to PM 2.5 within 1 day before onset is associated with the subsequent occurrence of ischemic stroke. © 2016 American Heart Association, Inc.

Stroke survivors' endorsement of a "stress belief model" of stroke prevention predicts control of risk factors for recurrent stroke.

PubMed

Phillips, L Alison; Tuhrim, Stanley; Kronish, Ian M; Horowitz, Carol R

2014-01-01

Perceptions that stress causes and stress-reduction controls hypertension have been associated with poorer blood pressure (BP) control in hypertension populations. The current study investigated these "stress-model perceptions" in stroke survivors regarding prevention of recurrent stroke and the influence of these perceptions on patients' stroke risk factor control. Stroke and transient ischemic attack survivors (N=600) participated in an in-person interview in which they were asked about their beliefs regarding control of future stroke; BP and cholesterol were measured directly after the interview. Counter to expectations, patients who endorsed a "stress-model" but not a "medication-model" of stroke prevention were in better control of their stroke risk factors (BP and cholesterol) than those who endorsed a medication-model but not a stress-model of stroke prevention (OR for poor control=.54, Wald statistic=6.07, p=.01). This result was not explained by between group differences in patients' reported medication adherence. The results have implications for theory and practice, regarding the role of stress belief models and acute cardiac events, compared to chronic hypertension.

Sexual dimorphism in ischemic stroke: lessons from the laboratory

PubMed Central

Manwani, Bharti; McCullough, Louise D

2011-01-01

Ischemic stroke is emerging as a major health problem for elderly women. Women have lower stroke incidence than men until an advanced age, when the epidemiology of ischemic stroke shifts and incidence rises dramatically in women. Experimental models of rodent stroke have replicated this clinical epidemiology, with exacerbated injury in older compared with young female rodents Many of the detrimental effects of aging on ischemic stroke outcome in females can be replicated by ovariectomy, suggesting that hormones such as estrogen play a neuroprotective role. However, emerging data suggest that the molecular mechanisms leading to ischemic cell death differ in the two sexes, and these effects may be independent of circulating hormone levels. This article highlights recent clinical and experimental literature on sex differences in stroke outcomes and mechanisms. PMID:21612353

Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke.

PubMed

Hanscombe, Ken B; Traylor, Matthew; Hysi, Pirro G; Bevan, Stephen; Dichgans, Martin; Rothwell, Peter M; Worrall, Bradford B; Seshadri, Sudha; Sudlow, Cathie; Williams, Frances M K; Markus, Hugh S; Lewis, Cathryn M

2015-08-01

Abnormal coagulation has been implicated in the pathogenesis of ischemic stroke, but how this association is mediated and whether it differs between ischemic stroke subtypes is unknown. We determined the shared genetic risk between 14 coagulation factors and ischemic stroke and its subtypes. Using genome-wide association study results for 14 coagulation factors from the population-based TwinsUK sample (N≈2000 for each factor), meta-analysis results from the METASTROKE consortium ischemic stroke genome-wide association study (12 389 cases, 62 004 controls), and genotype data for 9520 individuals from the WTCCC2 ischemic stroke study (3548 cases, 5972 controls-the largest METASTROKE subsample), we explored shared genetic risk for coagulation and stroke. We performed three analyses: (1) a test for excess concordance (or discordance) in single nucleotide polymorphism effect direction across coagulation and stroke, (2) an estimation of the joint effect of multiple coagulation-associated single nucleotide polymorphisms in stroke, and (3) an evaluation of common genetic risk between coagulation and stroke. One coagulation factor, factor XIII subunit B (FXIIIB), showed consistent effects in the concordance analysis, the estimation of polygenic risk, and the validation with genotype data, with associations specific to the cardioembolic stroke subtype. Effect directions for FXIIIB-associated single nucleotide polymorphisms were significantly discordant with cardioembolic disease (smallest P=5.7×10(-04)); the joint effect of FXIIIB-associated single nucleotide polymorphisms was significantly predictive of ischemic stroke (smallest P=1.8×10(-04)) and the cardioembolic subtype (smallest P=1.7×10(-04)). We found substantial negative genetic covariation between FXIIIB and ischemic stroke (rG=-0.71, P=0.01) and the cardioembolic subtype (rG=-0.80, P=0.03). Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype. © 2015 The Authors.

Genetic Variant of Kalirin Gene Is Associated with Ischemic Stroke in a Chinese Han Population.

PubMed

Li, Hong; Yu, Shasha; Wang, Rui; Sun, Zhaoqing; Zhou, Xinghu; Zheng, Liqiang; Yin, Zhihua; Zhang, Xingang; Sun, Yingxian

2017-01-01

Ischemic stroke is a complex disorder resulting from the interplay of genetic and environmental factors. Previous studies showed that kalirin gene variations were associated with cardiovascular disease. However, the association between this gene and ischemic stroke was unknown. We performed this study to confirm if kalirin gene variation was associated with ischemic stroke. We enrolled 385 ischemic stroke patients and 362 controls from China. Three SNPs of kalirin gene were genotyped by means of ligase detection reaction-PCR method. Data was processed with SPSS and SHEsis platform. SNP rs7620580 (dominant model: OR = 1.590, p = 0.002 and adjusted OR = 1.662, p = 0.014; additive model: OR = 1.490, p = 0.002 and adjusted OR = 1.636, p = 0.005; recessive model: OR = 2.686, p = 0.039) and SNP rs1708303 (dominant model: OR = 1.523, p = 0.007 and adjusted OR = 1.604, p = 0.028; additive model: OR = 1.438, p = 0.01 and adjusted OR = 1.476, p = 0.039) were associated with ischemic stroke. The GG genotype and G allele of SNP rs7620580 were associated with a risk for ischemic stroke with an adjusted OR of 3.195 and an OR of 1.446, respectively. Haplotype analysis revealed that A-T-G,G-T-A, and A-T-A haplotypes were associated with ischemic stroke. Our results provide evidence that kalirin gene variations were associated with ischemic stroke in the Chinese Han population.

Cerebral Microbleeds and the Risk of Incident Ischemic Stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy).

PubMed

Puy, Laurent; De Guio, François; Godin, Ophélia; Duering, Marco; Dichgans, Martin; Chabriat, Hugues; Jouvent, Eric

2017-10-01

Cerebral microbleeds are associated with an increased risk of intracerebral hemorrhage. Recent data suggest that microbleeds may also predict the risk of incident ischemic stroke. However, these results were observed in elderly individuals undertaking various medications and for whom causes of microbleeds and ischemic stroke may differ. We aimed to test the relationship between the presence of microbleeds and incident stroke in CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy)-a severe monogenic small vessel disease known to be responsible for both highly prevalent microbleeds and a high incidence of ischemic stroke in young patients. We assessed microbleeds on baseline MRI in all 378 patients from the Paris-Munich cohort study. Incident ischemic strokes were recorded during 54 months. Survival analyses were used to test the relationship between microbleeds and incident ischemic stroke. Three hundred sixty-nine patients (mean age, 51.4±11.4 years) were followed-up during a median time of 39 months (interquartile range, 19 months). The risk of incident ischemic stroke was higher in patients with microbleeds than in patients without (35.8% versus 19.6%, hazard ratio, 1.87; 95% confidence interval, 1.16-3.01; P =0.009). These results persisted after adjustment for history of ischemic stroke, age, sex, vascular risk factors, and antiplatelet agents use (hazard ratio, 1.89; 95% confidence interval, 1.10-3.26; P =0.02). The presence of microbleeds is an independent risk marker of incident ischemic stroke in CADASIL, emphasizing the need to carefully interpret MRI data. © 2017 American Heart Association, Inc.

Sleep Duration and the Risk of Mortality From Stroke in Japan: The Takayama Cohort Study.

PubMed

Kawachi, Toshiaki; Wada, Keiko; Nakamura, Kozue; Tsuji, Michiko; Tamura, Takashi; Konishi, Kie; Nagata, Chisato

2016-01-01

Few studies have assessed the associations between sleep duration and stroke subtypes. We examined whether sleep duration is associated with mortality from total stroke, ischemic stroke, and hemorrhagic stroke in a population-based cohort of Japanese men and women. Subjects included 12 875 men and 15 021 women aged 35 years or older in 1992, who were followed until 2008. The outcome variable was stroke death (ischemic stroke, hemorrhagic stroke, and total stroke). During follow-up, 611 stroke deaths (354 from ischemic stroke, 217 from hemorrhagic stroke, and 40 from undetermined stroke) were identified. Compared with 7 h of sleep, ≥9 h of sleep was significantly associated with an increased risk of total stroke and ischemic stroke mortality after controlling for covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were 1.51 (95% CI, 1.16-1.97) and 1.65 (95% CI, 1.16-2.35) for total stroke mortality and ischemic stroke mortality, respectively. Short sleep duration (≤6 h of sleep) was associated with a decreased risk of mortality from total stroke (HR 0.77; 95% CI, 0.59-1.01), although this association was of borderline significance (P = 0.06). The trends for total stroke and ischemic stroke mortality were also significant (P < 0.0001 and P = 0.0002, respectively). There was a significant risk reduction of hemorrhagic stroke mortality for ≤6 h of sleep as compared with 7 h of sleep (HR 0.64; 95% CI, 0.42-0.98; P for trend = 0.08). The risk reduction was pronounced for men (HR 0.31; 95% CI, 0.16-0.64). Data suggest that longer sleep duration is associated with increased mortality from total and ischemic stroke. Short sleep duration may be associated with a decreased risk of mortality from hemorrhagic stroke in men.

[Results of thrombolyses procedures in acute ischemic cerebral stroke realized in Kraków 2004-2007--Grant Ministry of Science and Information].

PubMed

Popiela, Tadeusz J; Urbanik, Andrzej; Słowik, Agnieszka

2010-01-01

To lower the number of complications of acute cerebral ischemic stroke and to reduce the time of rehabilitation in these patients it is necessary to induce treatment within the first 3 hours of the onset of the stroke. Early intervention however, is possible only in cases with the confirm localized ischemic focus visualized in one of the diagnostic imaging methods. The most widespread is CT, hovewer the first symptoms of ischemic stroke can be seen not beforel2 hours of the onset. The study evaluated the effectiveness of early diagnostics of ischemic stroke using perfusion CT (pCT) with subsequent intravenous or intra-arterial thrombolysis. The patients with ischemic stroke confirmed by pCT and qualified to thrombolysis in the first 3 hours of the onset of the stroke were randomly selected to intravenous or intra-arterial thrmobolysis. Those, who were 3 to 6 hours of the onset of the stroke were qualified to intra-arterial thrombolysis. A study group consisted of 377 patients hospitalized due to ischemic stroke. Of these pCT was performed in 76 cases, intravenous thrombolysis in 4 and intra-arterial thrombolysis in 2. Clinical condition substantially improved in 3 patients. Obtained results indicate the necessity to introduce pCT to the routine diagnostics of the acute ischemic stroke. A small number of patients eligible for thrombolysis does not allow to compare the effectiveness of intra-arterial and intravenous thrombolysis, however the project allowed to work out the efficient system of diagnostics and treatment of the acute ischemic stroke in the area of Krakow based on the standards used in the European countries.

Substitution of Linoleic Acid for Other Macronutrients and the Risk of Ischemic Stroke.

PubMed

Venø, Stine K; Schmidt, Erik B; Jakobsen, Marianne U; Lundbye-Christensen, Søren; Bach, Flemming W; Overvad, Kim

2017-12-01

Ischemic stroke is a major health problem worldwide, but the influence of dietary factors on stroke risk is not well known. This study aimed to investigate the risk of ischemic stroke and its subtypes with a higher intake from linoleic acid and a concomitant lower intake from saturated fatty acids, monounsaturated fatty acids, or glycemic carbohydrates. In the Danish prospective Diet, Cancer, and Health Study of 57 053 participants aged 50 to 64 years at baseline, information on diet was collected using a validated semiquantitative food frequency questionnaire. Information on ischemic stroke was obtained from the Danish National Patient Register, and cases were all validated and subclassified according to the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Substitution of linoleic acid for saturated fatty acid, monounsaturated fatty acid, or glycemic carbohydrates was investigated in relation to the risk of ischemic stroke and subtypes. Cox proportional hazards regression was used to estimate the associations with ischemic stroke adjusting for appropriate confounders. During 13.5 years of follow-up 1879 participants developed ischemic stroke. A slightly lower risk of ischemic stroke was found with a 5% higher intake of linoleic acid and a concomitant lower intake of saturated fatty acid (hazard ratio, 0.98; 95% confidence interval, 0.83-1.16), monounsaturated fatty acid (hazard ratio, 0.80; 95% confidence interval, 0.63-1.02), and glycemic carbohydrates (hazard ratio, 0.92; 95% confidence interval, 0.78-1.09), although not statistically significant. Similar patterns of association were found for large-artery atherosclerosis and small-vessel occlusions. This study suggests that replacing saturated fatty acid, glycemic carbohydrate, or monounsaturated fatty acid with linoleic acid may be associated with a lower risk of ischemic stroke. © 2017 American Heart Association, Inc.

Symptoms of Insomnia and Sleep Duration and Their Association with Incident Strokes: Findings from the Population-Based MONICA/KORA Augsburg Cohort Study.

PubMed

Helbig, A Katharina; Stöckl, Doris; Heier, Margit; Ladwig, Karl-Heinz; Meisinger, Christa

2015-01-01

To examine the relationship between symptoms of insomnia and sleep duration and incident total (non-fatal plus fatal) strokes, non-fatal strokes, and fatal strokes in a large cohort of men and women from the general population in Germany. In four population-based MONICA (monitoring trends and determinants in cardiovascular disease)/KORA (Cooperative Health Research in the Region of Augsburg) surveys conducted between 1984 and 2001, 17,604 men and women (aged 25 to 74 years) were asked about issues like sleep, health behavior, and medical history. In subsequent surveys and mortality follow-ups, incident stroke cases (cerebral hemorrhage, ischemic stroke, transient ischemic attack, unknown stroke type) were gathered prospectively until 2009. Sex-specific hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using sequential Cox proportional hazards regression models. During a mean follow-up of 14 years, 917 strokes (710 non-fatal strokes and 207 fatal strokes) were observed. Trouble falling asleep and difficulty staying asleep were not significantly related to any incident stroke outcome in either sex in the multivariable models. Among men, the HR for the association between short (≤5 hours) and long (≥10 hours) daily sleep duration and total strokes were 1.44 (95% CI: 1.01-2.06) and 1.63 (95% CI: 1.16-2.29), after adjustment for basic confounding variables. As for non-fatal strokes and fatal strokes, in the analyses adjusted for age, survey, education, physical activity, alcohol consumption, smoking habits, body mass index, hypertension, diabetes, and dyslipidemia, the increased risks persisted, albeit somewhat attenuated, but no longer remained significant. Among women, in the multivariable analyses the quantity of sleep was also not related to any stroke outcome. In the present study, symptoms of insomnia and exceptional sleep duration were not significantly predictive of incident total strokes, non-fatal strokes, and fatal strokes in either sex.

Symptoms of Insomnia and Sleep Duration and Their Association with Incident Strokes: Findings from the Population-Based MONICA/KORA Augsburg Cohort Study

PubMed Central

Helbig, A. Katharina; Stöckl, Doris; Heier, Margit; Ladwig, Karl-Heinz; Meisinger, Christa

2015-01-01

Objective To examine the relationship between symptoms of insomnia and sleep duration and incident total (non-fatal plus fatal) strokes, non-fatal strokes, and fatal strokes in a large cohort of men and women from the general population in Germany. Methods In four population-based MONICA (monitoring trends and determinants in cardiovascular disease)/KORA (Cooperative Health Research in the Region of Augsburg) surveys conducted between 1984 and 2001, 17,604 men and women (aged 25 to 74 years) were asked about issues like sleep, health behavior, and medical history. In subsequent surveys and mortality follow-ups, incident stroke cases (cerebral hemorrhage, ischemic stroke, transient ischemic attack, unknown stroke type) were gathered prospectively until 2009. Sex-specific hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using sequential Cox proportional hazards regression models. Results During a mean follow-up of 14 years, 917 strokes (710 non-fatal strokes and 207 fatal strokes) were observed. Trouble falling asleep and difficulty staying asleep were not significantly related to any incident stroke outcome in either sex in the multivariable models. Among men, the HR for the association between short (≤5 hours) and long (≥10 hours) daily sleep duration and total strokes were 1.44 (95% CI: 1.01–2.06) and 1.63 (95% CI: 1.16–2.29), after adjustment for basic confounding variables. As for non-fatal strokes and fatal strokes, in the analyses adjusted for age, survey, education, physical activity, alcohol consumption, smoking habits, body mass index, hypertension, diabetes, and dyslipidemia, the increased risks persisted, albeit somewhat attenuated, but no longer remained significant. Among women, in the multivariable analyses the quantity of sleep was also not related to any stroke outcome. Conclusion In the present study, symptoms of insomnia and exceptional sleep duration were not significantly predictive of incident total strokes, non-fatal strokes, and fatal strokes in either sex. PMID:26230576

Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke.

PubMed

Dawson, Jesse; Pierce, David; Dixit, Anand; Kimberley, Teresa J; Robertson, Michele; Tarver, Brent; Hilmi, Omar; McLean, John; Forbes, Kirsten; Kilgard, Michael P; Rennaker, Robert L; Cramer, Steven C; Walters, Matthew; Engineer, Navzer

2016-01-01

Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke. Twenty-one participants with ischemic stroke >6 months before and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three 2-hour sessions per week for 6 weeks, each involving >400 movement trials. In the VNS group, movements were paired with 0.5-second VNS. The primary objective was to assess safety and feasibility. Secondary end points included change in upper-limb measures (including the Fugl-Meyer Assessment-Upper Extremity). Nine participants were randomized to VNS plus rehabilitation and 11 to rehabilitation alone. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five had minor adverse device effects including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different (between-group difference, 5.7 points; 95% confidence interval, -0.4 to 11.8). In the per-protocol analysis, there was a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score (between-group difference, 6.5 points; 95% confidence interval, 0.4 to 12.6). This study suggests that VNS paired with rehabilitation is feasible and has not raised safety concerns. Additional studies of VNS in adults with chronic stroke will now be performed. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01669161. © 2015 The Authors.

Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke

PubMed Central

Pierce, David; Dixit, Anand; Kimberley, Teresa J.; Robertson, Michele; Tarver, Brent; Hilmi, Omar; McLean, John; Forbes, Kirsten; Kilgard, Michael P.; Rennaker, Robert L.; Cramer, Steven C.; Walters, Matthew; Engineer, Navzer

2016-01-01

Background and Purpose— Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke. Methods— Twenty-one participants with ischemic stroke >6 months before and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three 2-hour sessions per week for 6 weeks, each involving >400 movement trials. In the VNS group, movements were paired with 0.5-second VNS. The primary objective was to assess safety and feasibility. Secondary end points included change in upper-limb measures (including the Fugl–Meyer Assessment-Upper Extremity). Results— Nine participants were randomized to VNS plus rehabilitation and 11 to rehabilitation alone. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five had minor adverse device effects including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl–Meyer Assessment-Upper Extremity scores was not significantly different (between-group difference, 5.7 points; 95% confidence interval, −0.4 to 11.8). In the per-protocol analysis, there was a significant difference in change in Fugl–Meyer Assessment-Upper Extremity score (between-group difference, 6.5 points; 95% confidence interval, 0.4 to 12.6). Conclusions— This study suggests that VNS paired with rehabilitation is feasible and has not raised safety concerns. Additional studies of VNS in adults with chronic stroke will now be performed. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01669161. PMID:26645257

Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology).

PubMed

Reddy, Vivek Y; Möbius-Winkler, Sven; Miller, Marc A; Neuzil, Petr; Schuler, Gerhard; Wiebe, Jens; Sick, Peter; Sievert, Horst

2013-06-25

The purpose of this study was to assess the safety and efficacy of left atrial appendage (LAA) closure in nonvalvular atrial fibrillation (AF) patients ineligible for warfarin therapy. The PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that LAA closure with the Watchman device (Boston Scientific, Natick, Massachusetts) was noninferior to warfarin therapy. However, the PROTECT AF trial only included patients who were candidates for warfarin, and even patients randomly assigned to the LAA closure arm received concomitant warfarin for 6 weeks after Watchman implantation. A multicenter, prospective, nonrandomized study was conducted of LAA closure with the Watchman device in 150 patients with nonvalvular AF and CHADS₂ (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score ≥1, who were considered ineligible for warfarin. The primary efficacy endpoint was the combined events of ischemic stroke, hemorrhagic stroke, systemic embolism, and cardiovascular/unexplained death. The mean CHADS₂ score and CHA₂DS₂-VASc (CHADS₂ score plus 2 points for age ≥75 years and 1 point for vascular disease, age 65 to 74 years, or female sex) score were 2.8 ± 1.2 and 4.4 ± 1.7, respectively. History of hemorrhagic/bleeding tendencies (93%) was the most common reason for warfarin ineligibility. Mean duration of follow-up was 14.4 ± 8.6 months. Serious procedure- or device-related safety events occurred in 8.7% of patients (13 of 150 patients). All-cause stroke or systemic embolism occurred in 4 patients (2.3% per year): ischemic stroke in 3 patients (1.7% per year) and hemorrhagic stroke in 1 patient (0.6% per year). This ischemic stroke rate was less than that expected (7.3% per year) based on the CHADS₂ scores of the patient cohort. LAA closure with the Watchman device can be safely performed without a warfarin transition, and is a reasonable alternative to consider for patients at high risk for stroke but with contraindications to systemic oral anticoagulation. (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology [ASAP]; NCT00851578). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Interleukin-6 (IL-6) rs1800796 and cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) rs2383207 are associated with ischemic stroke in indigenous West African Men.

PubMed

Akinyemi, Rufus; Arnett, Donna K; Tiwari, Hemant K; Ovbiagele, Bruce; Sarfo, Fred; Srinivasasainagendra, Vinodh; Irvin, Marguerite Ryan; Adeoye, Abiodun; Perry, Rodney T; Akpalu, Albert; Jenkins, Carolyn; Owolabi, Lukman; Obiako, Reginald; Wahab, Kolawole; Sanya, Emmanuel; Komolafe, Morenikeji; Fawale, Michael; Adebayo, Philip; Osaigbovo, Godwin; Sunmonu, Taofiki; Olowoyo, Paul; Chukwuonye, Innocent; Obiabo, Yahaya; Akpa, Onoja; Melikam, Sylvia; Saulson, Raelle; Kalaria, Raj; Ogunniyi, Adesola; Owolabi, Mayowa

2017-08-15

Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub - Saharan African populations. Interleukin-6 polymorphisms have been previously associated with ischemic stroke in some non-African populations. Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6, CDKN2A- CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known cardiovascular disease risk factors were constructed to assess the associations of the 23 SNPs in rigorously phenotyped cases (N=429) of ischemic stroke (Men=198; Women=231) and stroke- free (N=483) controls (Men=236; Women=247). Interleukin-6 (IL6) rs1800796 (C minor allele; frequency: West Africans=8.6%) was significantly associated with ischemic stroke in men (OR=2.006, 95% CI=[1.065, 3.777], p=0.031) with hypertension in the model but not in women. In addition, rs2383207 in CDKN2A/CDKN2B (minor allele A with frequency: West Africans=1.7%) was also associated with ischemic stroke in men (OR=2.550, 95% CI=[1.027, 6.331], p=0.044) with primary covariates in the model, but not in women. Polymorphisms in other genes did not show significant association with ischemic stroke. Polymorphisms rs1800796 in IL6 gene and rs2383207 in CDKN2A/CDKN2B gene have significant associations with ischemic stroke in indigenous West African men. CDKN2A/CDKN2B SNP rs2383207 is independently associated with ischemic stroke in indigenous West African men. Further research should focus on the contributions of inflammatory genes and other genetic polymorphisms, as well as the influence of sex on the neurobiology of stroke in people of African ancestry. Copyright © 2017 Elsevier B.V. All rights reserved.

Transient ischemic attack: management in the emergency department and impact of an outpatient neurovascular clinic.

PubMed

Hosier, Gregory W; Phillips, Stephen J; Doucette, Steve P; Magee, Kirk D; Gubitz, Gordon J

2016-09-01

1) To evaluate whether transient ischemic attack (TIA) management in emergency departments (EDs) of the Nova Scotia Capital District Health Authority followed Canadian Best Practice Recommendations, and 2) to assess the impact of being followed up in a dedicated outpatient neurovascular clinic. Retrospective chart review of all patients discharged from EDs in our district from January 1, 2011 to December 31, 2012 with a diagnosis of TIA. Cox proportional hazards models, Kaplan-Meier survival curve, and propensity matched analyses were used to evaluate 90-day mortality and readmission. Of the 686 patients seen in the ED for TIA, 88.3% received computed tomography (CT) scanning, 86.3% received an electrocardiogram (ECG), 35% received vascular imaging within 24 hours of triage, 36% were seen in a neurovascular clinic, and 4.2% experienced stroke, myocardial infarction, or vascular death within 90 days. Rates of antithrombotic use were increased in patients seen in a neurovascular clinic compared to those who were not (94% v. 86.3%, p<0.0001). After adjustment for age, sex, vascular disease risk factors, and stroke symptoms, the risk of readmission for stroke, myocardial infarction, or vascular death was lower for those seen in a neurovascular clinic compared to those who were not (adjusted hazard ratio 0.28; 95% confidence interval 0.08-0.99, p=0.048). The majority of patients in our study were treated with antithrombotic agents in the ED and investigated with CT and ECG within 24 hours; however, vascular imaging and neurovascular clinic follow-up were underutilized. For those with neurovascular clinic follow-up, there was an association with reduced risk of subsequent stroke, myocardial infarction, or vascular death.

Community-Based Intervention to Improve Cardiometabolic Targets in Patients With Stroke: A Randomized Controlled Trial.

PubMed

Olaiya, Muideen T; Cadilhac, Dominique A; Kim, Joosup; Nelson, Mark R; Srikanth, Velandai K; Gerraty, Richard P; Bladin, Christopher F; Fitzgerald, Sharyn M; Phan, Thanh; Frayne, Judith; Thrift, Amanda G

2017-09-01

Many guidelines for secondary prevention of stroke focus on controlling cardiometabolic risk factors. We investigated the effectiveness of a management program for attaining cardiometabolic targets in survivors of stroke/transient ischemic attack. Randomized controlled trial of survivors of stroke/transient ischemic attack aged ≥18 years. General practices were randomized to usual care (control) or an intervention comprising specialist review of care plans and nurse education in addition to usual care. The outcome is attainment of pre-defined cardiometabolic targets based on Australian guidelines. Multivariable regression was undertaken to determine efficacy and identify factors associated with attaining targets. Overall, 283 subjects were randomized to the intervention and 280 to controls. Although we found no between-group difference in overall cardiometabolic targets achieved at 12 months, the intervention group more often achieved control of low-density lipoprotein cholesterol (odds ratio, 1.97; 95% confidence interval, 1.18-3.29) than controls. At 24 months, no between-group differences were observed. Medication adherence was ≥80% at follow-up, but uptake of lifestyle/behavioral habits was poor. Older age, being male, being married/living with partner, and having greater functional ability or a history of diabetes mellitus were associated with attaining targets. The intervention in this largely negative trial only had a detectable effect on attaining target for lipids but not for other factors at 12 months or any factor at 24 months. This limited effect may be attributable to inadequate uptake of behavioral/lifestyle interventions, highlighting the need for new or better approaches to achieve meaningful behavioral change. URL: http://www.clinicaltrials.gov. Unique identifier: ACTRN12608000166370. © 2017 American Heart Association, Inc.

Montreal Cognitive Assessment: One Cutoff Never Fits All.

PubMed

Wong, Adrian; Law, Lorraine S N; Liu, Wenyan; Wang, Zhaolu; Lo, Eugene S K; Lau, Alexander; Wong, Lawrence K S; Mok, Vincent C T

2015-12-01

The objective of this study is to examine the discrepancy between single versus age and education corrected cutoff scores in classifying performance on the Montreal Cognitive Assessment (MoCA) in patients with stroke or transient ischemic attack. MoCA norms were collected from 794 functionally independent and stroke- and dementia-free persons aged ≥65 years. magnetic resonance imaging was used to exclude healthy controls with significant brain pathology and medial temporal lobe atrophy. Cutoff scores at 16th, 7th, and 2nd percentiles by age and education were derived for the MoCA and MoCA 5-minute Protocol. MoCA performance in 919 patients with stroke or transient ischemic attack was classified using the single and norm-derived cutoff scores. The norms for the Hong Kong version of the MoCA total and domain scores and the total score of the MoCA 5-minute protocol are described. Only 65.1% and 25.7% healthy controls and 45.2% and 19.0% patients scored above the conventional cutoff scores of 21/22 and 25/26 on the MoCA. Using classification with norm-derived cutoff scores as reference, locally derived cutoff score of 21/22 yielded a classification discrepancy of ≤42.4%. Discrepancy increased with higher age and lower education level, with the majority being false positives by single cutoffs. With the 25/26 cutoff of the original MoCA, discrepancy further increased to ≤74.3%. Conventional single cutoff scores are associated with substantially high rates of misclassification especially in older and less-educated patients with stroke. These results caution against the use of one-size-fits-all cutoffs on the MoCA. © 2015 American Heart Association, Inc.

Neuroprotective Mechanisms of Taurine against Ischemic Stroke

PubMed Central

Menzie, Janet; Prentice, Howard; Wu, Jang-Yen

2013-01-01

Ischemic stroke exhibits a multiplicity of pathophysiological mechanisms. To address the diverse pathophysiological mechanisms observed in ischemic stroke investigators seek to find therapeutic strategies that are multifaceted in their action by either investigating multipotential compounds or by using a combination of compounds. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions. It exhibits antioxidative properties, stabilizes membrane, functions as an osmoregulator, modulates ionic movements, reduces the level of pro-inflammators, regulates intracellular calcium concentration; all of which contributes to its neuroprotective effect. Data are accumulating that show the neuroprotective mechanisms of taurine against stroke pathophysiology. In this review, we describe the neuroprotective mechanisms employed by taurine against ischemic stroke and its use in clinical trial for ischemic stroke. PMID:24961429

Effect of Aspirin in Postoperative Management of Adult Ischemic Moyamoya Disease.

PubMed

Zhao, Yahui; Zhang, Qian; Zhang, Dong; Zhao, Yuanli

2017-09-01

Aspirin has been implicated in the postoperative management of moyamoya disease (MMD) in order to avoid bypass failure and decrease the incidence of subsequent stroke. However, its effect has not been completely determined yet. In this study, we retrospectively reviewed data of 184 adult patients (197 hemispheres) presented with ischemic-onset MMD who had undergone direct or combined revascularization in our hospital, to clarify the effect of postoperative aspirin therapy in the management of moyamoya disease. Fifty-nine hemispheres that had been administered with aspirin (100 mg/day) after bypass surgery were defined as the "aspirin group," whereas 138 that hadn't been given aspirin postoperatively were defined as the "control group". Among 197 hemispheres, the mortality rate was 0. The incidence of postoperative newly developed infarction, transient ischemic attack, and hemorrhage were not significantly different between the aspirin and control groups. The patency rate of bypass graft was not significantly different between the groups, either. Notably, more patients experienced major stroke in the control group (9/138) than the aspirin group (1/59), but no statistical difference was found (P > 0.05). In the aspirin group, more patients had improved outcome than the control group (P = 0.04). Our findings showed that aspirin might not decrease the incidence of postoperative ischemic stroke or increase patency rate of bypass graft, but it does not increase the risk of hemorrhages, either. Also, postoperative aspirin therapy might improve outcome. More studies are needed to provide evidence for postoperative antiplatelet therapy in MMD management. Copyright © 2017 Elsevier Inc. All rights reserved.

Stroke: advances in medical therapy and acute stroke intervention.

PubMed

Barrett, Kevin M; Lal, Brajesh K; Meschia, James F

2015-10-01

Evidence-based therapeutic options for stroke continue to emerge based on results from well-designed clinical studies. Ischemic stroke far exceeds hemorrhagic stroke in terms of prevalence and incidence, both in the USA and worldwide. The public health effect of reducing death and disability related to ischemic stroke justifies the resources that have been invested in identifying safe and effective treatments. The emergence of novel oral anticoagulants for ischemic stroke prevention in atrial fibrillation has introduced complexity to clinical decision making for patients with this common cardiac arrhythmia. Some accepted ischemic stroke preventative strategies, such as carotid revascularization for asymptomatic carotid stenosis, require reassessment, given advances in risk factor management, antithrombotic therapy, and surgical techniques. Intra-arterial therapy, particularly with stent retrievers after intravenous tissue plasminogen activator, has recently been demonstrated to improve functional outcomes and will require investment in system-based care models to ensure that effective treatments are received by patients in a timely fashion. The purpose of this review is to describe recent advances in medical and surgical approaches to ischemic stroke prevention and acute treatment. Results from recently published clinical trials will be highlighted along with ongoing clinical trials addressing key questions in ischemic stroke management and prevention where equipoise remains.

CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke.

PubMed

Roy-O'Reilly, Meaghan; Ritzel, Rodney M; Conway, Sarah E; Staff, Ilene; Fortunato, Gilbert; McCullough, Louise D

2017-12-01

Circulating levels of the pro-inflammatory cytokine C-C motif chemokine 11 (CCL11, also known as eotaxin-1) are increased in several animal models of neuroinflammation, including traumatic brain injury and Alzheimer's disease. Increased levels of CCL11 have also been linked to decreased neurogenesis in mice. We hypothesized that circulating CCL11 levels would increase following ischemic stroke in mice and humans, and that higher CCL11 levels would correlate with poor long-term recovery in patients. As predicted, circulating levels of CCL11 in both young and aged mice increased significantly 24 h after experimental stroke. However, ischemic stroke patients showed decreased CCL11 levels compared to controls 24 h after stroke. Interestingly, lower post-stroke CCL11 levels were predictive of increased stroke severity and independently predictive of poorer functional outcomes in patients 12 months after ischemic stroke. These results illustrate important differences in the peripheral inflammatory response to ischemic stroke between mice and human patients. In addition, it suggests CCL11 as a candidate biomarker for the prediction of acute and long-term functional outcomes in ischemic stroke patients.

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

Premature Atrial Contractions on the Screening Electrocardiogram and Risk of Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

PubMed

O'Neal, Wesley T; Kamel, Hooman; Kleindorfer, Dawn; Judd, Suzanne E; Howard, George; Howard, Virginia J; Soliman, Elsayed Z

2016-01-01

It is currently unknown if premature atrial contractions (PACs) detected on the routine screening electrocardiogram are associated with an increased risk of ischemic stroke. We examined the association between PACs and ischemic stroke in 22,975 (mean age 64 ± 9.2; 56% women; 40% black) participants from the Reasons for Geographic and Racial Differences in Stroke study. Participants who were free of stroke at baseline were included. PACs were detected from centrally read electrocardiograms at baseline. Cox regression was used to examine the association between PACs and ischemic stroke events through March 31, 2014. PACs were present in 1,687 (7.3%) participants at baseline. In a Cox regression model adjusted for stroke risk factors and potential confounders, PACs were associated with an increased risk of ischemic stroke (hazards ratio (HR) 1.34, 95% CI 1.04-1.74). The relationship was limited to non-lacunar infarcts (HR 1.42, 95% CI 1.08-1.87), and not lacunar strokes (HR 1.01, 95% CI 0.51-2.03). An interaction by sex was detected, with the association between PACs and ischemic stroke being stronger among women (HR 1.82, 95% CI 1.29-2.56) than men (HR 1.03, 95% CI 0.69-1.52; p-interaction = 0.0095). PACs detected on the routine electrocardiogram are associated with an increased risk for non-lacunar ischemic strokes, especially in women. © 2016 S. Karger AG, Basel.

Temporal trends in stroke incidence in South Asian, Chinese and white patients: A population based analysis.

PubMed

Khan, Nadia A; McAlister, Finlay A; Pilote, Louise; Palepu, Anita; Quan, Hude; Hill, Michael D; Fang, Jiming; Kapral, Moira K

2017-01-01

Little is known about potential ethnic differences in stroke incidence. We compared incidence and time trends of ischemic stroke and primary intracerebral hemorrhage in South Asian, Chinese and white persons in a population-based study. Population based census and administrative data analysis in the provinces of Ontario and British Columbia, Canada using validated ICD 9/ICD 10 coding for acute ischemic and hemorrhagic stroke (1997-2010). There were 3290 South Asians, 4444 Chinese and 160944 white patients with acute ischemic stroke and 535 South Asian, 1376 Chinese and 21842 white patients with intracerebral hemorrhage. South Asians were younger than whites at onset of stroke (70 vs. 74 years for ischemic and 67 vs. 71 years for hemorrhagic stroke). Age and sex adjusted ischemic stroke incidence in 2010 was 43% lower in Chinese and 63% lower in South Asian than in White patients. Age and sex adjusted intracerebral hemorrhage incidence was 18% higher in Chinese patients, and 66% lower in South Asian relative to white patients. Stroke incidence declined in all ethnic groups (relative reduction 69% in South Asians, 25% in Chinese, and 34% in white patients for ischemic stroke and for intracerebral hemorrhage, 79% for South Asians, 51% for Chinese and 30% in white patients). Although stroke rates declined across all ethnic groups, these rates differed significantly by ethnicity. Further study is needed to understand mechanisms underlying the higher ischemic stroke incidence in white patients and intracerebral hemorrhage in Chinese patients.

Prescription frequency and predictors for the use of novel direct oral anticoagulants for secondary stroke prevention in the first year after their marketing in Europe--a multicentric evaluation.

PubMed

Luger, Sebastian; Hohmann, Carina; Kraft, Peter; Halmer, Ramona; Gunreben, Ignaz; Neumann-Haefelin, Tobias; Kleinschnitz, Christoph; Walter, Silke; Haripyan, Veronika; Steinmetz, Helmuth; Foerch, Christian; Pfeilschifter, Waltraud

2014-07-01

Direct oral anticoagulants (DOAC) are alternatives to the use of vitamin K antagonists (VKA) as oral anticoagulant therapies to prevent stroke in patients with atrial fibrillation. We assembled a representative secondary prevention cohort from four tertiary care stroke centers to identify factors that independently influence therapeutic decision making 1) not to anticoagulate with either VKA or DOAC and 2) to use DOAC if the patient appears suitable for oral anticoagulant therapy. We identified all patients discharged with the diagnoses 'ischemic stroke' (ICD-10 code I63) or 'transient ischemic attack' (G45) in combination with 'atrial fibrillation' (I48) during 1 year. We performed binary logistic regression analyses to identify factors independently influencing the aforementioned decisions. Our cohort comprised 758 patients. At discharge from the stroke service, 374 patients (49·3%) received oral anticoagulant therapy. Older age, severe stroke, poor recovery in the acute phase, and higher serum creatinine were independent factors to withhold oral anticoagulant therapy, whereas prior oral anticoagulant therapy favored the decision to anticoagulate. Among patients who were anticoagulated, prescription was balanced for VKA (50·3%) and DOAC (49·7%). Renal function and prior oral anticoagulant therapies were the most important factors in this decision. Shortly after their marketing, DOAC are used as frequently as VKA for secondary stroke prevention in patients with atrial fibrillation. The decision between VKA and DOAC is mainly determined by the patient's renal function and the absence or presence of prior oral anticoagulant therapy. © 2014 World Stroke Organization.

Large Artery Atherosclerotic Occlusive Disease.

PubMed

Cole, John W

2017-02-01

Extracranial or intracranial large artery atherosclerosis is often identified as a potential etiologic cause for ischemic stroke and transient ischemic attack. Given the high prevalence of large artery atherosclerosis in the general population, determining whether an identified atherosclerotic lesion is truly the cause of a patient's symptomatology can be difficult. In all cases, optimally treating each patient to minimize future stroke risk is paramount. Extracranial or intracranial large artery atherosclerosis can be broadly compartmentalized into four distinct clinical scenarios based upon the individual patient's history, examination, and anatomic imaging findings: asymptomatic and symptomatic extracranial carotid stenosis, intracranial atherosclerosis, and extracranial vertebral artery atherosclerotic disease. This review provides a framework for clinicians evaluating and treating such patients. Intensive medical therapy achieves low rates of stroke and death in asymptomatic carotid stenosis. Evidence indicates that patients with severe symptomatic carotid stenosis should undergo carotid revascularization sooner rather than later and that the risk of stroke or death is lower using carotid endarterectomy than with carotid stenting. Specific to stenting, the risk of stroke or death is greatest among older patients and women. Continuous vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy is the mainstay for stroke prevention in the setting of intracranial and vertebral artery origin atherosclerosis. Lifelong vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy are the key elements to reduce future stroke risk in the setting of large artery atherosclerosis. When considering a revascularization procedure for carotid stenosis, patient demographics, comorbidities, and the periprocedural risks of stroke and death should be carefully considered.

Large Artery Atherosclerotic Occlusive Disease

PubMed Central

Cole, John W.

2017-01-01

ABSTRACT Purpose of Review: Extracranial or intracranial large artery atherosclerosis is often identified as a potential etiologic cause for ischemic stroke and transient ischemic attack. Given the high prevalence of large artery atherosclerosis in the general population, determining whether an identified atherosclerotic lesion is truly the cause of a patient’s symptomatology can be difficult. In all cases, optimally treating each patient to minimize future stroke risk is paramount. Extracranial or intracranial large artery atherosclerosis can be broadly compartmentalized into four distinct clinical scenarios based upon the individual patient’s history, examination, and anatomic imaging findings: asymptomatic and symptomatic extracranial carotid stenosis, intracranial atherosclerosis, and extracranial vertebral artery atherosclerotic disease. This review provides a framework for clinicians evaluating and treating such patients. Recent Findings: Intensive medical therapy achieves low rates of stroke and death in asymptomatic carotid stenosis. Evidence indicates that patients with severe symptomatic carotid stenosis should undergo carotid revascularization sooner rather than later and that the risk of stroke or death is lower using carotid endarterectomy than with carotid stenting. Specific to stenting, the risk of stroke or death is greatest among older patients and women. Continuous vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy is the mainstay for stroke prevention in the setting of intracranial and vertebral artery origin atherosclerosis. Summary: Lifelong vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy are the key elements to reduce future stroke risk in the setting of large artery atherosclerosis. When considering a revascularization procedure for carotid stenosis, patient demographics, comorbidities, and the periprocedural risks of stroke and death should be carefully considered. PMID:28157748

PPARG gene C161T CT/TT associated with lower blood lipid levels and ischemic stroke from large-artery atherosclerosis in a Han population in Guangdong.

PubMed

Wei, Wei-Min; Wu, Xiao-Yan; Li, Shu-Ting; Shen, QingYu

2016-07-01

Peroxisome proliferator-activated receptor gamma (PPARG) is a transcription factor involved in atherosclerosis and related diseases. In this study, we aimed to investigate whether PPARG C161T was associated with lipid levels and large-artery atherosclerosis (LAA) ischemic stroke in a Han Chinese population in Guangdong province. The genotype PPARG C161T in 149 LAA ischemic stroke patients and 125 healthy controls was examined by polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. Associations with LAA ischemic stroke were analyzed for PPARG C161T genotype, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and a logistic regression analysis was performed to identify risk factors for LAA ischemic stroke. The frequency of CC was higher than that of CT + TT and was significantly associated with LAA ischemic stroke. In both the LAA and control groups, TC and LDL-C levels were significantly higher in the CC type than the CT + TT, but TG and HDL-C levels were comparable. The only verified independent risk factors for LAA ischemic stroke were ischemic heart disease (OR: 2.784, 95% CI: 1.377-5.632; p = 0.004) and systolic blood pressure (OR: 1.014, 95% CI: 1.001-1.026; p = 0.029); the PPARG C161T allele was not independently associated with an increased risk of LAA ischemic stroke (OR = 0.697, 95% CI: 0.372-1.305; p = 0.260). In this Han population, PPARG C161T CT/TT was associated with LAA ischemic stroke and lower levels of blood TC and LDL-C, but was not an independent risk factor for LAA ischemic stroke.

Left ventricular hypertrophy: a comparison among Kurdish patients with first-ever ischemic versus first-ever hemorrhagic stroke.

PubMed

Amin, Osama Shukir Muhammed

2013-01-01

Left ventricular hypertrophy (LVH) has been proposed to be associated with an increased risk of stroke. We compared the prevalence of LVH among patients with first-ever ischemic versus first-ever hemorrhagic strokes. This observational study, which was conducted at the Sulaimaniya general teaching hospital from November 2009 to March 2012, involved 100 consecutive patients with their first-ever stroke. Fifty patients had ischemic stroke while the rest (n = 50) developed hemorrhagic stroke. The presence of LVH was detected using transthoracic echocardiography and a comparison with respect to its prevalence between the 2 aforementioned groups was made. The mean age of patients in the hemorrhagic group was 61.7 +/- SD 11.2 years while in the ischemic group it was 63.9 +/- SD 6.1 years. Out of 100 patients, 66 (66%) patients were males (31 in the hemorrhagic group and 35 in the ischemic group) while the rest (n = 34; 34%) were females (19 in the hemorrhagic group and 15 in the ischemic one). Ninety one (91%) patients were hypertensive (47 in the hemorrhagic group and 34 in the ischemic group). Fifty three (53%) out of 100 patients demonstrated LVH (31 in the hemorrhagic group and 22 in the ischemic group). A head-to-head comparison between the two groups with respect to gender demonstrated no statistically significant difference in terms of the presence of LVH among patients with hemorrhagic versus ischemic strokes; males (P value < 0.26; 95% CI 3.4-39.3); females (P value < 0.43; 95% CI 16.7-43.8). However, a univariate analysis after correction for age and gender revealed a statistically significant difference between these groups (P-value < 0.001; 95% CI 2.7-46.2). LVH was more common in Kurdish patients with first-ever hemorrhagic stroke than in those who had sustained their first-ever ischemic stroke. Further analytic studies are required to clarify the prevalence of LVH in patients with ischemic stroke.

Long-term projections of temperature-related mortality risks for ischemic stroke, hemorrhagic stroke, and acute ischemic heart disease under changing climate in Beijing, China.

PubMed

Li, Tiantian; Horton, Radley M; Bader, Daniel A; Liu, Fangchao; Sun, Qinghua; Kinney, Patrick L

2018-03-01

Changing climates have been causing variations in the number of global ischemic heart disease and stroke incidences, and will continue to affect disease occurrence in the future. To project temperature-related mortality for acute ischemic heart disease, and ischemic and hemorrhagic stroke with concomitant climate warming. We estimated the exposure-response relationship between daily cause-specific mortality and daily mean temperature in Beijing. We utilized outputs from 31 downscaled climate models and two representative concentration pathways (RCPs) for the 2020s, 2050s, and 2080s. This strategy was used to estimate future net temperature along with heat- and cold-related deaths. The results for predicted temperature-related deaths were subsequently contrasted with the baseline period. In the 2080s, using the RCP8.5 and no population variation scenarios, the net total number of annual temperature-related deaths exhibited a median value of 637 (with a range across models of 434-874) for ischemic stroke; this is an increase of approximately 100% compared with the 1980s. The median number of projected annual temperature-related deaths was 660 (with a range across models of 580-745) for hemorrhagic stroke (virtually no change compared with the 1980s), and 1683 (with a range across models of 1351-2002) for acute ischemic heart disease (a slight increase of approximately 20% compared with the 1980s). In the 2080s, the monthly death projection for hemorrhagic stroke and acute ischemic heart disease showed that the largest absolute changes occurred in summer and winter while the largest absolute changes for ischemic stroke occurred in summer. We projected that the temperature-related mortality associated with ischemic stroke will increase dramatically due to climate warming. However, projected temperature-related mortality pertaining to acute ischemic heart disease and hemorrhagic stroke should remain relatively stable over time. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association of Phosphodiesterase 4D with ischemic stroke: a population-based case-control study.

PubMed

Woo, Daniel; Kaushal, Ritesh; Kissela, Brett; Sekar, Padmini; Wolujewicz, Michael; Pal, Prodipto; Alwell, Kathleen; Haverbusch, Mary; Ewing, Irene; Miller, Rosie; Kleindorfer, Dawn; Flaherty, Matthew; Chakraborty, Ranajit; Deka, Ranjan; Broderick, Joseph

2006-02-01

The Phosphodiesterase 4D (PDE4D) gene was reported recently to be associated with ischemic stroke in an Icelandic population. The association was found predominately with large vessel and cardioembolic stroke. However, 2 recent reports were unable to confirm this association, although a trend toward association with cardioembolic stroke was reported. None of the reports included significant proportions of blacks. We tested for genotype and haplotype association of polymorphisms of the PDE4D gene with ischemic stroke in a population-based, biracial, case-control study. A total of 357 cases of ischemic stroke and 482 stroke-free controls from the same community were examined. Single nucleotide polymorphisms (SNPs) were chosen based on significant associations reported previously. Linkage disequilibrium (LD), SNP, and haplotype association analysis was performed using PHASE 2.0 and Haploview 3.2. Although several univariate associations were identified, only 1 SNP (rs2910829) was found to be significantly associated with cardioembolic stroke among both whites and blacks. The rs152312 SNP was associated with cardioembolic stroke among whites after multiple comparison corrections. The same SNP was not associated with cardioembolic stroke among blacks. However, significant haplotype association was identified for both whites and blacks for all ischemic stroke, cardioembolic stroke, and stroke of unknown origin. Haplotype association was identified for small vessel stroke among whites. PDE4D is a risk factor for ischemic stroke and, in particular, for cardioembolic stroke, among whites and blacks. Further study of this gene is warranted.

Atherosclerosis and Stroke

MedlinePlus

... Stroke and atherosclerosis There are two types of ischemic stroke caused by blood clots, narrowing of blood vessels ... 2 What Is an Arteriovenous Malformation (AVM)? 3 Ischemic Strokes (Clots) 4 Hemorrhagic Strokes (Bleeds) 5 What You ...

Preventing stroke

MedlinePlus

... chap 65. Goldstein LB. Prevention and management of ischemic stroke. In: Mann DL, Zipes DP, Libby P, Bonow ... Editorial team. Related MedlinePlus Health Topics Hemorrhagic Stroke Ischemic Stroke Stroke Browse the Encyclopedia A.D.A.M., ...

Closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and a history of cryptogenic stroke or transient ischemic attack.

PubMed

Li, Jie; Liu, Junfeng; Liu, Ming; Zhang, Shihong; Hao, Zilong; Zhang, Jing; Zhang, Canfei

2015-09-08

The optimal therapy for preventing recurrent stroke in people with cryptogenic stroke and patent foramen ovale (PFO) has not been defined. The choice between medical therapy (antithrombotic treatment with antiplatelet agents or anticoagulants) and transcatheter device closure has been the subject of intense debate over the past several years. Despite the lack of scientific evidence, a substantial number of people undergo transcatheter device closure (TDC) for secondary stroke prevention. To: 1) compare the safety and efficacy of TDC with best medical therapy alone for preventing recurrent stroke (fatal or non-fatal) or transient ischemic attacks (TIAs) in people with PFO and a history of cryptogenic stroke or TIA; 2) identify specific subgroups of people most likely to benefit from closure for secondary prevention; and 3) assess the cost-effectiveness of this strategy, if possible. We searched the Cochrane Stroke Group Trials Register (July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2014), MEDLINE (1950 to July 2014) and EMBASE (1980 to July 2014). In an effort to identify unpublished and ongoing trials we searched seven trials registers and checked reference lists. We included randomized controlled trials (RCTs), irrespective of blinding, publication status, and language, comparing the safety and efficacy of device closure with medical therapy for preventing recurrent stroke or TIA in people with PFO and a history of cryptogenic stroke or TIA. Two review authors independently selected trials for inclusion, assessed quality and risk of bias, and extracted data. The primary outcome measures of this analysis were the composite endpoint of ischemic stroke or TIA events as well as recurrent fatal or non-fatal ischemic stroke. Secondary endpoints included all-cause mortality, serious adverse events (atrial fibrillation, myocardial infarction, bleeding) and procedural success and effective closure. We used the Mantel-Haenszel method to obtain pooled risk ratios (RRs) using the random-effects model regardless of the level of heterogeneity. We pooled data for the primary outcome measure with the generic inverse variance method using the random-effects model, yielding risk estimates as pooled hazard ratio (HR), which accounts for time-to-event outcomes. We included three RCTs involving a total of 2303 participants: 1150 participants were randomized to receive TDC and 1153 participants were randomized to receive medical therapy. Overall, the risk of bias was regarded as high. The mean follow-up period of all three included trials was less than five years. Baseline characteristics (age, sex, and vascular risk factors) were similar across trials. Intention-to-treat analyses did not show a statistically significant risk reduction in the composite endpoint of recurrent stroke or TIA in the TDC group when compared with medical therapy (RR 0.73, 95% CI 0.45 to 1.17). A time-to-event analysis combining the results of two RCTs also failed to show a significant risk reduction with TDC (HR 0.69, 95% CI 0.43 to 1.13). When assessing stroke prevention alone, TDC still did not show a statistically significant benefit (RR 0.61, 95% CI 0.29 to 1.27) (HR 0.55, 95% CI 0.26 to 1.18). In a sensitivity analysis including the two studies using the Amplatzer PFO occluder, TDC showed a possible protective effect on recurrent stroke compared with medical therapy (HR 0.38, 95% CI 0.14 to 1.02); however, it did not reach statistical significance. Safety analysis found that the overall risks for all-cause mortality and adverse events were similar in both the TDC and medical therapy groups. However, TDC increased the risk of new-onset atrial fibrillation (RR 3.50, 95% CI 1.47 to 8.35) and may be associated with the type of device used. The combined data from recent RCTs have shown no statistically significant differences between TDC and medical therapy in the prevention of recurrent ischemic stroke. TDC closure was associated with an increased risk of atrial fibrillation but not with serious adverse events.

Polygenic Risk for Depression Increases Risk of Ischemic Stroke: From the Stroke Genetics Network Study.

PubMed

Wassertheil-Smoller, Sylvia; Qi, Qibin; Dave, Tushar; Mitchell, Braxton D; Jackson, Rebecca D; Liu, Simin; Park, Ki; Salinas, Joel; Dunn, Erin C; Leira, Enrique C; Xu, Huichun; Ryan, Kathleen; Smoller, Jordan W

2018-03-01

Although depression is a risk factor for stroke in large prospective studies, it is unknown whether these conditions have a shared genetic basis. We applied a polygenic risk score (PRS) for major depressive disorder derived from European ancestry analyses by the Psychiatric Genomics Consortium to a genome-wide association study of ischemic stroke in the Stroke Genetics Network of National Institute of Neurological Disorders and Stroke. Included in separate analyses were 12 577 stroke cases and 25 643 controls of European ancestry and 1353 cases and 2383 controls of African ancestry. We examined the association between depression PRS and ischemic stroke overall and with pathogenic subtypes using logistic regression analyses. The depression PRS was associated with higher risk of ischemic stroke overall in both European ( P =0.025) and African ancestry ( P =0.011) samples from the Stroke Genetics Network. Ischemic stroke risk increased by 3.0% (odds ratio, 1.03; 95% confidence interval, 1.00-1.05) for every 1 SD increase in PRS for those of European ancestry and by 8% (odds ratio, 1.08; 95% confidence interval, 1.04-1.13) for those of African ancestry. Among stroke subtypes, elevated risk of small artery occlusion was observed in both European and African ancestry samples. Depression PRS was also associated with higher risk of cardioembolic stroke in European ancestry and large artery atherosclerosis in African ancestry persons. Higher polygenic risk for major depressive disorder is associated with increased risk of ischemic stroke overall and with small artery occlusion. Additional associations with ischemic stroke subtypes differed by ancestry. © 2018 American Heart Association, Inc.

Stroke Genetics Network (SiGN) Study: Design and rationale for a genome-wide association study of ischemic stroke subtypes

PubMed Central

Meschia, James F.; Arnett, Donna K.; Ay, Hakan; Brown, Robert D.; Benavente, Oscar; Cole, John W.; de Bakker, Paul I.W.; Dichgans, Martin; Doheny, Kimberly F.; Fornage, Myriam; Grewal, Raji; Gwinn, Katrina; Jern, Christina; Conde, Jordi Jimenez; Johnson, Julie A.; Jood, Katarina; Laurie, Cathy C.; Lee, Jin-Moo; Lindgren, Arne; Markus, Hugh S.; McArdle, Patrick F.; McClure, Leslie A.; Mitchell, Braxton D.; Schmidt, Reinhold; Rexrode, Kathryn M.; Rich, Stephen S.; Rosand, Jonathan; Rothwell, Peter M.; Rundek, Tatjana; Sacco, Ralph L.; Sharma, Pankaj; Shuldiner, Alan R.; Slowik, Agnieszka; Wassertheil-Smoller, Sylvia; Sudlow, Cathie; Thijs, Vincent; Woo, Daniel; Worrall, Bradford B.; Wu, Ona; Kittner, Steven J.

2014-01-01

Background and Purpose Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The NINDS Stroke Genetics Network (SiGN) contributes substantially to meta-analyses that focus on specific subtypes of stroke. Methods The NINDS Stroke Genetics Network (SiGN) includes ischemic stroke cases from 24 Genetic Research Centers (GRCs), 13 from the US and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the web-based Causative Classification of Stroke (CCS) system, with data entered by trained and certified adjudicators at participating GRCs. Through the Center for Inherited Diseases Research (CIDR), SiGN plans to genotype 10,296 carefully phenotyped stroke cases using genome-wide SNP arrays, and add to these another 4,253 previously genotyped cases for a total of 14,549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. CIDR-generated genotypes and corresponding phenotypic data will be shared with the scientific community through dbGaP, and brain MRI studies will be centrally archived. Conclusions The SiGN consortium, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke. PMID:24021684

Causes and Treatment of Acute Ischemic Stroke During Pregnancy.

PubMed

Terón, Ina; Eng, Melissa S; Katz, Jeffrey M

2018-05-21

Treatment recommendations for pregnancy associated ischemic stroke are scarce. This may be due to the fact that, in general, obstetricians tend not to make recommendations for stroke patients and neurologists are not commonly involved in the care of pregnant women. Herein, we review the multiple etiologies of ischemic stroke during pregnancy, considerations for diagnostic testing, and acute treatment and prevention options, including associated risks specific to the pregnant and puerperal state. Intravenous tissue plasminogen activator (tPA) and endovascular thrombectomy have been used successfully to treat pregnant women with acute ischemic stroke. Recent national guidelines recommend considering tPA use during pregnancy for moderate and severe strokes if the potential benefits offset the risks of uterine hemorrhage. Pregnancy-associated ischemic stroke is rare, but can be devastating, and recanalization therapy should not be systematically withheld. Women who are at risk for stroke should be followed carefully, and providers caring for pregnant women should be educated regarding stroke signs and symptoms. Many of the standard post stroke diagnostic modalities may be used safely in pregnancy, and primary and secondary stroke prevention therapy must be tailored to avoid fetal toxicity.

Ischemic Volume and Neurological Deficit: Correlation of Computed Tomography Perfusion with the National Institutes of Health Stroke Scale Score in Acute Ischemic Stroke.

PubMed

Furlanis, Giovanni; Ajčević, Miloš; Stragapede, Lara; Lugnan, Carlo; Ridolfi, Mariana; Caruso, Paola; Naccarato, Marcello; Ukmar, Maja; Manganotti, Paolo

2018-04-30

The National Institutes of Health Stroke Scale (NIHSS) is the most adopted stroke patients' evaluation tool in emergency settings to assess the severity of stroke and to determine the patients' eligibility for specific treatments. Computed tomography perfusion (CTP) is crucial to identify salvageable tissue that can benefit from the reperfusion treatment. The aim of this study is to identify the relation between the NIHSS scores and the hypoperfused volumes evaluated by CTP in patients with hyperacute ischemic stroke. This retrospective study was conducted on 105 patients with ischemic stroke who underwent NIHSS assessment and CTP in the hyperacute phase. Hypoperfused volume was evaluated by CTP maps processed with semi-automatic algorithm. An analysis was conducted to determine the degree of correlation between the NIHSS scores and the ischemic lesion volumes and to investigate the relation between the anterior and the posterior circulation strokes, as well as between the right and the left hemispheric strokes. A significant correlation was found between ischemic volume and NIHSS score at baseline (r = .82; P < .0001) in the entire cohort. A high NIHSS-volume correlation was identified in the anterior circulation stroke (r = .76; P < .0001); whereas, it was nonsignificant in the posterior circulation stroke. NIHSS score and volume correlated for the left and the right hemispheric strokes (r = .83 and .81; P < .0001), showing a slightly higher slope in the left. This study showed a strong correlation between the baseline NIHSS score and the ischemic volume estimated by CTP. We confirmed that NIHSS is a reliable predictor of perfusion deficits in acute ischemic stroke. CTP allows fast imaging assessment in the hyperacute phase. The results highlight the importance of these diagnostic tools in the assessment of stroke severity and in acute decision-making. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Association of kidney disease measures with ischemic versus hemorrhagic strokes: Pooled analyses of 4 prospective community-based cohorts

PubMed Central

Mahmoodi, Bakhtawar K.; Yatsuya, Hiroshi; Matsushita, Kunihiro; Sang, Yinying; Gottesman, Rebecca F.; Astor, Brad C.; Woodward, Mark; Longstreth, WT; Psaty, Bruce M.; Shlipak, Michael G.; Folsom, Aaron R.; Gansevoort, Ron T.; Coresh, Josef

2015-01-01

Background and purpose Although low glomerular filtration rate (GFR) and albuminuria are associated with increased risk of stroke, few studies compared their contribution to risk of ischemic versus hemorrhagic stroke separately. We contrasted the association of these kidney measures with ischemic versus hemorrhagic stroke. Methods We pooled individual participant data from four community-based cohorts: three from the United States and one from The Netherlands. GFR was estimated by using both creatinine and cystatin C, and albuminuria was quantified by urinary albumin-to-creatinine ratio (ACR). Associations of eGFR and ACR were compared for each stroke type (ischemic vs. intraparenchymal hemorrhagic) using study-stratified Cox-regression. Results Amongst 29,595 participants (mean age 61 [SD 12.5] years, 46% males, 17% black), 1,261 developed stroke (12% hemorrhagic) during 280,549 person-years. Low eGFR was significantly associated with increased risk of ischemic, but not hemorrhagic, stroke risk, while high ACR was associated with both stroke types. Adjusted HRs for ischemic and hemorrhagic stroke at eGFR of 45 (vs. 95) ml/min/1.73m2 were 1.30 (95% CI, 1.01–1.68) and 0.92 (0.47–1.81), respectively. In contrast, the corresponding HR for ACR 300 (vs. 5) mg/g were 1.62 (1.27–2.07) for ischemic and 2.57 (1.37–4.83) for hemorrhagic stroke, with significantly stronger association with hemorrhagic stroke (P =0.04). For hemorrhagic stroke, the association of elevated ACR was of similar magnitude as that of elevated systolic blood pressure. Conclusions Whereas albuminuria showed significant association with both stroke types, the association of decreased eGFR was only significant for ischemic stroke. The strong association of albuminuria with both stroke types warrants clinical attention and further investigations. PMID:24876078

The Siblings With Ischemic Stroke Study (SWISS) Protocol

PubMed Central

Meschia, James F; Brown, Robert D; Brott, Thomas G; Chukwudelunzu, Felix E; Hardy, John; Rich, Stephen S

2002-01-01

Background Family history and twins studies suggest an inherited component to ischemic stroke risk. Candidate gene association studies have been performed but have limited capacity to identify novel risk factor genes. The Siblings With Ischemic Stroke Study (SWISS) aims to conduct a genome-wide scan in sibling pairs concordant or discordant for ischemic stroke to identify novel genetic risk factors through linkage analysis. Methods Screening at multiple clinical centers identifies patients (probands) with radiographically confirmed ischemic stroke and a family history of at least 1 living full sibling with stroke. After giving informed consent, without violating privacy among other family members, the proband invites siblings concordant and discordant for stroke to participate. Siblings then contact the study coordinating center. The diagnosis of ischemic stroke in potentially concordant siblings is confirmed by systematic centralized review of medical records. The stroke-free status of potentially discordant siblings is confirmed by validated structured telephone interview. Blood samples for DNA analysis are taken from concordant sibling pairs and, if applicable, from 1 discordant sibling. Epstein-Barr virus-transformed lymphoblastoid cell lines are created, and a scan of the human genome is planned. Discussion Conducting adequately powered genomics studies of stroke in humans is challenging because of the heterogeneity of the stroke phenotype and the difficulty of obtaining DNA samples from clinically well-characterized members of a cohort of stroke pedigrees. The multicentered design of this study is intended to efficiently assemble a cohort of ischemic stroke pedigrees without invoking community consent or using cold-calling of pedigree members. PMID:11882254

A free radical scavenger edaravone suppresses systemic inflammatory responses in a rat transient focal ischemia model

PubMed Central

Fujiwara, Norio; Som, Angel T.; Pham, Loc-Duyen D.; Lee, Brian J.; Mandeville, Emiri T.; Lo, Eng H.; Arai, Ken

2017-01-01

A free radical scavenger edaravone is clinically used in Japan for acute stroke, and several basic researches have carefully examined the mechanisms of edaravone's protective effects. However, its actions on pro-inflammatory responses under stroke are still understudied. In this study, we subjected adult male Sprague-Dawley rats to 90-min middle cerebral artery (MCA) occlusion followed by reperfusion. Edaravone was treated twice via tail vein; after MCA occlusion and after reperfusion. As expected, edaravone-treated group showed less infarct volume and edema formation compared with control group at 24-hour after ischemic onset. Furthermore, edaravone reduced the levels of plasma interleukin (IL)-1β and matrix metalloproteinase-9 at 3-hour after ischemic onset. Several molecules besides IL-1β and MMP-9 are involved in inflammatory responses under stroke conditions. Therefore, we also examined whether edaravone treatment could decrease a wide range of pro-inflammatory cytokines/chemokines by testing rat plasma samples with a rat cytokine array. MCAO rats showed elevations in plasma levels of CINC-1, Fractalkine, IL-1α, IL-1ra, IL-6, IL-10, IP-10, MIG, MIP-1α, and MIP-3α, and all these increases were reduced by edaravone treatment. These data suggest that free radical scavengers may reduce systemic inflammatory responses under acute stroke conditions, and therefore, oxidative stress can be still a viable target for acute stroke therapy. PMID:27589890

Non-high-density lipoprotein cholesterol vs low-density lipoprotein cholesterol as a risk factor for ischemic stroke: a result from the Kailuan study.

PubMed

Wu, Jianwei; Chen, Shengyun; Liu, Liping; Gao, Xiang; Zhou, Yong; Wang, Chunxue; Zhang, Qian; Wang, Anxin; Hussain, Mohammed; Sun, Baoying; Wu, Shouling; Zhao, Xingquan

2013-06-01

To compare the predictive value of serum low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol levels for ischemic stroke in the Chinese population. We performed a four-year cohort study of 95 778 men and women, aged 18-98 years, selected from the Kailuan study (2006-2007). Baseline LDL cholesterol levels were estimated using direct test method. Total cholesterol levels were estimated using endpoint test method. The predictive values of LDL cholesterol and non-HDL cholesterol for ischemic stroke were compared. During the follow-up period, there were 1153 incident cases of ischemic stroke. The hazard ratio (HR) for ischemic stroke in the top quintile of LDL cholesterol was the highest among five quintiles (HR: 1·25; 95% confidence interval (CI), 1·01-1·53). The HR in the top quintile of non-HDL cholesterol for ischemic stroke was also the highest among five quintiles (HR: 1·53; 95% CI, 1·24-1·88). Analysis of trends showed a significant positive relationship between ischemic stroke incidence and serum LDL cholesterol level, and non-HDL cholesterol level, respectively (both P < 0·05). The area under the curve of LDL cholesterol and non-HDL cholesterol for ischemic stroke was 0·51 and 0·56, respectively (P < 0·05 for the difference). Serum Non-HDL cholesterol level is a stronger predictor for the risk of ischemic stroke than serum LDL cholesterol level in the Chinese population.

Ethnic Differences in Ambient Air Pollution and Risk of Acute Ischemic Stroke

PubMed Central

Wing, Jeffrey J.; Adar, Sara D.; Sánchez, Brisa N.; Morgenstern, Lewis B.; Smith, Melinda A.; Lisabeth, Lynda D.

2015-01-01

Objectives To investigate the association between short-term changes in ambient pollution (particulate matter < 2.5μm in aerodynamic diameter (PM2.5) and ozone (O3)) and the risk of ischemic stroke among individuals living in a bi-ethnic community and whether this association is modified by ethnicity. Methods We identified incident ischemic stroke cases from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project between 2000 and 2012. Associations between PM2.5 (mean 24-hour) and O3 (maximal 8-hour) levels, measured on the same-day and lags of 1-3 days, and odds of ischemic stroke were assessed using a time-stratified case-crossover design and modeled using conditional logistic regression. We explored race/ethnicity (Mexican American versus non-Hispanic white) as a modifier by including interaction terms in the models. Results There were 2,948 ischemic strokes with median age 71 years (IQR: 59-80). We observed no overall associations between the air pollutants and odds of ischemic stroke at any lag. When stratified by ethnicity, higher O3 was consistently associated with greater odds of ischemic stroke for non-Hispanic whites, but not for Mexican Americans. Higher PM2.5 was generally associated with lower odds of ischemic stroke for non-Hispanic whites but modestly greater odds for Mexican Americans. Conclusion Ethnic differences in the associations between ischemic stroke and short-term exposures to O3 and PM2.5 were suggested indicating that further study in diverse populations may be warranted. PMID:26451880

The "Know Stroke" Campaign

MedlinePlus

... brain. There are two forms of stroke: an ischemic stroke occurs when a blood vessel supplying the brain ... Why is there a need to act fast? —Ischemic strokes, the most common type of stroke, can be ...

Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial: rationale and design

PubMed Central

Johnston, S. Claiborne; Easton, J. Donald; Farrant, Mary; Barsan, William; Battenhouse, Holly; Conwit, Robin; Dillon, Catherine; Elm, Jordan; Lindblad, Anne; Morgenstern, Lewis; Poisson, Sharon N.; Palesch, Yuko

2015-01-01

Background Ischemic stroke and other vascular outcomes occur in 10–20% of patients in the 3 months following a TIA or minor ischemic stroke, and many are disabling. The highest risk period for these outcomes is the early hours and days immediately following the ischemic event. Aspirin is the most common antithrombotic treatment used for these patients. Aim The aim of POINT is to determine whether clopidogrel plus aspirin taken <12 hours after TIA or minor ischemic stroke symptom onset is more effective in preventing major ischemic vascular events at 90 days in the high-risk, and acceptably safe, compared to aspirin alone. Design POINT is a prospective, randomized, double-blind, multicenter trial in patients with TIA or minor ischemic stroke. Subjects are randomized to clopidogrel (600 mg loading dose followed by 75 mg/day) or matching placebo, and all will receive open-label aspirin 50–325 mg/day, with a dose of 162 mg daily for 5 days followed by 81 mg daily strongly recommended. Study Outcomes The primary efficacy outcome is the composite of new ischemic vascular events: ischemic stroke, myocardial infarction or ischemic vascular death, by 90 days. The primary safety outcome is major hemorrhage, which includes symptomatic intracranial hemorrhage. Discussion Aspirin is the most common antithrombotic given to patients with a stroke or TIA as it reduces the risk subsequent of stroke. This trial expects to determine whether more aggressive antithrombotic therapy with clopidogrel plus aspirin, initiated acutely, is more effective than aspirin alone. PMID:23879752

White Matter Hyperintensities Improve Ischemic Stroke Recurrence Prediction.

PubMed

Andersen, Søren Due; Larsen, Torben Bjerregaard; Gorst-Rasmussen, Anders; Yavarian, Yousef; Lip, Gregory Y H; Bach, Flemming W

2017-01-01

Nearly one in 5 patients with ischemic stroke will invariably experience a second stroke within 5 years. Stroke risk stratification schemes based solely on clinical variables perform only modestly in non-atrial fibrillation (AF) patients and improvement of these schemes will enhance their clinical utility. Cerebral white matter hyperintensities are associated with an increased risk of incident ischemic stroke in the general population, whereas their association with the risk of ischemic stroke recurrence is more ambiguous. In a non-AF stroke cohort, we investigated the association between cerebral white matter hyperintensities and the risk of recurrent ischemic stroke, and we evaluated the predictive performance of the CHA2DS2VASc score and the Essen Stroke Risk Score (clinical scores) when augmented with information on white matter hyperintensities. In a registry-based, observational cohort study, we included 832 patients (mean age 59.6 (SD 13.9); 42.0% females) with incident ischemic stroke and no AF. We assessed the severity of white matter hyperintensities using MRI. Hazard ratios stratified by the white matter hyperintensities score and adjusted for the components of the CHA2DS2VASc score were calculated based on the Cox proportional hazards analysis. Recalibrated clinical scores were calculated by adding one point to the score for the presence of moderate to severe white matter hyperintensities. The discriminatory performance of the scores was assessed with the C-statistic. White matter hyperintensities were significantly associated with the risk of recurrent ischemic stroke after adjusting for clinical risk factors. The hazard ratios ranged from 1.65 (95% CI 0.70-3.86) for mild changes to 5.28 (95% CI 1.98-14.07) for the most severe changes. C-statistics for the prediction of recurrent ischemic stroke were 0.59 (95% CI 0.51-0.65) for the CHA2DS2VASc score and 0.60 (95% CI 0.53-0.68) for the Essen Stroke Risk Score. The recalibrated clinical scores showed improved C-statistics: the recalibrated CHA2DS2VASc score 0.62 (95% CI 0.54-0.70; p = 0.024) and the recalibrated Essen Stroke Risk Score 0.63 (95% CI 0.56-0.71; p = 0.031). C-statistics of the white matter hyperintensities score were 0.62 (95% CI 0.52-0.68) to 0.65 (95% CI 0.58-0.73). An increasing burden of white matter hyperintensities was independently associated with recurrent ischemic stroke in a cohort of non-AF ischemic stroke patients. Recalibration of the CHA2DS2VASc score and the Essen Stroke Risk Score with one point for the presence of moderate to severe white matter hyperintensities led to improved discriminatory performance in ischemic stroke recurrence prediction. Risk scores based on white matter hyperintensities alone were at least as accurate as the established clinical risk scores in the prediction of ischemic stroke recurrence. © 2016 S. Karger AG, Basel.

Distal protection filter device efficacy with carotid artery stenting: comparison between a distal protection filter and a distal protection balloon.

PubMed

Iko, Minoru; Tsutsumi, Masanori; Aikawa, Hiroshi; Matsumoto, Yoshihisa; Go, Yoshinori; Nii, Kouhei; Abe, Gorou; Ye, Iwae; Nomoto, Yasuyuki; Kazekawa, Kiyoshi

2013-01-01

This retrospective study aimed to compare the effectiveness of the embolization prevention mechanism of two types of embolic protection device (EPD)-a distal protection balloon (DPB) and a distal protection filter (DPF). Subjects were 164 patients scheduled to undergo carotid artery stenting: a DPB was used in 82 cases (DPB group) from April 2007 until June 2010, and a DPF was used in 82 cases (DPF group) from July 2010 to July 2011. Rates of positive findings on postoperative diffusion-weighted imaging (DWI) and stroke incidence were compared. Positive postoperative DWI results were found in 34 cases in the DPB group (41.4 %), but in only 22 cases in the DPF group (26.8 %), and there was only a small significant difference within the DPF group. In the DPB group, there was one case of transient ischemic attack (TIA) (1.2 %) and four cases of brain infarction (2 minor strokes, 2 major strokes; 4.9 %), compared to the DFP group with one case of TIA (1.2 %) and no cases of minor or major strokes. In this study, significantly lower rates of occurrence of DWI ischemic lesions and intraoperative embolization were associated with use of the DPF compared to the DPB.

Sirtuin 3 mediates neuroprotection of ketones against ischemic stroke

PubMed Central

Yin, Junxiang; Han, Pengcheng; Tang, Zhiwei; Liu, Qingwei; Shi, Jiong

2015-01-01

Stroke is one of the leading causes of death. Growing evidence indicates that ketone bodies have beneficial effects in treating stroke, but their underlying mechanism remains unclear. Our previous study showed ketone bodies reduced reactive oxygen species by using NADH as an electron donor, thus increasing the NAD+/NADH ratio. In this study, we investigated whether mitochondrial NAD+-dependent Sirtuin 3 (SIRT3) could mediate the neuroprotective effects of ketone bodies after ischemic stroke. We injected mice with either normal saline or ketones (beta-hydroxybutyrate and acetoacetate) at 30 minutes after ischemia induced by transient middle cerebral artery (MCA) occlusion. We found that ketone treatment enhanced mitochondria function, reduced oxidative stress, and therefore reduced infarct volume. This led to improved neurologic function after ischemia, including the neurologic score and the performance in Rotarod and open field tests. We further showed that ketones' effects were achieved by upregulating NAD+-dependent SIRT3 and its downstream substrates forkhead box O3a (FoxO3a) and superoxide dismutase 2 (SOD2) in the penumbra region since knocking down SIRT3 in vitro diminished ketones' beneficial effects. These results provide us a foundation to develop novel therapeutics targeting this SIRT3-FoxO3a-SOD2 pathway. PMID:26058697

NOTCH3 variants and risk of ischemic stroke.

PubMed

Ross, Owen A; Soto-Ortolaza, Alexandra I; Heckman, Michael G; Verbeeck, Christophe; Serie, Daniel J; Rayaprolu, Sruti; Rich, Stephen S; Nalls, Michael A; Singleton, Andrew; Guerreiro, Rita; Kinsella, Emma; Wszolek, Zbigniew K; Brott, Thomas G; Brown, Robert D; Worrall, Bradford B; Meschia, James F

2013-01-01

Mutations within the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). CADASIL mutations appear to be restricted to the first twenty-four exons, resulting in the gain or loss of a cysteine amino acid. The role of other exonic NOTCH3 variation not involving cysteine residues and mutations in exons 25-33 in ischemic stroke remains unresolved. All 33 exons of NOTCH3 were sequenced in 269 Caucasian probands from the Siblings With Ischemic Stroke Study (SWISS), a 70-center North American affected sibling pair study and 95 healthy Caucasian control subjects. Variants identified by sequencing in the SWISS probands were then tested for association with ischemic stroke using US Caucasian controls collected at the Mayo Clinic (n=654), and further assessed in a Caucasian (n=802) and African American (n=298) patient-control series collected through the Ischemic Stroke Genetics Study (ISGS). Sequencing of the 269 SWISS probands identified one (0.4%) with small vessel type stroke carrying a known CADASIL mutation (p.R558C; Exon 11). Of the 19 common NOTCH3 variants identified, the only variant significantly associated with ischemic stroke after multiple testing adjustment was p.R1560P (rs78501403; Exon 25) in the combined SWISS and ISGS Caucasian series (Odds Ratio [OR] 0.50, P=0.0022) where presence of the minor allele was protective against ischemic stroke. Although only significant prior to adjustment for multiple testing, p.T101T (rs3815188; Exon 3) was associated with an increased risk of small-vessel stroke (OR: 1.56, P=0.008) and p.P380P (rs61749020; Exon 7) was associated with decreased risk of large-vessel stroke (OR: 0.35, P=0.047) in Caucasians. No significant associations were observed in the small African American series. Cysteine-affecting NOTCH3 mutations are rare in patients with typical ischemic stroke, however our observation that common NOTCH3 variants may be associated with risk of ischemic stroke warrants further study.

The Five Ps of Acute Ischemic Stroke Treatment: Parenchyma, Pipes, Perfusion, Penumbra, and Prevention of Complications

PubMed Central

Felberg, Robert A.; Naidech, Andrew

2003-01-01

Stroke is a treatable disease. Despite the therapeutic nihilism of the past, the advent of thrombolysis has changed the way stroke treatment is approached. Acute ischemic stroke is a challenging and heterogeneous disease, and treatment must be based on an understanding of the underlying pathophysiology of ischemia. Interventions are designed to improve neuronal salvage and outcome. The underlying tenets of stroke therapy focus on the brain parenchyma, arterial flow (pipes), perfusion, the ischemic milieu or penumbra, and prevention of complications. This article focuses on the practical issues of ischemic stroke care with a brief review of supporting literature. PMID:22470250

Cerebrovascular Accidents During Mechanical Circulatory Support: New Predictors of Ischemic and Hemorrhagic Strokes and Outcome.

PubMed

Izzy, Saef; Rubin, Daniel B; Ahmed, Firas S; Akbik, Feras; Renault, Simone; Sylvester, Katelyn W; Vaitkevicius, Henrikas; Smallwood, Jennifer A; Givertz, Michael M; Feske, Steven K

2018-05-01

Left ventricular assist devices (LVADs) have emerged as an effective treatment for patients with advanced heart failure refractory to medical therapy. Post-LVAD strokes are an important cause of morbidity and reduced quality of life. Data on risks that distinguish between ischemic and hemorrhagic post-LVAD strokes are limited. The aim of this study was to determine the incidence of post-LVAD ischemic and hemorrhagic strokes, their association with stroke risk factors, and their effect on mortality. Data are collected prospectively on all patients with LVADs implanted at Brigham and Women's Hospital. We added retrospectively collected clinical data for these analyses. From 2007 to 2016, 183 patients (median age, 57; 80% male) underwent implantation of HeartMate II LVAD as a bridge to transplant (52%), destination therapy (39%), or bridge to transplant candidacy (8%). A total of 48 strokes occurred in 39 patients (21%): 28 acute ischemic strokes in 24 patients (13%) and 20 intracerebral hemorrhages in 19 patients (10.3%). First events occurred at a median of 238 days from implantation (interquartile range, 93-515) among those who developed post-LVAD stroke. All but 9 patients (4.9%) were on warfarin (goal international normalized ratio, 2-3.5) and all received aspirin (81-325 mg). Patients with chronic obstructive pulmonary disease were more likely to have an ischemic stroke (odds ratio, 2.96; 95% confidence interval, 1.14-7.70). Dialysis-dependent patients showed a trend toward a higher risk of hemorrhagic stroke (odds ratio, 6.31; 95% confidence interval, 0.99-40.47). Hemorrhagic stroke was associated with higher mortality (odds ratio, 3.92; 95% confidence interval, 1.34-11.45) than ischemic stroke (odds ratio, 3.17; 95% confidence interval, 1.13-8.85). Stroke is a major cause of morbidity and mortality in patients on LVAD support. Chronic obstructive pulmonary disease increases the risk of ischemic stroke, whereas dialysis may increase the risk of hemorrhagic stroke. Although any stroke increases mortality, post-LVAD hemorrhagic stroke was associated with higher mortality compared with ischemic stroke. © 2018 American Heart Association, Inc.

Does non-central nervous system tuberculosis increase the risk of ischemic stroke? A population-based propensity score-matched follow-up study.

PubMed

Wu, Chueh-Hung; Chen, Li-Sheng; Yen, Ming-Fang; Chiu, Yueh-Hsia; Fann, Ching-Yuan; Chen, Hsiu-Hsi; Pan, Shin-Liang

2014-01-01

Previous studies on the association between tuberculosis and the risk of developing ischemic stroke have generated inconsistent results. We therefore performed a population-based, propensity score-matched longitudinal follow-up study to investigate whether contracting non-central nervous system (CNS) tuberculosis leads to an increased risk of ischemic stroke. We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 5804 persons with at least three ambulatory visits in 2001 with the principal diagnosis of non-CNS tuberculosis were enrolled in the tuberculosis group. The non-tuberculosis group consisted of 5804, propensity score-matched subjects without tuberculosis. The three-year ischemic stroke-free survival rates for these 2 groups were estimated using the Kaplan-Meier method. The stratified Cox proportional hazards regression was used to estimate the effect of tuberculosis on the occurrence of ischemic stroke. During three-year follow-up, 176 subjects in the tuberculosis group (3.0%) and 207 in the non-tuberculosis group (3.6%) had ischemic stroke. The hazard ratio for developing ischemic stroke in the tuberculosis group was 0.92 compared to the non-tuberculosis group (95% confidence interval: 0.73-1.14, P = 0.4299). Non-CNS tuberculosis does not increase the risk of subsequent ischemic stroke.

Elevated visfatin/pre-B-cell colony-enhancing factor plasma concentration in ischemic stroke.

PubMed

Lu, Li-Fen; Yang, Sheng-Shan; Wang, Chao-Ping; Hung, Wei-Chin; Yu, Teng-Hung; Chiu, Cheng-An; Chung, Fu-Mei; Shin, Shyi-Jang; Lee, Yau-Jiunn

2009-01-01

Visfatin/pre-B-cell colony-enhancing factor is a cytokine that is expressed as a protein in several tissues (e.g., liver, skeletal muscle, immune cells), including adipose tissue, and is reported to stimulate inflammatory cytokine expressions and promote vascular smooth cell maturation. Visfatin may act as a proinflammatory cytokine and be involved in the process of atherosclerosis. In this study, we investigated whether plasma visfatin levels were altered in patients with ischemic stroke. Plasma visfatin concentrations were measured through enzyme immunoassays in patients with ischemic stroke and in control subjects without stroke. The mean plasma concentration of visfatin in the 120 patients with ischemic stroke was significantly higher than that of the 120 control subjects without stroke (51.5 +/- 48.4 v 23.0 +/- 23.9 ng/mL, P < .001). Multiple logistic regression analysis confirmed plasma visfatin to be an independent factor associated with ischemic stroke. Increasing concentrations of visfatin were independently and significantly associated with a higher risk of ischemic stroke when concentrations were analyzed as both a quartile and a continuous variable. The multiple logistic regression analysis-adjusted odds ratios and 95% confidence intervals for ischemic stroke in the second, third, and fourth quartiles were 2.3 (0.7-7.7), 6.9 (2.2-23.3), and 20.1 (4.9-97.7), respectively. Plasma visfatin concentration was positively associated with high-sensitivity C-reactive protein levels and negatively associated with low-density lipoprotein cholesterol. Our results indicate that higher visfatin levels are associated with ischemic stroke in the Chinese population.

Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack

PubMed Central

Yoshida, Yoichi; Wang, Hao; Hiwasa, Takaki; Machida, Toshio; Kobayashi, Eiichi; Mine, Seiichiro; Tomiyoshi, Go; Nakamura, Rika; Shinmen, Natsuko; Kuroda, Hideyuki; Takizawa, Hirotaka; Kashiwado, Koichi; Kamitsukasa, Ikuo; Shin, Hideo; Wada, Takeshi; Aotsuka, Akiyo; Nishi, Eiichiro; Ohno, Mikiko; Takemoto, Minoru; Yokote, Koutaro; Takahashi, Sho; Matsushima, Jun; Zhang, Xiao-Meng; Takiguchi, Masaki; Iwadate, Yasuo

2018-01-01

Background Disease specific autoantibodies have been detected in the sera of patients with atherosclerosis-related diseases, such as cerebral infarction, cardiovascular disease. In the present study, we aimed to identify novel autoantibodies responsible for transient ischemic attack (TIA), a prodromal condition for cerebral infarction. Methods To identify candidate antigens, we screened a human aortic endothelial cell cDNA library using sera from 20 patients with TIA. Serum antibody levels were measured using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in 2 independent patient/healthy donor (HD) cohorts (n = 192 and n = 906 in the second screening and validation cohort, respectively). Results First screening identified 3 candidate antigens. Of these, programmed cell death 11 (PDCD11) was determined to be associated with stroke (p < 0.0001), as evidenced from the second screening using AlphaLISA. The validation cohort revealed significantly higher antibody levels against PDCD11 (PDCD11-Ab levels) in patients with TIA than in HDs. Multivariate logistic regression analysis indicated that the predictive value of PDCD11-Ab levels for TIA [Odds ratio (OR): 2.44, 95% confidence interval (CI): 1.33-4.57, p = 0.0039] was not inferior to other known risk factors for ischemic stroke, including age (OR: 4.97, 95% CI: 2.67–9.48, p < 0.0001); hypertension (OR: 3.21, 95% CI: 1.76–5.86, p = 0.0001); and diabetes (OR: 4.31, 95% CI: 1.74–11.2, p = 0.0015). Conclusion Serum PDCD11-Ab level may serve as a potential biomarker for TIA. PMID:29507658

Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke.

PubMed

Andersson, Charlotte; Preis, Sarah R; Beiser, Alexa; DeCarli, Charles; Wollert, Kai C; Wang, Thomas J; Januzzi, James L; Vasan, Ramachandran S; Seshadri, Sudha

2015-09-01

Growth differentiation factor-15 (GDF-15) and soluble (s)ST2 are markers of cardiac and vascular stress. We investigated the associations between circulating concentrations of these biomarkers and incident stroke and subclinical vascular brain injury in a sample from the Framingham Offspring cohort. We followed 3374 stroke- and dementia-free individuals (mean age, 59.0±9.7 years; 53% women) attending the Framingham Offspring sixth examination cycle 11.8±3.0 years for incident stroke. A subsample of 2463 individuals underwent brain magnetic resonance imaging and neuropsychological testing ≈4.0±1.7 years after the sixth examination. After adjustment for traditional cardiovascular risk factors, B-type natriuretic peptide, high-sensitivity C-reactive protein, and urine albumin levels, higher stress biomarker levels were associated cross-sectionally with lower brain volumes (β coefficients for intracranial volume comparing fourth [Q4] versus first biomarker [Q1] quartiles: -0.71% for GDF-15; P=0.002 and 0.47% for sST2; P=0.02) and worse performance on the visual reproduction test (β coefficients for Q4 versus Q1: -0.62 for GDF-15; P=0.009 and -0.40 for sST2; P=0.04). Higher GDF-15 concentrations were also associated with greater log-transformed white-matter hyperintensity volumes (β for Q4 versus Q1=0.19; P=0.01). Prospectively, a total of 203 (6%) individuals developed incident stroke/transient ischemic attack during follow-up. After multivariable adjustment, sST2 remained significantly associated with stroke/transient ischemic attack, hazard ratio for Q4 versus Q1 of 1.76, 95% confidence interval of 1.06 to 2.92, and P=0.03. Circulating GDF-15 and sST2 are associated with subclinical brain injury and cognitive impairment. Higher sST2 concentrations are also associated with incident stroke, suggesting potential links between cardiac stress biomarkers and brain injury. © 2015 American Heart Association, Inc.

Single nucleotide polymorphisms associated with coronary heart disease predict incident ischemic stroke in the atherosclerosis risk in communities study.

PubMed

Morrison, Alanna C; Bare, Lance A; Luke, May M; Pankow, James S; Mosley, Thomas H; Devlin, James J; Willerson, James T; Boerwinkle, Eric

2008-01-01

Ischemic stroke and coronary heart disease (CHD) may share genetic factors contributing to a common etiology. This study investigates whether 51 single nucleotide polymorphisms (SNPs) associated with CHD in multiple antecedent studies are associated with incident ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. From the multiethnic ARIC cohort of 14,215 individuals, 495 validated ischemic strokes were identified. Cox proportional hazards models, adjusted for age and gender, identified three SNPs in Whites and two SNPs in Blacks associated with incident stroke (p

Advanced interatrial block and ischemic stroke: The Atherosclerosis Risk in Communities Study.

PubMed

O'Neal, Wesley T; Kamel, Hooman; Zhang, Zhu-Ming; Chen, Lin Y; Alonso, Alvaro; Soliman, Elsayed Z

2016-07-26

Given that recent reports have suggested left atrial disease to be an independent risk factor for ischemic stroke, we sought to examine if advanced interatrial block (aIAB) is an independent stroke risk factor. We examined the association between aIAB and incident ischemic stroke in 14,716 participants (mean age 54 ± 5.8 years; 55% female; 26% black) from the Atherosclerosis Risk in Communities Study (ARIC). Cases of aIAB were identified from digital ECGs recorded during the baseline ARIC visit (1987-1989) and the first 3 follow-up study visits (1990-1992, 1993-1995, and 1996-1998). Adjudicated ischemic stroke events were ascertained through December 31, 2010. There were 266 (1.8%) participants who had evidence of aIAB. Over a median follow-up of 22 years, 916 (6.2%) ischemic stroke events were detected. The incidence rate (per 1,000 person-years) of ischemic stroke among those with aIAB (incidence rate 8.05, 95% confidence interval [CI] 5.7, 11.4) was more than twice the rate in those without aIAB (incidence rate 3.14, 95% CI 2.94, 3.35). In a multivariable Cox regression analysis adjusted for stroke risk factors and potential confounders, aIAB was associated with an increased risk of ischemic stroke (hazard ratio 1.63, 95% CI 1.13, 2.34). The results were consistent across subgroups of participants stratified by age, sex, and race. In the ARIC, aIAB was associated with incident ischemic stroke, which strengthens the hypothesis that left atrial disease should be considered an independent stroke risk factor. © 2016 American Academy of Neurology.

Is Migraine a Risk Factor for Pediatric Stroke?

PubMed Central

Gelfand, Amy A.; Fullerton, Heather J.; Jacobson, Alice; Sidney, Stephen; Goadsby, Peter J.; Kurth, Tobias; Pressman, Alice

2015-01-01

Importance Our understanding of risk factors for childhood stroke is incomplete. In adults, migraine with aura is associated with a two-fold increase in ischemic stroke risk. Objective In this cohort study we examine the association between migraine and stroke among children in Kaiser Permanente Northern California (KPNC). Design, Setting, and Participants Children ages 2-17 years who were members of KPNC for ≥6 months between1997-2007 were included. Migraine cohort members had one or more of: an ICD-9 code for migraine, migraine listed as a significant health problem, or a prescription for a migraine-specific medication. The comparison group was children with no evidence of headache. Main outcome measures stroke incidence rates and incidence rate ratios (IR). Results Among the 1,566,952 children within KPNC during the study period, 88,164 had migraine, and 1,323,142 had no evidence of headache. Eight migraineurs had a stroke (3 [38%] hemorrhagic; 5 [63%]ischemic). Eighty strokes occurred in children without headache, (53 [66%]hemorrhagic;27 [34%] ischemic). The ischemic stroke incidence rate was 0.9/100,000 person-years in migraineurs vs. 0.4/100,000 person-years in those without headache; IR 2.0 (95% CI 0.8-5.2). A post-hoc analysis of adolescents (12-17 years) showed an increased risk of ischemic stroke among those with migraine; IR 3.4(95% CI 1.2-9.5). The hemorrhagic stroke incidence rate was 0.5/100,000 person-years in migraineurs and 0.9/100,000 person-years in those without headache; IR 0.6 (95% CI 0.2-2.0). Conclusions There was no statistically significant increase in hemorrhagic or ischemic stroke risk in pediatric migraineurs in this cohort study. A post-hoc analysis found that ischemic stroke risk was significantly elevated in adolescents with migraine. Future studies should focus on identifying risk factors for ischemic stroke among adolescent migraineurs. Based on adult data, we recommend that migraine aura status should be studied as a possible risk factor for ischemic stroke among adolescent migraineurs. PMID:25754176

Is migraine a risk factor for pediatric stroke?

PubMed

Gelfand, Amy A; Fullerton, Heather J; Jacobson, Alice; Sidney, Stephen; Goadsby, Peter J; Kurth, Tobias; Pressman, Alice

2015-12-01

Our understanding of risk factors for childhood stroke is incomplete. In adults, migraine with aura is associated with a two-fold increase in ischemic stroke risk. In this cohort study we examine the association between migraine and stroke among children in Kaiser Permanente Northern California (KPNC). Children ages 2-17 years who were members of KPNC for ≥6 months between 1997 and 2007 were included. Migraine cohort members had one or more of: an ICD-9 code for migraine, migraine listed as a significant health problem, or a prescription for a migraine-specific medication. The comparison group was children with no evidence of headache. Main outcome measures included stroke incidence rates and incidence rate ratios (IR). Among the 1,566,952 children within KPNC during the study period, 88,164 had migraine, and 1,323,142 had no evidence of headache. Eight migraineurs had a stroke (three (38%) hemorrhagic; five (63%) ischemic). Eighty strokes occurred in children without headache (53 (66%) hemorrhagic; 27 (34%) ischemic). The ischemic stroke incidence rate was 0.9/100,000 person-years in migraineurs vs. 0.4/100,000 person-years in those without headache; IR 2.0 (95% CI 0.8-5.2). A post-hoc analysis of adolescents (12-17 years) showed an increased risk of ischemic stroke among those with migraine; IR 3.4 (95% CI 1.2-9.5). The hemorrhagic stroke incidence rate was 0.5/100,000 person-years in migraineurs and 0.9/100,000 person-years in those without headache; IR 0.6 (95% CI 0.2-2.0). There was no statistically significant increase in hemorrhagic or ischemic stroke risk in pediatric migraineurs in this cohort study. A post-hoc analysis found that ischemic stroke risk was significantly elevated in adolescents with migraine. Future studies should focus on identifying risk factors for ischemic stroke among adolescent migraineurs. Based on adult data, we recommend that migraine aura status should be studied as a possible risk factor for ischemic stroke among adolescent migraineurs. © International Headache Society 2015.

17q25 Locus Is Associated With White Matter Hyperintensity Volume in Ischemic Stroke, But Not With Lacunar Stroke Status

PubMed Central

Adib-Samii, Poneh; Rost, Natalia; Traylor, Matthew; Devan, William; Biffi, Alessandro; Lanfranconi, Silvia; Fitzpatrick, Kaitlin; Bevan, Steve; Kanakis, Allison; Valant, Valerie; Gschwendtner, Andreas; Malik, Rainer; Richie, Alexa; Gamble, Dale; Segal, Helen; Parati, Eugenio A.; Ciusani, Emilio; Holliday, Elizabeth G.; Maguire, Jane; Wardlaw, Joanna; Worrall, Bradford; Bis, Joshua; Wiggins, Kerri L.; Longstreth, Will; Kittner, Steve J.; Cheng, Yu-Ching; Mosley, Thomas; Falcone, Guido J.; Furie, Karen L.; Leiva-Salinas, Carlos; Lau, Benison C.; Khan, Muhammed Saleem; Sharma, Pankaj; Fornage, Myriam; Mitchell, Braxton D.; Psaty, Bruce M.; Sudlow, Cathie; Levi, Christopher; Boncoraglio, Giorgio B.; Rothwell, Peter M.; Meschia, James; Dichgans, Martin; Rosand, Jonathan; Markus, Hugh S.

2013-01-01

Background and Purpose Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke. Methods We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke. Results Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke. Conclusions This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction. PMID:23674528

Neutrophil counts, neutrophil ratio, and new stroke in minor ischemic stroke or TIA.

PubMed

Zhu, Bihong; Pan, Yuesong; Jing, Jing; Meng, Xia; Zhao, Xingquan; Liu, Liping; Wang, David; Johnston, S Claiborne; Li, Hao; Wang, Yilong; Wang, Zhimin; Wang, Yongjun

2018-05-22

Evidence about whether neutrophil counts or neutrophil ratio is associated with new stroke is scant. The aim of this study is to assess the association of neutrophil counts or neutrophil ratio with a new stroke in patients with minor stroke or TIA. We derived data from the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events trial. Patients with a minor stroke or TIA were categorized into 4 groups according to the quartile of neutrophil counts or neutrophil ratio. The primary outcome was a new stroke (ischemic or hemorrhagic), and secondary outcomes included a new composite vascular event (stroke, myocardial infarction, or death resulting from cardiovascular causes) and ischemic stroke during the 90-day follow-up. We assessed the association between neutrophil counts, neutrophil ratio, and risk of new stroke. A total of 4,854 participants were enrolled, among whom 495 had new strokes at 90 days. Compared with the first quartile, the second, third, and fourth quartiles of neutrophil counts were associated with increased risk of new stroke (adjusted hazard ratio 1.40 [95% confidence interval (CI) 1.05-1.87], 1.55 [95% CI 1.17-2.05], and 1.69 [95% CI 1.28-2.23], respectively, p for trend <0.001). Similar results were observed for the endpoint of composite events and ischemic stroke. Parallel results were found for neutrophil ratio. High levels of both neutrophil counts and neutrophil ratio were associated with an increased risk of new stroke, composite events, and ischemic stroke in patients with a minor ischemic stroke or TIA. © 2018 American Academy of Neurology.

Chickenpox and Risk of Stroke: A Self-controlled Case Series Analysis

PubMed Central

Thomas, Sara L.; Minassian, Caroline; Ganesan, Vijeya; Langan, Sinéad M.; Smeeth, Liam

2014-01-01

Background. There is good evidence that respiratory and other infections that cause systemic inflammation can trigger strokes; however, the role of specific infections is unclear. Case reports have highlighted chickenpox as a possible risk factor for arterial ischemic stroke, particularly in children, but rigorous studies are needed to determine and quantify any increased risk. Methods. We used anonymized electronic health records totaling >100 million person-years of observation from 4 UK primary care databases to identify individuals who had documented clinical chickenpox and a stroke or transient ischemic attack (TIA). Self-controlled case series methods were used to quantify any increased risk of first stroke or TIA in the 0–6 and 7–12 months following chickenpox compared to other observed time periods. We analyzed data within each database, and performed meta-analyses to obtain summary age-adjusted incidence ratios (IRs) separately for adults and children. Results. Five hundred sixty eligible individuals (including 60 children) were identified who experienced chickenpox and a stroke or TIA during follow-up. Among children, there was a 4-fold increased risk of stroke in the 0–6 months after chickenpox (summary IR = 4.07; 95% confidence interval [CI], 1.96–8.45; I2 = 0%). Among adults, there was a less marked increased risk with moderate between-database heterogeneity (random-effects summary IR = 2.13; 95% CI, 1.05–4.36; I2 = 51%). There was no significant increased risk of stroke in the 7–12 months after chickenpox in children or adults, nor was there evidence of increased risk of TIA in either time period. Conclusions. Our study provides new evidence that children who experience chickenpox are at increased risk of stroke in the subsequent 6 months. PMID:24092802

Chickenpox and risk of stroke: a self-controlled case series analysis.

PubMed

Thomas, Sara L; Minassian, Caroline; Ganesan, Vijeya; Langan, Sinéad M; Smeeth, Liam

2014-01-01

There is good evidence that respiratory and other infections that cause systemic inflammation can trigger strokes; however, the role of specific infections is unclear. Case reports have highlighted chickenpox as a possible risk factor for arterial ischemic stroke, particularly in children, but rigorous studies are needed to determine and quantify any increased risk. We used anonymized electronic health records totaling >100 million person-years of observation from 4 UK primary care databases to identify individuals who had documented clinical chickenpox and a stroke or transient ischemic attack (TIA). Self-controlled case series methods were used to quantify any increased risk of first stroke or TIA in the 0-6 and 7-12 months following chickenpox compared to other observed time periods. We analyzed data within each database, and performed meta-analyses to obtain summary age-adjusted incidence ratios (IRs) separately for adults and children. Five hundred sixty eligible individuals (including 60 children) were identified who experienced chickenpox and a stroke or TIA during follow-up. Among children, there was a 4-fold increased risk of stroke in the 0-6 months after chickenpox (summary IR = 4.07; 95% confidence interval [CI], 1.96-8.45; I(2) = 0%). Among adults, there was a less marked increased risk with moderate between-database heterogeneity (random-effects summary IR = 2.13; 95% CI, 1.05-4.36; I(2) = 51%). There was no significant increased risk of stroke in the 7-12 months after chickenpox in children or adults, nor was there evidence of increased risk of TIA in either time period. Our study provides new evidence that children who experience chickenpox are at increased risk of stroke in the subsequent 6 months.

The Montreal Cognitive Assessment is superior to National Institute of Neurological Disease and Stroke-Canadian Stroke Network 5-minute protocol in predicting vascular cognitive impairment at 1 year.

PubMed

Dong, YanHong; Xu, Jing; Chan, Bernard Poon-Lap; Seet, Raymond Chee Seong; Venketasubramanian, Narayanaswamy; Teoh, Hock Luen; Sharma, Vijay Kumar; Chen, Christopher Li-Hsian

2016-04-12

The predictive ability of National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute protocol and Montreal Cognitive Assessment (MoCA) administered sub-acutely and at the convalescent phase after stroke for significant vascular cognitive impairment (VCI) at 1 year is unknown. We compared prognostic values of these tests. Patients with ischemic stroke and transient ischemic attack (TIA) received MoCA sub-acutely (within 2 weeks) and 3-6 months after stroke followed by a formal neuropsychological evaluation at 1 year. The total score of NINDS-CSN 5-minutes protocol was derived from MoCA. Moderate-severe VCI was defined as neuropsychological impairment in ≥ 3 domains. Area under the receiver operating characteristic curve (AUC) analyses were conducted to establish the optimal cutoff points and discriminatory properties of the MoCA and NINDS-CSN 5-minute protocol in detecting moderate-severe VCI. Four hundre patients were recruited at baseline. Of these, 291 received a formal neuropsychological assessment 1 year after stroke. 19% patients had moderate-severe VCI. The MoCA was superior to the NINDS-CSN 5-minute protocol [sub-acute AUCs: 0.89 vs 0.80, p < 0.01; 3-6 months AUCs: 0.90 vs 0.83, p < 0.01] in predicting for moderate-severe VCI at 1 year. At respective cutoff points, MoCA had significantly higher sensitivity than the NINDS-CSN 5-minute protocol at baseline (p = 0.01) and 3-6 months (p = 0.04). MoCA administered sub-acutely and 3-6 months after stroke is superior to the NINDS-CSN 5-minute protocol in predicting moderate-severe VCI at 1 year.

Aspirin for Stroke Prevention in Elderly Patients With Vascular Risk Factors: Japanese Primary Prevention Project.

PubMed

Uchiyama, Shinichiro; Ishizuka, Naoki; Shimada, Kazuyuki; Teramoto, Tamio; Yamazaki, Tsutomu; Oikawa, Shinichi; Sugawara, Masahiro; Ando, Katsuyuki; Murata, Mitsuru; Yokoyama, Kenji; Minematsu, Kazuo; Matsumoto, Masayasu; Ikeda, Yasuo

2016-06-01

The effect of aspirin in primary prevention of stroke is controversial among clinical trials conducted in Western countries, and no data are available for Asian populations with a high risk of intracranial hemorrhage. The objective of this study was to evaluate the effect of aspirin on the risk of stroke and intracranial hemorrhage in the Japanese Primary Prevention Project (JPPP). A total of 14 464 patients (age, 60-85 years) with hypertension, dyslipidemia, and diabetes mellitus participated and were randomized into 2 treatment groups: 100 mg of aspirin or no aspirin. The median follow-up period was 5.02 years. The cumulative rate of fatal or nonfatal stroke was similar for the aspirin (2.068%; 95% confidence interval [CI], 1.750-2.443) and no aspirin (2.299%; 95% CI, 1.963-2.692) groups at 5 years; the estimated hazard ratio was 0.927 (95% CI, 0.741-1.160; P=0.509). Aspirin nonsignificantly reduced the risk of ischemic stroke or transient ischemic attack (hazard ratio, 0.783; 95% CI, 0.606-1.012; P=0.061) and nonsignificantly increased the risk of intracranial hemorrhage (hazard ratio, 1.463; 95% CI; 0.956-2.237; P=0.078). A Cox regression adjusted by the risk factors for all stroke, which were age >70 years, smoking, and diabetes mellitus, supported the above result. Aspirin did not show any net benefit for the primary prevention of stroke in elderly Japanese patients with risk factors for stroke, whereas age >70 years, smoking, and diabetes mellitus were risk factors for stroke regardless of aspirin treatment. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00225849. © 2016 American Heart Association, Inc.

Ischemic Stroke After Treatment of Intraprocedural Thrombosis During Stent-Assisted Coiling and Flow Diversion.

PubMed

Adeeb, Nimer; Griessenauer, Christoph J; Moore, Justin M; Foreman, Paul M; Shallwani, Hussain; Motiei-Langroudi, Rouzbeh; Gupta, Raghav; Baccin, Carlos E; Alturki, Abdulrahman; Harrigan, Mark R; Siddiqui, Adnan H; Levy, Elad I; Ogilvy, Christopher S; Thomas, Ajith J

2017-04-01

Intraprocedural thrombosis poses a formidable challenge during neuroendovascular procedures because the risks of aggressive thromboembolic treatment must be balanced against the risk of postprocedural hemorrhage. The aim of this study was to identify predictors of ischemic stroke after intraprocedural thrombosis after stent-assisted coiling and pipeline embolization device placement. A retrospective analysis of intracranial aneurysms treated with stent-assisted coiling or pipeline embolization device placement between 2007 and 2016 at 4 major academic institutions was performed to identify procedures that were complicated by intraprocedural thrombosis. Intraprocedural thrombosis occurred in 34 (4.6%) procedures. Postprocedural ischemic stroke and hemorrhage occurred in 20.6% (7/34) and 11.8% (4/34) of procedures complicated by intraprocedural thrombosis, respectively. Current smoking was an independent predictor of ischemic stroke. There was no statistically significant difference in the rate of ischemic stroke or postprocedural hemorrhage with the use of abciximab compared with the use of eptifibatide in treatment of intraprocedural thrombosis. Current protocols for treatment of intraprocedural thrombosis associated with placement of intra-arterial devices were effective in preventing ischemic stroke in ≈80% of cases. Current smoking was the only independent predictor of ischemic stroke. © 2017 American Heart Association, Inc.

Converting MMSE to MoCA and MoCA 5-minute protocol in an educationally heterogeneous sample with stroke or transient ischemic attack.

PubMed

Wong, Adrian; Black, Sandra E; Yiu, Stanley Y P; Au, Lisa W C; Lau, Alexander Y L; Soo, Yannie O Y; Chan, Anne Y Y; Leung, Thomas W H; Wong, Lawrence K S; Kwok, Timothy C Y; Cheung, Theodore C K; Leung, Kam-Tat; Lam, Bonnie Y K; Kwan, Joseph S K; Mok, Vincent C T

2018-05-01

The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA. A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment. The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859. We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy. Copyright © 2018 John Wiley & Sons, Ltd.

Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy

PubMed Central

Rossouw, Jacques E; Johnson, Karen C; Pettinger, Mary; Cushman, Mary; Sandset, Per Morten; Kuller, Lewis; Rosendaal, Frits; Rosing, Jan; Wasserthal-Smoller, Sylvia; Martin, Lisa W; Manson, JoAnn E; Lakshminarayan, Kamakshi; Merino, Jose G; Lynch, John

2012-01-01

Background and Purpose To test whether changes in plasma tissue factor pathway inhibitor (TFPI) levels or activated protein C resistance (normalized APC resistance ratio, nAPCsr) modify the increased risk of ischemic stroke due to postmenopausal hormone therapy (PHT). Methods Nested case-control study of 455 cases of ischemic stroke and 565 matched controls in the Women’s Health Initiative trials of PHT. Results Baseline free TFPI was associated with ischemic stroke risk, OR (95% CI) per SD increase = 1.17 (1.01, 1.37, p=0.039, but baseline nAPCsr was not, OR per SD increase = 0.89 (0.75, 1.05), p=0.15. Baseline TFPI levels and nAPCsr did not modify the effect of PHT on ischemic stroke. Treatment-induced mean changes of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic stroke (interaction p = 0.452 and 0.971 respectively). In subgroup analyses baseline nAPCsr was inversely associated with lacunar strokes, OR per SD increase = 0.74 (0.57, 0.96), p=0.025, and baseline free TFPI interacted with treatment to increase large vessel atherosclerotic strokes, p=0.008. Conclusions Pro-coagulant changes in TFPI or nAPCsr do not modify the increased ischemic stroke risk due to PHT. PMID:22363056

Surgery May Help More People After Stroke

MedlinePlus

... Stroke En español Send us your comments In ischemic stroke, blood vessels that supply the brain become blocked. ... blood vessel in the brain. These are called ischemic strokes. Strokes are a medical emergency. When blood can’ ...

Ischemic stroke occurring during intercourse in young women on oral contraceptives.

PubMed

Miller, P Elliott; Brown, Lorrel; Khandheria, Paras; Resar, Jon R

2014-08-01

Ischemic stroke occurring during intercourse in young patients is exceedingly rare. We present 2 cases of young women taking oral contraceptives, each presenting with an ischemic stroke. Transthoracic echocardiography revealed a patent foramen ovale in one patient and an atrial septal defect in the other. The most likely cause of stroke in both patients is embolic. Despite conflicting evidence, young patients presenting with ischemic stroke and found to have a patent foramen ovale or atrial septal defect should be considered for possible device-based closure. Copyright © 2014 Elsevier Inc. All rights reserved.

Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke

PubMed Central

Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Corte, Vittoriano Della; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

2016-01-01

Abstract Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile. PMID:27043681

Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke: A Randomized Trial.

PubMed

Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Della Corte, Vittoriano; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

2016-03-01

Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile.

Dynamic changes in plasma tissue plasminogen activator, plasminogen activator inhibitor-1 and beta-thromboglobulin content in ischemic stroke.

PubMed

Zhuang, Ping; Wo, Da; Xu, Zeng-Guang; Wei, Wei; Mao, Hui-ming

2015-07-01

The aim of this paper is to investigate the corresponding variations of plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities, and beta-thromboglobulin (β-TG) content in patients during different stages of ischemic stroke. Ischemic stroke is a common disease among aging people and its occurrence is associated with abnormalities in the fibrinolytic system and platelet function. However, few reports focus on the dynamic changes in the plasma fibrinolytic system and β-TG content in patients with ischemic stroke. Patients were divided into three groups: acute, convalescent and chronic. Plasma t-PA and PAI-1 activities were determined by chromogenic substrate analysis and plasma β-TG content was detected by radioimmunoassay. Patients in the acute stage of ischemic stroke had significantly increased levels of t-PA activity and β-TG content, but PAI-1 activity was significantly decreased. Negative correlations were found between plasma t-PA and PAI-1 activities and between plasma t-PA activity and β-TG content in patients with acute ischemic stroke. There were significant differences in plasma t-PA and PAI-1 activities in the aged control group, as well as in the acute, convalescent and chronic groups. It can be speculated that the increased activity of t-PA in patients during the acute stage was the result of compensatory function, and that the increase in plasma β-TG level not only implies the presence of ischemic stroke but is likely a cause of ischemic stroke. During the later stages of ischemic stroke, greater attention is required in monitoring levels of PAI-1. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Socioeconomic Status and Underlying Disease on the Association between Ambient Temperature and Ischemic Stroke.

PubMed

Cho, Seong Kyung; Sohn, Jungwoo; Cho, Jaelim; Noh, Juhwan; Ha, Kyoung Hwa; Choi, Yoon Jung; Pae, Sangjoon; Kim, Changsoo; Shin, Dong Chun

2018-07-01

Inconsistent findings have been reported regarding the effect of ambient temperature on ischemic stroke. Furthermore, little is known about how underlying disease and low socioeconomic status influence the association. We, therefore, investigated the relationship between ambient temperature and emergency department (ED) visits for ischemic stroke, and aimed to identify susceptible populations. Using medical claims data, we identified ED visits for ischemic stroke during 2005-2009 in Seoul, Korea. We conducted piecewise linear regression analyses to find optimum ambient temperature thresholds in summer and winter, and estimated the relative risks (RR) and 95% confidence intervals (CI) per a 1°C increase in temperature above/below the thresholds, adjusting for relative humidity, holidays, day of the week, and air pollutant levels. There were 63564 ED visits for ischemic stroke. In summer, the risk of ED visits for ischemic stroke was not significant, with the threshold at 26.8°C. However, the RRs were 1.055 (95% CI, 1.006-1.106) above 25.0°C in medical aid beneficiaries and 1.044 (1.007-1.082) above 25.8°C in patients with diabetes. In winter, the risk of ED visits for ischemic stroke significantly increased as the temperature decreased above the threshold at 7.2°C. This inverse association was significant also in patients with hypertension and diabetes mellitus above threshold temperatures. Ambient temperature increases above a threshold were positively associated with ED visits for ischemic stroke in patients with diabetes and medical aid beneficiaries in summer. In winter, temperature, to a point, and ischemic stroke visits were inversely associated. © Copyright: Yonsei University College of Medicine 2018.

Heart rate and ischemic stroke: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

PubMed

O'Neal, Wesley T; Qureshi, Waqas T; Judd, Suzanne E; Meschia, James F; Howard, Virginia J; Howard, George; Soliman, Elsayed Z

2015-12-01

The association between resting heart rate and ischemic stroke remains unclear. To examine the association between resting heart rate and ischemic stroke. A total of 24 730 participants (mean age: 64 ± 9·3 years; 59% women; 41% blacks) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who were free of stroke at the time of enrollment (2003-2007) were included in this analysis. Resting heart rate was determined from baseline electrocardiogram data. Heart rate was examined as a continuous variable per 10 bpm increase and also as a categorical variable using tertiles ( <61 bpm, 61 to 70 bpm, and >70 bpm). First-time ischemic stroke events were identified during follow-up and adjudicated by physician review. Over a median follow-up of 7·6 years, a total of 646 ischemic strokes occurred. In a Cox regression model adjusted for socio-demographics, cardiovascular risk factors, and potential confounders, each 10 bpm increase in heart rate was associated with a 10% increase in the risk of ischemic stroke (hazard ratio = 1·10, 95% confidence interval = 1·02, 1·18). In the categorical model, an increased risk of ischemic stroke was observed for heart rates in the middle (hazard ratio = 1·29, 95% confidence interval = 1·06, 1·57) and upper (hazard ratio = 1·37, 95% confidence interval = 1·12, 1·67) tertiles compared with the lower tertile. The results were consistent when the analysis was stratified by age, gender, race, exercise habits, hypertension, and coronary heart disease. In REGARDS, high resting heart rates were associated with an increased risk of ischemic stroke compared with low heart rates. Further research is needed to examine whether interventions aimed to reduce heart rate decrease stroke risk. © 2015 World Stroke Organization.

Etiologic Ischemic Stroke Phenotypes in the NINDS Stroke Genetics Network

PubMed Central

Ay, Hakan; Arsava, Ethem Murat; Andsberg, Gunnar; Benner, Thomas; Brown, Robert D.; Chapman, Sherita N.; Cole, John W.; Delavaran, Hossein; Dichgans, Martin; Engström, Gunnar; Giralt-Steinhauer, Eva; Grewal, Raji P.; Gwinn, Katrina; Jern, Christina; Jimenez-Conde, Jordi; Jood, Katarina; Katsnelson, Michael; Kissela, Brett; Kittner, Steven J.; Kleindorfer, Dawn O.; Labovitz, Daniel L.; Lanfranconi, Silvia; Lee, Jin-Moo; Lehm, Manuel; Lemmens, Robin; Levi, Chris; Li, Linxin; Lindgren, Arne; Markus, Hugh S.; McArdle, Patrick F.; Melander, Olle; Norrving, Bo; Peddareddygari, Leema Reddy; Pedersén, Annie; Pera, Joanna; Rannikmäe, Kristiina; Rexrode, Kathryn M.; Rhodes, David; Rich, Stephen S.; Roquer, Jaume; Rosand, Jonathan; Rothwell, Peter M.; Rundek, Tatjana; Sacco, Ralph L.; Schmidt, Reinhold; Schürks, Markus; Seiler, Stephan; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie; Thijs, Vincent; Woodfield, Rebecca; Worrall, Bradford B.; Meschia, James F.

2014-01-01

Background and Purpose NINDS Stroke Genetics Network (SiGN) is an international consortium of ischemic stroke studies that aims to generate high quality phenotype data to identify the genetic basis of etiologic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. Methods Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major etiologic groups without weighting towards the most likely cause) and causative ischemic stroke subtypes in 16,954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded re-adjudication of 1509 randomly selected cases. Results The distribution of etiologic categories varied by study, age, sex, and race (p<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke etiology (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (kappa 0.72, 95%CI:0.69-0.75) and phenotypic classifications (kappa 0.73, 95%CI:0.70-0.75). Conclusions This study demonstrates that etiologic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a stroke patient does not necessarily mean that it is the cause of stroke. PMID:25378430

Niaspan increases axonal remodeling after stroke in type 1 diabetes rats✩

PubMed Central

Yan, Tao; Chopp, Michael; Ye, Xinchun; Liu, Zhongwu; Zacharek, Alex; Cui, Yisheng; Roberts, Cynthia; Buller, Ben; Chen, Jieli

2012-01-01

Background and objective We investigated axonal plasticity in the bilateral motor cortices and the long term therapeutic effect of Niaspan on axonal remodeling after stroke in type-1 diabetic (T1DM) rats. Experimental approaches T1DM was induced in young adult male Wistar rats via injection of streptozotocin. T1DM rats were subjected to 2 h transient middle cerebral artery occlusion (MCAo) and were treated with 40 mg/kg Niaspan or saline starting 24 h after MCAo and daily for 28 days. Anterograde tracing using biotinylated dextran amine (BDA) injected into the contralateral motor cortex was performed to assess axonal sprouting in the ipsilateral motor cortex area. Functional outcome, SMI-31 (a pan-axonal microfilament marker), Bielschowsky silver and synaptophysin expression were measured. In vitro studies using primary cortical neuron (PCN) cultures and in vivo BDA injection into the brain to anterogradely label axons and terminals were employed. Results Niaspan treatment of stroke in T1DM–MCAo rats significantly improved functional outcome after stroke and increased SMI-31, Bielschowsky silver and synaptophysin expression in the ischemic brain compared to saline treated T1DM–MCAo rats (p<0.05). Using BDA to anterograde label axons and terminals, Niaspan treatment significantly increased axonal density in ipsilateral motor cortex in T1DM–MCAo rats (p<0.05, n=7/group). Niacin treatment of PCN significantly increased Ang1 expression under high glucose condition. Niacin and Ang1 significantly increased neurite outgrowth, and anti-Ang1 antibody marginally attenuated Niacin induced neurite outgrowth (p=0.06, n=6/group) in cultured PCN under high glucose condition. Conclusion Niaspan treatment increased ischemic brain Ang1 expression and promoted axonal remodeling in the ischemic brain as well as improved functional outcome after stroke. Ang1 may partially contribute to Niaspan-induced axonal remodeling after stroke in T1DM-rats. PMID:22266016

Rare and Coding Region Genetic Variants Associated With Risk of Ischemic Stroke: The NHLBI Exome Sequence Project.

PubMed

Auer, Paul L; Nalls, Mike; Meschia, James F; Worrall, Bradford B; Longstreth, W T; Seshadri, Sudha; Kooperberg, Charles; Burger, Kathleen M; Carlson, Christopher S; Carty, Cara L; Chen, Wei-Min; Cupples, L Adrienne; DeStefano, Anita L; Fornage, Myriam; Hardy, John; Hsu, Li; Jackson, Rebecca D; Jarvik, Gail P; Kim, Daniel S; Lakshminarayan, Kamakshi; Lange, Leslie A; Manichaikul, Ani; Quinlan, Aaron R; Singleton, Andrew B; Thornton, Timothy A; Nickerson, Deborah A; Peters, Ulrike; Rich, Stephen S

2015-07-01

Stroke is the second leading cause of death and the third leading cause of years of life lost. Genetic factors contribute to stroke prevalence, and candidate gene and genome-wide association studies (GWAS) have identified variants associated with ischemic stroke risk. These variants often have small effects without obvious biological significance. Exome sequencing may discover predicted protein-altering variants with a potentially large effect on ischemic stroke risk. To investigate the contribution of rare and common genetic variants to ischemic stroke risk by targeting the protein-coding regions of the human genome. The National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP) analyzed approximately 6000 participants from numerous cohorts of European and African ancestry. For discovery, 365 cases of ischemic stroke (small-vessel and large-vessel subtypes) and 809 European ancestry controls were sequenced; for replication, 47 affected sibpairs concordant for stroke subtype and an African American case-control series were sequenced, with 1672 cases and 4509 European ancestry controls genotyped. The ESP's exome sequencing and genotyping started on January 1, 2010, and continued through June 30, 2012. Analyses were conducted on the full data set between July 12, 2012, and July 13, 2013. Discovery of new variants or genes contributing to ischemic stroke risk and subtype (primary analysis) and determination of support for protein-coding variants contributing to risk in previously published candidate genes (secondary analysis). We identified 2 novel genes associated with an increased risk of ischemic stroke: a protein-coding variant in PDE4DIP (rs1778155; odds ratio, 2.15; P = 2.63 × 10(-8)) with an intracellular signal transduction mechanism and in ACOT4 (rs35724886; odds ratio, 2.04; P = 1.24 × 10(-7)) with a fatty acid metabolism; confirmation of PDE4DIP was observed in affected sibpair families with large-vessel stroke subtype and in African Americans. Replication of protein-coding variants in candidate genes was observed for 2 previously reported GWAS associations: ZFHX3 (cardioembolic stroke) and ABCA1 (large-vessel stroke). Exome sequencing discovered 2 novel genes and mechanisms, PDE4DIP and ACOT4, associated with increased risk for ischemic stroke. In addition, ZFHX3 and ABCA1 were discovered to have protein-coding variants associated with ischemic stroke. These results suggest that genetic variation in novel pathways contributes to ischemic stroke risk and serves as a target for prediction, prevention, and therapy.

Non-invasive detection of matrix-metalloproteinase activity in a mouse model of cerebral ischemia using multispectral optoacoustic tomography

NASA Astrophysics Data System (ADS)

Ni, Ruiqing; Vaas, Markus; Ren, Wuwei; Klohs, Jan

2018-02-01

Matrix metalloproteinases (MMPs) play important roles in the pathophysiology of cerebral ischemia. Here we visualized in vivo MMP activity in the transient middle cerebral artery occlusion (tMCAO) mouse model using multispectral optoacoustic imaging (MSOT) with a MMP-activatable probe. MSOT data was co-registered with structural magnetic resonance imaging (MRI) obtained at 7 T for localization of signal distribution. We demonstrated upregulated MMP signal within the focal ischemic lesion in the tMCAO mouse model using MSOT/MRI multimodal imaging. This convenient non-invasive method will allow repetitive measurement following the time course of MMP-lesion development in ischemic stroke animal model.

Quality Improvement in Acute Ischemic Stroke Care in Taiwan: The Breakthrough Collaborative in Stroke

PubMed Central

Chern, Chang-Ming; Lee, Tsong-Hai; Tang, Sung-Chun; Tsai, Li-Kai; Liao, Hsun-Hsiang; Chang, Hang; LaBresh, Kenneth A.; Lin, Hung-Jung; Chiou, Hung-Yi; Chiu, Hou-Chang; Lien, Li-Ming

2016-01-01

In the management of acute ischemic stroke, guideline adherence is often suboptimal, particularly for intravenous thrombolysis or anticoagulation for atrial fibrillation. We sought to improve stroke care quality via a collaborative model, the Breakthrough Series (BTS)-Stroke activity, in a nationwide, multi-center activity in Taiwan. A BTS Collaborative, a short-term learning system for a large number of multidisciplinary teams from hospitals, was applied to enhance acute ischemic stroke care quality. Twenty-four hospitals participated in and submitted data for this stroke quality improvement campaign in 2010–2011. Totally, 14 stroke quality measures, adopted from the Get With The Guideline (GWTG)-Stroke program, were used to evaluate the performance and outcome of the ischemic stroke patients. Data for a one-year period from 24 hospitals with 13,181 acute ischemic stroke patients were analyzed. In 14 hospitals, most stroke quality measures improved significantly during the BTS-activity compared with a pre-BTS-Stroke activity period (2006–08). The rate of intravenous thrombolysis increased from 1.2% to 4.6%, door-to-needle time ≤60 minutes improved from 7.1% to 50.8%, symptomatic hemorrhage after intravenous thrombolysis decreased from 11.0% to 5.6%, and anticoagulation therapy for atrial fibrillation increased from 32.1% to 64.1%. The yearly composite measures of five stroke quality measures revealed significant improvements from 2006 to 2011 (75% to 86.3%, p<0.001). The quarterly composite measures also improved significantly during the BTS-Stroke activity. In conclusion, a BTS collaborative model is associated with improved guideline adherence for patients with acute ischemic stroke. GWTG-Stroke recommendations can be successfully applied in countries besides the United States. PMID:27487190

Quality Improvement in Acute Ischemic Stroke Care in Taiwan: The Breakthrough Collaborative in Stroke.

PubMed

Hsieh, Fang-I; Jeng, Jiann-Shing; Chern, Chang-Ming; Lee, Tsong-Hai; Tang, Sung-Chun; Tsai, Li-Kai; Liao, Hsun-Hsiang; Chang, Hang; LaBresh, Kenneth A; Lin, Hung-Jung; Chiou, Hung-Yi; Chiu, Hou-Chang; Lien, Li-Ming

2016-01-01

In the management of acute ischemic stroke, guideline adherence is often suboptimal, particularly for intravenous thrombolysis or anticoagulation for atrial fibrillation. We sought to improve stroke care quality via a collaborative model, the Breakthrough Series (BTS)-Stroke activity, in a nationwide, multi-center activity in Taiwan. A BTS Collaborative, a short-term learning system for a large number of multidisciplinary teams from hospitals, was applied to enhance acute ischemic stroke care quality. Twenty-four hospitals participated in and submitted data for this stroke quality improvement campaign in 2010-2011. Totally, 14 stroke quality measures, adopted from the Get With The Guideline (GWTG)-Stroke program, were used to evaluate the performance and outcome of the ischemic stroke patients. Data for a one-year period from 24 hospitals with 13,181 acute ischemic stroke patients were analyzed. In 14 hospitals, most stroke quality measures improved significantly during the BTS-activity compared with a pre-BTS-Stroke activity period (2006-08). The rate of intravenous thrombolysis increased from 1.2% to 4.6%, door-to-needle time ≤60 minutes improved from 7.1% to 50.8%, symptomatic hemorrhage after intravenous thrombolysis decreased from 11.0% to 5.6%, and anticoagulation therapy for atrial fibrillation increased from 32.1% to 64.1%. The yearly composite measures of five stroke quality measures revealed significant improvements from 2006 to 2011 (75% to 86.3%, p<0.001). The quarterly composite measures also improved significantly during the BTS-Stroke activity. In conclusion, a BTS collaborative model is associated with improved guideline adherence for patients with acute ischemic stroke. GWTG-Stroke recommendations can be successfully applied in countries besides the United States.

Identification of nine genes as novel susceptibility loci for early-onset ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage.

PubMed

Yamada, Yoshiji; Kato, Kimihiko; Oguri, Mitsutoshi; Horibe, Hideki; Fujimaki, Tetsuo; Yasukochi, Yoshiki; Takeuchi, Ichiro; Sakuma, Jun

2018-07-01

Given that substantial genetic components have been shown in ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), heritability may be higher in early-onset than late-onset individuals with these conditions. Although genome-wide association studies (GWASs) have identified various genes and loci significantly associated with ischemic stroke, ICH, or intracranial aneurysm mainly in European ancestry populations, genetic variants that contribute to susceptibility to these disorders remain to be identified definitively. We performed exome-wide association studies (EWASs) to identify genetic variants that confer susceptibility to ischemic stroke, ICH, or SAH in early-onset subjects with these conditions. A total of 6,649 individuals aged ≤65 years were examined. For the EWAS of ischemic or hemorrhagic stroke, 6,224 individuals (450 subjects with ischemic stroke, 5,774 controls) or 6,179 individuals (261 subjects with ICH, 176 subjects with SAH, 5,742 controls), respectively, were examined. EWASs were performed with the use of Illumina Human Exome-12 v1.2 DNA Analysis BeadChip or Infinium Exome-24 v1.0 BeadChip. To compensate for multiple comparisons of allele frequencies with ischemic stroke, ICH, or SAH, we applied a false discovery rate (FDR) of <0.05 for statistical significance of association. The association of allele frequencies of 31,245 single nucleotide polymorphisms (SNPs) that passed quality control to ischemic stroke was examined with Fisher's exact test, and 31 SNPs were significantly (FDR <0.05) associated with ischemic stroke. The association of allele frequencies of 31,253 or 30,970 SNPs to ICH or SAH, respectively, was examined with Fisher's exact test, and six or two SNPs were significantly associated with ICH or SAH, respectively. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of hypertension and diabetes mellitus revealed that 12 SNPs were significantly [P<0.0004 (0.05/124)] related to ischemic stroke. Similar analysis with adjustment for age, sex, and the prevalence of hypertension revealed that six or two SNPs were significantly [P<0.0016 (0.05/32)] related to ICH or SAH, respectively. After examination of linkage disequilibrium of identified SNPs and results of previous GWASs, we identified HHIPL2, CTNNA3, LOC643770, UTP20 , and TRIB3 as susceptibility loci for ischemic stroke, DNTTIP2 and FAM205A as susceptibility loci for ICH, and FAM160A1 and OR52E4 as such loci for SAH. Therefore, to the best of our knowledge, we have newly identified nine genes that confer susceptibility to early-onset ischemic stroke, ICH, or SAH. Determination of genotypes for the SNPs in these genes may prove informative for assessment of the genetic risk for ischemic stroke, ICH, or SAH in Japanese.

Relation of dietary glycemic load with ischemic and hemorrhagic stroke: a cohort study in Greece and a meta-analysis.

PubMed

Rossi, Marta; Turati, Federica; Lagiou, Pagona; Trichopoulos, Dimitrios; La Vecchia, Carlo; Trichopoulou, Antonia

2015-03-01

High glycemic load (GL) has been associated with excess stroke risk. Data suggest a different role of diet in the etiology of ischemic and hemorrhagic stroke. We analyzed data from 19,824 participants of the Greek cohort of the population-based European Prospective Investigation into Cancer and nutrition (EPIC), who were free of cardiovascular diseases, cancer, and diabetes at baseline and had not developed diabetes. Diet was assessed at enrollment through a validated, interviewer-administered semi-quantitative food frequency questionnaire. The average daily GL was derived using standard tables. We also conducted a meta-analysis on GL and stroke (overall, ischemic and hemorrhagic), using random-effects models. In the Greek EPIC cohort, 304 incident stroke cases were identified (67 ischemic, 49 hemorrhagic). Using Cox proportional hazards regression models adjusted for potential confounders, the hazard ratios for the highest versus the lowest GL tertiles were 1.07 [95 % confidence interval (CI) 0.74-1.54] for overall stroke, 1.55 (95 % CI 0.72-3.36) for ischemic and 0.48 (95 % CI 0.18-1.25) for hemorrhagic stroke (p-heterogeneity <0.01). The meta-analysis, including a total of 3,088 incident cases and 247 deaths from stroke (1,469 cases and 126 deaths ischemic; 576 cases and 94 deaths hemorrhagic), estimated pooled relative risks for the highest versus the lowest GL levels of 1.23 (95 % CI 1.07-1.41) for overall, 1.35 (95 % CI 1.06-1.72) for ischemic, and 1.09 (95 % CI 0.81-1.47) for hemorrhagic stroke (p-heterogeneity = 0.275). This study indicates that GL is an important determinant of the more common ischemic-though not of the hemorrhagic-stroke.

Rivaroxaban does not influence hemorrhagic transformation in a diabetes ischemic stroke and endovascular thrombectomy model.

PubMed

Liu, Feng-Di; Zhao, Rong; Feng, Xiao-Yan; Shi, Yan-Hui; Wu, Yi-Lan; Shen, Xiao-Lei; Li, Ge-Fei; Liu, Yi-Sheng; Zhao, Ying; He, Xin-Wei; Yin, Jia-Wen; Zhuang, Mei-Ting; Zhao, Bing-Qiao; Liu, Jian-Ren

2018-05-09

Managing endovascular thrombectomy (ET) in diabetic ischemic stroke (IS) with novel anticoagulants is challenging due to putative risk of intracerebral hemorrhage. The study evaluates increased hemorrhagic transformation (HT) risk in Rivaroxaban-treated diabetic rats post ET. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 60 mg/kg streptozotocin. After 4-weeks, rats were pretreated orally with 30 mg/kg Rivaroxaban/saline; prothrombin time was monitored. IS and ET was induced after 1 h, by thread-induced transient middle cerebral artery occlusion (tMCAO) that mimicked mechanical ET for proximal MCA occlusion at 60 min. After 24 h reperfusion, infarct volumes, HT, blood-brain barrier (BBB) permeability, tight junction at peri-ischemic lesion and matrix metalloproteinase-9 (MMP-9) activity was measured. Diabetic rats seemed to exhibit increased infarct volume and HT at 24 h after ET than normal rats. Infarct volumes and functional outcomes did not differ between Rivaroxaban and diabetic control groups. A significant increase in HT volumes and BBB permeability under Rivaroxaban treatment was not detected. Compared to diabetic control group, neither the occludin expression was remarkably lower in the Rivaroxaban group nor the MMP-9 activity was higher. Together, Rivaroxaban does not increase HT after ET in diabetic rats with proximal MCA occlusion, since Rivaroxaban has fewer effects on post-ischemic BBB permeability.

Morphological changes in carotid arteries in stroke cases.

PubMed

Thapa, Guna Bahadur; Sundas, Alin; Rauniyar, Raj Kumar

2013-01-01

Majority of stroke is due to ischemic infarction and occurs in carotid artery territory. The extra cranial parts of carotid arteries are the common sites for the atherosclerotic plaque formation. Ultrasonography is the first line of investigation for screening of the carotid artery diseases to localize and characterize the plaques. Objective was to study the morphological changes in extra cranial part of carotid arteries in cases of ischemic infarction using Ultrasonography. It was an institution based prospective study and convenience sampling method was used. Computed Tomography proven ischemic infarct, lacunar infarction and transient ischemic infarction cases were included in the study. Fifty four cases were included in the study. Mean of Intimo-medial Complex Thickness was 0.89 mm and 0.88 mm in right and left side respectively. Sixty five percent cases had plaque in extra cranial part of carotid artery. Ninety three percent of plaque was found in and adjacent to the carotid bulb region. Ipsilateral plaque was found in 76% and 65% cases on right and left side respectively. Fifty three percent of cases had soft plaque. Majority of cases had less than 50% narrowing of the lumen diameter in term of cross-sectional area due to plaque. Thirteen (24%) cases had plaque in internal carotid artery. Carotid ultrasound can be used for screening of the asymptomatic but high-risk cases and following up of the symptomatic cases to plan for necessary management as required.

Risk stratification for large artery or chronic coronary artery disease-related ischemic stroke in octogenarians undergoing exercise stress myocardial perfusion imaging: A cohort study.

PubMed

Katsikis, Athanasios; Theodorakos, Athanasios; Drosatos, Alexandros; Konstantinou, Konstantinos; Papaioannou, Spyridon; Koutelou, Maria

2017-04-01

To test, if in octogenarians, treadmill exercise with myocardial perfusion imaging (exercise-MPI) can risk stratify for large artery or chronic CAD-related ischemic stroke (LACCIS). Exercise-MPI-related data of 237 octogenarians (55% prior MI or revascularization) without previous stroke were registered and prospective follow-up was performed to document LACCIS. LACCIS was defined as acute onset of neurological symptoms with CT/MRI findings of non-lacunar-type infarcts in the absence of atrial fibrillation or intracardiac embolic sources. After 7.3 years, 10 LACCIS were documented. SSS [HR 1.08 (1.02-1.13 95% CIs), SDS [HR 1.1 (1.04-1.16 95% CIs)], and non-sustained VT or transient AV block during exercise [HR 3.9 (1.7-9.0 95% CIs)] were predictors of LACCIS (P < .01 for all). A SSS threshold of 16 had 81% specificity for identification of future LACCIS and risk groups formed according to this cut-off had significantly different LACCIS-free survival (P = .015). Exercise-MPI in octogenarians can provide risk stratification markers for LACCIS.

Efficacy and Safety of Ticagrelor in Relation to Aspirin Use Within the Week Before Randomization in the SOCRATES Trial.

PubMed

Wong, K S Lawrence; Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Himmelmann, Anders; Kasner, Scott E; Knutsson, Mikael; Ladenvall, Per; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Johnston, S Claiborne

2018-07-01

SOCRATES (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), comparing ticagrelor with aspirin in patients with acute cerebral ischemia, found a nonsignificant 11% relative risk reduction for stroke, myocardial infarction, or death ( P =0.07). Aspirin intake before randomization could enhance the effect of ticagrelor by conferring dual antiplatelet effect during a high-risk period for subsequent stroke. Therefore, we explored the efficacy and safety of ticagrelor versus aspirin in the patients who received any aspirin the week before randomization. A prespecified subgroup analysis in SOCRATES (n=13 199), randomizing patients with acute ischemic stroke (National Institutes of Health Stroke Scale score of ≤5) or transient ischemic attack (ABCD 2 score of ≥4) to 90-day treatment with ticagrelor or aspirin. Patients in the prior-aspirin group had received any aspirin within the week before randomization. Primary end point was time to stroke, myocardial infarction, or death. Safety end point was PLATO (Study of Platelet Inhibition and Patient Outcomes) major bleeding. The 4232 patients in the prior-aspirin group were older, had more vascular risk factors, and vascular disease than the other patients. In the prior-aspirin group, the primary end point occurred in 138/2130 (6.5%) of patients on ticagrelor and in 177/2102 (8.3%) on aspirin (hazard ratio, 0.76; 95% confidence interval, 0.61-0.95; P =0.02); in patients with no prior-aspirin usage an event occurred in 304/4459 (6.9%) and 320/4508 (7.1%) on ticagrelor and aspirin, respectively (hazard ratio, 0.96; 95% confidence interval, 0.82-1.12; P =0.59). The treatment-by-prior-aspirin interaction was not statistically significant ( P =0.10). In the prior-aspirin group, major bleeding occurred in 0.7% and 0.4% of patients on ticagrelor and aspirin, respectively (hazard ratio, 1.58; 95% confidence interval, 0.68-3.65; P =0.28). In this secondary analysis from SOCRATES, fewer primary end points occurred on ticagrelor treatment than on aspirin in patients receiving aspirin before randomization, but there was no significant treatment-by-prior-aspirin interaction. A new study will investigate the benefit-risk of combining ticagrelor and aspirin in patients with acute cerebral ischemia (URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429). URL: https://www.clinicaltrials.gov. Unique identifier: NCT01994720. © 2018 American Heart Association, Inc.

Sickle cell trait and incident ischemic stroke in the Atherosclerosis Risk in Communities study.

PubMed

Caughey, Melissa C; Loehr, Laura R; Key, Nigel S; Derebail, Vimal K; Gottesman, Rebecca F; Kshirsagar, Abhijit V; Grove, Megan L; Heiss, Gerardo

2014-10-01

Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association. A population-based sample of blacks (n=3497; mean age=54 years; female=62%) was followed from 1987 to 2011 in the Atherosclerosis Risk in Communities (ARIC) study, contributing a total of 65 371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A. Models were adjusted for age, sex, smoking, diabetes mellitus, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease. SCT was identified in 223 (6.4%) participants. During a median follow-up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than those with homozygous hemoglobin A (10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0-2.0) and an incidence rate difference amounting to 1.9 (0.4-3.8) extra strokes per 1000 person-years. We observed an increased risk of ischemic stroke in blacks with SCT. Further investigation of the incidence and pathophysiology of stroke in patients with SCT is warranted. © 2014 American Heart Association, Inc.

Premature Ventricular Complexes on Screening Electrocardiogram and Risk of Ischemic Stroke

PubMed Central

Agarwal, Sunil K.; Chao, Jennifer; Peace, Frederick; Judd, Suzanne E.; Kissela, Brett; Kleindorfer, Dawn; Howard, Virginia J.; Howard, George; Soliman, Elsayed Z.

2015-01-01

Background and Purpose Premature ventricular complexes (PVCs) detected from long-term electrocardiogram (ECG) recordings have been associated with an increased risk of ischemic stroke. Whether PVCs seen on routine ECG, commonly used in clinical practice, are associated with an increased risk of ischemic stroke remains unstudied. Methods This analysis included 24,460 participants (age 64.5+9.3 years, 55.1% Female, 40.0% African Americans) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who were free of stroke at the time of enrollment. PVCs were ascertained from baseline ECG (2003-2007), and incident stroke cases through 2011 were confirmed by an adjudication committee. Results A total of 1,415 (5.8%) participants had at least one PVC at baseline, and 591 developed incident ischemic stroke during an average (SD) follow-up of 6.0 (2.0) years. In a Cox Proportional hazards model adjusted for age, sex, race, geographic region, education, prior heart disease, systolic blood pressure, blood pressure lowering medications, current smoking, diabetes, left ventricular hypertrophy by ECG, aspirin use and warfarin use, presence of PVCs was associated with 38% increased risk of ischemic stroke (HR (95% CI): 1.38 (1.05, 1.81)). Conclusions PVCs are common on routine screening ECGs, and are associated with an increased risk of ischemic stroke. PMID:25873602

Window Of Opportunity: Estrogen As A Treatment For Ischemic Stroke✰

PubMed Central

Liu, Ran; Yang, Shao-Hua

2013-01-01

The neuroprotection research in the last 2 decades has witnessed a growing interest in the functions of estrogens as neuroprotectants against neurodegenerative diseases including stroke. The neuroprotective action of estrogens has been well demonstrated in both in vitro and in vivo models of ischemic stroke. However, the major conducted clinical trials so far have raised concern for the protective effect of estrogen replacement therapy in postmenopausal women. The discrepancy could be partly due to the mistranslation between the experimental stroke research and clinical trials. While predominant experimental studies tested the protective action of estrogens on ischemic stroke using acute treatment paradigm, the clinical trials have mainly focused on the effect of estrogen replacement therapy on the primary and secondary stroke prevention which has not been adequately addressed in the experimental stroke study. Although the major conducted clinical trials have indicated that estrogen replacement therapy has an adverse effect and raise concern for long term estrogen replacement therapy for stroke prevention, these are not appropriate for assessing the potential effects of acute estrogen treatment on stroke protection. The well established action of estrogen in the neurovascular unit and its potential interaction with recombinant tissue plasminogen activator (rtPA) makes it a candidate for the combined therapy with rtPA for the acute treatment of ischemic stroke. On the other hand, the “critical period” and newly emerged “biomarkers window” hypotheses have indicated that many clinical relevant factors have been underestimated in the experimental ischemic stroke research. The development and application of ischemic stroke models that replicate the clinical condition is essential for further evaluation of acute estrogen treatment on ischemic stroke which might provide critical information for future clinical trials. PMID:23340160

Cardiovascular, Rheumatologic, and Pharmacologic Predictors of Stroke in Patients With Rheumatoid Arthritis: A Nested, Casee–Control Study

PubMed Central

Nadareishvili, Zurab; Michaud, Kaleb; Hallenbeck, John M.; Wolfe, Frederick

2009-01-01

Objective To determine the risk of stroke in patients with rheumatoid arthritis (RA) and risk factors associated with stroke. Methods We performed nested case–control analyses within a longitudinal databank, matching up to 20 controls for age, sex, and time of cohort entry to each patient with stroke. Conditional logistic regression was performed as an estimate of the relative risk of stroke in RA patients compared with those with noninflammatory rheumatic disorders, and to examine severity and anti–tumor necrosis factor (anti-TNF) treatment effects in RA. Results We identified 269 patients with first-ever all-category strokes and 67 with ischemic stroke, including 41 in RA patients. The odds ratio (OR) for the risk of all-category stroke in RA was 1.64 (95% confidence interval [95% CI] 1.16–2.30, P = 0.005), and for ischemic stroke was 2.66 (95% CI 1.24–5.70, P = 0.012). Ischemic stroke was predicted by hypertension, myocardial infarction, low-dose aspirin, comorbidity score, Health Assessment Questionnaire score, and presence of total joint replacement, but not by diabetes, smoking, exercise, or body mass index. Adjusted for cardiovascular and RA risk factors, ischemic stroke was associated with rofecoxib (P = 0.060, OR 2.27 [95% CI 0.97–5.28]), and possibly with corticosteroid use. Anti-TNF therapy was not associated with ischemic stroke (P = 0.584, OR 0.80 [95% CI 0.34–1.82]). Conclusion RA is associated with increased risk of stroke, particularly ischemic stroke. Stroke is predicted by RA severity, certain cardiovascular risk factors, and comorbidity. Except for rofecoxib, RA treatment does not appear to be associated with stroke, although the effect of corticosteroids remains uncertain. PMID:18668583

Risk factors, mortality, and timing of ischemic and hemorrhagic stroke with left ventricular assist devices.

PubMed

Frontera, Jennifer A; Starling, Randall; Cho, Sung-Min; Nowacki, Amy S; Uchino, Ken; Hussain, M Shazam; Mountis, Maria; Moazami, Nader

2017-06-01

Stroke is a major cause of mortality after left ventricular assist device (LVAD) placement. Prospectively collected data of patients with HeartMate II (n = 332) and HeartWare (n = 70) LVADs from October 21, 2004, to May 19, 2015, were reviewed. Predictors of early (during index hospitalization) and late (post-discharge) ischemic and hemorrhagic stroke and association of stroke subtypes with mortality were assessed. Of 402 patients, 83 strokes occurred in 69 patients (17%; 0.14 events per patient-year [EPPY]): early ischemic stroke in 18/402 (4%; 0.03 EPPY), early hemorrhagic stroke in 11/402 (3%; 0.02 EPPY), late ischemic stroke in 25/402 (6%; 0.04 EPPY) and late hemorrhagic stroke in 29/402 (7%; 0.05 EPPY). Risk of stroke and death among patients with stroke was bimodal with highest risks immediately post-implant and increasing again 9-12 months later. Risk of death declined over time in patients without stroke. Modifiable stroke risk factors varied according to timing and stroke type, including tobacco use, bacteremia, pump thrombosis, pump infection, and hypertension (all p < 0.05). In multivariable analysis, early hemorrhagic stroke (adjusted odds ratio [aOR] 4.3, 95% confidence interval [CI] 1.0-17.8, p = 0.04), late ischemic stroke (aOR 3.2, 95% CI 1.1-9.0, p = 0.03), and late hemorrhagic stroke (aOR 3.7, 95% CI 1.5-9.2, p = 0.005) predicted death, whereas early ischemic stroke did not. Stroke is a leading cause and predictor of death in patients with LVADs. Risk of stroke and death among patients with stroke is bimodal, with highest risk at time of implant and increasing risk again after 9-12 months. Management of modifiable risk factors may reduce stroke and mortality rates. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Oxfordshire community stroke project clinical stroke syndrome and appearances of tissue and vascular lesions on pretreatment ct in hyperacute ischemic stroke among the first 510 patients in the Third International Stroke Trial (IST-3).

PubMed

Kobayashi, Adam; Wardlaw, Joanna M; Lindley, Richard I; Lewis, Steff C; Sandercock, Peter A G; Czlonkowska, Anna

2009-03-01

The Oxfordshire Community Stroke Project (OCSP) clinical stroke syndrome classification correlates well with the stroke lesion in established ischemic stroke, but there are few data in patients with hyperacute stroke. We wished to assess whether the OCSP correlated with the site and size of the ischemic lesion and location of cerebral vessel lesion on computed tomography (CT) in hyperacute stroke. Prospective study of ischemic stroke patients presenting within 6 hours of onset in the Third International Stroke Trial (IST-3), a randomized, controlled trial of rt-PA. OCSP syndrome was assigned by a computer-based algorithm. The CT assessment was made by a neuroradiologist blinded to clinical details. We assessed baseline data and CT findings for the first 510 patients; early tissue ischemic changes were present in 329/510 (65%) total anterior circulation syndrome (TACS) - 79%; partial anterior circulation syndrome (PACS) - 57%, lacunar syndrome (LACS) - 40%; posterior circulation syndrome (POCS) - 33%. The site and size of ischemic change on CT was compatible with the clinical syndrome in 79%, 37%, 2%, and 14%, respectively. Assuming that all patients with a normal CT scan will develop an incompatible lesion these numbers reflected the "worst possible scenario." For the "best possible scenario" we presumed that those with a normal CT will develop concordant ischemic change and the proportions were 100%, 80%, 62% and 81%, respectively. The hyperattenuated artery sign was seen in 206/510 (40%); (TACS 54%; PACS 35%, LACS 5%, and POCS 19%). Within 6 hours of stroke, in patients with a nonlacunar syndrome, the OCSP syndrome correlated well with the pattern of ischemic change on CT. For clinicians who wish to restrict the use of thrombolytic therapy to large-artery ischemic stroke, concordance of clinical and CT appearances may give greater confidence in making therapeutic decisions in hyperacute stroke. In centers where immediate access to MR is limited, use of the classification may help focus use of MR on patients with suspected LACS and POCS. The utility of the classification may further increase if IST-3 establishes that the OCSP syndrome significantly modifies response to thrombolytic therapy.

Role of Blood Lipids in the Development of Ischemic Stroke and its Subtypes

PubMed Central

Engström, Gunnar; Larsson, Susanna C.; Traylor, Matthew; Markus, Hugh S.; Melander, Olle; Orho-Melander, Marju

2018-01-01

Background and Purpose— Statin therapy is associated with a lower risk of ischemic stroke supporting a causal role of low-density lipoprotein (LDL) cholesterol. However, more evidence is needed to answer the question whether LDL cholesterol plays a causal role in ischemic stroke subtypes. In addition, it is unknown whether high-density lipoprotein cholesterol and triglycerides have a causal relationship to ischemic stroke and its subtypes. Our aim was to investigate the causal role of LDL cholesterol, high-density lipoprotein cholesterol, and triglycerides in ischemic stroke and its subtypes through Mendelian randomization (MR). Methods— Summary data on 185 genome-wide lipids-associated single nucleotide polymorphisms were obtained from the Global Lipids Genetics Consortium and the Stroke Genetics Network for their association with ischemic stroke (n=16 851 cases and 32 473 controls) and its subtypes, including large artery atherosclerosis (n=2410), small artery occlusion (n=3186), and cardioembolic (n=3427) stroke. Inverse-variance–weighted MR was used to obtain the causal estimates. Inverse-variance–weighted multivariable MR, MR-Egger, and sensitivity exclusion of pleiotropic single nucleotide polymorphisms after Steiger filtering and MR-Pleiotropy Residual Sum and Outlier test were used to adjust for pleiotropic bias. Results— A 1-SD genetically elevated LDL cholesterol was associated with an increased risk of ischemic stroke (odds ratio: 1.12; 95% confidence interval: 1.04–1.20) and large artery atherosclerosis stroke (odds ratio: 1.28; 95% confidence interval: 1.10–1.49) but not with small artery occlusion or cardioembolic stroke in multivariable MR. A 1-SD genetically elevated high-density lipoprotein cholesterol was associated with a decreased risk of small artery occlusion stroke (odds ratio: 0.79; 95% confidence interval: 0.67–0.90) in multivariable MR. MR-Egger indicated no pleiotropic bias, and results did not markedly change after sensitivity exclusion of pleiotropic single nucleotide polymorphisms. Genetically elevated triglycerides did not associate with ischemic stroke or its subtypes. Conclusions— LDL cholesterol lowering is likely to prevent large artery atherosclerosis but may not prevent small artery occlusion nor cardioembolic strokes. High-density lipoprotein cholesterol elevation may lead to benefits in small artery disease prevention. Finally, triglyceride lowering may not yield benefits in ischemic stroke and its subtypes. PMID:29535274

Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke

PubMed Central

Martynov, Mikhail Yu; Gusev, Eugeny I

2015-01-01

Ischemic stroke is one of the leading causes of long-lasting disability and death. Two main strategies have been proposed for the treatment of ischemic stroke: restoration of blood flow by thrombolysis or mechanical thrombus extraction during the first few hours of ischemic stroke, which is one of the most effective treatments and leads to a better functional and clinical outcome. The other direction of treatment, which is potentially applicable to most of the patients with ischemic stroke, is neuroprotection. Initially, neuroprotection was mainly targeted at protecting gray matter, but during the past few years there has been a transition from a neuron-oriented approach toward salvaging the whole neurovascular unit using multimodal drugs. Citicoline is a multimodal drug that exhibits neuroprotective and neuroregenerative effects in a variety of experimental and clinical disorders of the central nervous system, including acute and chronic cerebral ischemia, intracerebral hemorrhage, and global cerebral hypoxia. Citicoline has a prolonged therapeutic window and is active at various temporal and biochemical stages of the ischemic cascade. In acute ischemic stroke, citicoline provides neuroprotection by attenuating glutamate exitotoxicity, oxidative stress, apoptosis, and blood–brain barrier dysfunction. In the subacute and chronic phases of ischemic stroke, citicoline exhibits neuroregenerative effects and activates neurogenesis, synaptogenesis, and angiogenesis and enhances neurotransmitter metabolism. Acute and long-term treatment with citicoline is safe and in most clinical studies is effective and improves functional outcome. PMID:27186142

Physical activity and risk of ischemic stroke in the Northern Manhattan Study

PubMed Central

Willey, J Z.; Moon, Y P.; Paik, M C.; Boden-Albala, B; Sacco, R L.; Elkind, M S.V.

2009-01-01

Background: It is controversial whether physical activity is protective against first stroke among older persons. We sought to examine whether physical activity, as measured by intensity of exercise and energy expended, is protective against ischemic stroke. Methods: The Northern Manhattan Study is a prospective cohort study in older, urban-dwelling, multiethnic, stroke-free individuals. Baseline measures of leisure-time physical activity were collected via in-person questionnaires. Cox proportional hazards models were constructed to examine whether energy expended and intensity of physical activity were associated with the risk of incident ischemic stroke. Results: Physical inactivity was present in 40.5% of the cohort. Over a median follow-up of 9.1 years, there were 238 incident ischemic strokes. Moderate- to heavy-intensity physical activity was associated with a lower risk of ischemic stroke (adjusted hazard ratio [HR] 0.65, 95% confidence interval [0.44–0.98]). Engaging in any physical activity vs none (adjusted HR 1.16, 95% CI 0.88–1.51) and energy expended in kcal/wk (adjusted HR per 500-unit increase 1.01, 95% CI 0.99–1.03) were not associated with ischemic stroke risk. There was an interaction of sex with intensity of physical activity (p = 0.04), such that moderate to heavy activity was protective against ischemic stroke in men (adjusted HR 0.37, 95% CI 0.18–0.78), but not in women (adjusted HR 0.92, 95% CI 0.57–1.50). Conclusions: Moderate- to heavy-intensity physical activity, but not energy expended, is protective against risk of ischemic stroke independent of other stroke risk factors in men in our cohort. Engaging in moderate to heavy physical activities may be an important component of primary prevention strategies aimed at reducing stroke risk. GLOSSARY CI = confidence interval; HR = hazard ratio; MET = metabolic equivalents. PMID:19933979

Expert opinion paper on atrial fibrillation detection after ischemic stroke.

PubMed

Haeusler, Karl Georg; Gröschel, Klaus; Köhrmann, Martin; Anker, Stefan D; Brachmann, Johannes; Böhm, Michael; Diener, Hans-Christoph; Doehner, Wolfram; Endres, Matthias; Gerloff, Christian; Huttner, Hagen B; Kaps, Manfred; Kirchhof, Paulus; Nabavi, Darius Günther; Nolte, Christian H; Pfeilschifter, Waltraud; Pieske, Burkert; Poli, Sven; Schäbitz, Wolf Rüdiger; Thomalla, Götz; Veltkamp, Roland; Steiner, Thorsten; Laufs, Ulrich; Röther, Joachim; Wachter, Rolf; Schnabel, Renate

2018-04-27

This expert opinion paper on atrial fibrillation detection after ischemic stroke includes a statement of the "Heart and Brain" consortium of the German Cardiac Society and the German Stroke Society. This paper was endorsed by the Stroke Unit-Commission of the German Stroke Society and the German Atrial Fibrillation NETwork. In patients with ischemic stroke, detection of atrial fibrillation should usually lead to a change in secondary stroke prevention, since oral anticoagulation is superior to antiplatelet drugs. The detection of previously undiagnosed atrial fibrillation can be improved in patients with ischemic stroke to optimize stroke prevention. This paper summarizes the present knowledge on atrial fibrillation detection after ischemic stroke. We propose an interdisciplinary standard for a "structured analysis of ECG monitoring" on the stroke unit as well as a staged diagnostic scheme for the detection of atrial fibrillation. Since the optimal duration and mode of ECG monitoring has not yet been finally established, this paper is intended to give advice to physicians who are involved in stroke care. In line with the nature of an expert opinion paper, labeling of classes of recommendations is not provided, since many statements are based on the expert opinion, reported case series and clinical experience. Therefore, this paper is not intended as a guideline.

Inflammatory Disequilibrium in Stroke

PubMed Central

Petrovic-Djergovic, Danica; Goonewardena, Sascha N.; Pinsky, David J.

2016-01-01

Over the past several decades, there have been substantial advances in our knowledge of the pathophysiology of stroke. Understanding the benefits of timely reperfusion has led to the development of thrombolytic therapy as the cornerstone of current management of ischemic stroke, but there remains much to be learned about mechanisms of neuronal ischemic and reperfusion injury and associated inflammation. For ischemic stroke, novel therapeutic targets have continued to remain elusive. When considering modern molecular biologic techniques, advanced translational stroke models, and clinical studies, a consistent pattern emerges, implicating perturbation of the immune equilibrium by stroke in both central nervous system injury and repair responses. Stroke triggers activation of the neuroimmune axis, comprised of multiple cellular constituents of the immune system resident within the parenchyma of the brain, leptomeninges, and vascular beds, as well as through secretion of biological response modifiers and recruitment of immune effector cells. This neuroimmune activation can directly impact the initiation, propagation, and resolution phases of ischemic brain injury. In order to leverage a potential opportunity to modulate local and systemic immune responses to favorably affect the stroke disease curve, it is necessary to expand our mechanistic understanding of the neuroimmune axis in ischemic stroke. This review explores the frontiers of current knowledge of innate and adaptive immune responses in the brain and how these responses together shape the course of ischemic stroke. PMID:27340273

The Migraine-Ischemic Stroke Relation in Young Adults

PubMed Central

Pezzini, Alessandro; Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Dalla Volta, Giorgio; Padovani, Alessandro

2011-01-01

In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2) migraine is associated with an increased prevalence of cardiovascular risk factors; (3) the link is caused by migraine-specific drugs; (4) migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions. PMID:21197470

Role of inflammation and its mediators in acute ischemic stroke

PubMed Central

Jin, Rong; Liu, Lin; Zhang, Shihao; Nanda, Anil; Li, Guohong

2013-01-01

Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Increasing evidence suggests that inflammatory response is a double-edged sword, as it not only exacerbates secondary brain injury in the acute stage of stroke but also beneficially contributes to brain recovery after stroke. In this article, we provide an overview on the role of inflammation and its mediators in acute ischemic stroke. We discuss various pro-inflammatory and anti-inflammatory responses in different phases after ischemic stroke and the possible reasons for their failures in clinical trials. Undoubtedly, there is still much to be done in order to translate promising pre-clinical findings into clinical practice. A better understanding of the dynamic balance between pro- and anti-inflammatory responses and identifying the discrepancies between pre-clinical studies and clinical trials may serve as a basis for designing effective therapies. PMID:24006091

[Primary emergencies: management of acute ischemic stroke].

PubMed

Leys, Didier; Goldstein, Patrick

2012-01-01

The emergency diagnostic strategy for acute ischemic stroke consists of:--identification of stroke, based on clinical examination (sudden onset of a focal neurological deficit);--identification of the ischemic or hemorrhagic nature by MRI or CT;--determination of the early time-course (clinical examination) and the cause. In all strokes (ischemic or hemorrhagic), treatment consists of:--the same general management (treatment of a life-threatening emergency, ensuring normal biological parameters except for blood pressure, and prevention of complications);--decompressive surgery in the rare cases of intracranial hypertension. For proven ischemic stroke, other therapies consist of: rt-PA for patients admitted with 4.5 hours of stroke onset who have no contraindications, and aspirin (160 to 300 mg) for patients who are not eligible for rt-PA. These treatments should be administered within a few hours. A centralized emergency call system (phone number 15 in France) is the most effective way of achieving this objective.

[Association Between SNP rs6007897 of CELSR1 and Acute Ischemic Stroke in Western China Han Population: a Case-control Study].

PubMed

Qin, Feng-qin; Yu, Li-hua; Hu, Wen-ting; Guo, Jian; Chen, Ning; Guo, Jiang; Fang, Jing-huan; He, Li

2015-07-01

To investigate the relationship between single nucleotide polymorphism (SNP) rs6007897 of CELSR1 and acute ischemic stroke in Western China Han population. All subjects (759 acute ischemic stroke patients and 786 controls) were genotyped using ligation detection reaction (LDR). We analyzed the differences between SNP rs6007897 genotypes and allele frequencies between two groups. Two genotypes (AA, AG) of rs6007897 were found in both stroke and control group. There was no statistically significance between two groups about genotype and allele frequency. After adjusting for risk factors, we found there was no significant association between rs6007897 and ischemic stroke CP = 0.797, odds ratio (OR) = 0.886, 95% confidence interval (CI) = 0.352-2.227). SNP rs6007897 of CELSR1 was not significantly associated with ischemic stroke in Western China Han population.

The Neuroprotective Effects of Flaxseed Oil Supplementation on Functional Motor Recovery in a Model of Ischemic Brain Stroke: Upregulation of BDNF and GDNF.

PubMed

Bagheri, Abolqasem; Talei, Sahand; Hassanzadeh, Negar; Mokhtari, Tahmineh; Akbari, Mohammad; Malek, Fatemeh; Jameie, Seyed Behnamedin; Sadeghi, Yousef; Hassanzadeh, Gholamreza

2017-12-01

Cerebral ischemic stroke is a common leading cause of disability. Flaxseed is a richest plant-based source of antioxidants. In this study, the effects of flaxseed oil (FSO) pretreatment on functional motor recovery and gene expression and protein content of neurotrophic factors in motor cortex area in rat model of brain ischemia/reperfusion (I/R) were assessed. Transient middle cerebral artery occlusion (tMCAo) in rats was used as model brain I/R. Rats (6 in each group) were randomly divided into four groups of Control (Co+normal saline [NS]), Sham (Sh+NS), tMCAo+NS and tMCAo+FSO. After three weeks of pretreatment with vehicle or FSO (0.2 ml~800 mg/kg body weight), the rats were operated in sham and ischemic groups. Ischemia was induced for 1 h and then reperfused. After 24 h of reperfusion, neurological examination was performed, and animals were sacrificed, and their brains were used for molecular and histopathological studies. FSO significantly improved the functional motor recovery compared with tMCAo+NS group (P<0.05). A significant reduction in brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) mRNAs and protein levels were observed in the tMCAo+NS group compared with Co+NS and Sh+NS group (P<0.05). A significant increase of BDNF and GDNF mRNAs and proteins was recorded in the tMCAo+FSO group compared with Co+NS, Sh+NS and tMCAO+NS groups (P<0.05). The results of the current study demonstrated that pretreatment with FSO had neuroprotective effects on motor cortex area following cerebral ischemic stroke by increasing the neurotrophic factors (BDNF, GDNF).

Clinical Use of CT Perfusion For Diagnosis and Prediction of Lesion Growth in Acute Ischemic Stroke

PubMed Central

Huisa, Branko N; Neil, William P; Schrader, Ronald; Maya, Marcel; Pereira, Benedict; Bruce, Nhu T; Lyden, Patrick D

2012-01-01

Background and Purpose CT perfusion (CTP) mapping in research centers correlates well with diffusion weighted imaging (DWI) lesions and may accurately differentiate the infarct core from ischemic penumbra. The value of CTP in real-world clinical practice has not been fully established. We investigated the yield of CTP– derived cerebral blood volume (CBV) and mean transient time (MTT) for the detection of cerebral ischemia and ischemic penumbra in a sample of acute ischemic stroke (AIS) patients. Methods We studied 165 patients with initial clinical symptoms suggestive of AIS. All patients had an initial non-contrast head CT, CT Perfusion (CTP), CT angiogram (CTA) and follow up brain MRI. The obtained perfusion images were used for image processing. CBV, MTT and DWI lesion volumes were visually estimated and manually traced. Statistical analysis was done using R-2.14.and SAS 9.1. Results All normal DWI sequences had normal CBV and MTT studies (N=89). Seventy-three patients had acute DWI lesions. CBV was abnormal in 23.3% and MTT was abnormal in 42.5% of these patients. There was a high specificity (91.8%)but poor sensitivity (40.0%) for MTT maps predicting positive DWI. Spearman correlation was significant between MTT and DWI lesions (ρ=0.66, p>0.0001) only for abnormal MTT and DWI lesions>0cc. CBV lesions did not correlate with final DWI. Conclusions In real-world use, acute imaging with CTP did not predict stroke or DWI lesions with sufficient accuracy. Our findings argue against the use of CTP for screening AIS patients until real-world implementations match the accuracy reported from specialized research centers. PMID:23253533