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Sample records for chronic ischemic stroke

  1. 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 ...

  2. Fantasies About Stem Cell Therapy in Chronic Ischemic Stroke Patients

    PubMed Central

    Kim, Young Seo; Chung, Dan-il; Choi, Hojin; Baek, Wonki; Kim, Hyun Young; Heo, Sung Hyuk; Chang, Dae-Il; Na, Hae Ri; Kim, Seung Hyun

    2013-01-01

    Stem cell therapy (SCT) has been proposed for the treatment of neurological disorders. Although there is insufficient clinical evidence to support its efficacy, unproven SCTs are being performed worldwide. In this study, we investigated the perspectives and expectations of chronic ischemic stroke patients and physicians about SCTs. A total of 250 chronic ischemic stroke patients were interviewed at 4 hospitals. Structured open and closed questions about SCT for chronic stroke were asked by trained interviewers using the conventional in-person method. In addition, 250 stroke-related physicians were randomly interviewed via an e-mail questionnaire. Of the 250 patients (mean 63 years, 70% male), 121 (46%) responded that they wanted to receive SCT in spite of its unknown side effects. Around 60% of the patients anticipated physical, emotional, and psychological improvement after SCT, and 158 (63%) believed that SCT might prevent strokes. However, physicians had much lower expectations about the effectiveness of SCTs, which was not in line with patient expectations. Multivariate analysis revealed that the male gender [odds ratio (OR): 2.00, 95% confidence interval (CI): 1.10–3.64], longer disease duration (OR: 1.01, 95% CI: 1.00–1.02), higher modified Rankin Scale score (OR: 1.30, 95% CI: 1.06–1.60), and familiarity with stem cells (OR: 1.86, 95% CI: 1.10–3.15) were independently associated with wanting SCT. The major source of information about SCT was television (68%), and the most reliable source was physicians (49%). Patients have unfounded expectations that SCT will improve their functioning. Considering our finding that the major source of information on stem cells is media channels, but not the physician, to decrease patients' inappropriate exposure, doctors should make more effort to educate patients using mass media with accurate information. PMID:22784218

  3. Ischemic Strokes (Clots)

    MedlinePlus

    ... Quiz 5 Things to Know About Stroke Ischemic Strokes (Clots) Updated:Nov 9,2016 Ischemic stroke accounts ... strokes. Read more about silent strokes . TIA and Stroke: Medical Emergencies When someone has shown symptoms of ...

  4. Chronic hyperglycemia is related to poor functional outcome after acute ischemic stroke.

    PubMed

    Luitse, Merel Ja; Velthuis, Birgitta K; Kappelle, L Jaap; van der Graaf, Yolanda; Biessels, Geert Jan

    2017-02-01

    Background Acute hyperglycemia is associated with poor functional outcome after ischemic stroke, but the association between chronic antecedent hyperglycemia and outcome is unclear. Aim We assessed the association between chronic hyperglycemia, measured by hemoglobin A1c, and functional outcome in patients with acute ischemic stroke. Methods We included 812 patients with acute ischemic stroke (mean age 66 ± 14 years; 61.5% male). Patients were categorized per hemoglobin A1c level: no (<39 mmol/mol), moderate (39-42 mmol/mol), or severe chronic hyperglycemia (>42 mmol/mol). Poor functional outcome was defined as modified Rankin Scale score > 2 after 3 months. The relation between chronic hyperglycemia and functional outcome was assessed with a Poisson regression analysis and expressed as risk ratios with 95% confidence intervals with no chronic hyperglycemia as the reference. Results Moderate chronic hyperglycemia was present in 234 (28.8%) patients and severe chronic hyperglycemia in 183 (22.5%) patients. Acute hyperglycemia on admission was present in 338 (41.6%) patients. Severe chronic hyperglycemia was associated with poor outcome (risk ratios 1.40; 95% confidence interval 1.09-1.79). After adjustment for age, sex, stroke severity, vascular risk factors, and acute hyperglycemia on admission the risk ratios was 1.35 (95% confidence interval 1.04-1.76). Moderate chronic hyperglycemia was not associated with poor outcome (risk ratios 1.12; 95% confidence interval 0.87-1.44). Conclusion Severe chronic hyperglycemia is associated with poor functional outcome in patients with acute ischemic stroke. This association is independent of hyperglycemia in the acute stage of stroke and of an unfavorable vascular risk factor profile.

  5. Ischemic Stroke

    MedlinePlus

    ... Spread the Word Advocate Share Spread the Word Contact Us Contact Us 1-800-STROKES (787-6537) 9707 E. ... Stroke En Espanol Stroke Facts Come Back Strong Contact Us 1-800-787-6537 9707 E. Easter ...

  6. Ischemic Stroke.

    PubMed

    Capriotti, Teri; Murphy, Teresa

    2016-05-01

    Each year, more than 795,000 people in the United States suffer a stroke and by 2030, it is estimated that 4% of the U.S. population will have had a stroke. Home healthcare clinicians will be increasingly called upon to assist stroke survivors and their caregivers adjust to disability and assist the survivor during their reintegration into the community. Therapeutic modalities are changing with advanced technology. Great strides are being made in the treatment of acute stroke; particularly endovascular interventions. More patients are surviving the acute stroke event and therefore will need to learn how to live with various degrees of disability. It is important for home healthcare clinicians to understand the process from acute event to medical stabilization, and from rehabilitation to long-term adaptation.

  7. Chronic Systemic Immune Dysfunction in African-Americans with Small Vessel-Type Ischemic Stroke.

    PubMed

    Brown, Candice M; Bushnell, Cheryl D; Samsa, Gregory P; Goldstein, Larry B; Colton, Carol A

    2015-12-01

    The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained >6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide (LPS) to assess immune responsiveness in a subset of cases (n = 5) and controls (n = 4). After adjustment for covariates, the pro-inflammatory biomarkers, soluble vascular cadherin adhesion molecule-1 (sVCAM-1) and thrombin anti-thrombin (TAT), were independently associated with lacunar stroke. Immune responsiveness to LPS challenge was abnormal in cases compared to controls. African-Americans with lacunar stroke had elevated blood levels of VCAM-1 and TAT and an abnormal response to acute immune challenge >6 weeks post-stroke, suggesting a chronically compromised systemic inflammatory response.

  8. Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

    PubMed Central

    Srinivasan, Vivek J.; Mandeville, Emiri T.; Can, Anil; Blasi, Francesco; Climov, Mihail; Daneshmand, Ali; Lee, Jeong Hyun; Yu, Esther; Radhakrishnan, Harsha; Lo, Eng H.; Sakadžić, Sava; Eikermann-Haerter, Katharina; Ayata, Cenk

    2013-01-01

    Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties. PMID:23940761

  9. Multiparametric, longitudinal optical coherence tomography imaging reveals acute injury and chronic recovery in experimental ischemic stroke.

    PubMed

    Srinivasan, Vivek J; Mandeville, Emiri T; Can, Anil; Blasi, Francesco; Climov, Mihail; Daneshmand, Ali; Lee, Jeong Hyun; Yu, Esther; Radhakrishnan, Harsha; Lo, Eng H; Sakadžić, Sava; Eikermann-Haerter, Katharina; Ayata, Cenk

    2013-01-01

    Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties.

  10. Influence of Kinesitherapy on Gait in Patients with Ischemic Stroke in the Chronic Period

    PubMed Central

    Vasileva, Danche; Lubenova, Daniela; Mihova, Marija; Dimitrova, Antoaneta; Grigorova-Petrova, Kristin

    2015-01-01

    AIM: The study aims to trace the influence of specialized kinesitherapeutic methodology (SKTM) on gait in patients with ischemic stroke in the chronic period (ISChP). MATERIAL AND METHODS: The study was conducted with 56 patients with ISChP (duration of the disease up to 1 year). For determining changes in gait before and after the treatment a cadence of gait and maximum movement speed were taken into consideration. To determine the cadence, steps are counted for covering 6 meters and 10 meters respectively. The maximum speed of the gait is determined in m / min by dividing undergone distance (m) and time (min). RESULTS: Patients were found to significantly normalize the parameters of gait. Compared to the initial data, there is a significant reduction in the number of steps on 6 and 10 meters and a tendency to increase the speed of gait, with the significant change during the 1st month with a level of significance of p <0.001. CONCLUSION: The applied specialized kinesitherapeutic methodology continued later as exercise program at home, which significantly improved gait cadence and speed of movement in patients with ischemic stroke in the chronic period and is with a supportive prolonged exposure. PMID:27275297

  11. Influence of Kinesitherapy on Balance Reactions in Patients with Ischemic Stroke in the Chronic Period

    PubMed Central

    Vasileva, Danche; Lubenova, Daniela; Mihova, Marija; Dimitrova, Antoaneta; Grigorova-Petrova, Kristin

    2015-01-01

    AIM: The study aims to trace the influence of specialized kinesitherapeutic methodology (SKTM) on balance reactions in patients with ischemic stroke in the chronic period (ISChP). MATERIAL AND METHODS: A prospective, multicenter study with 56 patients with ISChP. Evaluation of balance reactions using Berg Balance Scale - BBS, includes implementation of 14 tasks with increasing difficulty reflecting the usual activities of everyday life. The first 5 assignments are used to assess the main balance potential and the remaining 9 (6th to 14th task) include more sophisticated balance tasks. RESULTS: The patients were found with a significant improvement in balance opportunities, according to the scale of Berg. Compared to initial data there is a significant increase in the number of points in the measured indicators for functional and static balance. In absolute terms, positive change is most pronounced during the 1st month with a level of significance of p <0.001. CONCLUSION: The applied specialized kinesitherapeutic methodology continued later as adapted exercise program at home, and significantly improved equilibrium reactions in patients with postural disorders because of ischemic stroke and is with a supportive prolonged exposure. PMID:27275294

  12. Acute ischemic stroke update.

    PubMed

    Baldwin, Kathleen; Orr, Sean; Briand, Mary; Piazza, Carolyn; Veydt, Annita; McCoy, Stacey

    2010-05-01

    Stroke is the third most common cause of death in the United States and is the number one cause of long-term disability. Legislative mandates, largely the result of the American Heart Association, American Stroke Association, and Brain Attack Coalition working cooperatively, have resulted in nationwide standardization of care for patients who experience a stroke. Transport to a skilled facility that can provide optimal care, including immediate treatment to halt or reverse the damage caused by stroke, must occur swiftly. Admission to a certified stroke center is recommended for improving outcomes. Most strokes are ischemic in nature. Acute ischemic stroke is a heterogeneous group of vascular diseases, which makes targeted treatment challenging. To provide a thorough review of the literature since the 2007 acute ischemic stroke guidelines were developed, we performed a search of the MEDLINE database (January 1, 2004-July 1, 2009) for relevant English-language studies. Results (through July 1, 2009) from clinical trials included in the Internet Stroke Center registry were also accessed. Results from several pivotal studies have contributed to our knowledge of stroke. Additional data support the efficacy and safety of intravenous alteplase, the standard of care for acute ischemic stroke since 1995. Due to these study results, the American Stroke Association changed its recommendation to extend the time window for administration of intravenous alteplase from within 3 hours to 4.5 hours of symptom onset; this recommendation enables many more patients to receive the drug. Other findings included clinically useful biomarkers, the role of inflammation and infection, an expanded role for placement of intracranial stents, a reduced role for urgent carotid endarterectomy, alternative treatments for large-vessel disease, identification of nontraditional risk factors, including risk factors for women, and newly published pediatric stroke guidelines. In addition, new devices for

  13. Paracrine Mechanisms of Intravenous Bone Marrow-Derived Mononuclear Stem Cells in Chronic Ischemic Stroke

    PubMed Central

    Bhasin, Ashu; Srivastava, M.V. Padma; Mohanty, Sujata; Vivekanandhan, Sivasubramaniam; Sharma, Sakshi; Kumaran, Senthil; Bhatia, Rohit

    2016-01-01

    Background The emerging role of stem cell technology and transplantation has helped scientists to study their potential role in neural repair and regeneration. The fate of stem cells is determined by their niche, consisting of surrounding cells and the secreted trophic growth factors. This interim report evaluates the safety, feasibility and efficacy (if any) of bone marrow-derived mononuclear stem cells (BM-MNC) in chronic ischemic stroke by studying the release of serum vascular endothelial growth factor (VEGF) and brain-derived neurotrophic growth factor (BDNF). Methods Twenty stroke patients and 20 age-matched healthy controls were recruited with the following inclusion criteria: 3 months to 1.5 years from the index event, Medical Research Council (MRC) grade of hand muscles of at least 2, Brunnstrom stage 2-5, conscious, and comprehendible. They were randomized to one group receiving autologous BM-MNC (mean 60-70 million) and to another group receiving saline infusion (placebo). All patients were administered a neuromotor rehabilitation regime for 8 weeks. Clinical assessments [Fugl Meyer scale (FM), modified Barthel index (mBI), MRC grade, Ashworth tone scale] were carried out and serum VEGF and BDNF levels were assessed at baseline and at 8 weeks. Results No serious adverse events were observed during the study. There was no statistically significant clinical improvement between the groups (FM: 95% CI 15.2-5.35, p = 0.25; mBI: 95% CI 14.3-4.5, p = 0.31). VEGF and BDNF expression was found to be greater in group 1 compared to group 2 (VEGF: 442.1 vs. 400.3 pg/ml, p = 0.67; BDNF: 21.3 vs. 19.5 ng/ml) without any statistically significant difference. Conclusion Autologous mononuclear stem cell infusion is safe and tolerable by chronic ischemic stroke patients. The released growth factors (VEGF and BDNF) in the microenvironment could be due to the paracrine hypothesis of stem cell niche and neurorehabilitation regime. PMID:27846623

  14. DRESS and Ischemic Stroke.

    PubMed

    Cahyanur, Rahmat; Oktavia, Dina; Koesno, Sukamto

    2012-07-01

    DRESS (drug rash eosinophilia and systemic symptoms) is a life threatening condition characterized by skin rash, fever, leucocytosis with eosinophilia or atypical lymphocytosis, lymphadenopathy, and internal organ involvement. This case report would like to describe an interesting case of DRESS coincidence with ischemic stroke. A 38 year old woman had been admitted with skin rash and fever since four days before. Four weeks before admission she received antibiotic and multivitamin for one week. The patient looked ill, with body temperature 38.0°C. Marked physical findings were cervical lymphadenopathy and hepatomegaly. Dermatological examination finding was generalized exanthema. Laboratory evaluation showed leucocytosis, eosinophilia, and increased level of ALT and AST. During hospitalization the patient also suffered from ischemic stroke. Treatments administered in this patient were oxygen, adequate intravenous fluid, parenteral nutrition, methyl prednisolone, cethirizin bid, ranitidin bid, and antibiotic. The antibiotic treatment in this case was performed with graded challenge or test dosing.

  15. [Cerebrolysin for acute ischemic stroke].

    PubMed

    iganshina, L E; Abakumova, T R

    2013-01-01

    The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke.

  16. Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

    PubMed Central

    Kim, Yu Ri; Kim, Ha Neui; Hong, Ki Whan; Shin, Hwa Kyoung; Choi, Byung Tae

    2017-01-01

    The aim of this study was to determine the effects and underlying mechanism of aripiprazole (APZ) augmentation for cilostazol (CLS)-treated post-ischemic stroke mice that were exposed to chronic mild stress (CMS). Compared to treatment with either APZ or CLS alone, the combined treatment resulted in a greater reduction in depressive behaviors, including anhedonia, despair-like behaviors, and memory impairments. This treatment also significantly reduced atrophic changes in the striatum, cortex, and midbrain of CMS-treated ischemic mice, and inhibited neuronal cell apoptosis, particularly in the striatum and the dentate gyrus of the hippocampus. Greater proliferation of neuronal progenitor cells was also observed in the ipsilateral striatum of the mice receiving combined treatment compared to mice receiving either drug alone. Phosphorylation of the cyclic adenosine monophosphate response element binding protein (CREB) was increased in the striatum, hippocampus, and midbrain of mice receiving combined treatment compared to treatment with either drug alone, particularly in the neurons of the striatum and hippocampus, and dopaminergic neurons of the midbrain. Our results suggest that APZ may augment the antidepressant effects of CLS via co-regulation of the CREB signaling pathway, resulting in the synergistic enhancement of their neuroprotective effects. PMID:28208711

  17. Arterial ischemic stroke in HIV

    PubMed Central

    Bryer, Alan; Lucas, Sebastian; Stanley, Alan; Allain, Theresa J.; Joekes, Elizabeth; Emsley, Hedley; Turnbull, Ian; Downey, Colin; Toh, Cheng-Hock; Brown, Kevin; Brown, David; Ison, Catherine; Smith, Colin; Corbett, Elizabeth L.; Nath, Avindra; Heyderman, Robert S.; Connor, Myles D.; Solomon, Tom

    2016-01-01

    HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID:27386505

  18. Functional versus Nonfunctional Rehabilitation in Chronic Ischemic Stroke: Evidences from a Randomized Functional MRI Study

    PubMed Central

    Pelicioni, Maristela C. X.; Novaes, Morgana M.; Peres, Andre S. C.; Lino de Souza, Altay A.; Minelli, Cesar; Fabio, Soraia R. C.; Pontes-Neto, Octavio M.; Santos, Antonio C.; de Araujo, Draulio B.

    2016-01-01

    Motor rehabilitation of stroke survivors may include functional and/or nonfunctional strategy. The present study aimed to compare the effect of these two rehabilitation strategies by means of clinical scales and functional Magnetic Resonance Imaging (fMRI). Twelve hemiparetic chronic stroke patients were selected. Patients were randomly assigned a nonfunctional (NFS) or functional (FS) rehabilitation scheme. Clinical scales (Fugl-Meyer, ARA test, and modified Barthel) and fMRI were applied at four moments: before rehabilitation (P1) and immediately after (P2), 1 month after (P3), and three months after (P4) the end of rehabilitation. The NFS group improved significantly and exclusively their Fugl-Meyer scores at P2, P3, and P4, when compared to P1. On the other hand, the FS group increased significantly in Fugl-Meyer at P2, when compared to P1, and also in their ARA and Barthel scores. fMRI inspection at the individual level revealed that both rehabilitation schemes most often led to decreased activation sparseness, decreased activity of contralesional M1, increased asymmetry of M1 activity to the ipsilesional side, decreased perilesional activity, and decreased SMA activity. Increased M1 asymmetry with rehabilitation was also confirmed by Lateralization Indexes. Our clinical analysis revealed subtle differences between FS and NFS. PMID:26839716

  19. Posterior Circulation Ischemic Stroke.

    PubMed

    Go, Steven

    2015-01-01

    Approximately 20-25% of all acute strokes occur in the posterior circulation. These strokes can be rather difficult to diagnose because they present in such diverse ways, and can easily be mistaken for more benign entities. A fastidious history, physical exam, high clinical suspicion, and appropriate use of imaging are essential for the emergency physician to properly diagnose and treat these patients. Expert stroke neurologist consultation should be utilized liberally.

  20. [Antioxidant therapy in ischemic stroke].

    PubMed

    Suslina, Z A; Federova, T N; Maksimova, M Iu; Riasina, T V; Stvolinskiĭ, S L; Khrapova, E V; Boldyrev, A A

    2000-01-01

    The paper presents the results of investigation of emoxipin, an antioxidant synthetic drug, for treatment of patients with ischemic disorders of cerebral circulation. The drug produced a beneficial clinical effect in patients with lacunar and cardioembolic strokes of moderate severity. Therapy with emoxipin increased endogenic antioxidant activity and improved a clinical status of the patients. The protective effect of carnosine was demonstrated in experimental acute hypobaric hypoxia and cerebral ischemia in rats. The results obtained permit to recommend an inclusion of both emoxipin and carnosine in a combined treatment of ischemic disorders of cerebral circulation.

  1. Cost and Outcome in Pediatric Ischemic Stroke.

    PubMed

    Hamilton, William; Huang, Haijuan; Seiber, Eric; Lo, Warren

    2015-10-01

    The cost of childhood stroke receives little notice. The authors examined potential drivers of cost and outcome to test whether (1) neonatal strokes cost less than childhood strokes, (2) associated diseases influence cost, (3) arterial ischemic stroke is more costly than sinovenous thrombosis, and (4) cost correlates with outcome. The authors reviewed records of 111 children who sustained arterial ischemic stroke or sinovenous thrombosis between 2005 and 2010 to identify costs for the following year. They assessed outcomes in 46 with the Recovery and Recurrence Questionnaire and the Pediatric Quality of Life Inventory. Neonatal strokes cost less than childhood stroke. Strokes associated with congenital heart disease or vasculopathy cost the most, while perinatal or idiopathic strokes cost the least. Higher costs are correlated with worse impairment and poorer quality of life. Stroke etiology significantly influences the cost of pediatric stroke. Future cost-benefit studies must consider etiology when estimating the incremental costs associated with stroke.

  2. Genistein: A Boon for Mitigating Ischemic Stroke.

    PubMed

    Nabavi, Seyed Fazel; Daglia, Maria; Tundis, Rosa; Loizzo, Monica Rosa; Sobarzo-Sanchez, Eduardo; Orhan, Ilkay Erdogan; Nabavi, Seyed Mohammad

    2015-01-01

    In last decades, diet and dietary components have been regarded as important strategies to prevent the development or mitigate numerous chronic diseases, including inflammation, cardiovascular pathologies, cancer, etc. One of the most common dietary components of Asian population is soy. A plethora of research shows the promising effect of soy soy-based foodstuffs and genistein, which is one of the predominant isoflavone compounds, in the prevention and mitigation of stroke. Growing evidence shows that genistein, which is a selective estrogen receptor modulator, mitigates ischemic stroke-induced damages through the modification of oxidative stress and molecular pathways. The promising pharmacological role of genistein is attributed to its ability to suppress nuclear factor (NF)-kappa B and Akt signaling pathway, direct antioxidant action, and targeting estrogen and androgen-mediated molecular pathways which help to mitigate stroke damages and prolong cell survival. In this work, we systematically review the current reports on the therapeutic role of genistein against ischemic stroke and its molecular mechanism of actions.

  3. Radionuclide imaging in ischemic stroke.

    PubMed

    Heiss, Wolf-Dieter

    2014-11-01

    Ischemic stroke is caused by interruption or significant impairment of blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphologic damage. The changes in regional cerebral blood flow and regional metabolism can be assessed by radionuclide imaging, especially SPECT and PET. SPECT and PET have broadened our understanding of flow and metabolic thresholds critical for maintenance of brain function and morphology: PET was essential in the transfer of the concept of the penumbra to clinical stroke and thereby had a great impact on developing treatment strategies. Receptor ligands can be applied as early markers of irreversible neuronal damage and can predict the size of the final infarcts, which is important for decisions on invasive therapy in large ("malignant") infarction. With SPECT and PET, the reserve capacity of the blood supply can be tested in obstructive arteriosclerosis, which is essential for planning interventions. The effect of a stroke on surrounding and contralateral primarily unaffected tissue can be investigated, helping to understand symptoms caused by disturbance in functional networks. Activation studies are useful to demonstrate alternative pathways to compensate for lesions and to test the effect of rehabilitative therapy. Radioisotope studies help to detect neuroinflammation and its effect on extension of tissue damage. Despite the limitations of broad clinical application of radionuclide imaging, this technology has a great impact on research in cerebrovascular diseases and still has various applications in the management of stroke.

  4. Cardiovascular risk factors for acute stroke: Risk profiles in the different subtypes of ischemic stroke

    PubMed Central

    Arboix, Adrià

    2015-01-01

    Timely diagnosis and control of cardiovascular risk factors is a priority objective for adequate primary and secondary prevention of acute stroke. Hypertension, atrial fibrillation and diabetes mellitus are the most common risk factors for acute cerebrovascular events, although novel risk factors, such as sleep-disordered breathing, inflammatory markers or carotid intima-media thickness have been identified. However, the cardiovascular risk factors profile differs according to the different subtypes of ischemic stroke. Atrial fibrillation and ischemic heart disease are more frequent in patients with cardioembolic infarction, hypertension and diabetes in patients with lacunar stroke, and vascular peripheral disease, hypertension, diabetes, previous transient ischemic attack and chronic obstructive pulmonary disease in patients with atherothrombotic infarction. This review aims to present updated data on risk factors for acute ischemic stroke as well as to describe the usefulness of new and emerging vascular risk factors in stroke patients. PMID:25984516

  5. Heart Failure in Acute Ischemic Stroke

    PubMed Central

    Cuadrado-Godia, Elisa; Ois, Angel; Roquer, Jaume

    2010-01-01

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Due to the aging of the population it has become a growing public health problem in recent decades. Diagnosis of HF is clinical and there is no diagnostic test, although some basic complementary testing should be performed in all patients. Depending on the ejection fraction (EF), the syndrome is classified as HF with low EF or HF with normal EF (HFNEF). Although prognosis in HF is poor, HFNEF seems to be more benign. HF and ischemic stroke (IS) share vascular risk factors such as age, hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation. Persons with HF have higher incidence of IS, varying from 1.7% to 10.4% per year across various cohort studies. The stroke rate increases with length of follow-up. Reduced EF, independent of severity, is associated with higher risk of stroke. Left ventricular mass and geometry are also related with stroke incidence, with concentric hypertrophy carrying the greatest risk. In HF with low EF, the stroke mechanism may be embolism, cerebral hypoperfusion or both, whereas in HFNEF the mechanism is more typically associated with chronic endothelial damage of the small vessels. Stroke in patients with HF is more severe and is associated with a higher rate of recurrence, dependency, and short term and long term mortality. Cardiac morbidity and mortality is also high in these patients. Acute stroke treatment in HF includes all the current therapeutic options to more carefully control blood pressure. For secondary prevention, optimal control of all vascular risk factors is essential. Antithrombotic therapy is mandatory, although the choice of a platelet inhibitor or anticoagulant drug depends on the cardiac disease. Trials are ongoing to evaluate anticoagulant therapy for prevention of embolism in patients with low EF who are at

  6. Migraine prophylaxis, ischemic depolarizations and stroke outcomes in mice

    PubMed Central

    Eikermann-Haerter, Katharina; Lee, Jeong Hyun; Yalcin, Nilufer; Yu, Esther Sori; Daneshmand, Ali; Wei, Ying; Zheng, Yi; Can, Anil; Sengul, Buse; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.; Ayata, Cenk

    2014-01-01

    Background and Purpose Migraine with aura is an established stroke risk factor, and excitatory mechanisms such as spreading depression are implicated in the pathogenesis of both migraine and stroke. Spontaneous spreading depression waves originate within the peri-infarct tissue and exacerbate the metabolic mismatch during focal cerebral ischemia. Genetically enhanced spreading depression susceptibility facilitates anoxic depolarizations and peri-infarct spreading depressions and accelerates infarct growth, suggesting that susceptibility to spreading depression is a critical determinant of vulnerability to ischemic injury. Because chronic treatment with migraine prophylactic drugs suppresses spreading depression susceptibility, we tested whether migraine prophylaxis can also suppress ischemic depolarizations and improve stroke outcome. Methods We measured the cortical susceptibility to spreading depression and ischemic depolarizations, and determined tissue and neurological outcome after middle cerebral artery occlusion in wild type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing. Results Chronic treatment with topiramate or lamotrigine reduces the susceptibility to KCl- or electrical stimulation-induced spreading depressions as well as ischemic depolarizations in both wild-type and familial hemiplegic migraine type 1 mutant mice. Consequently, both tissue and neurological outcomes are improved. Notably, treatment with a single dose of either drug is ineffective. Conclusions These data underscore the importance of hyperexcitability as a mechanism for increased stroke risk in migraineurs, and suggest that migraine prophylaxis may not only prevent migraine attacks but also protect migraineurs against ischemic injury. PMID:25424478

  7. 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

  8. Stroke bricks - spatial brain regions to assess ischemic stroke localization.

    PubMed

    Ciszek, Bogdan; Jóźwiak, Rafał; Sobieszczuk, Ewa; Przelaskowski, Artur; Skadorwa, Tymon

    2017-03-29

    Computer-aided analysis of non-contrast CT (NCCT) images for rapid diagnosis of ischemic stroke is based on the augmented visualization of evolving ischemic lesions. Computerized support of NCCT often leads to overinterpretation of ischemic areas, thus it is of great interest to provide neurologically verified regions in order to improve accuracy of subsequent radiological assessment. We propose Stroke Bricks (StBr) as an arbitrary spatial division of brain tissue into the regions associated with specific clinical symptoms of ischemic stroke. Neurological stroke deficit is formally translated into respective areas of possible ischemic lesions. StBr were designed according to formalized mapping of neurological symptoms and were attributed to the uniquely defined areas of impaired blood supply. StBr concept may be useful for an integrated radiological CT-based assessment of suspected stroke cases or can be included into computer-aided tools to optimize the evaluation of stroke site and its extent. These data in turn are appropriable for further diagnosis, predicting the therapeutic outcome as well as for patients' qualification for an appropriate form of reperfusion therapy. The usefulness of Stroke Bricks was illustrated in the case studies.

  9. [Ischemic stroke in the young adult].

    PubMed

    Calvet, D

    2016-01-01

    Ischemic stroke is not rare in young adults since one in ten stroke patients are less than 50 years old. This incidence increased over the past last years, mainly due to the rise in the prevalence of traditional vascular risk factors in this sub-group of age but also of illegal drug use. Even though both survival and functional outcome of young stroke patients are better than those observed in older patients, socio-economic and quality of life consequences make this disease a main objective in terms of primary and secondary prevention. Identifying the cause of ischemic stroke in young adults is of major importance to prevent stroke recurrence. However, given the wide variety of potential underlying causes, the etiologic work-up of stroke in young adults requires a different approach from that in the elderly. In this context, a sequential diagnostic work-up is needed in order to optimize the yield of diagnostic tests, to reduce their cost and risks for the patient. Arterial dissection is the most frequent cause of stroke in young adults but other less frequent causes are numerous. Despite a comprehensive work-up, about one third of cases remains unexplained leading to the diagnosis of cryptogenic ischemic stroke.

  10. Genetic Predisposition to Ischemic Stroke

    PubMed Central

    Kamatani, Yoichiro; Takahashi, Atsushi; Hata, Jun; Furukawa, Ryohei; Shiwa, Yuh; Yamaji, Taiki; Hara, Megumi; Tanno, Kozo; Ohmomo, Hideki; Ono, Kanako; Takashima, Naoyuki; Matsuda, Koichi; Wakai, Kenji; Sawada, Norie; Iwasaki, Motoki; Yamagishi, Kazumasa; Ago, Tetsuro; Ninomiya, Toshiharu; Fukushima, Akimune; Hozawa, Atsushi; Minegishi, Naoko; Satoh, Mamoru; Endo, Ryujin; Sasaki, Makoto; Sakata, Kiyomi; Kobayashi, Seiichiro; Ogasawara, Kuniaki; Nakamura, Motoyuki; Hitomi, Jiro; Kita, Yoshikuni; Tanaka, Keitaro; Iso, Hiroyasu; Kitazono, Takanari; Kubo, Michiaki; Tanaka, Hideo; Tsugane, Shoichiro; Kiyohara, Yutaka; Yamamoto, Masayuki; Sobue, Kenji; Shimizu, Atsushi

    2017-01-01

    Background and Purpose— The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk. Methods— We genotyped 13 214 Japanese individuals with IS and 26 470 controls (derivation samples) and generated both multilocus genetic risk scores and polyGRS, using the same derivation data set. The predictive abilities of each scoring system were then assessed using 2 independent sets of Japanese samples (KyushuU and JPJM data sets). Results— In both validation data sets, polyGRS was shown to be significantly associated with IS, but weighted multilocus genetic risk scores was not. Comparing the highest with the lowest polyGRS quintile, the odds ratios for IS were 1.75 (95% confidence interval, 1.33–2.31) and 1.99 (95% confidence interval, 1.19–3.33) in the KyushuU and JPJM samples, respectively. Using the KyushuU samples, the addition of polyGRS to a nongenetic risk model resulted in a significant improvement of the predictive ability (net reclassification improvement=0.151; P<0.001). Conclusions— The polyGRS was shown to be superior to weighted multilocus genetic risk scores as an IS prediction model. Thus, together with the nongenetic risk factors, polyGRS will provide valuable information for individual risk assessment and management of modifiable risk factors. PMID:28034966

  11. White matter injury in ischemic stroke.

    PubMed

    Wang, Yuan; Liu, Gang; Hong, Dandan; Chen, Fenghua; Ji, Xunming; Cao, Guodong

    2016-06-01

    Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions.

  12. Aspirin resistant patients with recent ischemic stroke.

    PubMed

    Castilla-Guerra, L; Navas-Alcántara, M S; Fernández-Moreno, M C

    2014-04-01

    Some patients with a recent ischemic stroke who are being treated with aspirin as an antiaggregant suffer a new ischemic stroke. These patients (15-25%) have been called unresponsive to aspirin or aspirin resistant. The aspirin-resistant patients have a four-time greater risk of suffering a stroke. Furthermore, these strokes are generally more severe, with increased infarct volume and greater risk of recurrence. There is currently no ideal laboratory test to detect the resistance to the antiaggregant effect of aspirin. The study of resistance to aspirin would only be indicated in selected cases. In these patients, one should first rule out any "pseudo-resistance" to aspirin (lack of compliance, concomitant treatments that interfere with the action of the aspirin).

  13. Spontaneous sternocleidomastoid muscle hematoma following thrombolysis for acute ischemic stroke.

    PubMed

    Giannantoni, Nadia Mariagrazia; Della Marca, Giacomo; Broccolini, Aldobrando; Pilato, Fabio; Profice, Paolo; Morosetti, Roberta; Caliandro, Pietro; Frisullo, Giovanni

    2014-06-15

    Spontaneous or traumatic bleeding is a common complication of systemic thrombolysis in patients with acute ischemic stroke. We report the case of an 83 y.o. woman with right facio-brachio-crural hemiparesis, left deviation of the head and aphasia who developed, after thrombolytic therapy, a spontaneous sternocleidomastoid muscle hematoma that regressed few days later. To our knowledge, this is the first case reported in the literature of asymptomatic and spontaneous skeletal muscle hematoma following thrombolysis for the treatment of acute ischemic stroke. The occurrence of lateral cervical tuberculosis lymphadenitis ipsilateral to sternocleidomastoid muscle hematoma may suggest a causal relationship between local chronic inflammation of active mycobacterial infection and thrombolysis-related extravasation. This case should suggest caution in thrombolytic treatment in patients with chronic immune dysregulation and vascular inflammation such as extra-pulmonary tuberculosis.

  14. Promoting recovery from ischemic stroke.

    PubMed

    Schmidt, Antje; Minnerup, Jens

    2016-01-01

    Over recent decades, experimental and clinical stroke studies have identified a number of neurorestorative treatments that stimulate neural plasticity and promote functional recovery. In contrast to the acute stroke treatments thrombolysis and endovascular thrombectomy, neurorestorative treatments are still effective when initiated days after stroke onset, which makes them applicable to virtually all stroke patients. In this article, selected physical, pharmacological and cell-based neurorestorative therapies are discussed, with special emphasis on interventions that have already been transferred from the laboratory to the clinical setting. We explain molecular and structural processes that promote neural plasticity, discuss potential limitations of neurorestorative treatments, and offer a speculative viewpoint on how neurorestorative treatments will evolve.

  15. Stroke Code Improves Intravenous Thrombolysis Administration in Acute Ischemic Stroke

    PubMed Central

    Chen, Chih-Hao; Tang, Sung-Chun; Tsai, Li-Kai; Hsieh, Ming-Ju; Yeh, Shin-Joe; Huang, Kuang-Yu; Jeng, Jiann-Shing

    2014-01-01

    Background and Purpose Timely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with “Stroke Code” (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis. Methods The study period was divided into the “pre-SC era” (January 2006 to July 2010) and “SC era” (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras. Results During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9%) to the SC era (n = 216, 33.3%) (P<0.001). SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001) and the percentage of door-to-needle times ≤60 min increased (14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with good outcome (modified Rankin Scale ≤2) at discharge (49.5 vs. 39.6%, P = 0.11), with no difference in symptomatic hemorrhage events or in-hospital mortality. Conclusion The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time. PMID:25111200

  16. 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

  17. Applicability of biomarkers in ischemic stroke.

    PubMed

    Castellanos, Mar; Serena, Joaquín

    2007-01-01

    Cerebral ischemia results in the activation of a cascade of molecular events as a result of which several substances with the potential characteristics of biomarkers are released into the peripheral blood. Although still in the research phase, the analysis of these biomarkers in the serum has proved to be useful for stroke diagnosis, as well as for the prediction of the evolution of the ischemic lesion and the clinical prognosis. In fact, the feasibility and applicability of a panel of biomarkers for the diagnosis of stroke has recently been tested. Biomarkers of excitotoxicity, inflammation and oxidative stress have been demonstrated as being useful in the prediction of ischemic lesion enlargement and secondary neurological deterioration. On the other hand, biomarkers of endothelial damage have been shown to be especially helpful in the prediction of hemorrhagic transformation of the ischemic lesion, both spontaneously and after the administration of thrombolytic therapy, as well as in the prediction of brain edema with the secondary development of malignant middle-cerebral-artery infarction. Moreover, coagulation and fibrinolytic-cascade markers have been reported as being correlated with the recanalization rate after the administration of thrombolysis, and they might therefore be useful in estimating the effectiveness of thrombolytic therapy. However, for these biomarkers to become applicable to routine clinical practice, faster tests to perform the analyses are required and further studies must be undertaken to validate and generalize the results.

  18. Screening for coagulation disorders in patients with ischemic stroke.

    PubMed

    de Lau, Lonneke Ml; Leebeek, Frank Wg; de Maat, Moniek Pm; Koudstaal, Peter J; Dippel, Diederik Wj

    2010-08-01

    The role of coagulation disorders in the pathogenesis of (recurrent) ischemic stroke is uncertain. Therefore, the clinical utility of screening patients with ischemic stroke for these conditions and the therapeutic implications of a detected coagulation disorder in a patient who experienced ischemic stroke are uncertain. We reviewed the currently available data on the relationship between various inherited and acquired coagulation abnormalities (factor V Leiden and prothrombin G20210A mutations, deficiencies of protein C, protein S and anti-thrombin, hyperhomocysteinemia, the antiphospholipid syndrome and increased levels of fibrinogen) and ischemic stroke. Based on the existing evidence we discuss the usefulness of screening stroke patients for prothrombotic conditions and current recommendations regarding the optimal management of ischemic stroke patients in whom a coagulation disorder is found.

  19. Human Data Supporting Glyburide in Ischemic Stroke

    PubMed Central

    Sheth, Kevin N.; Simard, J. Marc; Elm, Jordan; Kronenberg, Golo; Kunte, Hagen; Kimberly, W. Taylor

    2016-01-01

    The SUR1-TRPM4 channel is a critical determinant of edema and hemorrhagic transformation after focal ischemia. Blockade of this channel by the small molecule glyburide results in improved survival and neurological outcome in multiple preclinical models of ischemic stroke. A robust, compelling body of evidence suggests that an intravenous (IV) formulation of glyburide, RP-1127, can prevent swelling and improve outcome in patients with stroke. Retrospective studies of diabetic stroke patients show improved outcomes in patients who are continued on sulfonylureas after stroke onset. Early phase II study of MRI and plasma biomarkers support the conclusion that RP-1127 may decrease swelling and hemorrhagic transformation. Finally, the ongoing phase II RP-1127 development program has demonstrated continued safety as well as feasibility of enrollment and tolerability of the intervention. Continued efforts to complete the ongoing phase IIb study and definitive efficacy studies are urgently needed to bring a candidate pharmacotherapy to a population of severe stroke patients that currently have no alternative. PMID:26463916

  20. Plasma desmoplakin I biomarker of vascular recurrence after ischemic stroke.

    PubMed

    López-Farré, Antonio J; Zamorano-León, José J; Segura, Antonio; Mateos-Cáceres, Petra J; Modrego, Javier; Rodríguez-Sierra, Pablo; Calatrava, Laura; Tamargo, Juan; Macaya, Carlos

    2012-04-01

    Stroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substudy (n = 134) of a large prospective multicenter study of post-stroke patients with an ischemic stroke. Plasma samples were obtained at inclusion. Among the identified proteins, only plasma levels of desmoplakin I were associated with protection against a new vascular event (Odds ratio: 0.64; 95% CI: 0.46-0.89; p = 0.009) after adjustment for hypercholesterolemia, statins and previous atherothrombotic stroke subtype. A greater number of patients without vascular recurrence had been treated with statins within three months of the recent ischemic stroke. Only patients who had been taking statins for 3 months after the ischemic stroke and did not suffer vascular recurrence over a follow-up year, have higher levels of desmoplakin I at the time of inclusion (Odds ratio 0.49; 95% CI: 0.28-0.86; p = 0.013). Increased desmoplakin I levels, determined within 1-3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post-ischemic stroke patients taking statins early (1-3 months) after the ischemic stroke.

  1. Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke.

    PubMed

    Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro

    2010-07-08

    Cannabis contains the psychoactive component delta⁸-tetrahydrocannabinol (delta⁸-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta⁸-THC and other cannabinoid CB₁ receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta⁸-THC also mediates psychological effects through the activation of the CB₁ receptor in the central nervous system. In addition to the CB₁ receptor agonists, cannabis also contains therapeutically active components which are CB₁ receptor independent. Of the CB₁ receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson's disease, Alzheimer's disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB₁ receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.

  2. PTEN degradation after ischemic stroke: a double-edged sword.

    PubMed

    Li, W; Huang, R; Chen, Z; Yan, L-J; Simpkins, J W; Yang, S-H

    2014-08-22

    Tumor suppressor phosphatase and tensin homolog (PTEN) is highly expressed in neurons and PTEN inhibition has been reported to be neuroprotective against ischemic stroke in experimental models. On the other hand, PTEN deletion has been shown to lead to cognitive impairment. In the current study, we examined the expression and functions of PTEN in an ischemic stroke rodent model. We found rapid S-nitrosylation and degradation of PTEN after cerebral ischemia/reperfusion injury. PTEN degradation leads to activation of Akt. PTEN partial deletion or PTEN inhibition increased the expression of GABAA receptor (GABAAR) γ2 subunit and enhanced GABAA receptor current. After cerebral ischemia, increased expression of GABAAR γ2 subunit was observed in the ischemia region and the penumbra area. We also observed PTEN loss in astrocytes after cerebral ischemia. Astrocytic PTEN partial knockout increased astrocyte activation and exacerbated ischemic damage. We speculated that ischemic stroke induced neuronal PTEN degradation, hence enhanced GABAA receptor-medicated neuronal activity inhibition which could attenuate excitotoxicity and provide neuroprotection during the acute phase after stroke, while inhibiting long-term functional recovery and contributing to vascular cognitive impairment after stroke. On the other hand, ischemic stroke induced astrocytic PTEN loss and enhanced ischemic damage and astrogliosis. Taken together, our study indicates that ischemic stroke induces rapid PTEN degradation in both neurons and astrocytes which play both protective and detrimental action in a spatiotemporal- and cell-type-dependent manner. Our study provides critical insight for targeting PTEN signaling pathway for stroke treatment.

  3. [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.

  4. 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

  5. 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

  6. Persistent Ischemic Stroke Disparities despite Declining Incidence in Mexican Americans

    PubMed Central

    Morgenstern, Lewis B.; Smith, Melinda A.; Sanchez, Brisa N.; Brown, Devin L.; Zahuranec, Darin B.; Garcia, Nelda; Kerber, Kevin A.; Skolarus, Lesli E.; Meurer, William J.; Burke, James F.; Adelman, Eric E.; Baek, Jonggyu; Lisabeth, Lynda D.

    2015-01-01

    Objective To determine trends in ischemic stroke incidence among Mexican Americans and non-Hispanic whites. Methods We performed population-based stroke surveillance from January 1, 2000 to December 31, 2010 in Corpus Christi, Texas. Ischemic stroke patients 45 years and older were ascertained from potential sources, and charts were abstracted. Neurologists validated cases based on source documentation blinded to ethnicity and age. Crude and age-, sex-, and ethnicity-adjusted annual incidence was calculated for first ever completed ischemic stroke. Poisson regression models were used to calculate adjusted ischemic stroke rates, rate ratios, and trends. Results There were 2,604 ischemic strokes in Mexican Americans and 2,042 in non-Hispanic whites. The rate ratios (Mexican American:non-Hispanic white) were 1.94 (95% confidence interval [CI] = 1.67–2.25), 1.50 (95% CI = 1.35– 1.67), and 1.00 (95% CI = 0.90–1.11) among those aged 45 to 59, 60 to 74, and 75 years and older, respectively, and 1.34 (95% CI = 1.23–1.46) when adjusted for age. Ischemic stroke incidence declined during the study period by 35.9% (95% CI = 25.9–44.5). The decline was limited to those aged ≥60 years, and happened in both ethnic groups similarly (p > 0.10), implying that the disparities seen in the 45- to 74-year age group persist unabated. Interpretation Ischemic stroke incidence rates have declined dramatically in the past decade in both ethnic groups for those aged ≥60 years. However, the disparity between Mexican American and non-Hispanic white stroke rates persists in those <75 years of age. Although the decline in stroke is encouraging, additional prevention efforts targeting young Mexican Americans are warranted. PMID:23868398

  7. Developing practice recommendations for endovascular revascularization for acute ischemic stroke

    PubMed Central

    Lazzaro, Marc A.; Alexandrov, Andrei V.; Darkhabani, Ziad; Edgell, Randall C.; English, Joey; Frei, Donald; Jamieson, Dara G.; Janardhan, Vallabh; Janjua, Nazli; Janjua, Rashid M.; Katzan, Irene; Khatri, Pooja; Kirmani, Jawad F.; Liebeskind, David S.; Linfante, Italo; Nguyen, Thanh N.; Saver, Jeffrey L.; Shutter, Lori; Xavier, Andrew; Yavagal, Dileep; Zaidat, Osama O.

    2012-01-01

    Guidelines have been established for the management of acute ischemic stroke; however, specific recommendations for endovascular revascularization therapy are lacking. Burgeoning investigation of endovascular revascularization therapies for acute ischemic stroke, rapid device development, and a diverse training background of the providers performing the procedures underscore the need for practice recommendations. This review provides a concise summary of the Society of Vascular and Interventional Neurology endovascular acute ischemic stroke roundtable meeting. This document was developed to review current clinical efficacy of pharmacologic and mechanical revascularization therapy, selection criteria, periprocedure management, and endovascular time metrics and to highlight current practice patterns. It therefore provides an outline for the future development of multisociety guidelines and recommendations to improve patient selection, procedural management, and organizational strategies for revascularization therapies in acute ischemic stroke. PMID:23008406

  8. IL1RN VNTR Polymorphism in Ischemic Stroke

    PubMed Central

    Worrall, Bradford B.; Brott, Thomas G.; Brown, Robert D.; Brown, W. Mark; Rich, Stephen S.; Arepalli, Sampath; Wavrant-De Vrièze, Fabienne; Duckworth, Jaime; Singleton, Andrew B.; Hardy, John; Meschia, James F.

    2008-01-01

    Background and Purpose Genetic factors influence risk for ischemic stroke and likely do so at multiple steps in the pathogenic process. Variants in genes related to inflammation contribute to risk of stroke. The purpose of this study was to confirm our earlier finding of an association between allele 2 of a variable number tandem repeat of the IL-1 receptor antagonist gene (IL1RN) and cerebrovascular disease. Methods An association study of the variable number tandem repeat genotype with ischemic stroke and stroke subtypes was performed on samples from a North American study of affected sibling pairs concordant for ischemic stroke and 2 North American cohorts of prospectively ascertained ischemic stroke cases and unrelated controls. DNA analysis was performed on cases and controls, stratified by race. Results After adjustment for age, sex, and stroke risk factors, the odds ratio for association of allele 2 and ischemic stroke was 2.80 (95% confidence interval, 1.29 to 6.11; P=0.03) for the white participants. The effect of allele 2 of IL1RN on stroke risk most closely fits a recessive genetic model (P=0.009). For the smaller sample of nonwhite participants, the results were not significant. Conclusions Allele 2 of IL1RN, present in nearly one-quarter of stroke patients, may contribute to genetic risk for ischemic stroke and confirm the previously identified association with cerebrovascular disease. These results are driven by the association in the white participants. Further exploration in a larger nonwhite sample is warranted. PMID:17332449

  9. Systemic chemokine levels, coronary heart disease, and ischemic stroke events

    PubMed Central

    Canouï-Poitrine, F.; Luc, G.; Mallat, Z.; Machez, E.; Bingham, A.; Ferrieres, J.; Ruidavets, J.-B.; Montaye, M.; Yarnell, J.; Haas, B.; Arveiler, D.; Morange, P.; Kee, F.; Evans, A.; Amouyel, P.; Ducimetiere, P.

    2011-01-01

    Objectives: To quantify the association between systemic levels of the chemokine regulated on activation normal T-cell expressed and secreted (RANTES/CCL5), interferon-γ-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease (CHD) and ischemic stroke events and to assess their usefulness for CHD and ischemic stroke risk prediction in the PRIME Study. Methods: After 10 years of follow-up of 9,771 men, 2 nested case-control studies were built including 621 first CHD events and 1,242 matched controls and 95 first ischemic stroke events and 190 matched controls. Standardized hazard ratios (HRs) for each log-transformed chemokine were estimated by conditional logistic regression. Results: None of the 4 chemokines were independent predictors of CHD, either with respect to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70; 95% confidence interval [CI] 1.05–2.74), IP-10 (HR = 1.53; 95% CI 1.06–2.20), and eotaxin-1 (HR = 1.59; 95% CI 1.02–2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68–1.46), were associated with ischemic stroke independently of traditional cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines were included in the same multivariate model, RANTES and IP-10 remained predictive of ischemic stroke. Their addition to a traditional risk factor model predicting ischemic stroke substantially improved the C-statistic from 0.6756 to 0.7425 (p = 0.004). Conclusions: In asymptomatic men, higher systemic levels of RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk prediction over traditional risk factors. PMID:21849651

  10. Ischemic stroke patients are biologically older than their chronological age

    PubMed Central

    Soriano-Tárraga, Carolina; Giralt-Steinhauer, Eva; Mola-Caminal, Marina; Vivanco-Hidalgo, Rosa M.; Ois, Angel; Rodríguez-Campello, Ana; Cuadrado-Godia, Elisa; Sayols-Baixeras, Sergi; Elosua, Roberto; Roquer, Jaume; Jiménez-Conde, Jordi

    2016-01-01

    Ischemic stroke is associated with aging. It is possible to predict chronological age by measuring age-related changes in DNA methylation from multiple CpG sites across the genome, known as biological age. The difference between biological age and actual chronological age would indicate an individual's level of aging. Our aim was to determine the biological age of ischemic stroke patients and compare their aging with controls of the same chronological age. A total of 123 individuals, 41 controls and 82 patients with ischemic stroke were paired by chronological age, ranging from 39 to 82 years. Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites in both groups, and biological age was estimated using methylation values of specific CpGs. Ischemic stroke patients were biologically an average 2.5 years older than healthy controls (p-value=0.010). Stratified by age tertiles, younger stroke patients (≤57 years old) were biologically older than controls (OR=1.19; 95%CI 1.00-1.41, p-value=0.046). The older groups showed no biological age differences between cases and controls, but were close to reaching the significance level. Ischemic stroke patients are biologically older than controls. Biological age should be considered as a potential new biomarker of stroke risk. PMID:27922817

  11. Rotating night shift work and the risk of ischemic stroke.

    PubMed

    Brown, Devin L; Feskanich, Diane; Sánchez, Brisa N; Rexrode, Kathryn M; Schernhammer, Eva S; Lisabeth, Lynda D

    2009-06-01

    Rotating night shift work disrupts circadian rhythms and is associated with coronary heart disease. The relation between rotating night shift work and ischemic stroke is unclear. The Nurses' Health Study, an ongoing cohort study of registered female nurses, assessed in 1988 the total number of years the nurses had worked rotating night shifts. The majority (69%) of stroke outcomes from 1988 to 2004 were confirmed by physician chart review. The authors used Cox proportional hazards models to assess the relation between years of rotating night shift work and ischemic stroke, adjusting for multiple vascular risk factors. Of 80,108 subjects available for analysis, 60% reported at least 1 year of rotating night shift work. There were 1,660 ischemic strokes. Rotating night shift work was associated with a 4% increased risk of ischemic stroke for every 5 years (hazard ratio = 1.04, 95% confidence interval: 1.01, 1.07; P(trend) = 0.01). This increase in risk was similar when limited to the 1,152 confirmed ischemic strokes (hazard ratio = 1.03, 95% confidence interval: 0.99, 1.07; P(trend) = 0.10) and may be confined to women with a history of 15 or more years of rotating shift work. Women appear to have a modestly increased risk of stroke after extended periods of rotating night shift work.

  12. Delay time between onset of ischemic stroke and hospital arrival.

    PubMed

    Biller, J; Patrick, J T; Shepard, A; Adams, H P

    1993-01-01

    Some current experimental protocols for acute ischemic stroke require the initiation of treatment within hours of the onset of stroke symptoms. We prospectively evaluated 30 patients with acute ischemic stroke based on clinical and computed tomography findings. The time between the onset of stroke symptoms and arrival in the emergency room and subsequently on the stroke service was determined. Within 3, 6,12, and 24 h of the onset of stroke symptoms, 16 (53%), 19 (63%), 22 (73%), and 25 (83%) patients had arrived at the emergency room and 0 (0%), 4 (13%), 14 (47%), and 22 (73%) of them on the stroke service, respectively. From the onset of stroke symptoms, the mean arrival time to the emergency room was 24 h (range, 30 min to 144 h) and to the stroke service was 61 h (range, 4-150 h). The mean time between arrival in the emergency room and stroke service was 8.6 h (range, 0-47 h). Even though 53% and 63% of our patients arrived at the emergency room within 3 and 6 h of the onset of stroke symptoms, only 0% and 13% of them arrived on the stroke service within the same time period for the initiation of treatment, respectively. Thus, in order for more patients to qualify for current experimental protocols, they must arrive on the stroke service more quickly or treatment must be initiated in the emergency room.

  13. Trypanosomiasis, cardiomyopathy and the risk of ischemic stroke.

    PubMed

    Carod-Artal, Francisco Javier

    2010-05-01

    American (Chagas disease) and African (sleeping sickness) trypanosomiasis are neglected tropical diseases and are a heavy burden in Latin America and Africa, respectively. Chagas disease is an independent risk factor for stroke. Apical aneurysm, heart failure and cardiac arrhythmias are associated with ischemic stroke in chagasic cardiomyopathy. Not all chagasic patients who suffer an ischemic stroke have a severe cardiomyopathy, and stroke may be the first manifestation of Chagas disease. Cardioembolism affecting the middle cerebral artery is the most common stroke subtype. Risk of recurrence is high and careful evaluation of recurrence risk should be addressed. Repolarization changes, low voltage and prolonged QT interval are common electrocardiography alterations in human African trypanosomiasis, and can be found in more than 70% of patients. Epidemiological studies are needed to asses the risk of stroke in African trypanosomiasis perimyocarditis.

  14. Normobaric oxygen treatment in acute ischemic stroke: a clinical perspective

    PubMed Central

    Shi, Shu-hai; Qi, Zhi-feng; Luo, Yu-min; Ji, Xun-ming; Liu, Ke Jian

    2016-01-01

    Acute ischemic stroke is a common and serious neurological disease. Oxygen therapy has been shown to increase oxygen supply to ischemic tissues and improve outcomes after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBO), an easily applicable and non-invasive method, shows protective effects on acute ischemic stroke animals and patients in pilot studies. However, many critical scientific questions are still unclear, such as the therapeutic time window of NBO, the long-term effects and the benefits of NBO in large clinic trials. In this article, we review the current literatures on NBO treatment of acute ischemic stroke in preclinical and clinical studies and try to analyze and identify the key gaps or unknowns in our understanding about NBO. Based on these analyses, we provide suggestions for future studies. PMID:27867482

  15. Ischemic Stroke and Its Risk Factors in a Registry-Based Large Cross-Sectional Diabetic Cohort in a Country Facing a Diabetes Epidemic

    PubMed Central

    Al-Rubeaan, Khalid; Al-Hussain, Fawaz; Youssef, Amira M.; Subhani, Shazia N.; Al-Sharqawi, Ahmad H.; Ibrahim, Heba M.

    2016-01-01

    The main aim of this study is to determine the prevalence and risk factors of ischemic stroke among diabetic patients registered in the Saudi National Diabetes Registry (SNDR) database. A cross-sectional sample of 62,681 diabetic patients aged ≥25 years was used to calculate ischemic stroke prevalence and its risk factors. Univariate and multivariate logistic regression analyses were used to assess the roles of different risk factors. The prevalence of ischemic stroke was 4.42% and was higher in the older age group with longer diabetes duration. Poor glycemic control and the presence of chronic diabetes complications were associated with a high risk of ischemic stroke. History of smoking and type 2 diabetes were more frequent among stroke patients. Obesity significantly decreased the risk for ischemic stroke. Regression analysis for ischemic stroke risk factors proved that age ≥45 years, male gender, hypertension, coronary artery disease (CAD), diabetes duration ≥10 years, insulin use, and hyperlipidemia were significant independent risk factors for ischemic stroke. We conclude that ischemic stroke is prevalent among diabetic individuals, particularly among those with type 2 diabetes. Good glycemic, hypertension, and hyperlipidemia control, in addition to smoking cessation, are the cornerstones to achieve a significant reduction in ischemic stroke risk. PMID:26989695

  16. Factoring in Factor VIII With Acute Ischemic Stroke.

    PubMed

    Siegler, James E; Samai, Alyana; Albright, Karen C; Boehme, Amelia K; Martin-Schild, Sheryl

    2015-10-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke.

  17. Perfusion Angiography in Acute Ischemic Stroke

    PubMed Central

    Liebeskind, David S.

    2016-01-01

    Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. This paper lays out a methodological framework, named perfusion angiography, for the quantitative analysis and visualization of blood flow parameters from DSA images. The parameters, including cerebral blood flow (CBF) and cerebral blood volume (CBV), mean transit time (MTT), time-to-peak (TTP), and Tmax, are computed using a bolus tracking method based on the deconvolution of the time-density curve on a pixel-by-pixel basis. The method is tested on 66 acute ischemic stroke patients treated with thrombectomy and/or tissue plasminogen activator (tPA) and also evaluated on an estimation task with known ground truth. This novel imaging tool provides unique insights into flow mechanisms that cannot be observed directly in DSA sequences and might be used to evaluate the impact of endovascular interventions more precisely. PMID:27446232

  18. The effects of citicoline on acute ischemic stroke: a review.

    PubMed

    Overgaard, Karsten

    2014-08-01

    Early reopening of the occluded artery is, thus, important in ischemic stroke, and it has been calculated that 2 million neurons die every minute in an ischemic stroke if no effective therapy is given; therefore, "Time is Brain." In massive hemispheric infarction and edema, surgical decompression lowers the risk of death or severe disability defined as a modified Rankin Scale score greater than 4 in selected patients. The majority, around 80%-85% of all ischemic stroke victims, does not fulfill the criteria for revascularization therapy, and also for these patients, there is no effective acute therapy. Also there is no established effective acute treatment of spontaneous intracerebral bleeding. Therefore, an effective therapy applicable to all stroke victims is needed. The neuroprotective drug citicoline has been extensively studied in clinical trials with volunteers and more than 11,000 patients with various neurologic disorders, including acute ischemic stroke (AIS). The conclusion is that citicoline is safe to use and may have a beneficial effect in AIS patients and most beneficial in less severe stroke in older patients not treated with recombinant tissue plasminogen activator. No other neuroprotective agent had any beneficial effect in confirmative clinical trials or had any positive effect in the subgroup analysis. Citicoline is the only drug that in a number of different clinical stroke trials continuously had some neuroprotective benefit.

  19. Expression profile based gene clusters for ischemic stroke detection Whole blood gene clusters for ischemic stroke detection

    PubMed Central

    Adamski, Mateusz G; Li, Yan; Wagner, Erin; Yu, Hua; Seales-Bailey, Chloe; Soper, Steven A; Murphy, Michael; Baird, Alison E

    2014-01-01

    In microarray studies alterations in gene expression in circulating leukocytes have shown utility for ischemic stroke diagnosis. We studied forty candidate markers identified in three gene expression profiles to (1) quantitate individual transcript expression, (2) identify transcript clusters and (3) assess the clinical diagnostic utility of the clusters identified for ischemic stroke detection. Using high throughput next generation qPCR 16 of the 40 transcripts were significantly up-regulated in stroke patients relative to control subjects (p<0.05). Six clusters of between 5 and 7 transcripts discriminated between stroke and control (p values between 1.01e-9 and 0.03). A 7 transcript cluster containing PLBD1, PYGL, BST1, DUSP1, FOS, VCAN and FCGR1A showed high accuracy for stroke classification (AUC=0.854). These results validate and improve upon the diagnostic value of transcripts identified in microarray studies for ischemic stroke. The clusters identified show promise for acute ischemic stroke detection. PMID:25135788

  20. Moderate alcohol intake reduces risk of ischemic stroke in Korea

    PubMed Central

    Lee, Soo Joo; Cho, Yong-Jin; Kim, Jae Guk; Ko, Youngchai; Hong, Keun-Sik; Park, Jong-Moo; Kang, Kyusik; Park, Tai Hwan; Park, Sang-Soon; Lee, Kyung Bok; Cha, Jae Kwan; Kim, Dae-Hyun; Lee, Jun; Kim, Joon-Tae; Lee, Juneyoung; Lee, Ji Sung; Jang, Myung Suk; Han, Moon-Ku; Gorelick, Philip B.

    2015-01-01

    Objective: We undertook a population-based, case-control study to examine a dose-response relationship between alcohol intake and risk of ischemic stroke in Koreans who had different alcoholic beverage type preferences than Western populations and to examine the effect modifications by sex and ischemic stroke subtypes. Methods: Cases (n = 1,848) were recruited from patients aged 20 years or older with first-ever ischemic stroke. Stroke-free controls (n = 3,589) were from the fourth and fifth Korean National Health and Nutrition Examination Survey and were matched to the cases by age (±3 years), sex, and education level. All participants completed an interview using a structured questionnaire about alcohol intake. Results: Light to moderate alcohol intake, 3 or 4 drinks (1 drink = 10 g ethanol) per day, was significantly associated with a lower odds of ischemic stroke after adjusting for potential confounders (no drinks: reference; <1 drink: odds ratio 0.38, 95% confidence interval 0.32–0.45; 1–2 drinks: 0.45, 0.36–0.57; and 3–4 drinks: 0.54, 0.39–0.74). The threshold of alcohol effect in women was slightly lower than that in men (up to 1–2 drinks in women vs up to 3–4 drinks in men), but this difference was not statistically significant. There was no statistical interaction between alcohol intake and the subtypes of ischemic stroke (p = 0.50). The most frequently used alcoholic beverage was one native to Korea, soju (78% of the cases), a distilled beverage with 20% ethanol by volume. Conclusions: Our findings suggest that light to moderate distilled alcohol consumption may reduce the risk of ischemic stroke in Koreans. PMID:26519539

  1. Ischemic Stroke in the Elderly: Septuagenarians Versus Octogenarians

    PubMed Central

    BAŞTAN, Birgül; GÜNAYDIN, Sefer; BALCI, Fatma Belgin; ACAR, Hürtan; MUTLU, Aytül; ÖZER, Feriha; ÇOKAR, Özlem

    2016-01-01

    Introduction Stroke prevalence is known to increase with age. Approximately 50% of acute ischemic stroke patients are aged between 70 and 89 years. Methods In this study, records of 770 ischemic stroke patients who were 70–89 years old were retrospectively examined (407 septuagenarians and 363 octogenarians). The demographics, comorbid conditions, ischemic stroke type, and stroke outcome for the two age groups were analyzed. Results Comorbid hypertension, diabetes mellitus, and HbA1c levels of ≥6.5% more frequently occurred in septuagenarians than in octogenarians (80.6% versus 70.8%, p=0.002; 32.2% versus 21.8%, p=0.001; and 35% versus 23.2%, p=0.003, respectively), whereas atrial fibrillation was significantly higher in octogenarians (49.3% versus 41.5%, p=0.03). Hypercholesterolemia, previous stroke history, and antiaggregant and/or anticoagulant use were not significantly different between the two age groups. Based on the Oxfordshire Community Stroke Project classification, the most common stroke subtype in the septuagenarian group was a lacunar infarction and in the octogenarian group, it was a partial anterior circulation infarct. According to the Modified Ranking Score, the number of patients living independently was higher for septuagenarians (42.8% versus 27.8%, p<0.001). Conclusion The present findings indicate that the clinical characteristics of ischemic stroke differed between septuagenarians and octogenarians. Therefore, elderly stroke patients cannot be accepted as a homogeneous group. Because this is a hospital-based study, our findings need to be tested via additional epidemiological studies. PMID:28360808

  2. Ischemic Stroke in Young Adults and Preexisting Psychiatric Disorders

    PubMed Central

    Chiu, Yu-Chuan; Bai, Ya-Mei; Su, Tung-Ping; Chen, Tzeng-Ji; Chen, Mu-Hong

    2015-01-01

    Abstract Previous studies showed that psychiatric disorders such as major depression, bipolar disorders, and alcohol misuse are associated with an increased risk of ischemic stroke. However, the link between psychiatric disorders and stroke in the young population is rarely investigated. Using the Taiwan National Health Insurance Research Database, 2063 young adults aged between 18 and 45 years with ischemic stroke and 8252 age- and sex-matched controls were enrolled in our study between 1998 and 2011. Participants who had preexisting psychiatric disorders were identified. After adjusting for preexisting physical disorders and demographic data, patients with ischemic stroke had an increased risk of having preexisting psychiatric disorders, including bipolar disorder (odds ratio [OR]: 2.23, 95% confidence interval [CI]: 1.06∼4.67), unipolar depression (OR: 2.15, 95% CI: 1.62∼2.86), anxiety disorders (OR: 2.63, 95% CI: 1.87∼3.69), and alcohol use disorders (OR: 2.86, 95% CI: 1.79∼4.57). Young ischemic stroke (age ≥30 years) was related to the risk of preexisting unipolar depression (OR: 1.49, 95% CI: 1.05∼2.11), anxiety disorders (OR: 1.99, 95% CI: 1.33∼2.97), and alcohol use disorders (OR: 2.54, 95% CI: 1.55∼4.14); very young stroke (age <30 years) was only associated with the risk of preexisting unipolar depression (OR: 4.15, 95% CI: 1.47∼11.72). Patients who had experienced ischemic stroke at age younger than 45 years had a higher risk of having pre-existing bipolar disorder, unipolar depression, anxiety disorders, and alcohol use disorders than those who did not after adjusting for demographic data and stroke-related medical comorbidities. PMID:26402806

  3. NLRP3 deficiency ameliorates neurovascular damage in experimental ischemic stroke.

    PubMed

    Yang, Fan; Wang, Ziying; Wei, Xinbing; Han, Huirong; Meng, Xianfang; Zhang, Yan; Shi, Weichen; Li, Fengli; Xin, Tao; Pang, Qi; Yi, Fan

    2014-04-01

    Although the innate immune response to induce postischemic inflammation is considered as an essential step in the progression of cerebral ischemia injury, the role of innate immunity mediator NLRP3 in the pathogenesis of ischemic stroke is unknown. In this study, focal ischemia was induced by middle cerebral artery occlusion in NLRP3(-/-), NOX2(-/-), or wild-type (WT) mice. By magnetic resonance imaging (MRI), Evans blue permeability, and electron microscopic analyses, we found that NLRP3 deficiency ameliorated cerebral injury in mice after ischemic stroke by reducing infarcts and blood-brain barrier (BBB) damage. We further showed that the contribution of NLRP3 to neurovascular damage was associated with an autocrine/paracrine pattern of NLRP3-mediated interleukin-1β (IL-1β) release as evidenced by increased brain microvessel endothelial cell permeability and microglia-mediated neurotoxicity. Finally, we found that NOX2 deficiency improved outcomes after ischemic stroke by mediating NLRP3 signaling. This study for the first time shows the contribution of NLRP3 to neurovascular damage and provides direct evidence that NLRP3 as an important target molecule links NOX2-mediated oxidative stress to neurovascular damage in ischemic stroke. Pharmacological targeting of NLRP3-mediated inflammatory response at multiple levels may help design a new approach to develop therapeutic strategies for prevention of deterioration of cerebral function and for the treatment of stroke.

  4. A novel useful tool of computerized touch panel-type screening test for evaluating cognitive function of chronic ischemic stroke patients.

    PubMed

    Deguchi, Kentaro; Kono, Syoichiro; Deguchi, Shoko; Morimoto, Nobutoshi; Kurata, Tomoko; Ikeda, Yoshio; Abe, Koji

    2013-10-01

    Cognitive and affective impairments are important non-motor features of ischemic stroke (IS) related to white-matter hyperintensity, including periventricular hyperintensity (PVH). To confirm the usefulness of a novel computerized touch panel-type screening test, we investigated cognitive and affective functioning among 142 IS patients and 105 age-and gender-matched normal control subjects. Assessment using the mini-mental state examination, Hasegawa Dementia Scale-Revised, and frontal assessment battery revealed reduced cognitive function in IS patients, with the most severe reduction exhibited by cardiogenic embolism patients, followed by lacunar infarction patients, and atherothrombotic infarction patients. Our novel touch panel screening test revealed a similar pattern of results. In addition, PVH grading, classified using Fazekas' magnetic resonance imaging method, was also correlated with cognitive decline and touch panel screening test performance. In contrast, affective function, assessed with the 15-item Geriatric Depression Scale, vitality index, and apathy scale, was not significantly decreased in IS, and did not correlate with touch panel screening test results or PVH, although the number of microbleeds was correlated with apathy scale results. The present findings revealed that IS and PVH grading were significantly correlated with decline in general cognitive status (mini-mental state examination and Hasegawa Dementia Scale-Revised) and frontal lobe function (frontal assessment battery). Performance on all touch panel screening tests was correlated with IS and PVH grading, but was largely independent of depression or apathy. Touch panel screening tests were easily understood and performed by almost all patients with mild cognitive and motor dysfunction, due to visually clear images and simple methods not involving detailed manual-handling tasks such as writing. Touch panel screening tests may provide a useful tool for the early screening of cognitive

  5. Positive effects of intermittent fasting in ischemic stroke.

    PubMed

    Fann, David Yang-Wei; Ng, Gavin Yong Quan; Poh, Luting; Arumugam, Thiruma V

    2017-03-01

    Intermittent fasting (IF) is a dietary protocol where energy restriction is induced by alternate periods of ad libitum feeding and fasting. Prophylactic intermittent fasting has been shown to extend lifespan and attenuate the progress and severity of age-related diseases such as cardiovascular (e.g. stroke and myocardial infarction), neurodegenerative (e.g. Alzheimer's disease and Parkinson's disease) and cancerous diseases in animal models. Stroke is the second leading cause of death, and lifestyle risk factors such as obesity and physical inactivity have been associated with elevated risks of stroke in humans. Recent studies have shown that prophylactic IF may mitigate tissue damage and neurological deficit following ischemic stroke by a mechanism(s) involving suppression of excitotoxicity, oxidative stress, inflammation and cell death pathways in animal stroke models. This review summarizes data supporting the potential hormesis mechanisms of prophylactic IF in animal models, and with a focus on findings from animal studies of prophylactic IF in stroke in our laboratory.

  6. Coupling of Neurogenesis and Angiogenesis After Ischemic Stroke

    PubMed Central

    Ruan, Linhui; Wang, Brian; ZhuGe, Qichuan; Jin, Kunlin

    2015-01-01

    Stroke is a leading cause of mortality and severe long-term disability worldwide. Development of effective treatment or new therapeutic strategies for ischemic stroke patients is therefore crucial. Ischemic stroke promotes neurogenesis by several growth factors including FGF-2, IGF-1, BDNF, VEGF and chemokines including SDF-1, MCP-1. Stroke-induced angiogenesis is similarly regulated by many factors most notably, eNOS and CSE, VEGF/VEGFR2, and Ang-1/Tie2. Important findings in the last decade have revealed that neurogenesis is not the stand-alone consideration in the fight for full functional recovery from stroke. Angiogenesis has been also shown to be critical in improving post-stroke neurological functional recovery. More than that, recent evidence has shown a highly possible interplay or dependence between stroke-induced neurogenesis and angiogenesis. Moving forward, elucidating the underlying mechanisms of this coupling between stroke-induced neurogenesis and angiogenesis will be of great importance, which will provide the basis for neurorestorative therapy. PMID:25736182

  7. Minor Stroke and Transient Ischemic Attack: Research and Practice

    PubMed Central

    Yakhkind, Aleksandra; McTaggart, Ryan A.; Jayaraman, Mahesh V.; Siket, Matthew S.; Silver, Brian; Yaghi, Shadi

    2016-01-01

    A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA. PMID:27375548

  8. Alpha 1-Antitrypsin Therapy Mitigated Ischemic Stroke Damage in Rats

    PubMed Central

    Moldthan, Huong L.; Hirko, Aaron C.; Thinschmidt, Jeffrey S.; Grant, Maria; Li, Zhimin; Peris, Joanna; Lu, Yuanqing; Elshikha, Ahmed; King, Michael A.; Hughes, Jeffrey A.; Song, Sihong

    2014-01-01

    Currently, the only effective therapy for acute ischemic stroke is the thrombolytic agent recombinant tissue plasminogen activator. α1-Antitrypsin, an endogenous inhibitor of serine proteinases and a primary acute phase protein with potent anti-inflammatory, anti-apoptotic, antimicrobial and cytoprotective activities, could be beneficial in stroke.. The goal of this study was to test whether α1-antitrypsin could improve ischemic stroke outcome in an established rat model. Middle cerebral artery occlusion was induced in male rats via intracranial microinjection of endothelin-1. Five to ten minutes following stroke induction rats received either intracranial or intravenous delivery of human α1-antitrypsin. Cylinder and vibrissae tests were used to evaluate sensorimotor function before and 72 hours after middle cerebral artery occlusion. Infarct volumes were examined via either 2,3,5-triphenyltetrazolium chloride assay or magnetic resonance imaging 72 hours after middle cerebral artery occlusion. Despite equivalent initial strokes, at 72 hours the infarct volumes of the human α1-antitrypsin treatment groups (local and systemic injection) were statistically significantly reduced by 83% and 63% (p<0.0001 and p < 0.05 respectively) compared with control rats. Human α1-antitrypsin significantly limited sensory motor systems deficits. Human α1-antitrypsin could be a potential novel therapeutic drug for the protection against neurodegeneration following ischemic stroke, but more studies are needed to investigate the protective mechanisms and efficacy in other animal models. PMID:24582784

  9. Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

    SciTech Connect

    Lee, Ching-Chih; Su, Yu-Chieh; Ho, Hsu-Chueh; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Chou, Pesus; Huang, Yung-Sung

    2011-12-01

    Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35-54 had a 1.66 times (95% CI, 1.16-2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55-64 years (hazard ratio = 0.87; 95% CI, 0.56-1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.

  10. Cranial anatomy and detection of ischemic stroke in the cat by nuclear magnetic resonance imaging

    SciTech Connect

    Buonanno, F.S.; Pykett, I.L.; Kistler, J.P.; Vielma, J.; Brady, T.J.; Hinshaw, W.S.; Goldman, M.R.; Newhouse, J.H.; Pohost, G.M.

    1982-04-01

    Proton nuclear magnetic resonance (NMR) images of cat heads were obtained using a small, experimental imaging system. As a prelude to the study of experimental ischemic brain infarction, the normal cat head was imaged for identification of anatomical features. Images of one cat which had undergone ligation of the middle cerebral artery three weeks previously showed brain changes associated with chronic ischemic stroke and compared favorably with findings on computed tomography (CT). The NMR images have millimetric spatial resolution. NMR parameters inherent in the tissues provide intensity variations and are sufficiently sensitive to yield contrast resolution surpassing that of CT.

  11. Loss of the Mexican American survival advantage after ischemic stroke

    PubMed Central

    Morgenstern, Lewis B.; Brown, Devin L.; Smith, Melinda A.; Sánchez, Brisa N.; Zahuranec, Darin B.; Garcia, Nelda; Kerber, Kevin A.; Skolarus, Lesli E.; Meurer, William J; Burke, James F; Adelman, Eric E.; Baek, Jonggyu; Lisabeth, Lynda D.

    2014-01-01

    Background and Purpose Mexican Americans (MAs) were previously found to have lower mortality following ischemic stroke than non Hispanic Whites (NHWs). We studied mortality trends in a population-based design. Methods Active and passive surveillance were used to find all ischemic stroke cases from January, 2000–December, 2011 in Nueces County, Texas. Deaths were ascertained from the Texas Department of Health through December 31 2012. Cumulative 30-day and 1 year mortality adjusted for covariates was estimated using log-binomial models with a linear term for year of stroke onset used to model time trends. Models used data from the entire study period to estimate adjusted mortality among stroke cases in 2000 and 2011, and to calculate projected ethnic differences. Results There were 1,974 ischemic strokes among NHWs and 2,439 among MAs. Between 2000 and 2011, model estimated mortality declined among NHWs at 30 days (7.6% to 5.6%, p=0.24) and 1 year (20.8% to 15.5%, p=0.02). Among MAs, 30-day model estimated mortality remained stagnant at 5.1% to 5.2% (p=0.92), and a slight decline from 17.4% to 15.3% was observed for 1 year mortality (p=0.26). While ethnic differences in 30-day (p=0.01) and 1 year (p=0.06) mortality were apparent in 2000, they were not so in 2011 (30-day, p=0.63; 1 year p=0.92). Conclusions Overall, mortality following ischemic stroke has declined in the last decade, although significant declines were only observed for NHWs and not MAs at 1 year. The survival advantage previously documented among MAs vanished by 2011. Renewed stroke prevention and treatment efforts for MAs are needed. PMID:25074514

  12. [Neuroprotective treatment with citicoline (ceraxon) in patients with ischemic stroke].

    PubMed

    Martynov, M Iu; Boĭko, A N; Kamchatnov, P R; Kabanov, A A; Iasamanova, A N; Shchukin, I A; Kolesnikova, T I; Chubykin, V I; Glukhareva, A P; Gusev, E I

    2012-01-01

    The dynamics of neurological symptoms assessed with the Scandinavian stroke scale, the Barthel index and the modified Rankin scale was studied in 89 patients with moderate ischemic stroke who received citicoline (ceraxone) intravenously and orally. The results were compared to a group of 52 age-, sex- and stroke-matched patients who did not receive citicoline. To the date of discharge from the hospital (days 21-24), the full restoration (p<0.05) was noted in patients of the main group. Efficacy of citicoline was significantly (p<0.05) higher in patients younger than 70 years and when the drug was used in the first hours of disease.

  13. [Neuroprotective therapy for the treatment of acute ischemic stroke].

    PubMed

    Naritomi, H

    2001-12-01

    Following cerebral ischemia, various biochemical reactions are provoked in a stepwise manner leading neuronal cells to ischemic death. The prevention of these biochemical reactions may exert neuroprotective actions and consequently reduce the magnitude of ischemic cerebral injury. On the basis of such a view, numerous neuroprotective drugs have been developed during the last decade. Quite a few drugs were found effective in reducing the infarct volume in experimental studies, and more than 15 of them were subjected to clinical phase III trials to see a therapeutic effectiveness. However, the results of phase III trials were disappointing in the majority drugs. Only three drugs, nicaravene, ebselen and edaravone, all radical scavengers, were judged effective by small-sized trials with a wide therapeutic window, 48-72 hours after stroke, in Japan. The fact suggests that a one-point prevention of biochemical reactions by single drug is unable to rescue ischemic neuronal cells. Ischemic insult causes damages of vascular wall including the endothelium which play an important role in the development of hemorrhagic changes or cerebral edema. Vascular protection is considered as important as neuroprotection in treatment of clinical stroke. Mild hypothermia has neuroprotective and vascular protective actions and hence may be more effective than neuroprotective drugs for the treatment of stroke. The prevention of fever, which often occurs in severe stroke, may exert the similar effect as hypothermia in neuroprotection. Neuroprotective therapy in the future should proceed toward the simultaneous protections of neurons and vessels using combination of multiple drugs.

  14. Ambient Air Pollution and the Risk of Acute Ischemic Stroke

    PubMed Central

    Wellenius, Gregory A.; Burger, Mary R.; Coull, Brent A.; Schwartz, Joel; Suh, Helen H.; Koutrakis, Petros; Schlaug, Gottfried; Gold, Diane R.; Mittleman, Murray A.

    2013-01-01

    Background The link between daily changes in ambient fine particulate matter air pollution (PM2.5) and cardiovascular morbidity and mortality is well established. Whether PM2.5 at levels below current US National Ambient Air Quality Standards also increases the risk of ischemic stroke remains uncertain. Methods We reviewed the medical records of 1705 Boston-area patients hospitalized with neurologist-confirmed ischemic stroke and abstracted data on the time of symptom onset and clinical characteristics. PM2.5 concentrations were measured at a central monitoring station. We used the time-stratified case-crossover study design to assess the association between the risk of ischemic stroke onset and PM2.5 levels in the hours and days preceding each event. We examined whether the association with PM2.5 differed by ischemic stroke etiology and patient characteristics. Results The estimated odds ratio of ischemic stroke onset was 1.34 (95% confidence interval (CI): 1.13, 1.58; p<0.001) following a 24-hour period classified as “moderate” (PM2.5 15–40 μg/m3) by the US Environmental Protection Agency’s (EPA) Air Quality Index compared to a 24-hour period classified as “good” (≤15 μg/m3). Considering PM2.5 as a continuous variable, the estimated odds ratio of ischemic stroke onset was 1.11 (95% CI: 1.03, 1.20; p=0.006) per interquartile range increase in PM2.5 (6.4 μg/m3). The increase in risk was greatest within 12–14 hours of exposure to PM2.5 and was most strongly associated with markers of traffic-related pollution. Conclusion These results suggest that exposure to PM2.5 levels considered generally safe by the US EPA increase the risk of ischemic stroke onset within hours of exposure. PMID:22332153

  15. Intermittent fasting attenuates inflammasome activity in ischemic stroke.

    PubMed

    Fann, David Yang-Wei; Santro, Tomislav; Manzanero, Silvia; Widiapradja, Alexander; Cheng, Yi-Lin; Lee, Seung-Yoon; Chunduri, Prasad; Jo, Dong-Gyu; Stranahan, Alexis M; Mattson, Mark P; Arumugam, Thiruma V

    2014-07-01

    Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity.

  16. Asymmetric Dimethyarginine as Marker and Mediator in Ischemic Stroke

    PubMed Central

    Chen, Shufen; Li, Na; Deb-Chatterji, Milani; Dong, Qiang; Kielstein, Jan T.; Weissenborn, Karin; Worthmann, Hans

    2012-01-01

    Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, is known as mediator of endothelial cell dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. Accordingly, clinical studies found evidence that increased ADMA levels are associated with a higher risk of cerebrovascular events. After the acute event of ischemic stroke, levels of ADMA and its analog symmetric dimethylarginine (SDMA) are elevated through augmentation of protein methylation and oxidative stress. Furthermore, cleavage of ADMA through dimethylarginine dimethylaminohydrolases (DDAHs) is reduced. This increase of dimethylarginines might be predictive for adverse clinical outcome. However, the definite role of ADMA after acute ischemic stroke still needs to be clarified. On the one hand, ADMA might contribute to brain injury by reduction of cerebral blood flow. On the other hand, ADMA might be involved in NOS-induced oxidative stress and excitotoxic neuronal death. In the present review, we highlight the current knowledge from clinical and experimental studies on ADMA and its role for stroke risk and ischemic brain injury in the hyperacute stage after stroke. Finally, further studies are warranted to unravel the relevance of the close association of dimethylarginines with stroke. PMID:23443106

  17. Targeting neutrophils in ischemic stroke: translational insights from experimental studies

    PubMed Central

    Jickling, Glen C; Liu, DaZhi; Ander, Bradley P; Stamova, Boryana; Zhan, Xinhua; Sharp, Frank R

    2015-01-01

    Neutrophils have key roles in ischemic brain injury, thrombosis, and atherosclerosis. As such, neutrophils are of great interest as targets to treat and prevent ischemic stroke. After stroke, neutrophils respond rapidly promoting blood–brain barrier disruption, cerebral edema, and brain injury. A surge of neutrophil-derived reactive oxygen species, proteases, and cytokines are released as neutrophils interact with cerebral endothelium. Neutrophils also are linked to the major processes that cause ischemic stroke, thrombosis, and atherosclerosis. Thrombosis is promoted through interactions with platelets, clotting factors, and release of prothrombotic molecules. In atherosclerosis, neutrophils promote plaque formation and rupture by generating oxidized-low density lipoprotein, enhancing monocyte infiltration, and degrading the fibrous cap. In experimental studies targeting neutrophils can improve stroke. However, early human studies have been met with challenges, and suggest that selective targeting of neutrophils may be required. Several properties of neutrophil are beneficial and thus may important to preserve in patients with stroke including antimicrobial, antiinflammatory, and neuroprotective functions. PMID:25806703

  18. Thrombolysis in Chinese Ischemic Stroke Patients with Renal Dysfunction

    PubMed Central

    Lo, Wai Ting; Cheung, Chi Yuen; Li, Chung Ki; Chau, Ka Foon; Fong, Wing Chi

    2015-01-01

    Background Current data concerning the relationship between renal function and clinical outcome among stroke patients treated with intravenous thrombolytic therapy are conflicting. Our aim is to analyze whether the clinical outcome of Chinese ischemic stroke patients treated with thrombolytic therapy is affected by the presence of renal dysfunction. Methods Chinese patients who received intravenous thrombolytic therapy for acute ischemic stroke were recruited. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2. The primary outcome was independent function (modified Rankin Scale, mRS, 0-2) at 3 months, while secondary outcomes included early improvement of the National Institute of Health Stroke Scale (NIHSS) score of ≥4 points at 24 h, symptomatic intracerebral hemorrhage (ICH) within 36 h of treatment and 30-day mortality. Results A total of 199 patients were recruited, of whom 51.3% had renal dysfunction. There were no significant differences in functional independence at 3 months, NIHSS improvement at 24 h post-thrombolysis and 30-day mortality between patients with or without renal dysfunction. Multivariate analysis showed that eGFR as a continuous variable was not an independent risk factor for symptomatic ICH. Conclusion Chinese ischemic stroke patients with renal dysfunction who received thrombolytic therapy had clinical outcomes similar to those without renal dysfunction. PMID:26019713

  19. Long Sleep Duration and Risk of Ischemic Stroke and Hemorrhagic Stroke: the Kailuan Prospective Study

    PubMed Central

    Song, Qiaofeng; Liu, Xiaoxue; Zhou, Wenhua; Wang, Ling; Zheng, Xiang; Wang, Xizhu; Wu, Shouling

    2016-01-01

    The objective of this study was to examine the relationship between sleep duration and ischemic and hemorrhagic stroke in a community-based cohort. The current analysis included 95,023 Chinese participants who were free of stroke at the baseline survey (2006–2007). Cox proportional hazards models were used to calculate hazard ratios (HRs) and their confidence intervals (CIs) for stroke, according to sleep duration. After a mean follow-up period of 7.9 years, 3,135 participants developed stroke (2,504 ischemic stroke and 631 hemorrhagic stroke). The full adjusted hazard ratio (95% CI) of total stroke (with 6–8 hours of night sleep being considered for the reference group) for individuals reporting greater than 8 hours was 1.29 (1.01–1.64). More significant association between long sleep duration and total stroke was found in the elderly (HR, 1.47; 95% CI, 1.05–2.07). Compared with participants getting 6–8 hours of sleep, only women who reported sleeping more than 8 hours per night were associated with hemorrhagic stroke (HR, 3.58; 95% CI, 1.28–10.06). This study suggested that long sleep duration might be a potential predictor/ marker for total stroke, especially in the elderly. And long sleep duration increased the risk of hemorrhagic stroke only in women. PMID:27633270

  20. 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.

  1. The Siblings With Ischemic Stroke Study (SWISS): A Progress Report

    PubMed Central

    Meschia, James F.; Kissela, Brett M.; Brott, Thomas G.; Brown, Robert D.; Worrall, Bradford B.; Beck, Jeanne; Skarp, Alexa N.

    2006-01-01

    There is increasing evidence that genetic factors are associated with ischemic stroke, including multiple recent reports of association with the gene PDE4D, encoding phosphodiesterase 4D, on chromosome 5q12. Genetic studies of stroke are important but can be logistically difficult to perform. This article reviews the design of the Siblings With Ischemic Stroke Study (SWISS) and discusses problems in performing a sibling-based pedigree study where proband-initiated consent is used to enroll pedigree members. Proband-initiated enrollment optimizes privacy protections for family members, but it is associated with a substantial pedigree non-completion rate such that 3 to 4 probands must be identified to obtain one completed sibling pedigree. This report updates the progress of enrollment in the SWISS protocol, discusses barriers to pedigree completion and describes innovative approaches used by the SWISS investigators to enhance enrollment. PMID:16595789

  2. High blood pressure in acute ischemic stroke and clinical outcome.

    PubMed

    Manabe, Yasuhiro; Kono, Syoichiro; Tanaka, Tomotaka; Narai, Hisashi; Omori, Nobuhiko

    2009-11-16

    This study aimed to evaluate the prognostic value of acute phase blood pressure in patients with acute ischemic stroke by determining whether or not it contributes to clinical outcome. We studied 515 consecutive patients admitted within the first 48 hours after the onset of ischemic strokes, employing systolic and diastolic blood pressure measurements recorded within 36 hours after admission. High blood pressure was defined when the mean of at least 2 blood pressure measurements was ≥200 mmHg systolic and/or ≥110 mmHg diastolic at 6 to 24 hours after admission or ≥180 mmHg systolic and/or ≥105 mmHg diastolic at 24 to 36 hours after admission. The high blood pressure group was found to include 16% of the patients. Age, sex, diabetes mellitus, hypercholesterolemia, atrial fibrillation, ischemic heart disease, stroke history, carotid artery stenosis, leukoaraiosis, NIH Stroke Scale (NIHSS) on admission and mortality were not significantly correlated with either the high blood pressure or non-high blood pressure group. High blood pressure on admission was significantly associated with a past history of hypertension, kidney disease, the modified Rankin Scale (mRS) on discharge and the length of stay. On logistic regression analysis, with no previous history of hypertension, diabetes mellitus, atrial fibrillation, and kidney disease were independent risk factors associated with the presence of high blood pressure [odds ratio (OR), 1.85 (95% confidence interval (CI): 1.06-3.22), 1.89 (95% CI: 1.11-3.22), and 3.31 (95% CI: 1.36-8.04), respectively]. Multi-organ injury may be presented in acute stroke patients with high blood pressure. Patients with high blood pressure had a poor functional outcome after acute ischemic stroke.

  3. Sex differences in neuroinflammation and neuroprotection in ischemic stroke.

    PubMed

    Spychala, Monica S; Honarpisheh, Pedram; McCullough, Louise D

    2017-01-02

    Stroke is not only a leading cause of mortality and morbidity worldwide it also disproportionally affects women. There are currently over 500,000 more women stroke survivors in the US than men, and elderly women bear the brunt of stroke-related disability. Stroke has dropped to the fifth leading cause of death in men, but remains the third in women. This review discusses sex differences in common stroke risk factors, the efficacy of stroke prevention therapies, acute treatment responses, and post-stroke recovery in clinical populations. Women have an increased lifetime risk of stroke compared to men, largely due to a steep increase in stroke incidence in older postmenopausal women, yet most basic science studies continue to only evaluate young male animals. Women also have an increased lifetime prevalence of many common stroke risk factors, including hypertension and atrial fibrillation, as well as abdominal obesity and metabolic syndrome. None of these age-related risk factors have been well modeled in the laboratory. Evidence from the bench has implicated genetic and epigenetic factors, differential activation of cell-death programs, cell-cell signaling pathways, and systemic immune responses as contributors to sex differences in ischemic stroke. The most recent basic scientific findings have been summarized in this review, with an emphasis on factors that differ between males and females that are pertinent to stroke outcomes. Identification and understanding of the underlying biological factors that contribute to sex differences will be critical to the development of translational targets to improve the treatment of women after stroke. © 2016 Wiley Periodicals, Inc.

  4. Ischemic stroke selectively inhibits REM sleep of rats.

    PubMed

    Ahmed, Samreen; Meng, He; Liu, Tiecheng; Sutton, Blair C; Opp, Mark R; Borjigin, Jimo; Wang, Michael M

    2011-12-01

    Sleep disorders are important risk factors for stroke; conversely, stroke patients suffer from sleep disturbances including disruptions of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and a decrease in total sleep. This study was performed to characterize the effect of stroke on sleep architecture of rats using continuous electroencephalography (EEG) and activity monitoring. Rats were implanted with transmitters which enabled continuous real time recording of EEG, electromyography (EMG), and locomotor activity. Baseline recordings were performed prior to induction of either transient middle cerebral artery (MCA) occlusion or sham surgery. Sleep recordings were obtained for 60 h after surgery to identify periods of wakefulness, NREM, and REM sleep before and after stroke. Spectral analysis was performed to assess the effects of stroke on state-dependent EEG. Finally, we quantified the time in wake, NREM, and REM sleep before and after stroke. Delta power, a measure of NREM sleep depth, was increased the day following stroke. At the same time, there was a significant shift in theta rhythms to a lower frequency during REM and wake periods. The awake EEG slowed after stroke over both hemispheres. The EEG of the ischemic hemisphere demonstrated diminished theta power specific to REM in excess of the slowing seen over the contralateral hemisphere. In contrast to rats exposed to sham surgery which had slightly increased total sleep, rats undergoing stroke experienced decreased total sleep. The decrease in total sleep after stroke was the result of dramatic reduction in the amount of REM sleep after ischemia. The suppression of REM after stroke was due to a decrease in the number of REM bouts; the length of the average REM bout did not change. We conclude that after stroke in this experimental model, REM sleep of rats is specifically and profoundly suppressed. Further experiments using this experimental model should be performed to investigate the

  5. Cell-based therapy in ischemic stroke

    PubMed Central

    2009-01-01

    Cell-based therapy for stroke represents a third wave of therapeutics for stroke and one focused on restorative processes with a longer time window of opportunity than neuroprotective therapies. An early time window, within the first week after stroke, is an opportunity for intravenously delivered bone-marrow and perinatally-derived cells that can home to areas of tissue injury and target brain remodeling. Allogeneic cells will likely be the most scalable and commercially viable product. Later time windows, months after stroke, may be opportunities for intracerebral transplantation of neuronally-differentiated cell types. An integrated approach of cell-based therapy with early phase clinical trials and continued pre-clinical work with focus on mechanisms of action is needed. PMID:18671663

  6. Oxidative stress in the chronic phase after stroke.

    PubMed

    Alexandrova, Margarita L; Bochev, Petyo G; Markova, Vanya I; Bechev, Blagovest G; Popova, Marina A; Danovska, Maya P; Simeonova, Virginia K

    2003-01-01

    The spontaneous and the stimulated extracellular generation of reactive oxygen species (ROS) by peripheral phagocytes, the blood antioxidant capacity and the degree of oxidative damage were evaluated in patients with severe ischemic and hemorrhagic stroke in the chronic phase of disease. It was found in patients compared to the control group that: (i) the spontaneous phagocyte oxidative activity was enhanced independently of the type of stroke and the time elapsed after stroke onset; (ii) there was no difference in the extracellular ROS generation stimulated by opsonin-dependent and independent receptor mechanisms; (iii) there was no change in the indices of blood antioxidant capacity; (iv) the concentration of plasma lipid peroxides was enhanced regardless of the type of stroke, but it significantly increased over time; and (v) the concentration of blood thiobarbituric acid-reactive material was also enhanced. It was independent of the type of stroke and remained elevated during the whole period studied. We have demonstrated an enhanced spontaneous phagocyte oxidative activity and oxidative damage to lipids in patients in the chronic phase after stroke. The elimination of generated ROS and products of lipid peroxidation from the circulation could prevent the aggravation of chronic vascular injury in patients and could reduce the possibility of a subsequent stroke. This suggests the need for complex therapy, including antioxidant treatment directed to exclude the effects of free radicals, after the oxidative stress of stroke.

  7. Tea consumption and risk of ischemic stroke: a brief review of the literature.

    PubMed

    Nabavi, Seyed M; Daglia, Maria; Moghaddam, Akbar H; Nabavi, Seyed F; Curti, Valeria

    2014-01-01

    Stroke is an important cerebrovascular disease which causes chronic disability and death in patients. Despite of its high morbidity and mortality, there are limited available effective neuroprotective agents for stroke. In recent years, the research aimed at finding novel neuroprotective agents from natural origins has been intensified. Camellia sinensis L. (tea) is the second most consumed beverage worldwide, after water. It is classified into green and white, oolong, black and red, and Pu-erh tea based on the manufacturing process. Catechins are the main phytochemical constituents of Camellia sinensis which are known for their high antioxidant capacity. On other hand, it is well known that oxidative stress plays an important role in the initiation and progression of different cardiovascular diseases such as stroke. Therefore, the present article is aimed to review scientific studies that show the protective effects of tea consumption against ischemic stroke.

  8. Temporal Expression of Apelin/Apelin Receptor in Ischemic Stroke and its Therapeutic Potential

    PubMed Central

    Wu, Yili; Wang, Xin; Zhou, Xuan; Cheng, Baohua; Li, Gongying; Bai, Bo

    2017-01-01

    Stroke is one of the leading causes of death and disability worldwide, and ischemic stroke accounts for approximately 87% of cases. Improving post-stroke recovery is a major challenge in stroke treatment. Accumulated evidence indicates that the apelinergic system, consisting of apelin and apelin receptor (APLNR), is temporally dysregulated in ischemic stroke. Moreover, the apelinergic system plays a pivotal role in post-stroke recovery by inhibiting neuronal apoptosis and facilitating angiogenesis through various molecular pathways. In this review article, we summarize the temporal expression of apelin and APLNR in ischemic stroke and the mechanisms of their dysregulation. In addition, the protective role of the apelinergic system in ischemic stroke and the underlying mechanisms of its protective effects are discussed. Furthermore, critical issues in activating the apelinergic system as a potential therapy will also be discussed. The aim of this review article is to shed light on exploiting the activation of the apelinergic system to treat ischemic stroke. PMID:28167898

  9. Infection after Acute Ischemic Stroke: Risk Factors, Biomarkers, and Outcome

    PubMed Central

    Wartenberg, Katja E.; Stoll, Anett; Funk, Andreas; Meyer, Andreas; Schmidt, J. Michael; Berrouschot, Joerg

    2011-01-01

    Background. The activation of inflammatory cascades triggered by ischemic stroke may play a key role in the development of infections. Methods. Patients admitted with ischemic stroke within 24 hours were prospectively enrolled. Biomarkers of infection were measured on days 1, 3, and 5. The patients were continuously monitored for predefined infections. Results. Patients with infection were older (OR 1.06 per year, 95% CI 1.01–1.11) and had a higher National Institute of Health Stroke Scale Score (NIHSS, OR 1.21, 95% CI 1.10–1.34), localization in the insula, and higher stroke volumes on diffusion-weighted imaging. The maximum temperature on days 1 and 3, leukocytes, interleukin-6, lipopolysaccharide-binding protein on days 1, 3, and 5, C-reactive protein on days 3 and 5, and procalcitonin on day 5 were higher and HLA-DR-expression on monocytes on days 1, 3, and 5 lower in patients with infection. Age and NIHSS predicted the development of infections. Infection was an independent predictor of poor functional outcome. Conclusions. Severe stroke and increasing age were shown to be early predictors for infections after stroke. PMID:21789273

  10. Treatment with Evasin-3 reduces atherosclerotic vulnerability for ischemic stroke, but not brain injury in mice

    PubMed Central

    Copin, Jean-Christophe; da Silva, Rafaela F; Fraga-Silva, Rodrigo A; Capettini, Luciano; Quintao, Silvia; Lenglet, Sébastien; Pelli, Graziano; Galan, Katia; Burger, Fabienne; Braunersreuther, Vincent; Schaller, Karl; Deruaz, Maud; Proudfoot, Amanda E; Dallegri, Franco; Stergiopulos, Nikolaos; Santos, Robson A S; Gasche, Yvan; Mach, François; Montecucco, Fabrizio

    2013-01-01

    Neutrophilic inflammation might have a pathophysiological role in both carotid plaque rupture and ischemic stroke injury. Here, we investigated the potential benefits of the CXC chemokine-binding protein Evasin-3, which potently inhibits chemokine bioactivity and related neutrophilic inflammation in two mouse models of carotid atherosclerosis and ischemic stroke, respectively. In the first model, the chronic treatment with Evasin-3 as compared with Vehicle (phosphate-buffered saline (PBS)) was investigated in apolipoprotein E-deficient mice implanted of a ‘cast' carotid device. In the second model, acute Evasin-3 treatment (5 minutes after cerebral ischemia onset) was assessed in mice subjected to transient left middle cerebral artery occlusion. Although CXCL1 and CXCL2 were upregulated in both atherosclerotic plaques and infarcted brain, only CXCL1 was detectable in serum. In carotid atherosclerosis, treatment with Evasin-3 was associated with reduction in intraplaque neutrophil and matrix metalloproteinase-9 content and weak increase in collagen as compared with Vehicle. In ischemic stroke, treatment with Evasin-3 was associated with reduction in ischemic brain neutrophil infiltration and protective oxidants. No other effects in clinical and histological outcomes were observed. We concluded that Evasin-3 treatment was associated with reduction in neutrophilic inflammation in both mouse models. However, Evasin-3 administration after cerebral ischemia onset failed to improve poststroke outcomes. PMID:23250107

  11. Endovascular vs medical management of acute ischemic stroke

    PubMed Central

    Ding, Dale; Starke, Robert M.; Mehndiratta, Prachi; Crowley, R. Webster; Liu, Kenneth C.; Southerland, Andrew M.; Worrall, Bradford B.

    2015-01-01

    Objective: To compare the outcomes between endovascular and medical management of acute ischemic stroke in recent randomized controlled trials (RCT). Methods: A systematic literature review was performed, and multicenter, prospective RCTs published from January 1, 2013, to May 1, 2015, directly comparing endovascular therapy to medical management for patients with acute ischemic stroke were included. Meta-analyses of modified Rankin Scale (mRS) and mortality at 90 days and symptomatic intracranial hemorrhage (sICH) for endovascular therapy and medical management were performed. Results: Eight multicenter, prospective RCTs (Interventional Management of Stroke [IMS] III, Local Versus Systemic Thrombolysis for Acute Ischemic Stroke [SYNTHESIS] Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy [MR RESCUE], Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands [MR CLEAN], Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE], Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial [EXTEND-IA], Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment [SWIFT PRIME], and Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours [REVASCAT]) comprising 2,423 patients were included. Meta-analysis of pooled data demonstrated functional independence (mRS 0–2) at 90 days in favor of endovascular therapy (odds ratio [OR] = 1.71; p = 0.005). Subgroup analysis of the 6 trials with large vessel occlusion (LVO) criteria also demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.23; p < 0.00001). Subgroup analysis of the 5 trials that primarily utilized stent retriever devices (≥70%) in the intervention arm demonstrated functional independence at 90 days in favor of endovascular therapy

  12. Arterial Spin Label Imaging of Acute Ischemic Stroke and Transient Ischemic Attack

    PubMed Central

    Zaharchuk, Greg

    2011-01-01

    Since acute ischemic stroke and transient ischemic attack (TIA) are fundamentally disruptions of brain hemodynamics, neuroimaging of brain perfusion might be expected to be of clinical utility. Recently, a noncontrast method of measuring CBF using arterial spin labeling (ASL) has become feasible in the clinical setting. It has advantages when compared to dynamic susceptibility contrast (DSC) bolus contrast perfusion-weighted imaging (PWI) that include lack of exposure to gadolinium-based contrast materials, improved quantitation, and decreased sensitivity to susceptibility artifacts and motion. Drawbacks of ASL include reduced signal-to-noise (SNR) and high sensitivity to arterial transit delays. While deleterious for quantitative perfusion measurements, the sensitivity of ASL to late arriving blood can be beneficial to visualize collateral flow. This chapter will discuss ASL imaging findings in patients presenting with acute ischemic stroke and TIA, focusing on typical appearances, common artifacts, and comparisons with bolus contrast PWI. PMID:21640300

  13. Neuroanatomical correlates of severe cardiac arrhythmias in acute ischemic stroke.

    PubMed

    Seifert, Frank; Kallmünzer, Bernd; Gutjahr, Isabell; Breuer, Lorenz; Winder, Klemens; Kaschka, Iris; Kloska, Stephan; Doerfler, Arnd; Hilz, Max-Josef; Schwab, Stefan; Köhrmann, Martin

    2015-05-01

    Neurocardiological interactions can cause severe cardiac arrhythmias in patients with acute ischemic stroke. The relationship between the lesion location in the brain and the occurrence of cardiac arrhythmias is still discussed controversially. The aim of the present study was to correlate the lesion location with the occurrence of cardiac arrhythmias in patients with acute ischemic stroke. Cardiac arrhythmias were systematically assessed in patients with acute ischemic stroke during the first 72 h after admission to a monitored stroke unit. Voxel-based lesion-symptom mapping (VLSM) was used to correlate the lesion location with the occurrence of clinically relevant severe arrhythmias. Overall 150 patients, 56 with right-hemispheric and 94 patients with a left-hemispheric lesion, were eligible to be included in the VLSM study. Severe cardiac arrhythmias were present in 49 of these 150 patients (32.7%). We found a significant association (FDR correction, q < 0.05) between lesions in the right insular, right frontal and right parietal cortex as well as the right amygdala, basal ganglia and thalamus and the occurrence of cardiac arrhythmias. Because left- and right-hemispheric lesions were analyzed separately, the significant findings rely on the 56 patients with right-hemispheric lesions. The data indicate that these areas are involved in central autonomic processing and that right-hemispheric lesions located to these areas are associated with an elevated risk for severe cardiac arrhythmias.

  14. Protein methionine oxidation augments reperfusion injury in acute ischemic stroke

    PubMed Central

    Gu, Sean X.; Blokhin, Ilya O.; Wilson, Katina M.; Dhanesha, Nirav; Doddapattar, Prakash; Grumbach, Isabella M.; Chauhan, Anil K.; Lentz, Steven R.

    2016-01-01

    Reperfusion injury can exacerbate tissue damage in ischemic stroke, but little is known about the mechanisms linking ROS to stroke severity. Here, we tested the hypothesis that protein methionine oxidation potentiates NF-κB activation and contributes to cerebral ischemia/reperfusion injury. We found that overexpression of methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that reverses protein methionine oxidation, attenuated ROS-augmented NF-κB activation in endothelial cells, in part, by protecting against the oxidation of methionine residues in the regulatory domain of calcium/calmodulin-dependent protein kinase II (CaMKII). In a murine model, MsrA deficiency resulted in increased NF-κB activation and neutrophil infiltration, larger infarct volumes, and more severe neurological impairment after transient cerebral ischemia/reperfusion injury. This phenotype was prevented by inhibition of NF-κB or CaMKII. MsrA-deficient mice also exhibited enhanced leukocyte rolling and upregulation of E-selectin, an endothelial NF-κB–dependent adhesion molecule known to contribute to neurovascular inflammation in ischemic stroke. Finally, bone marrow transplantation experiments demonstrated that the neuroprotective effect was mediated by MsrA expressed in nonhematopoietic cells. These findings suggest that protein methionine oxidation in nonmyeloid cells is a key mechanism of postischemic oxidative injury mediated by NF-κB activation, leading to neutrophil recruitment and neurovascular inflammation in acute ischemic stroke. PMID:27294204

  15. Reperfusion Therapies for Acute Ischemic Stroke: An Update

    PubMed Central

    Dorado, Laura; Millán, Mònica; Dávalos, Antoni

    2014-01-01

    Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke. PMID:24646159

  16. Reperfusion therapies for acute ischemic stroke: an update.

    PubMed

    Dorado, Laura; Millán, Mònica; Dávalos, Antoni

    2014-11-01

    Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke.

  17. Association of serum uric acid with ischemic stroke.

    PubMed

    Khalil, M I; Islam, M J; Ullah, M A; Khan, R K; Munira, S; Haque, M A; Mamun, M A; Islam, M T; Khan, M H

    2013-04-01

    The present study has examined the association between ischemic stroke and hyperuricemia in Bangladeshi population. This age and sex matched case control study was carried out in the Department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh during the period of January 2007 to December 2008. A total of 120 subjects were included in this study, among them 60 were cases and another 60 were controls. Data were collected purposively. Multiple logistic regressions were done to identify the risk factors for ischemic stroke. In this study 68.3% were male and 31.7% were female in both the groups. Male and female ratio of stroke patients was 2.16:1. Mean±SD of serum uric acid level of case and control group was 4.94±1.76 and 3.72±1.09 respectively. Among the case group 76.7% had normal and 23.3% had abnormal serum uric acid level. On the other hand, 93.3% respondents of control group had normal and 6.7% had abnormal serum uric acid (SUA) level. Significant differences was found between case and control group in term of SUA level (p<0.05). Since SUA level is a quantitative numerical variable, an increase in 1mg/dl has a 47.0% (95% CI 1.0% to 2.16%) increase in odds ratio (OR) of having ischemic stroke. This 47.0% is obtained by taking OR for uric acid-1. Elevated serum uric acid level is not significant for ischemic stroke among the Bangladeshi population.

  18. Rodent models of ischemic stroke lack translational relevance... are baboon models the answer?

    PubMed

    Kwiecien, Timothy D; Sy, Christopher; Ding, Yuchuan

    2014-05-01

    Rodent models of ischemic stroke are associated with many issues and limitations, which greatly diminish the translational potential of these studies. Recent studies demonstrate that significant differences exist between rodent and human ischemic stroke. These differences include the physical characteristics of the stroke, as well as changes in the subsequent inflammatory and molecular pathways following the acute ischemic insult. Non-human primate (NHP) models of ischemic stroke, however, are much more similar to humans. In addition to evident anatomical similarities, the physiological responses that NHPs experience during ischemic stroke are much more applicable to the human condition and thus make it an attractive model for future research. The baboon ischemic stroke model, in particular, has been studied extensively in comparison to other NHP models. Here we discuss the major shortcomings associated with rodent ischemic stroke models and provide a comparative overview of baboon ischemic stroke models. Studies have shown that baboons, although more difficult to obtain and handle, are more representative of ischemic events in humans and may have greater translational potential that can offset these deficiencies. There remain critical issues within these baboon stroke studies that need to be addressed in future investigations. The most critical issue revolves around the size and the variability of baboon ischemic stroke. Compared to rodent models, however, issues such as these can be addressed in future studies. Importantly, baboon models avoid many drawbacks associated with rodent models including vascular variability and inconsistent inflammatory responses - issues that are inherent to the species and cannot be avoided.

  19. Physical exercise training and neurovascular unit in ischemic stroke.

    PubMed

    Wang, X; Zhang, M; Feng, R; Li, W B; Ren, S Q; Zhang, J; Zhang, F

    2014-06-20

    Physical exercise could exert a neuroprotective effect in both clinical studies and animal experiments. A series of related studies have indicated that physical exercise could reduce infarct volume, alleviate neurological deficits, decrease blood-brain barrier dysfunction, promote angiogenesis in cerebral vascular system and increase the survival rate after ischemic stroke. In this review, we summarized the protective effects of physical exercise on neurovascular unit (NVU), including neurons, astrocytes, pericytes and the extracellular matrix. Furthermore, it was demonstrated that exercise training could decrease the blood-brain barrier dysfunction and promote angiogenesis in cerebral vascular system. An awareness of the exercise intervention benefits pre- and post stroke may lead more stroke patients and people with high-risk factors to accept exercise therapy for the prevention and treatment of stroke.

  20. Blood-brain barrier tight junction permeability and ischemic stroke.

    PubMed

    Sandoval, Karin E; Witt, Ken A

    2008-11-01

    The blood-brain barrier (BBB) is formed by the endothelial cells of cerebral microvessels, providing a dynamic interface between the peripheral circulation and the central nervous system. The tight junctions (TJs) between the endothelial cells serve to restrict blood-borne substances from entering the brain. Under ischemic stroke conditions decreased BBB TJ integrity results in increased paracellular permeability, directly contributing to cerebral vasogenic edema, hemorrhagic transformation, and increased mortality. This loss of TJ integrity occurs in a phasic manner, which is contingent on several interdependent mechanisms (ionic dysregulation, inflammation, oxidative and nitrosative stress, enzymatic activity, and angiogenesis). Understanding the inter-relation of these mechanisms is critical for the development of new therapies. This review focuses on those aspects of ischemic stroke impacting BBB TJ integrity and the principle regulatory pathways, respective to the phases of paracellular permeability.

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

    PubMed Central

    2013-01-01

    Background 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. Methods 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). Results 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. Conclusions For ischemic stroke, the lack of formal education and diabetes were significant independent predictors of poor long-term survival. PMID:23706067

  2. Copolymer-1 promotes neurogenesis and improves functional recovery after acute ischemic stroke in rats.

    PubMed

    Cruz, Yolanda; Lorea, Jonathan; Mestre, Humberto; Kim-Lee, Jennifer Hyuna; Herrera, Judith; Mellado, Raúl; Gálvez, Vanesa; Cuellar, Leopoldo; Musri, Carolina; Ibarra, Antonio

    2015-01-01

    Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing with peptides derived from CNS proteins can stimulate protective autoimmunity (PA). The most renowned of these peptides is copolymer-1 (Cop-1) also known as glatiramer acetate. This peptide has been approved for use in the treatment of multiple sclerosis. Cop-1-specific T cells cross the blood-brain barrier and secrete neurotrophins and anti-inflammatory cytokines that could stimulate proliferation of neural precursor cells and recruit them to the injury site; making it an ideal therapy for acute ischemic stroke. The aim of this work was to evaluate the effect of Cop-1 on neurogenesis and neurological recovery during the acute phase (7 days) and the chronic phase of stroke (60 days) in a rat model of transient middle cerebral artery occlusion (tMCAo). BDNF and NT-3 were quantified and infarct volumes were measured. We demonstrated that Cop-1 improves neurological deficit, enhances neurogenesis (at 7 and 60 days) in the SVZ, SGZ, and cerebral cortex through an increase in NT-3 production. It also decreased infarct volume even at the chronic phase of tMCAo. The present manuscript fortifies the support for the use of Cop-1 in acute ischemic stroke.

  3. VEGF expression in human brain tissue after acute ischemic stroke.

    PubMed

    Mărgăritescu, Otilia; Pirici, D; Mărgăritescu, Cl

    2011-01-01

    Ischemic stroke is the third most common cause of death in humans, requiring further studies to elucidate its pathophysiological background. One potential mechanism to increase oxygen delivery to the affected tissue is induction of angiogenesis. The most potent proangiogenic factor is VEGF. For this reason, our study investigated immunohistochemically VEGF reactivity in different cellular brain compartments from 15 ischemic stroke patients, as well as from 2 age control cases. By enzymatic immunohistochemistry, we investigate VEGF expression in different brain cell compartments and then we quantified its signal intensity by assessing integrated optical densities (IOD). To establish the exact cellular brain topography of VEGF immunoreactivity we performed double fluorescent immunohistochemistry series (VEGF÷NeuN, GFAP, CD68, CD105). In control samples, VEGF reactivity was observed especially in neurons from the Brodmann cortical layers IV to VI and in protoplasmic astrocytes from the deeper layers of gray matter and in endothelial cells from normal blood vessels because of systemic hypoxia generated after death. In acute ischemic stroke samples, this reactivity was noticed in all brain cellular compartments but with different intensities. The most reactive compartment was the neurons, the intensity of VEGF reaction decreasing with the lesional age from the core infarct toward intact adjacent brain cortex. With a lower intensity, VEGF reaction was noticed in astrocytes compartments, especially in gemistocytic astrocytes adjacent to the liquefaction zone. We also noticed a weak reaction in activated non-phagocytic microglia from the periphery of liquefaction zones, and high VEGF-CD105 colocalization values at the level of microvessels that surround the infarcted brain area. In conclusion, this reactivity could suggest that VEGF might exhibit neuronal and glial protective effects and also a neoangiogenic property in acute ischemic stroke, facts that may have

  4. Classifiers for Ischemic Stroke Lesion Segmentation: A Comparison Study

    PubMed Central

    Maier, Oskar; Schröder, Christoph; Forkert, Nils Daniel; Martinetz, Thomas; Handels, Heinz

    2015-01-01

    Motivation Ischemic stroke, triggered by an obstruction in the cerebral blood supply, leads to infarction of the affected brain tissue. An accurate and reproducible automatic segmentation is of high interest, since the lesion volume is an important end-point for clinical trials. However, various factors, such as the high variance in lesion shape, location and appearance, render it a difficult task. Methods In this article, nine classification methods (e.g. Generalized Linear Models, Random Decision Forests and Convolutional Neural Networks) are evaluated and compared with each other using 37 multiparametric MRI datasets of ischemic stroke patients in the sub-acute phase in terms of their accuracy and reliability for ischemic stroke lesion segmentation. Within this context, a multi-spectral classification approach is compared against mono-spectral classification performance using only FLAIR MRI datasets and two sets of expert segmentations are used for inter-observer agreement evaluation. Results and Conclusion The results of this study reveal that high-level machine learning methods lead to significantly better segmentation results compared to the rather simple classification methods, pointing towards a difficult non-linear problem. The overall best segmentation results were achieved by a Random Decision Forest and a Convolutional Neural Networks classification approach, even outperforming all previously published results. However, none of the methods tested in this work are capable of achieving results in the range of the human observer agreement and the automatic ischemic stroke lesion segmentation remains a complicated problem that needs to be explored in more detail to improve the segmentation results. PMID:26672989

  5. Mechanical Thrombectomy in Acute Ischemic Stroke: A Systematic Review.

    PubMed

    Lambrinos, Anna; Schaink, Alexis K; Dhalla, Irfan; Krings, Timo; Casaubon, Leanne K; Sikich, Nancy; Lum, Cheemun; Bharatha, Aditya; Pereira, Vitor Mendes; Stotts, Grant; Saposnik, Gustavo; Kelloway, Linda; Xie, Xuanqian; Hill, Michael D

    2016-07-01

    Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke.

  6. Do energy drinks cause epileptic seizure and ischemic stroke?

    PubMed

    Dikici, Suber; Saritas, Ayhan; Besir, Fahri Halit; Tasci, Ahmet Hakan; Kandis, Hayati

    2013-01-01

    Energy drinks are popular among young individuals and marketed to college students, athletes, and active individuals between the ages of 21 and 35 years. We report a case that had ischemic stroke and epileptic seizure after intake of energy drink with alcohol. To the best of our knowledge, the following case is the first report of ischemic stroke after intake of energy drink. A previously healthy 37-year-old man was brought to the emergency department after a witnessed tonic-clonic seizure. According to his wife's testimony, just before loss of consciousness, the patient had been drinking 3 boxes of energy drinks (Redbull, Istanbul, Turkey, 250 mL) with vodka on an empty stomach. He did not have a history of seizures, head trauma, or family history of seizures or another disease. In cranial diffusion magnetic resonance imaging, there were hyperintense signal changes in bilateral occipital area (more pronounced in the left occipital lobe), right temporal lobe, frontal lobe, and posterior parietal lobe. All tests associated with possible etiologic causes of ischemic stroke in young patients were negative. Herein, we want to attract attention to adverse effect of energy drink usage.

  7. Ginsenoside Rd and ischemic stroke; a short review of literatures☆

    PubMed Central

    Nabavi, Seyed Fazel; Sureda, Antoni; Habtemariam, Solomon; Nabavi, Seyed Mohammad

    2015-01-01

    Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products—ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke-induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase-1, protein tyrosine kinase activation, as well as reduction of cytochrome c-releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect. PMID:26869821

  8. Integrated analysis of ischemic stroke datasets revealed sex and age difference in anti-stroke targets.

    PubMed

    Li, Wen-Xing; Dai, Shao-Xing; Wang, Qian; Guo, Yi-Cheng; Hong, Yi; Zheng, Jun-Juan; Liu, Jia-Qian; Liu, Dahai; Li, Gong-Hua; Huang, Jing-Fei

    2016-01-01

    Ischemic stroke is a common neurological disorder and the burden in the world is growing. This study aims to explore the effect of sex and age difference on ischemic stroke using integrated microarray datasets. The results showed a dramatic difference in whole gene expression profiles and influenced pathways between males and females, and also in the old and young individuals. Furthermore, compared with old males, old female patients showed more serious biological function damage. However, females showed less affected pathways than males in young subjects. Functional interaction networks showed these differential expression genes were mostly related to immune and inflammation-related functions. In addition, we found ARG1 and MMP9 were up-regulated in total and all subgroups. Importantly, IL1A, ILAB, IL6 and TNF and other anti-stroke target genes were up-regulated in males. However, these anti-stroke target genes showed low expression in females. This study found huge sex and age differences in ischemic stroke especially the opposite expression of anti-stroke target genes. Future studies are needed to uncover these pathological mechanisms, and to take appropriate pre-prevention, treatment and rehabilitation measures.

  9. Physical activity in the prevention of ischemic stroke and improvement of outcomes: a narrative review.

    PubMed

    Middleton, Laura E; Corbett, Dale; Brooks, Dina; Sage, Michael D; Macintosh, Bradley J; McIlroy, William E; Black, Sandra E

    2013-02-01

    Physical activity is an integral component of stroke prevention. Although approximately 80% of strokes are due to cerebral ischemia, the mechanisms linking physical activity to the incidence of and recovery from ischemic stroke are not completely understood. This review summarizes evidence from human and animal studies regarding physical activity in the prevention of overt and covert ischemic stroke and associated injury. In cohort studies, people who are physically active have reduced rates of overt ischemic stroke and ischemic stroke mortality. However, few human studies have examined physical activity and the incidence of covert stroke. Evidence from animal models of ischemic stroke indicates that physical activity reduces injury after ischemic stroke by reducing infarct size and apoptotic cell death. Accordingly, physical activity may reduce the magnitude of injury from ischemic stroke so that there are fewer or less severe symptoms. Future research should investigate physical activity and incidence of covert stroke prospectively, ascertain the optimal dose and type of exercise to prevent ischemic injury, and identify the underlying neuroprotective mechanisms.

  10. Bayés syndrome and acute cardioembolic ischemic stroke

    PubMed Central

    Arboix, Adrià; Martí, Lucía; Dorison, Sebastien; Sánchez, María José

    2017-01-01

    Bayés syndrome is an under-recognized clinical condition characterized by advanced interatrial block. Bayés syndrome is a subclinical disease that manifests electrocardiographically as a prolonged P wave duration > 120 ms with biphasic morphology ± in the inferior leads. The clinical relevance of Bayés syndrome lies in the fact that is a clear arrhythmological syndrome and has a strong association with supraventricular arrhythmias, particularly atypical atrial flutter and atrial fibrillation. Likewise, Bayés syndrome has been recently identified as a novel risk factor for non-lacunar cardioembolic ischemic stroke and vascular dementia. Advanced interatrial block can be a risk for embolic stroke due to its known sequelae of left atrial dilation, left atrial electromechanical dysfunction or atrial tachyarrhythmia (paroxysmal or persistent atrial fibrillation), conditions predisposing to thromboembolism. Bayés syndrome may be responsible for some of the unexplained ischemic strokes and shall be considered and investigated as a possible cause for cryptogenetic stroke. In summary, Bayés syndrome is a poorly recognized cardiac rhythm disorder with important cardiologic and neurologic implications. PMID:28352633

  11. Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials

    PubMed Central

    Liu, Jialing; Wang, Yongting; Akamatsu, Yosuke; Lee, Chih Cheng; Stetler, R Anne; Lawton, Michael T.; Yang, Guo-Yuan

    2014-01-01

    The brain vasculature has been increasingly recognized as a key player that directs brain development, regulates homeostasis, and contributes to pathological processes. Following ischemic stroke, the reduction of blood flow elicits a cascade of changes and leads to vascular remodeling. However, the temporal profile of vascular changes after stroke is not well understood. Growing evidence suggests that the early phase of cerebral blood volume (CBV) increase is likely due to the improvement in collateral flow, also known as arteriogenesis, whereas the late phase of CBV increase is attributed to the surge of angiogenesis. Arteriogenesis is triggered by shear fluid stress followed by activation of endothelium and inflammatory processes, while angiogenesis induces a number of pro-angiogenic factors and circulating endothelial progenitor cells (EPCs). The status of collaterals in acute stroke has been shown to have several prognostic implications, while the causal relationship between angiogenesis and improved functional recovery has yet to be established in patients. A number of interventions aimed at enhancing cerebral blood flow including increasing collateral recruitment are under clinical investigation. Transplantation of EPCs to improve angiogenesis is also underway. Knowledge in the underlying physiological mechanisms for improved arteriogenesis and angiogenesis shall lead to more effective therapies for ischemic stroke. PMID:24291532

  12. MicroRNA in ischemic stroke etiology and pathology

    PubMed Central

    Rink, Cameron

    2011-01-01

    Small, noncoding, microRNAs (miRNAs) have emerged as key mediators of posttranscriptional gene silencing in both pathogenic and pathological aspects of ischemic stroke biology. In stroke etiology, miRNA have distinct expression patterns that modulate pathogenic processes including atherosclerosis (miR-21, miR-126), hyperlipidemia (miR-33, miR-125a-5p), hypertension (miR-155), and plaque rupture (miR-222, miR-210). Following focal cerebral ischemia, significant changes in the miRNA transcriptome, independent of an effect on expression of miRNA machinery, implicate miRNA in the pathological cascade of events that include blood brain barrier disruption (miR-15a) and caspase mediated cell death signaling (miR-497). Early activation of miR-200 family members improves neural cell survival via prolyl hydroxylase mRNA silencing and subsequent HIF-1α stabilization. Pro- (miR-125b) and anti-inflammatory (miR-26a, -34a, -145, and let-7b) miRNA may also be manipulated to positively influence stroke outcomes. Recent examples of successfully implemented miRNA-therapeutics direct the future of gene therapy and offer new therapeutic strategies by regulating large sets of genes in related pathways of the ischemic stroke cascade. PMID:20841499

  13. [Cerebrolysin in treatment of acute ischemic stroke].

    PubMed

    Domzał, T; Zaleska, B

    1995-01-01

    Cerebrolysin is composed of low molecular peptides and free amino-acids and as a nootropic drug it administered in various diseases of central nervous system. In an open clinical trial patients with acute ischaemic stroke in the region of the middle cerebral artery, were treated. Cerebrolysin was administered as intravenous infusion in daily dose of 15 ml during 21 days. Recovery in 10 patients and improvement in 3 was obtained and only one patient died. The results were compared to the large group of 108 patients treated earlier with other drugs. Therapeutic effect was similar in all groups.

  14. Association between pneumonia in acute stroke stage and 3-year mortality in patients with acute first-ever ischemic stroke.

    PubMed

    Yu, Yi-Jing; Weng, Wei-Chieh; Su, Feng-Chieh; Peng, Tsung-I; Chien, Yu-Yi; Wu, Chia-Lun; Lee, Kuang-Yung; Wei, Yi-Chia; Lin, Shun-Wen; Zhu, Jun-Xiao; Huang, Wen-Yi

    2016-11-01

    The influence of pneumonia in acute stroke stage on the clinical presentation and long-term outcomes of patients with acute ischemic stroke is still controversial. We investigate the influence of pneumonia in acute stroke stage on the 3-year outcomes of patients with acute first-ever ischemic stroke. Nine-hundred and thirty-four patients with acute first-ever ischemic stroke were enrolled and had been followed for 3years. Patients were divided into two groups according to whether pneumonia occurred during acute stroke stage or not. Clinical presentations, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. The result showed that a total of 100 patients (10.7%) had pneumonia in acute stroke stage. The prevalence of older age, atrial fibrillation was significantly higher in patients with pneumonia in acute stroke stage. Total anterior circulation syndrome and posterior circulation syndrome occurred more frequently among patients with pneumonia in acute stroke stage (P<0.001 and P=0.009, respectively). Multivariate Cox regression revealed that pneumonia in acute stroke stage is a significant predictor of 3-year mortality (hazard ratio=6.39, 95% confidence interval=4.03-10.11, P<0.001). In conclusion, pneumonia during the acute stroke stage is associated with increased risk of 3-year mortality. Interventions to prevent pneumonia in acute stroke stage might improve ischemic stroke outcome.

  15. Hyperbaric oxygen therapy and preconditioning for ischemic and hemorrhagic stroke

    PubMed Central

    Hu, Sheng-li; Feng, Hua; Xi, Guo-hua

    2016-01-01

    To date, the therapeutic methods for ischemic and hemorrhagic stroke are still limited. The lack of oxygen supply is critical for brain injury following stroke. Hyperbaric oxygen (HBO), an approach through a process in which patients breathe in 100% pure oxygen at over 101 kPa, has been shown to facilitate oxygen delivery and increase oxygen supply. Hence, HBO possesses the potentials to produce beneficial effects on stroke. Actually, accumulated basic and clinical evidences have demonstrated that HBO therapy and preconditioning could induce neuroprotective functions via different mechanisms. Nevertheless, the lack of clinical translational study limits the application of HBO. More translational studies and clinical trials are needed in the future to develop effective HBO protocols. PMID:28217297

  16. Ischemic Stroke Injury Is Mediated by Aberrant Cdk5

    PubMed Central

    Meyer, Douglas A.; Torres-Altoro, Melissa I.; Tan, Zhenjun; Tozzi, Alessandro; Di Filippo, Massimiliano; DiNapoli, Vincent; Plattner, Florian; Kansy, Janice W.; Benkovic, Stanley A.; Huber, Jason D.; Miller, Diane B.; Greengard, Paul; Calabresi, Paolo; Rosen, Charles L.

    2014-01-01

    Ischemic stroke is one of the leading causes of morbidity and mortality. Treatment options are limited and only a minority of patients receive acute interventions. Understanding the mechanisms that mediate neuronal injury and death may identify targets for neuroprotective treatments. Here we show that the aberrant activity of the protein kinase Cdk5 is a principal cause of neuronal death in rodents during stroke. Ischemia induced either by embolic middle cerebral artery occlusion (MCAO) in vivo or by oxygen and glucose deprivation in brain slices caused calpain-dependent conversion of the Cdk5-activating cofactor p35 to p25. Inhibition of aberrant Cdk5 during ischemia protected dopamine neurotransmission, maintained field potentials, and blocked excitotoxicity. Furthermore, pharmacological inhibition or conditional knock-out (CKO) of Cdk5 prevented neuronal death in response to ischemia. Moreover, Cdk5 CKO dramatically reduced infarctions following MCAO. Thus, targeting aberrant Cdk5 activity may serve as an effective treatment for stroke. PMID:24920629

  17. Impact of baseline characteristics on outcomes of carotid artery stenting in acute ischemic stroke patients

    PubMed Central

    Yu, Cheng-Sheng; Lin, Chih-Ming; Liu, Chi-Kuang; Lu, Henry Horng-Shing

    2016-01-01

    Carotid artery stenting is an effective treatment for ischemic stroke patients with moderate-to-severe carotid artery stenosis. However, the midterm outcome for patients undergoing this procedure varies considerably with baseline characteristics. To determine the impact of baseline characteristics on outcomes following carotid artery stenting, data from 107 eligible patients with a first episode of ischemic stroke were collected by retrospective chart review. A modified Rankin Scale (mRS) was used to divide patients into two baseline groups, mRS ≤2 and mRS >2. A three-step decision-tree statistical analysis was conducted. After weighting the decision-tree parameters, the following impact hierarchy was obtained: admission low-density lipoprotein, gouty arthritis, chronic kidney disease, ipsilateral common carotid artery resistance index, contralateral ophthalmic artery resistance index, sex, and dyslipidemia. The finite-state machine model demonstrated that, in patients with baseline mRS ≤2, 46% had an improved mRS score at follow-up, whereas 54% had a stable mRS score. In patients with baseline mRS >2, a stable mRS score was observed in 75%, improved score in 23%, and a poorer score in 2%. Admission low-density lipoprotein was the strongest predictive factor influencing poststenting outcome. In addition, our study provides further evidence that carotid artery stenting can be of benefit in first-time ischemic stroke patients with baseline mRS scores >2. PMID:27099508

  18. Angiographic findings of ischemic stroke in children.

    PubMed

    Shirane, R; Sato, S; Yoshimoto, T

    1992-12-01

    A cooperative study was undertaken in the Tohoku district of Japan to investigate the relatively rare phenomenon of cerebral infarction in children. The purpose of the present paper is to describe the cerebral angiographic findings in 48 children whose ischemic lesions were confirmed by CT scan. The majority of lesions were considered to be idiopathic. The areas of cerebral infarction appearing in the CT scans were located in the territory of the middle cerebral artery including the basal ganglia. Angiographical abnormalities were observed in 40 patients (83%). The majority occurred in the supraclinoid portion of the internal carotid artery and in the cisternal portion of the middle and anterior cerebral arteries. Multiple lesions, such as in the C1, A1, and M1 or the C1, M1, and M2 segments were observed in 22 cases. These lesions generally appeared in continuation; no bilateral intracranial lesions were observed. Repeated angiography was performed in 22 cases, and in 55% of these some recovery of the lesions was seen.

  19. Recurrent Ischemic Stroke Characteristics and Assessment of Sufficiency of Secondary Stroke Prevention

    PubMed Central

    KOCAMAN, Gülşen; DÜRÜYEN, Hümeyra; KOÇER, Abdulkadir; ASİL, Talip

    2015-01-01

    Introduction Disabilities due to stroke lead to a serious individual and socioeconomic burden. In this presented hospital-based study, we aimed to evaluate recurrent ischemic stroke (RIS) characteristics and the sufficiency of secondary prevention regarding the most common modifiable risk factors. Methods The records of patients with a diagnosis of ischemic stroke between November 2009 and November 2011 in our unit were retrospectively investigated. Results Ninety-one (18%) out of 500 patients with ischemic stroke had RIS. Hypertension, diabetes mellitus, ischemic heart disease, hyperlipidemia, atrial fibrillation, and smoking were found in 88%, 43%, 36%, 30%, 11%, and 14% of the patients, respectively. Thirty-eight percent of the patients had more than two risk factors. While 14% of the hypertensive patients did not use antihypertensive medications, antihypertensive treatment was insufficient in 39% of those who already used antihypertensive medications. Twenty-three percent of the patients received no prophylactic agents. Sixty percent of the patients with a history of atrial fibrillation were on oral anticoagulant therapy (warfarin), and the international normalized ratio was <2.0 in 73% of them. Of the diabetic patients, 87% had an HgbA1C level above 6%. The LDL level was higher than 100 mg/dL in 72% of the patients. Conclusion The incidence of RIS and risk factors in our retrospective study was compatible with the results of those in literature. Secondary prophylactic treatment and modification of risk factors in the stroke patients were not satisfactory. The improvement of the patients’ adherence to treatment is also very important in addition to the optimal treatment and follow-up strategy for decreasing the incidence of RIS. A multidisciplinary outpatient model of stroke care may be beneficial for decreasing the incidence of RIS.

  20. Gender differences in patients with acute ischemic stroke.

    PubMed

    Caso, Valeria; Paciaroni, Maurizio; Agnelli, Giancarlo; Corea, Francesco; Ageno, Walter; Alberti, Andrea; Lanari, Alessia; Micheli, Sara; Bertolani, Luca; Venti, Michele; Palmerini, Francesco; Billeci, Antonia M R; Comi, Giancarlo; Previdi, Paolo; Silvestrelli, Giorgio

    2010-01-01

    Stroke has a greater effect on women than men owing to the fact that women have more stroke events and are less likely to recover. Age-specific stroke rates are higher in men; however, because of women's longer life expectancy and the much higher incidence of stroke at older ages, women have more stroke events than men overall. The aims of this prospective study in consecutive patients were to assess whether there are gender differences in stroke risk factors, treatment or outcome. Consecutive patients with ischemic stroke were included in this prospective study at four study centers. Disability was assessed using a modified Rankin Scale score (>or=3 indicating disabling stroke) in both genders at 90 days. Outcomes and risk factors in both genders were compared using the chi(2) test. Multiple logistic regression analysis was used to identify any independent predictors of outcome. A total of 1136 patients were included in this study; of these, 494 (46%) were female. Women were statistically older compared with men: 76.02 (+/- 12.93) and 72.68 (+/- 13.27) median years of age, respectively. At admission, females had higher NIH Stroke Scale scores compared with males (9.4 [+/- 6.94] vs 7.6 [+/- 6.28] for men; p = 0.0018). Furthermore, females tended to have more cardioembolic strokes (153 [30%] vs 147 [23%] for men; p = 0.004). Males had lacunar and atherosclerotic strokes more often (146 [29%] vs 249 [39%] for men; p = 0.002, and 68 [13%] vs 123 [19%] for men; p = 0.01, respectively). The mean modified Rankin Scale score at 3 months was also significantly different between genders, at 2.5 (+/- 2.05) for women and 2.1 (+/- 2.02) for men (p = 0.003). However, at multivariate analysis, female gender was not an indicator for negative outcome. It was concluded that female gender was not an independent factor for negative outcome. In addition, both genders demonstrated different stroke pathophysiologies. These findings should be taken into account when diagnostic workup and

  1. Ischemic penumbra in acute stroke: Demonstration by PET with fluorine-18 fluoromisonidazole

    SciTech Connect

    Yeh, S.H.; Liu, R.S.; Hu, H.H.

    1994-05-01

    Ischemic penumbra (IP) in acute stroke has gained clinical interest since tissue functions may be recovered if perfusion can be reestablished. However, such therapeutic intervention is {open_quotes}blind{close_quotes} since clinical examination can not distinguish IP from developing infarction. In vivo demonstration of IP may have significance for stroke patient management. This study was a preliminary evaluation of detecting IP in vivo by F-18 fluoromisonidazole ([F-18]-FMISO), a hypoxic imaging agent. Static PET imaging was performed after IV injection of 370 MBq of [F-18]-FMISO at 20 and 120 min. Tomograms were reconstructed and evaluated visually in correlation with CT or MR scans. In acute stroke, patients (pts) were called back for the second PET study one month after the initial study. CT was used for confirming infarction. In 6 pts with acute cerebral infarction, three of them had intense [F-18]-FMISO retention in the penumbra surrounding the central, eclipse-like zone of absent radio-activity (infarction) at 2 hr in the acute state, and the penumbra disappeared in association with increased area of infarction on CT in one case in the chronic state. In five pts with chronic infarction, all had no penumbra of [F-18]-FMISO retention. In summary, our preliminary results demonstrate the feasibility of using [F-18]-FMISO PET to detect ischemic penumbra in vivo.

  2. Early neurological stability predicts adverse outcome after acute ischemic stroke.

    PubMed

    Irvine, Hannah J; Battey, Thomas Wk; Ostwaldt, Ann-Christin; Campbell, Bruce Cv; Davis, Stephen M; Donnan, Geoffrey A; Sheth, Kevin N; Kimberly, W Taylor

    2016-10-01

    Background Deterioration in the National Institutes of Health Stroke Scale (NIHSS) in the early days after stroke is associated with progressive infarction, brain edema, and/or hemorrhage, leading to worse outcome. Aims We sought to determine whether a stable NIHSS score represents an adverse or favorable course. Methods Brain magnetic resonance images from a research cohort of acute ischemic stroke patients were analyzed. Using NIHSS scores at baseline and follow-up (day 3-5), patients were categorized into early neurological deterioration (ΔNIHSS ≥ 4), early neurological recovery (ΔNIHSS ≤ -4) or early neurological stability (ΔNIHSS between -3 and 3). The association between these categories and volume of infarct growth, volume of swelling, parenchymal hemorrhage, and 3-month modified Rankin Scale score were evaluated. Results Patients with early neurological deterioration or early neurological stability were less likely to be independent (modified Rankin Scale = 0-2) at 3 months compared to those with early neurological recovery ( P < 0.001). Patients with early neurological deterioration or early neurological stability were observed to have significantly greater infarct growth and swelling volumes than those with early neurological recovery ( P = 0.03; P < 0.001, respectively). Brain edema was more common than the other imaging markers investigated and was independently associated with a stable or worsening NIHSS score after adjustment for age, baseline stroke volume, infarct growth volume, presence of parenchymal hemorrhage, and reperfusion ( P < 0.0001). Conclusions Stable NIHSS score in the subacute period after ischemic stroke may not be benign and is associated with tissue injury, including infarct growth and brain edema. Early improvement is considerably more likely to occur in the absence of these factors.

  3. Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy.

    PubMed

    Zhang, Zaijun; Zhang, Gaoxiao; Sun, Yewei; Szeto, Samuel S W; Law, Henry C H; Quan, Quan; Li, Guohui; Yu, Pei; Sho, Eiketsu; Siu, Michael K W; Lee, Simon M Y; Chu, Ivan K; Wang, Yuqiang

    2016-11-14

    TBN, a novel tetramethylpyrazine derivative armed with a powerful free radical-scavenging nitrone moiety, has been reported to reduce cerebral infarction in rats through multi-functional mechanisms of action. Here we study the therapeutic effects of TBN on non-human primate model of stroke. Thirty male Cynomolgus macaques were subjected to stroke with 4 hours ischemia and then reperfusion. TBN were injected intravenously at 3 or 6 hours after the onset of ischemia. Cerebral infarction was examined by magnetic resonance imaging at 1 and 4 weeks post ischemia. Neurological severity scores were evaluated during 4 weeks observation. At the end of experiment, protein markers associated with the stroke injury and TBN treatment were screened by quantitative proteomics. We found that TBN readily penetrated the blood brain barrier and reached effective therapeutic concentration after intravenous administration. It significantly reduced brain infarction and modestly preserved the neurological function of stroke-affected arm. TBN suppressed over-expression of neuroinflammatory marker vimentin and decreased the numbers of GFAP-positive cells, while reversed down-regulation of myelination-associated protein 2', 3'-cyclic-nucleotide 3'-phosphodiesterase and increased the numbers of NeuN-positive cells in the ipsilateral peri-infarct area. TBN may serve as a promising new clinical candidate for the treatment of ischemic stroke.

  4. Low-frequency and common genetic variation in ischemic stroke

    PubMed Central

    Malik, Rainer; Traylor, Matthew; Pulit, Sara L.; Bevan, Steve; Hopewell, Jemma C.; Holliday, Elizabeth G.; Zhao, Wei; Abrantes, Patricia; Amouyel, Philippe; Attia, John R.; Battey, Thomas W.K.; Berger, Klaus; Boncoraglio, Giorgio B.; Chauhan, Ganesh; Cheng, Yu-Ching; Chen, Wei-Min; Clarke, Robert; Cotlarciuc, Ioana; Debette, Stephanie; Falcone, Guido J.; Ferro, Jose M.; Gamble, Dale M.; Ilinca, Andreea; Kittner, Steven J.; Kourkoulis, Christina E.; Lemmens, Robin; Levi, Christopher R.; Lichtner, Peter; Lindgren, Arne; Liu, Jingmin; Meschia, James F.; Mitchell, Braxton D.; Oliveira, Sofia A.; Pera, Joana; Reiner, Alex P.; Rothwell, Peter M.; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie L.M.; Tatlisumak, Turgut; Thijs, Vincent; Vicente, Astrid M.; Woo, Daniel; Seshadri, Sudha; Saleheen, Danish; Rosand, Jonathan; Markus, Hugh S.; Worrall, Bradford B.

    2016-01-01

    Objective: To investigate the influence of common and low-frequency genetic variants on the risk of ischemic stroke (all IS) and etiologic stroke subtypes. Methods: We meta-analyzed 12 individual genome-wide association studies comprising 10,307 cases and 19,326 controls imputed to the 1000 Genomes (1 KG) phase I reference panel. We selected variants showing the highest degree of association (p < 1E-5) in the discovery phase for replication in Caucasian (13,435 cases and 29,269 controls) and South Asian (2,385 cases and 5,193 controls) samples followed by a transethnic meta-analysis. We further investigated the p value distribution for different bins of allele frequencies for all IS and stroke subtypes. Results: We showed genome-wide significance for 4 loci: ABO for all IS, HDAC9 for large vessel disease (LVD), and both PITX2 and ZFHX3 for cardioembolic stroke (CE). We further refined the association peaks for ABO and PITX2. Analyzing different allele frequency bins, we showed significant enrichment in low-frequency variants (allele frequency <5%) for both LVD and small vessel disease, and an enrichment of higher frequency variants (allele frequency 10% and 30%) for CE (all p < 1E-5). Conclusions: Our findings suggest that the missing heritability in IS subtypes can in part be attributed to low-frequency and rare variants. Larger sample sizes are needed to identify the variants associated with all IS and stroke subtypes. PMID:26935894

  5. Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy

    PubMed Central

    Zhang, Zaijun; Zhang, Gaoxiao; Sun, Yewei; Szeto, Samuel S. W.; Law, Henry C. H.; Quan, Quan; Li, Guohui; Yu, Pei; Sho, Eiketsu; Siu, Michael K. W.; Lee, Simon M. Y.; Chu, Ivan K.; Wang, Yuqiang

    2016-01-01

    TBN, a novel tetramethylpyrazine derivative armed with a powerful free radical-scavenging nitrone moiety, has been reported to reduce cerebral infarction in rats through multi-functional mechanisms of action. Here we study the therapeutic effects of TBN on non-human primate model of stroke. Thirty male Cynomolgus macaques were subjected to stroke with 4 hours ischemia and then reperfusion. TBN were injected intravenously at 3 or 6 hours after the onset of ischemia. Cerebral infarction was examined by magnetic resonance imaging at 1 and 4 weeks post ischemia. Neurological severity scores were evaluated during 4 weeks observation. At the end of experiment, protein markers associated with the stroke injury and TBN treatment were screened by quantitative proteomics. We found that TBN readily penetrated the blood brain barrier and reached effective therapeutic concentration after intravenous administration. It significantly reduced brain infarction and modestly preserved the neurological function of stroke-affected arm. TBN suppressed over-expression of neuroinflammatory marker vimentin and decreased the numbers of GFAP-positive cells, while reversed down-regulation of myelination-associated protein 2′, 3′-cyclic-nucleotide 3′-phosphodiesterase and increased the numbers of NeuN-positive cells in the ipsilateral peri-infarct area. TBN may serve as a promising new clinical candidate for the treatment of ischemic stroke. PMID:27841332

  6. Effect of dexamethasone on brain oedema following acute ischemic stroke.

    PubMed

    Shaikh, A K; Mohammad, Q D; Ullah, M A; Ahsan, M M; Rahman, A; Shakoor, M A

    2011-07-01

    A randomized clinical trial was conducted to asses the effects of dexamethasone on brain oedema following acute ischemic stroke in the departments of Medicine of different hospitals from July, 2003 to December, 2006. A total of 60 patients were included in the study. They were divided into two groups keeping the similarity regarding the age, sex and severity of the stroke between two groups. There were 30 patients in experimental group and 30 in control group. The level of consciousness was compared by Glasgow Coma Scale (GCS) on 3rd, 7th and 10th day of intervention and improvement was found in both the groups, but the improvement of level of consciousness was statistically significant in Dexamethasone treated group. The volume of hypodense area did not differ significantly in two groups in CT scans before and after treatment (p=0.74). The study results demonstrate that Dexamethasone improves the level of consciousness in acute ischemic stroke associated with brain oedema but did not reduce volume of hypodense area.

  7. Laryngeal Elevation Velocity and Aspiration in Acute Ischemic Stroke Patients

    PubMed Central

    Zhang, Jing; Zhou, Yun; Wei, Na; Yang, Bo; Wang, Anxin; Zhou, Hai; Zhao, Xingquan; Wang, Yongjun; Liu, Liping; Ouyoung, Melody; Villegas, Brenda; Groher, Michael

    2016-01-01

    Objectives Aspiration after stroke has been associated with aspiration pneumonia, which contributes to increased mortality of stroke. Laryngeal elevation is a core mechanism for protection from aspiration. Few studies have explored the predictive value of laryngeal elevation velocity for aspiration after stroke. This study aimed to explore the ability of laryngeal elevation velocity to predict aspiration in patients with acute ischemic stroke. Methods This was a prospective cohort study that included consecutive acute ischemic stroke patients treated at a teaching hospital during a 10-month period. Patients underwent magnetic resonance imaging (MRI) to confirm the diagnosis of acute ischemic stroke. Patients who were at risk of aspiration and could swallow 5 ml of diluted barium (40%, w/v) for a videofluoroscopic swallowing (VFS) study were included. The association between abnormal indices in the oral and pharyngeal phase of the VFS study and aspiration was examined using univariate analyses. These indices included the lip closure, tongue movement and control, laryngeal elevation velocity and range, the latency of pharyngeal swallowing, pharyngeal transit time (PTT), abnormal epiglottis tilt, residual barium in the pharynx, and the duration of upper esophageal sphincter (UES) opening. The laryngeal elevation velocity (%/s) was calculated as the range of laryngeal elevation (%) from the resting position to the maximum superior position or to the position where the laryngeal vestibule is fully closed divided by the corresponding duration of laryngeal elevation. The range of laryngeal elevation (%) was the percentage calculated as the distance between the resting laryngeal position and the maximum superior excursion position or position where the laryngeal vestibule is fully closed divided by the distance between the resting laryngeal position and the lowest edge of the mandible. A logistic regression analysis was used to determine the predictive value for aspiration

  8. Neuroprotection in acute ischemic stroke – current status

    PubMed Central

    Auriel, E; Bornstein, NM

    2010-01-01

    Abstract With the growing understanding of the mechanism of cell death in ischemia, new approaches for treatment such as neuroprotection have emerged. The basic aim of this strategy is to interfere with the events of the ischemic cascade, blocking the pathological processes and preventing the death of nerve cells in the ischemic penumebra. This concept involves inhibition of the pathological molecular events which eventually leads to the influx of calcium, activation of free radicals and neuronal death. Despite encouraging data from experimental animal models, all clinical trials of neuroprotective therapies have to date been unsuccessful. This article reviews some of the reasons for the failure of neuroprotection in the clinical trials so far. Despite all the negative reports, we believe it would be wrong to give up at this point, since there is still reasonable hope of finding an effective neuroprotection for stroke. PMID:20716132

  9. A more consistent intraluminal rhesus monkey model of ischemic stroke

    PubMed Central

    Zhao, Bo; Shang, Guowei; Chen, Jian; Geng, Xiaokun; Ye, Xin; Xu, Guoxun; Wang, Ju; Zheng, Jiasheng; Li, Hongjun; Akbary, Fauzia; Li, Shengli; Lu, Jing; Ling, Feng; Ji, Xunming

    2014-01-01

    Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group: middle cerebral artery occlusion at origin segment (M1) and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique (1 mm × 10 cm) (undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research. PMID:25657726

  10. A more consistent intraluminal rhesus monkey model of ischemic stroke.

    PubMed

    Zhao, Bo; Shang, Guowei; Chen, Jian; Geng, Xiaokun; Ye, Xin; Xu, Guoxun; Wang, Ju; Zheng, Jiasheng; Li, Hongjun; Akbary, Fauzia; Li, Shengli; Lu, Jing; Ling, Feng; Ji, Xunming

    2014-12-01

    Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group: middle cerebral artery occlusion at origin segment (M1) and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique (1 mm × 10 cm) (undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research.

  11. [Efficacy of сerebrolysin in acute ischemic stroke].

    PubMed

    Petrova, O P; Chuprasov, A V; Matveev, N V

    2014-01-01

    Objective. To study the effect of cerebrolysin used in dose 30 ml daily during 10 days on rehabilitation measures in patients with acute ischemic stroke. Material and methods. The 1st group consisited of 23 patients who received standard treatment and cerebrolysin, the 2nd group included 89 patients who received standard treatment only. The severity of neurological deficits (NIHSS) and the level of disability (mRS) were assessed. Results and conclusion. A significantly earlier recovery (p<0,05) and decrease in disability were identified. A more pronounced effect was seen in young patinets and when treatment started early.

  12. [Use of cerebrolysin in the treatment of ischemic stroke].

    PubMed

    Koppi, S; Barolin, G S

    1998-01-01

    Comparative analysis was performed of results of the treatment of patients with ischemic stroke, including 140 ones treated by means of hemodilution method (control group) and 40 patients treated with cerebrolysin (test group). Barolin's scale of the neurorehabilitation was used for the analysis of the results. Statistically significant results of rehabilitation were better in the test group. Improvement of the parameters characterizing social contacts, working activity and behaviour was more pronounced than an improvement of motor functions. Cerebrolysin had accelerating effect on restoration of damaged functions, by creating more stable basis for rehabilitation.

  13. [Ischemic stroke in childhood. A complication of tonsillectomy].

    PubMed

    Matilla Álvarez, A; García Serrano, E; González de la Huebra Labrador, T; Morales Martín, A C; Yusta Martín, G; Vaquero Roncero, L M

    2016-02-01

    Tonsillectomy is one of the most frequently performed otorhinolaryngological procedures on children. The postoperative complications are classified into primary or intermediate, which generally appear within 24h, and as secondary or delayed, after 48 h. We present the case of an ischemic stroke after performing a tonsillectomy on a 3 year-old boy, which was diagnosed in the immediate postoperative period. Using brain echo-doppler and angio-CT, an intraluminal clot was observed in the left internal carotid artery, probably as a result of direct vessel injury during arterial ligature for hemostasis.

  14. Ischemic stroke subtypes among Mexican Americans and non-Hispanic whites: the BASIC Project.

    PubMed

    Uchino, K; Risser, J M H; Smith, M A; Moyé, L A; Morgenstern, L B

    2004-08-10

    Ischemic stroke subtype distribution was compared between Mexican Americans (MAs) and non-Hispanic whites (NHWs) in a community-based stroke surveillance study in Nueces County, TX. There was no difference in the distribution of stroke subtype by ethnicity (p = 0.19). There was a similar proportion of small-vessel and large-artery strokes between the two ethnic groups (p = 0.32). Differences in stroke rates among MAs and NHWs are not explained by the distribution of ischemic stroke subtypes.

  15. Phosphodiesterase 4D and 5-Lipoxygenase Activating Protein in Ischemic Stroke

    PubMed Central

    Meschia, James F.; Brott, Thomas G.; Brown, Robert D.; Crook, Richard; Worrall, Bradford B.; Kissela, Brett; Brown, W. Mark; Rich, Stephen S.; Case, L. Douglas; Evans, E. Whitney; Hague, Stephen; Singleton, Andrew; Hardy, John

    2006-01-01

    Risk for ischemic stroke is mediated by both environmental and genetic factors. Although several environmental exposures have been implicated, relatively little is known about the genetic basis of predisposition to this disease. Recent studies in Iceland identified risk polymorphisms in two putative candidate genes for ischemic stroke: phosphodiesterase 4D (PDE4D) and 5-lipoxygenase activating protein (ALOX5AP). A collection of North American sibling pairs concordant for ischemic stroke and two cohorts of prospectively ascertained North American ischemic stroke cases and control subjects were used for evaluation of PDE4D and ALOX5AP. Although no evidence supported linkage of ischemic stroke with either of the two candidate genes, single-nucleotide polymorphisms and haplotypic associations were observed between PDE4D and ischemic stroke. There was no evidence of association between variants of ALOX5AP and ischemic stroke. These data suggest that common variants in PDE4D may contribute to the genetic risk for ischemic stroke in multiple populations. PMID:16130105

  16. Simulation of human ischemic stroke in realistic 3D geometry

    NASA Astrophysics Data System (ADS)

    Dumont, Thierry; Duarte, Max; Descombes, Stéphane; Dronne, Marie-Aimée; Massot, Marc; Louvet, Violaine

    2013-06-01

    In silico research in medicine is thought to reduce the need for expensive clinical trials under the condition of reliable mathematical models and accurate and efficient numerical methods. In the present work, we tackle the numerical simulation of reaction-diffusion equations modeling human ischemic stroke. This problem induces peculiar difficulties like potentially large stiffness which stems from the broad spectrum of temporal scales in the nonlinear chemical source term as well as from the presence of steep spatial gradients in the reaction fronts, spatially very localized. Furthermore, simulations on realistic 3D geometries are mandatory in order to describe correctly this type of phenomenon. The main goal of this article is to obtain, for the first time, 3D simulations on realistic geometries and to show that the simulation results are consistent with those obtain in experimental studies or observed on MRI images in stroke patients. For this purpose, we introduce a new resolution strategy based mainly on time operator splitting that takes into account complex geometry coupled with a well-conceived parallelization strategy for shared memory architectures. We consider then a high order implicit time integration for the reaction and an explicit one for the diffusion term in order to build a time operator splitting scheme that exploits efficiently the special features of each problem. Thus, we aim at solving complete and realistic models including all time and space scales with conventional computing resources, that is on a reasonably powerful workstation. Consequently and as expected, 2D and also fully 3D numerical simulations of ischemic strokes for a realistic brain geometry, are conducted for the first time and shown to reproduce the dynamics observed on MRI images in stroke patients. Beyond this major step, in order to improve accuracy and computational efficiency of the simulations, we indicate how the present numerical strategy can be coupled with spatial

  17. The Prognostic Values of Leukocyte Rho Kinase Activity in Acute Ischemic Stroke

    PubMed Central

    Cheng, Cheng-I.; Lin, Yu-Chun; Tsai, Tzu-Hsien; Lin, Hung-Sheng; Liou, Chia-Wei; Chang, Wen-Neng; Lu, Cheng-Hsien; Yuen, Chun-Man; Yip, Hon-Kan

    2014-01-01

    Objective. It has been reported that leukocyte ROCK activity is elevated in patients after ischemic stroke, but it is unclear whether leukocyte ROCK activity is associated with clinical outcomes following acute stroke events. The objective of this study is to investigate if leukocyte ROCK activity can predict the outcomes in patients with acute ischemic stroke. Materials and Methods. We enrolled 110 patients of acute ischemic stroke and measured the leukocyte ROCK activity and plasma level of inflammatory cytokines to correlate the clinical outcomes of these patients. Results. The leukocyte ROCK activity at 48 hours after admission in acute ischemic stroke patients was higher as compared to a risk-matched population. The leukocyte ROCK activity significantly correlated with National Institute of Health Stroke Scale (NIHSS) difference between admission and 90 days after stroke event. Kaplan-Meier survival estimates showed lower stroke-free survival during follow-up period in patients with high leukocyte ROCK activity or plasma hsCRP level. Leukocyte ROCK activity independently predicted the recurrent stroke in patients with atherosclerotic stroke. Conclusions. This study shows elevated leukocyte ROCK activity in patients with ischemic stroke as compared to risk-matched subjects and is an independent predictor for recurrent stroke. PMID:24716192

  18. Hemorrhagic Transformation after Tissue Plasminogen Activator Reperfusion Therapy for Ischemic Stroke: Mechanisms, Models, and Biomarkers.

    PubMed

    Wang, Wei; Li, Mingchang; Chen, Qianxue; Wang, Jian

    2015-12-01

    Intracerebral hemorrhagic transformation (HT) is well recognized as a common cause of hemorrhage in patients with ischemic stroke. HT after acute ischemic stroke contributes to early mortality and adversely affects functional recovery. The risk of HT is especially high when patients receive thrombolytic reperfusion therapy with tissue plasminogen activator, the only available treatment for ischemic stroke. Although many important publications address preclinical models of ischemic stroke, there are no current recommendations regarding the conduct of research aimed at understanding the mechanisms and prediction of HT. In this review, we discuss the underlying mechanisms for HT after ischemic stroke, provide an overview of the models commonly used for the study of HT, and discuss biomarkers that might be used for the early detection of this challenging clinical problem.

  19. Hemorrhagic Transformation After Tissue Plasminogen Activator Reperfusion Therapy for Ischemic Stroke: Mechanisms, Models, and Biomarkers

    PubMed Central

    Wang, Wei; Li, Mingchang; Chen, Qianxue; Wang, Jian

    2014-01-01

    Summary Intracerebral hemorrhagic transformation (HT) is well recognized as a common cause of hemorrhage in patients with ischemic stroke. HT after acute ischemic stroke contributes to early mortality and adversely affects functional recovery. The risk of HT is especially high when patients receive thrombolytic reperfusion therapy with tissue plasminogen activator, the only available treatment for ischemic stroke. Although many important publications address preclinical models of ischemic stroke, there are no current recommendations regarding the conduct of research aimed at understanding the mechanisms and prediction of HT. In this review, we discuss the underlying mechanisms for HT after ischemic stroke, provide an overview of the models commonly used for the study of HT, and discuss biomarkers that might be used for early detection of this challenging clinical problem. PMID:25367883

  20. Mitochondrial DNA haplogroups and short-term neurological outcomes of ischemic stroke

    PubMed Central

    Cai, Biyang; Zhang, Zhizhong; Liu, Keting; Fan, Wenping; Zhang, Yumeng; Xie, Xia; Dai, Minhui; Cao, Liping; Bai, Wen; Du, Juan; Dai, Qiliang; Zhou, Shuyu; Zhang, Hao; Zhu, Wusheng; Ma, Minmin; Liu, Wenhua; Liu, Xinfeng; Xu, Gelin

    2015-01-01

    Stroke is one of the leading causes of death and long-term disability worldwide. Mitochondrial DNA (mtDNA) is a potential contributor for the sex differences of ischemic stroke heritability. Although mtDNA haplogroups were associated with stroke onset, their impacts on stroke outcomes remain unclear. This study aimed to evaluate the impacts of mtDNA haplogroups on short-term outcomes of neurological functions in patients with ischemic stroke. A total of 303 patients were included, and their clinical data and mtDNA sequences were analyzed. Based on the changes between baseline and 14-day follow-up stroke severity, our results showed that haplogroup N9 was an independent protective factor against neurological worsening in acute ischemic stroke patients. These findings supported that mtDNA variants play a role in post-stroke neurological recovery, thus providing evidences for future pharmacological intervention in mitochondrial function. PMID:25993529

  1. Thrombolysis and Thrombectomy for Acute Ischemic Stroke: Strengths and Synergies.

    PubMed

    Campbell, Bruce C V

    2017-03-01

    Acute ischemic stroke is responsible for around 80% of all strokes and is a leading cause of disability and death globally. There are two potential treatment strategies: restoring blood flow (reperfusion) and preventing cellular injury (neuroprotection). As yet, all the successful trials have involved reperfusion with numerous failures of neuroprotectants. There are two proven reperfusion strategies. Intravenous thrombolysis with alteplase was first demonstrated to reduce disability with publication of the National Institute of Neurological Disorders and Stroke tissue plasminogen activator trial in 1995. Since that time further trials have solidified the evidence base and demonstrated benefit when alteplase is administered within 4.5 hours of stroke onset. Exploration of potentially more effective thrombolytics is still underway with tenecteplase but others, such as desmoteplase, have been unsuccessful in clinical trials. The second proven reperfusion strategy is endovascular clot retrieval. This has been practiced for several years but came of age with the publication of five strongly positive trials in 2015. This review discusses the evidence for intravenous and intra-arterial reperfusion strategies and the advantages, disadvantages, and synergies of the two approaches.

  2. Ischemic stroke assessment with near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Chen, Weiguo; Li, Pengcheng; Zeng, Shaoqun; Luo, Qingming; Hu, Bo

    1999-09-01

    Many authors have elucidated the theory about oxygenated hemoglobin, deoxygenated hemoglobin absorption in near-infrared spectrum. And the theory has opened a window to measure the hemodynamic changes caused by stroke. However, no proper animal model still has established to confirm the theory. The aim of this study was to validate near-infrared cerebral topography (NCT) as a practical tool and to try to trace the focal hemodynamic changes of ischemic stroke. In the present study, middle cerebral artery occlusion model and the photosensitizer induced intracranial infarct model had been established. NCT and functional magnetic resonance image (fMRI) were obtained during pre- and post-operation. The geometric shape and infarct area of NCT image was compared with the fMRI images and anatomical samples of each rat. The results of two occlusion models in different intervene factors showed the NCT for infarct focus matched well with fMRI and anatomic sample of each rats. The instrument might become a practical tool for short-term prediction of stroke and predicting the rehabilitation after stroke in real time.

  3. Limb apraxia in acute ischemic stroke: a neglected clinical challenge?

    PubMed

    Schell, Caroline; Suchan, Julia; Himmelbach, Marc; Haarmeier, Thomas; Borchers, Svenja

    2014-04-01

    Symptoms of limb apraxia and executive dysfunctions are currently not explicitly considered by the National Institutes of Health Stroke Scale and, thus, not routinely tested by clinicians in the acute care of patients with suspected stroke. Neuropsychological testing, clinical examination, MRI, and functional magnetic resonance imaging (fMRI) were performed in a right-handed patient with acute onset of left-sided sensorimotor hemiparesis due to a right hemisphere ischemic stroke. Deficits in the execution of meaningless and meaningful gestures were not detected properly on initial clinical examination but were revealed later on through neuropsychological testing. Instead, the patient's inability to respond to specific instructions in the acute care setting was mistaken to reflect severe deficits in auditory comprehension. fMRI revealed right-hemispheric localization of language in the right-handed patient. We suggest including a bedside test for limb apraxia symptoms in acute clinical care of stroke patients. The distinction between deficits in limb praxis and impairments of language can be complicated owing to the common hemispheric co-localization of the two functions.

  4. Stroke neuroprotection revisited: Intra-arterial verapamil is profoundly neuroprotective in experimental acute ischemic stroke.

    PubMed

    Maniskas, Michael E; Roberts, Jill M; Aron, Ishi; Fraser, Justin F; Bix, Gregory J

    2016-04-01

    While clinical trials have now solidified the role of thrombectomy in emergent large vessel occlusive stroke, additional therapies are needed to optimize patient outcome. Using our previously described experimental ischemic stroke model for evaluating adjunctive intra-arterial drug therapy after vessel recanalization, we studied the potential neuroprotective effects of verapamil. A calcium channel blocker, verapamil is often infused intra-arterially by neurointerventionalists to treat cerebral vasospasm. Such a direct route of administration allows for both focused targeting of stroke-impacted brain tissue and minimizes potential systemic side effects. Intra-arterial administration of verapamil at a flow rate of 2.5 µl/min and injection volume of 10 µl immediately after middle cerebral artery recanalization in C57/Bl6 mice was shown to be profoundly neuroprotective as compared to intra-arterial vehicle-treated stroke controls. Specifically, we noted a significant (P ≤ 0.05) decrease in infarct volume, astrogliosis, and cellular apoptosis as well as a significant increase in neuronal survival and functional outcome over seven days. Furthermore, intra-arterial administration of verapamil was well tolerated with no hemorrhage, systemic side effects, or increased mortality. Thus, verapamil administered intra-arterially immediately following recanalization in experimental ischemic stroke is both safe and neuroprotective and merits further study as a potential therapeutic adjunct to thrombectomy.

  5. Matrix metalloproteinase-3 gene polymorphisms are associated with ischemic stroke.

    PubMed

    Kim, Su Kang; Kang, Sung Wook; Kim, Dong Hwan; Yun, Dong Hwan; Chung, Joo-Ho; Ban, Ju Yeon

    2012-02-01

    Stroke is a heterogeneous disease caused by different pathogenic mechanisms. Several candidate genes for stroke have been proposed, but few have been replicated. Matrix metalloproteinases (MMPs) are expressed following stroke. We investigated the association of single nucleotide polymorphisms (SNPs) of the MMP3 gene with stroke in the Korean population. This study included 186 stroke patients [116 ischemic stroke (IS) and 70 intracerebral hemorrhage (ICH)] and 668 age-matched control subjects (267 for IS and 401 for ICH). Three SNPs [rs520540 (Ala362Ala), rs602128 (Asp96Asp), and rs679620 (Lys45Glu)] in the coding region of MMP3 were selected and genotyped by direct sequencing. HelixTree, SNPAnalyzer, SNPStats, and Haploview version 4.2 were used to analyze genetic data. Multiple logistic regression models (codominant, dominant, and recessive models) were conducted to evaluate odds ratio, 95% confidence interval, and P value. Three SNPs in the MMP3 gene were significantly associated with IS (P<0.05). The genotype distribution of 3 SNPs differed between the IS and control subjects. However, there was no association of the SNPs between the ICH and control. In analysis of gender, 3 SNPs were also associated with IS in female group (P<0.05). These SNPs remained significantly associated with IS after the Bonferroni correction for multiple testing (P(c)<0.05). Haplotype analysis revealed that no haplotypes were associated with IS or ICH. Overall, the results of our study demonstrate an association of the MMP3 gene with development of IS, and no association of MMP3 with ICH.

  6. Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke

    PubMed Central

    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.

    2015-01-01

    Background and Purpose— 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. Methods— 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. Results— 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). Conclusions— Genetic markers associated with low FXIIIB levels

  7. 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

  8. Hyperglycemia and diabetes have different impacts on outcome of ischemic and hemorrhagic stroke

    PubMed Central

    Snarska, Katarzyna K.; Bachórzewska-Gajewska, Hanna; Kapica-Topczewska, Katarzyna; Drozdowski, Wiesław; Chorąży, Monika; Kułakowska, Alina

    2016-01-01

    Introduction 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. Material and methods 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. Results 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. Conclusions 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. PMID:28144261

  9. Association Between Ischemic Stroke and Tumor Necrosis Factor Inhibitor Therapy in Patients With Rheumatoid Arthritis

    PubMed Central

    Low, Audrey S. L.; Lunt, Mark; Mercer, Louise K.; Watson, Kath D.; Dixon, William G.; Symmons, Deborah P. M.

    2016-01-01

    Objective Patients with rheumatoid arthritis (RA) are at an increased risk of ischemic stroke. Tumor necrosis factor inhibitors (TNFi) may influence risk and mortality after ischemic stroke by reducing inflammation. This study was undertaken to examine the association of TNFi with the risk of incident ischemic stroke and with 30‐day and 1‐year mortality after ischemic stroke. Methods Patients with RA starting therapy with TNFi and a biologics‐naive comparator group treated with synthetic disease‐modifying antirheumatic drugs (DMARDs) only were recruited to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis from 2001 to 2009. Patients were followed up via clinical and patient questionnaires as well as the national death register. Incident strokes were classified as ischemic if brain imaging reports suggested ischemia or if ischemic stroke was reported as the underlying cause of death on a death certificate. Patients with a previous stroke were excluded. Risk of ischemic stroke was compared between patients receiving synthetic DMARDs only and those ever‐exposed to TNFi using a Cox proportional hazards regression model adjusted for potential confounders. Mortality after ischemic stroke was compared between synthetic DMARD–treated patients and TNFi‐treated patients using logistic regression, adjusted for age and sex. Results To April 2010, 127 verified incident ischemic strokes (21 in 3,271 synthetic DMARD–treated patients and 106 in 11,642 TNFi‐treated patients) occurred during 11,973 and 61,226 person‐years of observation, respectively (incidence rate 175 versus 173 per 100,000 person‐years). After adjustment for confounders, there was no association between ever‐exposure to TNFi and ischemic stroke (hazard ratio 0.99 [95% confidence interval (95% CI) 0.54–1.81]). Mortality 30 days or 1 year after ischemic stroke was not associated with concurrent TNFi exposure (odds ratio 0.18 [95% CI 0.03–1.21] and 0.60 [95

  10. Circadian variation in stroke onset: identical temporal pattern in ischemic and hemorrhagic events.

    PubMed

    Manfredini, Roberto; Boari, Benedetta; Smolensky, Michael H; Salmi, Raffaella; la Cecilia, Olga; Maria Malagoni, Anna; Haus, Erhard; Manfredini, Fabio

    2005-01-01

    Stroke is the culmination of a heterogeneous group of cerebrovascular diseases that is manifested as ischemia or hemorrhage of one or more blood vessels of the brain. The occurrence of many acute cardiovascular events--such as myocardial infarction, sudden cardiac death, pulmonary embolism, critical limb ischemia, and aortic aneurysm rupture--exhibits prominent 24 h patterning, with a major morning peak and secondary early evening peak. The incidence of stroke exhibits the same 24 h pattern. Although ischemic and hemorrhagic strokes are different entities and are characterized by different pathophysiological mechanisms, they share an identical double-peak 24 h pattern. A constellation of endogenous circadian rhythms and exogenous cyclic factors are involved. The staging of the circadian rhythms in vascular tone, coagulative balance, and blood pressure plus temporal patterns in posture, physical activity, emotional stress, and medication effects play central and/or triggering roles. Features of the circadian rhythm of blood pressure, in terms of their chronic and acute effects on cerebral vessels, and of coagulation are especially important. Clinical medicine has been most concerned with the prevention of stroke in the morning, when population-based studies show it is of greatest risk during the 24 h; however, improved protection of at-risk patients against stroke in the early evening, the second most vulnerable time of cerebrovascular accidents, has received relatively little attention thus far.

  11. Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

    PubMed Central

    Bonaventura, Aldo; Liberale, Luca; Vecchié, Alessandra; Casula, Matteo; Carbone, Federico; Dallegri, Franco; Montecucco, Fabrizio

    2016-01-01

    After an acute ischemic stroke (AIS), inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity. Inflammation in AIS is characterized by a storm of cytokines, chemokines, and Damage-Associated Molecular Patterns (DAMPs) released by several cells contributing to exacerbate the tissue injury both in the acute and reparative phases. Interestingly, many biomarkers have been studied, but none of these reflected the complexity of systemic immune response. Reperfusion therapies showed a good efficacy in the recovery after an AIS. New therapies appear promising both in pre-clinical and clinical studies, but still need more detailed studies to be translated in the ordinary clinical practice. In spite of clinical progresses, no beneficial long-term interventions targeting inflammation are currently available. Our knowledge about cells, biomarkers, and inflammatory markers is growing and is hoped to better evaluate the impact of new treatments, such as monoclonal antibodies and cell-based therapies. PMID:27898011

  12. An Inflammatory Polymorphisms Risk Scoring System for the Differentiation of Ischemic Stroke Subtypes

    PubMed Central

    Muiño, Elena; Krupinski, Jurek; Carrera, Caty; Gallego-Fabrega, Cristina; Montaner, Joan; Fernández-Cadenas, Israel

    2015-01-01

    Inflammation has been associated with atherothrombotic stroke and recently with cardioembolic stroke. Different genetic risk factors have been specifically associated with the subtypes of ischemic stroke (cardioembolic, atherothrombotic, and lacunar). However, there are no studies that have generated genetic risk scores for the different subtypes of ischemic stroke using polymorphisms associated with inflammation. Methods. We have analyzed 68 polymorphisms of 30 inflammatory mediator genes in 2,685 subjects: 1,987 stroke cases and 698 controls. We generated a genetic scoring system with the most significant polymorphisms weighted by the odds ratio of every polymorphism and taken into consideration the stroke subtype. Results. Three polymorphisms, rs1205 (CRP gene), rs1800779, and rs2257073 (NOS3 gene), were associated with cardioembolic stroke (p value <0.05). The score generated was only associated with the cardioembolic stroke subtype (p value: 0.001) and was replicated in an independent cohort (p value: 0.017). The subjects with the highest score presented a cardioembolic stroke in 92.2% of the cases (p value: 0.002). Conclusion. The genetics of inflammatory markers is more closely associated with cardioembolic strokes than with atherothrombotic or lacunar strokes. The genetic risk scoring system could be useful in the prediction and differentiation of ischemic stroke; however, it might be specific to particular ischemic stroke subtypes. PMID:26355258

  13. [EEG and ischemic stroke in full-term newborns].

    PubMed

    Selton, D; André, M; Hascoët, J M

    2003-06-01

    The aims of this study were to describe EEG anomalies in unilateral neonatal ischemic stroke without hypoxic-ischemic encephalopathy, and to determine possible links between these abnormalities and long-term outcome. In 6 full-term newborns without severe fetal distress ischemic stroke was confirmed by computed tomography and/or magnetic resonance imaging. Twenty EEGs were recorded during the neonatal period, 5 in acute stage and 15 later. The duration of the follow-up ranged from 3 to 9 years. All newborns developed unilateral clonic seizures, right-sided (5 cases) or left-sided (1 case); seizures began between 14 and 48 h of life. At follow-up, 3 children were normal at 2 and 6 years of age, while the 3 others had sequelae: epilepsy at 9 years of age in one, and unilateral mild cerebral palsy in the 2 others (3 and 4 years of age), with behavioral problems in one of them. Critical EEG discharges, rhythmic sharp waves and/or slow waves were recorded on the injured side. Abnormalities of interictal activity were excess of alpha or theta rhythms, transitory EEG discontinuity or low voltage. The 2 children with cerebral palsy had numerous unilateral post-ictal positive rolandic slow sharp waves (PRSSWs), which were similar to the positive rolandic sharp waves of premature infants; the child with behavioral problems had numerous positive left-sided temporal fast sharp waves. PRSSWs could be associated with contralateral motor sequelae, while positive left temporal fast sharp waves were associated with long term behavioral problems. These findings may be used for future prospective studies aimed at specifying the relation between EEG abnormalities and long-term outcome.

  14. IV thrombolysis in very severe and severe ischemic stroke

    PubMed Central

    Lees, Kennedy R.; Collas, David; Rand, Viiu-Marika; Mikulik, Robert; Toni, Danilo; Wahlgren, Nils; Ahmed, Niaz

    2015-01-01

    Objective: To study the safety of off-label IV thrombolysis in patients with very severe stroke (NIH Stroke Scale [NIHSS] scores >25) compared with severe stroke (NIHSS scores 15–25), where treatment is within European regulations. Methods: Data were analyzed from 57,247 patients with acute ischemic stroke receiving IV tissue plasminogen activator in 793 hospitals participating in the Safe Implementation of Thrombolysis in Stroke (SITS) International Stroke Thrombolysis Registry (2002–2013). Eight hundred sixty-eight patients (1.5%) had NIHSS scores >25 and 19,995 (34.9%) had NIHSS scores 15–25. Outcome measures were parenchymal hemorrhage, symptomatic intracerebral hemorrhage, mortality, and functional outcome. Results: Parenchymal hemorrhage occurred in 10.7% vs 11.0% (p = 0.79), symptomatic intracerebral hemorrhage per SITS-MOST (SITS–Monitoring Study) in 1.4% vs 2.5% (p = 0.052), death at 3 months in 50.4% vs 26.9% (p < 0.001), and functional independence at 3 months in 14.0% vs 29.0% (p < 0.001) of patients with NIHSS scores >25 and NIHSS scores 15–25, respectively. Multivariate adjustment did not change findings from univariate comparisons. Posterior circulation stroke was more common in patients with NIHSS scores >25 (36.2% vs 7.4%, p < 0.001), who were also more often obtunded or comatose on presentation (58.4% vs 7.1%, p < 0.001). Of patients with NIHSS scores >25, 26.2% were treated >3 hours from symptom onset vs 14.5% with NIHSS scores of 15–25. Conclusions: Our data show no excess risk of cerebral hemorrhage in patients with NIHSS score >25 compared to score 15–25, suggesting that the European contraindication to IV tissue plasminogen activator treatment at NIHSS levels >25 may be unwarranted. Increased mortality and lower rates of functional independence in patients with NIHSS score >25 are explained by higher stroke severity, impaired consciousness on presentation due to posterior circulation ischemia, and longer treatment delays. PMID

  15. Low ADAMTS13 activity is associated with an increased risk of ischemic stroke.

    PubMed

    Sonneveld, Michelle A H; de Maat, Moniek P M; Portegies, Marileen L P; Kavousi, Maryam; Hofman, Albert; Turecek, Peter L; Rottensteiner, Hanspeter; Scheiflinger, Fritz; Koudstaal, Peter J; Ikram, M Arfan; Leebeek, Frank W G

    2015-12-17

    ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin motif repeats 13) has antithrombotic properties because it cleaves von Willebrand factor (VWF) in smaller, less active multimers. The aim of our study was to investigate prospectively the association between ADAMTS13 activity and ischemic stroke. We included 5941 individuals ≥55 years without a history of stroke or transient ischemic attack (TIA) of the Rotterdam Study, a population-based cohort study. ADAMTS13 activity was measured at inclusion with the FRETS-VWF73 assay and VWF antigen (VWF:Ag) levels by enzyme-linked immunosorbent assay. We assessed the association among ADAMTS13 activity, VWF:Ag levels, and ischemic stroke by Cox proportional hazard analysis. The added value of ADAMTS13 activity above the traditional risk factors for ischemic stroke risk prediction was examined by the C-statistic and the net reclassification improvement index (NRI). All individuals were followed for incident stroke or TIA. Over a median follow-up time of 10.7 years (56,403 total person-years), 461 participants had a stroke, 306 of which were ischemic. After adjustment for cardiovascular risk factors, individuals with ADAMTS13 activity in the lowest quartile had a higher risk of ischemic stroke (absolute risk, 7.3%) than did those in the reference highest quartile (absolute risk, 3.8%; hazard ratio, 1.65; 95% confidence interval [CI], 1.16-2.32). Adding ADAMTS13 to the model in prediction of ischemic stroke, increased the C-statistic by 0.013 (P = .003) and provided 0.058 (95% CI, -0.002 to 0.119) NRI. Low ADAMTS13 activity is associated with the risk of ischemic stroke and improves the accuracy of risk predictions for ischemic stroke beyond traditional risk factors.

  16. Sirtuin 3 mediates neuroprotection of ketones against ischemic stroke.

    PubMed

    Yin, Junxiang; Han, Pengcheng; Tang, Zhiwei; Liu, Qingwei; Shi, Jiong

    2015-11-01

    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.

  17. Discovery of Metabolite Biomarkers for Acute Ischemic Stroke Progression.

    PubMed

    Liu, Peifang; Li, Ruiting; Antonov, Anton A; Wang, Lihua; Li, Wei; Hua, Yunfei; Guo, Huimin; Wang, Lijuan; Liu, Peijia; Chen, Lixia; Tian, Yuan; Xu, Fengguo; Zhang, Zunjian; Zhu, Yulan; Huang, Yin

    2017-02-03

    Stroke remains a major public health problem worldwide; it causes severe disability and is associated with high mortality rates. However, early diagnosis of stroke is difficult, and no reliable biomarkers are currently established. In this study, mass-spectrometry-based metabolomics was utilized to characterize the metabolic features of the serum of patients with acute ischemic stroke (AIS) to identify novel sensitive biomarkers for diagnosis and progression. First, global metabolic profiling was performed on a training set of 80 human serum samples (40 cases and 40 controls). The metabolic profiling identified significant alterations in a series of 26 metabolites with related metabolic pathways involving amino acid, fatty acid, phospholipid, and choline metabolism. Subsequently, multiple algorithms were run on a test set consisting of 49 serum samples (26 cases and 23 controls) to develop different classifiers for verifying and evaluating potential biomarkers. Finally, a panel of five differential metabolites, including serine, isoleucine, betaine, PC(5:0/5:0), and LysoPE(18:2), exhibited potential to differentiate AIS samples from healthy control samples, with area under the receiver operating characteristic curve values of 0.988 and 0.971 in the training and test sets, respectively. These findings provided insights for the development of new diagnostic tests and therapeutic approaches for AIS.

  18. Arterial ischemic stroke and hemorrhagic stroke in Chinese children: a retrospective analysis.

    PubMed

    Xie, Ling-Ling; Jiang, Li

    2014-02-01

    To study the characteristics of pediatric arterial ischemic stroke (AIS) and hemorrhagic stroke (HS) in southwest of China, and analyze the etiology and risk factor. This study retrospectively reviewed the records of all patients in both department of neurology and department of neurosurgery in Children's hospital of Chongqing medical university from January 2003 to March 2011, and patients were eligible for analysis if they had been diagnosed with AIS or HS. And SPSS 17.0 software was used for statistical analysis. The χ(2) test was used to exam relationships between stroke types and sex, age, and that between neuroradiological images and sex. 119 Boys (70.4%) and 50 girls (29.6%) were included. In these cases, HS accounted for the majority of the cases (n=109, 64.1%), and vitamin K deficiency was a major etiology in 65 out of 109 HS (59.6%), most of which occurred in breastfeeding infants (87.7%) and those who received no vitamin K after birth. AIS accounted for 35.3% of the cases, and minor head injury associated stroke (40.0%) was more common than vasculopathy associated stroke (16.6%) and other kinds of stroke. HS in children is more common than AIS. Vitamin K deficiency was a major etiology in these young infants who experienced HS, and many cases of AIS were associated with minor head injury.

  19. Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine

    PubMed Central

    Seto, Sai-Wang; Chang, Dennis; Jenkins, Anita; Bensoussan, Alan; Kiat, Hosen

    2016-01-01

    Stroke is one of the major causes of death and adult disability worldwide. The underlying pathophysiology of stroke is highly complicated, consisting of impairments of multiple signalling pathways, and numerous pathological processes such as acidosis, glutamate excitotoxicity, calcium overload, cerebral inflammation and reactive oxygen species (ROS) generation. The current treatment for ischemic stroke is limited to thromolytics such as recombinant tissue plasminogen activator (tPA). tPA has a very narrow therapeutic window, making it suitable to only a minority of stroke patients. Hence, there is great urgency to develop new therapies that can protect brain tissue from ischemic damage. Recent studies have shown that new vessel formation after stroke not only replenishes blood flow to the ischemic area of the brain, but also promotes neurogenesis and improves neurological functions in both animal models and patients. Therefore, drugs that can promote angiogenesis after ischemic stroke can provide therapeutic benefits in stroke management. In this regard, Chinese herbal medicine (CHM) has a long history in treating stroke and the associated diseases. A number of studies have demonstrated the pro-angiogenic effects of various Chinese herbs and herbal formulations in both in vitro and in vivo settings. In this article, we present a comprehensive review of the current knowledge on angiogenesis in the context of ischemic stroke and discuss the potential use of CHM in stroke management through modulation of angiogenesis. PMID:27275837

  20. 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

  1. Shared genetic contribution to ischemic stroke and Alzheimer's disease

    PubMed Central

    Adib‐Samii, Poneh; Harold, Denise; Dichgans, Martin; Williams, Julie; Lewis, Cathryn M.; Markus, Hugh S.; Fornage, Myriam; Holliday, Elizabeth G; Sharma, Pankaj; Bis, Joshua C; Psaty, Bruce M; Seshadri, Sudha; Nalls, Mike A; Devan, William J; Boncoraglio, Giorgio; Malik, Rainer; Mitchell, Braxton D; Kittner, Steven J; Ikram, M Arfan; Clarke, Robert; Rosand, Jonathan; Meschia, James F; Sudlow, Cathie; Rothwell, Peter M; Levi, Christopher; Bevan, Steve; Kilarski, Laura L; Walters, Matthew; Thijs, Vincent; Slowik, Agnieszka; Lindgren, Arne; de Bakker, Paul I W; Lambert, Jean‐Charles; Ibrahim‐Verbaas, Carla A; Harold, Denise; Naj, Adam C; Sims, Rebecca; Bellenguez, Céline; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier‐Boley, Benjamin; Russo, Giancarlo; Thornton‐Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao‐Feng; Gerrish, Amy; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie‐Thçrèse; Choi, Seung‐Hoan; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Ramirez, Alfredo; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Morón, Francisco J; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiçvet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger‐Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Green, Robert; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; St George‐Hyslop, Peter; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petroula; Collinge, John; Sorbi, Sandro; Sanchez‐Garcia, Florentino; Fox, Nick C; Hardy, John; Deniz Naranjo, Maria Candida; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Matthews, Fiona; Moebus, Susanne; Mecocci, Patrizia; Del Zompo, Maria; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton‐Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O'Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Wang, Li‐San; Dartigues, Jean‐François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Jones, Lesley; Haines, Jonathan L; Holmans, Peter A; Lathrop, Mark; Pericak‐Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broeckhoven, Christine; Moskvina, Valentina; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D; Amouyel, Philippe

    2016-01-01

    Objective Increasing evidence suggests epidemiological and pathological links between Alzheimer's disease (AD) and ischemic stroke (IS). We investigated the evidence that shared genetic factors underpin the two diseases. Methods Using genome‐wide association study (GWAS) data from METASTROKE + (15,916 IS cases and 68,826 controls) and the International Genomics of Alzheimer's Project (IGAP; 17,008 AD cases and 37,154 controls), we evaluated known associations with AD and IS. On the subset of data for which we could obtain compatible genotype‐level data (4,610 IS cases, 1,281 AD cases, and 14,320 controls), we estimated the genome‐wide genetic correlation (rG) between AD and IS, and the three subtypes (cardioembolic, small vessel, and large vessel), using genome‐wide single‐nucleotide polymorphism (SNP) data. We then performed a meta‐analysis and pathway analysis in the combined AD and small vessel stroke data sets to identify the SNPs and molecular pathways through which disease risk may be conferred. Results We found evidence of a shared genetic contribution between AD and small vessel stroke (rG [standard error] = 0.37 [0.17]; p = 0.011). Conversely, there was no evidence to support shared genetic factors in AD and IS overall or with the other stroke subtypes. Of the known GWAS associations with IS or AD, none reached significance for association with the other trait (or stroke subtypes). A meta‐analysis of AD IGAP and METASTROKE + small vessel stroke GWAS data highlighted a region (ATP5H/KCTD2/ICT1) associated with both diseases (p = 1.8 × 10−8). A pathway analysis identified four associated pathways involving cholesterol transport and immune response. Interpretation Our findings indicate shared genetic susceptibility to AD and small vessel stroke and highlight potential causal pathways and loci. Ann Neurol 2016;79:739–747 PMID:26913989

  2. Elevated blood pressure management in acute ischemic stroke remains controversial: could this issue be resolved?

    PubMed

    Hadjiev, Dimiter I; Mineva, Petya P

    2013-01-01

    A transient elevated arterial blood pressure is common in acute ischemic stroke and is often associated with a poor prognosis. The underlying mechanisms of blood pressure elevation are not well understood and its management is still unresolved. This article focuses on pathophysiology and management of elevated blood pressure in acute ischemic stroke. There is evidence that the main causes of a transient blood pressure elevation in acute ischemic stroke are the focal cerebral hypoperfusion and the stress responses with neuroendocrine systems activation. Clinical trials have reported that blood pressure lowering in acute ischemic stroke may have detrimental effect, probably because of impaired cerebral autoregulation. However, quantitative assessment of cerebral perfusion has not been performed during emergency blood pressure reduction in acute ischemic stroke. We suggest that ultrasound carotid artery disease evaluation and cerebral hemodynamics monitoring using bilateral transcranial ultrasonography, during blood pressure management in acute ischemic stroke might contribute to maintaining of an adequate penumbral perfusion and prevent infarct enlargement. Such an approach could individualize the antihypertensive treatment in acute ischemic stroke and improve functional outcome. Prospective studies are needed to confirm such a treatment strategy.

  3. Effect of β-adrenergic antagonists on in-hospital mortality after ischemic stroke

    PubMed Central

    Phelan, Christopher; Alaigh, Vivek; Fortunato, Gil; Staff, Ilene; Sansing, Lauren

    2015-01-01

    Background Ischemic stroke accounts for 85–90% of all strokes and currently has very limited therapeutic options. Recent studies of β-adrenergic antagonists suggest they may have neuroprotective effects that lead to improved functional outcomes in rodent models of ischemic stroke, however there is limited data in patients. We aimed to determine whether there was an improvement in mortality rates among patients who were taking β-blockers during the acute phase of their ischemic stroke. Methods A retrospective analysis of a prospectively collected database of ischemic stroke patients was performed. Patients who were on β-adrenergic antagonists both at home and during the first three days of hospitalization were compared to patients who were not on β-adrenergic antagonists to determine the association with patient mortality rates. Results The study included a patient population of 2804 patients. In univariate analysis, use of β-adrenergic antagonists was associated with older age, atrial fibrillation, hypertension and more severe initial stroke presentation. Despite this, multivariable analysis revealed a reduction in in-hospital mortality among patients who were treated with β-adrenergic antagonists (odds ratio 0.657; 95% confidence interval 0.655–0.658). Conclusions The continuation of home β-adrenergic antagonist medication during the first three days of hospitalization after an ischemic stroke is associated with a decrease in patient mortality. This supports the work done in rodent models suggesting neuroprotective effects of β-blockers after ischemic stroke. PMID:26163891

  4. 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

    2016-08-11

    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

  5. Intravenous Thrombolysis for Acute Ischemic Stroke: Review of 97 Patients

    PubMed Central

    Mehta, Anish; Mahale, Rohan; Buddaraju, Kiran; Majeed, Anas; Sharma, Suryanarayana; Javali, Mahendra; Acharya, Purushottam; Srinivasa, Rangasetty

    2017-01-01

    Background: Intravenous thrombolysis (IVT) has now become a standard treatment in eligible patients with acute ischemic stroke (AIS) who present within 4.5 h of symptom onset. Objective: To determine the usefulness of IVT and the subset of patients who will benefit from IVT in AIS within 4.5 h. Materials and Methods: Patients with AIS within 4.5 h of symptom onset who underwent IVT were studied prospectively. The study period was from October 2011 to October 2015. Results: A total of 97 patients were thrombolysed intravenously. The mean onset to needle time in all patients was 177.2 ± 62 min (range: 60–360). At 3 months follow-up, favorable outcome was seen in 65 patients (67.1%) and poor outcome including death in the remaining 32 patients (32.9%). Factors predicting favorable outcome was age <65 years (P = 0.02), the National Institute of Health Stroke Scale (NIHSS) <15 (P < 0.001), small vessel occlusion (P = 0.006), cardioembolism (P = 0.006), and random blood sugar (RBS) <250 mg/dl (P < 0.001). Factors predicting poor outcome was diabetes mellitus (P = 0.01), dyslipidemia (P = 0.01), NIHSS at admission >15 (P = 0.03), RBS >250 mg/dl (P = 0.01), Dense cerebral artery sign, age, glucose level on admission, onset-to-treatment time, NIHSS on admission score >5 (P = 0.03), and occlusion of large artery (P = 0.02). Conclusion: Milder baseline stroke severity, blood glucose <250 mg/dL, younger patients (<65 years), cardioembolic stroke, and small vessel occlusion benefit from recombinant tissue plasminogen activator. PMID:28149079

  6. [NDT-Bobath method used in the rehabilitation of patients with a history of ischemic stroke].

    PubMed

    Klimkiewicz, Paulina; Kubsik, Anna; Woldańska-Okońska, Marta

    2012-01-01

    Ischemic stroke is the third leading cause of death and disability in human. The vitally important problem after ischemic stroke is hemiparesis of the body. The most common methods used in improving the mobility of patients after ischemic stroke is a Bobath-NDT (Neuro-Developmental Treatment - Bobath), which initiated the Berta and Karel Bobath for children with cerebral palsy. It is a method designed to neurophysiological recovery of these vital functions that the patient was lost due to illness, and wants it back.

  7. Platelets Proteomic Profiles of Acute Ischemic Stroke Patients

    PubMed Central

    Baykal, Ahmet Tarik; Sener, Azize

    2016-01-01

    Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets’ tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight

  8. Serum Hepcidin Levels in Childhood-Onset Ischemic Stroke

    PubMed Central

    Azab, Seham F.; Akeel, Nagwa E.; Abdalhady, Mohamed A.; Elhewala, Ahmed A.; Ali, Al Shymaa A.; Amin, Ezzat K.; Sarhan, Dina T.; Almalky, Mohamed A.A.; Elhindawy, Eman M.; Salam, Mohamed M.A.; Soliman, Attia A.; Abdellatif, Sawsan H.; Ismail, Sanaa M.; Elsamad, Nahla A.; Hashem, Mustafa I.A.; Aziz, Khalid A.; Elazouni, Osama M.A.; Arafat, Manal S.

    2016-01-01

    Abstract Recently, hepcidin, an antimicrobial-like peptide hormone, has evolved as the master regulator of iron homeostasis. Despite the growing evidence of iron imbalance in childhood-onset ischemic stroke, serum hepcidin level in those patients has not yet been researched. In this study, we aimed to estimate serum (hepcidin) level in acute ischemic stroke (AIS) patients and to investigate whether subcutaneous enoxaparin sodium, which is a low-molecular-weight heparin (LMWH) derivative, could modulate serum hepcidin level in those patients. This was a case–control study included 60 (AIS) cases, and 100 healthy children with comparable age and gender as control group. For all subjects’ serum hepcidin, interleukin-6 (IL-6), and soluble transferrin receptor [sTfR]) levels were assessed by (enzyme-linked immunosorbent assay [ELISA] method). Iron parameters including (serum iron, ferritin, transferrin, and total iron binding capacity [TIBC]) were also measured. The patients were subdivided according to treatment with an LMWH derivative into 2 groups and serum hepcidin levels were assessed initially and 1 week after stroke onset for all cases. We found that AIS cases had higher serum iron, ferritin, and IL6 levels compared to the control group (all P < 0.01). Serum hepcidin was significantly higher in AIS cases (median, 36[15–73]ng/mL) compared to the control group (median, 24[10–41]ng/mL; P < 0.01). On the 1st day of AIS diagnosis, serum hepcidin levels were similar in both stroke subgroups (P > 0.05). However, on the 7th day of diagnosis serum hepcidin level decreased significantly in AIS cases treated with LMWH (group 1) (median, 36 vs 21 ng/mL; P < 0.01, respectively). Meanwhile, no significant change was observed in serum hepcidin level in AIS cases not treated with LMWH (group 2) (P > 0.05). Serum hepcidin showed significant positive correlations with serum iron, transferrin saturation, ferritin, and IL6 (r = 0.375, P < 0

  9. [Comparative analysis of efficacy of certain neuroprotectors in ischemic stroke].

    PubMed

    Skorokhodov, A P; Dudina, A A; Kolesnikova, E A; Koron, A E; Kobantsev, Iu A; Sedova, A A

    2006-01-01

    Cortexin, nootropil and cerebrolysin have been used as neuroprotective medications in the acute period of ischemic stroke (IS). Clinical efficacy of cortexin and nootropil has been compared in 2 therapeutic series in 35 patients and that of cortexin and cerebrolysin--in 45 patients. The efficacy was assessed using several clinical and psychometric scales with statistical processing of the results. The data obtained suggest that in patients with moderate IS the drugs exert a similar and rather marked effect which was stronger comparing to the treatment without these drugs. At the same time, a domestic neuroprotector cortexin has some advantages, especially with regard to the absence of side-effects and "price-dose-therapeutic effect" criterion.

  10. Ischemic stroke subtype and presence of sleep-disordered breathing: the BASIC Sleep Apnea Study

    PubMed Central

    Brown, Devin L.; Mowla, Ashkan; McDermott, Mollie; Morgenstern, Lewis B.; Hegeman, Garnett; Smith, Melinda A.; Garcia, Nelda M.; Chervin, Ronald D.; Lisabeth, Lynda D.

    2014-01-01

    Goal Little is known about the prevalence of sleep apnea (SA) across ischemic stroke subtypes. Given the important implications for SA screening, we tested the association between SA and ischemic stroke subtype in a population-based study. Methods Within the Brain Attack Surveillance in Corpus Christi Project, ischemic stroke patients were offered SA screening with the ApneaLink Plus™ (n=355). A neurologist assigned TOAST subtype (with an additional category for nonlacunar infarctions of unknown etiology) using hospital records. Unadjusted and adjusted (demographics, BMI, NIHSS, diabetes, history of stroke/TIA) logistic and linear regression models were used to test the association between subtype and SA or apnea-hypopnea index (AHI). Findings Median age was 65 and 55% were male; 59% were Mexican American. Median time from stroke onset to SA screen was 13 days (IQR: 6, 21). Overall, 215 (61%) had SA (AHI ≥ 10). Median AHI was 13 (IQR: 6, 27). Prevalence of SA by subtype was: cardioembolism, 66%; large artery atherosclerosis, 57%; small vessel occlusion, 68%; other determined, 50%; undetermined etiology, 58%; and nonlacunar stroke of unknown etiology, 63%. Ischemic stroke subtype was not associated with SA in unadjusted (p=0.72) or adjusted models (p=0.91) models. Ischemic stroke subtype was not associated with AHI in unadjusted (p=0.41) or adjusted models (p=0.62). Conclusion In this population-based stroke surveillance study, ischemic stroke subtype was not associated with the presence or severity of SA. Sleep apnea is likely to be present after ischemic stroke, and the subtype should not influence decisions about SA screening. PMID:25497720

  11. Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke.

    PubMed

    Hu, Xiaoming; De Silva, T Michael; Chen, Jun; Faraci, Frank M

    2017-02-03

    The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury after ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in blood-brain barrier integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events.

  12. A critical velocity of squeezing a droplet through a circular constriction: implications on ischemic stroke

    NASA Astrophysics Data System (ADS)

    Zhang, Zhifeng; Drapaca, Corina

    2016-11-01

    Ischemic stroke accounts for about 87 percent of all stroke cases. In these cases, models of squeezing a droplet through a smaller constriction channel can help better understand the pathology and capillary restoring after a Stroke. In the present research, we analytical expressed the minimum impulse of squeezing a droplet through a circular channel as well as its critical velocity. By comparison with a previously defined critical velocity, we find the difference between these two. Applications of this research in the understanding of ischemic stroke are also discussed. Zhifeng Zhang thanks the support of Robert A. Sebrosky Graduate Fellowship in Engineering Science and Mechanics, the Pennsylvania State University.

  13. The role for infarct volume as a surrogate measure of functional outcome following ischemic stroke

    PubMed Central

    Turner, Ryan C; DiPasquale, Kenneth; Logsdon, Aric F; Tan, Zhenjun; Naser, Zachary J; Huber, Jason D; Rosen, Charles L; Lucke-Wold, Brandon P

    2016-01-01

    The failed translation of proposed therapeutic agents for ischemic stroke from preclinical to clinical studies has led to increased scrutiny of preclinical studies, namely the model and outcome measures utilized. Preclinical studies routinely use infarct volume as an experimental endpoint or measure in studies employing young-adult, healthy male animals despite the fact that clinically, ischemic stroke is a disease of the elderly and improvements in functional outcome from pre- to post-intervention remains the most widely utilized assessment. The validity of infarct volume as a surrogate measure for functional outcome remains unclear in clinical studies as well as preclinical studies, particularly those utilizing a more clinically relevant aged thromboembolic model. In this work, we will address the relationship between acute and chronic functional outcome and infarct volume using a variety of functional assessments ranging from more simplistic, subjective measurements such as the modified Neurologic Severity Score (mNSS), to more complex, objective measurements such as grip strength and inclined plane.

  14. Acute development of collateral circulation and therapeutic prospects in ischemic stroke.

    PubMed

    Iwasawa, Eri; Ichijo, Masahiko; Ishibashi, Satoru; Yokota, Takanori

    2016-03-01

    In acute ischemic stroke, collateral circulation plays an important role in maintaining blood flow to the tissue that is at risk of progressing into ischemia, and in increasing the successful recanalization rate without hemorrhagic transformation. We have reported that well-developed collateral circulation is associated with smaller infarct volume and better long-term neurological outcome, and it disappears promptly once the effective recanalization is achieved. Contrary to the belief that collateral vessels develop over time in chronic stenotic condition, there exists a phenomenon that collateral circulation develops immediately in acute stenosis or occlusion of the arteries and it seems to be triggered by fluid shear stress, which occurs between the territories of stenotic/occluded arteries and those fed by surrounding intact arteries. We believe that this acute development of collateral circulation is a target of novel therapeutics in ischemic stroke and refer our recent attempt in enhancing collateral circulation by modulating sphingosine-1-phosphate receptor 1, which is a known shear-stress mechanosensing protein.

  15. Intake of antioxidants and B vitamins is inversely associated with ischemic stroke and cerebral atherosclerosis

    PubMed Central

    Choe, Hansaem; Hwang, Ji-Yun; Yun, Jin A; Kim, Ji-Myung; Song, Tae-Jin; Chang, Namsoo; Kim, Yong-Jae

    2016-01-01

    BACKGROUND/OBJECTIVES This study was conducted to examine relationships between dietary habits and intakes of antioxidants and B vitamins and the risk of ischemic stroke, and to compare dietary factors according to the presence of cerebral artery atherosclerosis and stroke subtypes. SUBJECTS/METHODS A total of 147 patients and 144 control subjects were recruited consecutively in the metropolitan area of Seoul, Korea. Sixty participants each in the case and control groups were included in analyses after 1:1 frequency matching. In addition, 117 acute ischemic stroke patients were classified into subtypes according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) guidelines. Dietary intake was measured using a semi-quantitative food frequency questionnaire composed of 111 food items and plasma lipid and homocysteine levels were analyzed. RESULTS When compared with control subjects, stroke patients had unfavorable dietary behaviors and lower intakes of fruits (73.1 ± 83.2 g vs. 230.9 ± 202.1 g, P < 0.001), vegetables (221.1 ± 209.0 g vs. 561.7 ± 306.6 g, P < 0.001), and antioxidants, including vitamins C, E, B6, β-carotene, and folate. The intakes of fruits, vegetables, vitamin C, and folate were inversely associated with the risk of ischemic stroke after adjusting for confounding factors. Intakes of vegetables, vitamins C, B6, B12, and folate per 1,000 kcal were lower in ischemic stroke with cerebral atherosclerosis than in those without. Overall vitamin B12 intake per 1,000 kcal differed according to the TOAST classification (P = 0.004), but no differences among groups existed based on the post-hoc test. CONCLUSIONS When compared with control subjects, ischemic stroke patients, particularly those with cerebral atherosclerosis, had unfavorable dietary intake, which may have contributed to the development of ischemic stroke. These results indicate that proper dietary recommendations are important for the prevention of ischemic stroke. PMID:27698959

  16. Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance

    PubMed Central

    Lehotský, Ján; Tothová, Barbara; Kovalská, Maria; Dobrota, Dušan; Beňová, Anna; Kalenská, Dagmar; Kaplán, Peter

    2016-01-01

    Homocysteine (Hcy) is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy), as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS) and posttranslational modifications of proteins via homocysteinylation and thiolation. Ischemic preconditioning (IPC) is an adaptive response of the CNS to sub-lethal ischemia, which elevates tissues tolerance to subsequent ischemia. The main focus of this review is on the recent data on homocysteine metabolism and mechanisms of its neurotoxicity. In this context, the review documents an increased oxidative stress and functional modification of enzymes involved in redox balance in experimentally induced hyperhomocysteinemia. It also gives an interpretation whether hyperhomocysteinemia alone or in combination with IPC affects the ischemia-induced neurodegenerative changes as well as intracellular signaling. Studies document that hHcy alone significantly increased Fluoro-Jade C- and TUNEL-positive cell neurodegeneration in the rat hippocampus as well as in the cortex. IPC, even if combined with hHcy, could still preserve the neuronal tissue from the lethal ischemic effects. This review also describes the changes in the mitogen-activated protein kinase (MAPK) protein pathways following ischemic injury and IPC. These studies provide evidence for the interplay and tight integration between ERK and p38 MAPK signaling mechanisms in response to the hHcy and also in association of hHcy with ischemia/IPC challenge in the rat brain. Further investigations of the protective factors leading to ischemic

  17. Incidence of Recurrence in Posterior Circulation Childhood Arterial Ischemic Stroke

    PubMed Central

    Uohara, Michael Y.; Beslow, Lauren A.; Billinghurst, Lori; Jones, Brianna M.; Kessler, Sudha K.; Licht, Daniel J.; Ichord, Rebecca N.

    2017-01-01

    IMPORTANCE Childhood arterial ischemic stroke (CAIS) affects approximately 1.6 per 100 000 children per year, while stroke recurs in up to 20%of patients at 5 years. Factors determining the risk of recurrence are incompletely understood. OBJECTIVE To investigate the incidence of the recurrence of CAIS in the posterior and anterior circulations to determine if the risk differs between the 2 locations. DESIGN, SETTING, AND PARTICIPANTS A retrospective analysis of CAIS was conducted among children enrolled in a single-center prospective consecutive cohort at The Children’s Hospital of Philadelphia between January 1, 2006, and January 1, 2015. Children with confirmed CAIS occurring between 29 days and 17.99 years were evaluated for inclusion. Patients were excluded if infarcts were located in both the anterior and posterior distributions or if CAIS occurred as a complication of intracranial surgery or brain tumor. MAIN OUTCOMES AND MEASURES Stroke recurrence. RESULTS The study population included 107 patients (75 boys [70.1%] and 32 girls [29.9%]; median age at AIS, 7.7 years [interquartile range, 3.1–13.6 years]). Sixty-one children had anterior circulation CAIS (ACAIS) and 46 had posterior circulation CAIS (PCAIS). Median follow-up was 20.9 months (interquartile range, 8.7–40.4 months). For ACAIS, recurrence-free survival was 100% at 1 month and 96%(95%CI, 85%–99%) at 1 and 3 years. For PCAIS, recurrence-free survival was 88%(95%CI, 75%–95%) at 1 month and 81%(95% CI, 66%–90%) at 1 and 3 years. The hazard ratio for recurrence after PCAIS compared with ACAIS was 6.4 (95%CI, 1.4–29.8; P = .02) in univariable analysis and 5.3 (95%CI, 1.1–26.4; P = .04) after adjusting for sex and cervical dissection. CONCLUSIONS AND RELEVANCE We identified a subgroup of patients that comprise more than 80% of recurrences of CAIS. Three years after incident stroke, 19% of children with PCAIS had a recurrence compared with 4%of patients with ACAIS. Different mechanisms of

  18. Proteinuria is an independent risk factor for ischemic stroke among diabetic patients.

    PubMed

    Mondol, G; Rahman, K M; Uddin, M J; Bhattacharjee, M; Dey, S K; Israil, A; Miah, A H; Sarkar, U K; Islam, S S; Rahman, M M; Hossain, F; Bhuiya, M M; Bhowmik, R; Chowdhury, A H; Kabir, M S; Uddin, M S

    2012-07-01

    This study was done to assess the relationship between proteinuria and ischemic stroke in subjects with diabetes mellitus, and to determine whether proteinuria is an independent risk factor for stroke. This comparative study was conducted in Mymensingh Medical College Hospital from January 2009 to June 2010. It was done to establish the relationship between proteinuria (Microalbuminuria) and ischemic stroke among diabetic patients. Other risk factors were also assessed. Patients were divided in Group A - diabetic patients with ischemic stroke (n=50) and Group B diabetic patients without stroke (n=50). Mean age of the Group A & B were 60.16±8.33 and 57.19±7.73 years (p=0.068). Mean Blood sugar (2 hours after Break Fast) was 14.68±4.32mmol/L in Group A and 14.75±4.02mmol/L in Group B (p>0.05). Albumin Creatinine ratio was abnormal in 84.0% in Group A and 22.0% in Group A (p=0.001) [Odds ratio (95%CI) = 18.61 (6.78-51.09)]. Logistic regression analysis has also shown that microalbuminuria (ACR) is an independent risk factor for ischemic stroke (p=0.001), [Odds ratio (95%CI) = 19.811(5.915-66.348)]. In diabetic patients increased urinary protein is a risk factor for stroke. Estimation of urinary protein (Microalbuminuria) may be used as a predictor for ischemic stroke in patients with diabetes.

  19. Inducible pluripotent stem cells for the treatment of ischemic stroke: current status and problems.

    PubMed

    Zhu, Yu; Wan, Shu; Zhan, Ren-ya

    2012-01-01

    Despite dramatic advancements in medical and surgical care, effective clinical therapies for ischemic stroke are limited. Stem-cell transplantation has emerged as a potential therapeutic approach for cell replacement in ischemic brain injuries. Inducible pluripotent stem cells (iPSCs) have become an alternative cell source for transplantation. They possess efficient capacities for neural differentiation without ethical and immune-rejection concerns. Substantial function of iPSCs in pre-clinical models of ischemic brain injury has been observed. However, several problems remain regarding the treatment of ischemic stroke with iPSCs: tumorigenicity, poor iPSC derivation methods, and undefined delivery variables. With the development of iPSC research, safer and more effective strategies will be achieved for highly effective and tumor-free cell treatment of ischemic stroke.

  20. Inflammation after Ischemic Stroke: The Role of Leukocytes and Glial Cells

    PubMed Central

    Kim, Jong Youl; Park, Joohyun; Chang, Ji Young; Kim, Sa-Hyun

    2016-01-01

    The immune response after stroke is known to play a major role in ischemic brain pathobiology. The inflammatory signals released by immune mediators activated by brain injury sets off a complex series of biochemical and molecular events which have been increasingly recognized as a key contributor to neuronal cell death. The primary immune mediators involved are glial cells and infiltrating leukocytes, including neutrophils, monocytes and lymphocyte. After ischemic stroke, activation of glial cells and subsequent release of pro- and anti-inflammatory signals are important for modulating both neuronal cell damage and wound healing. Infiltrated leukocytes release inflammatory mediators into the site of the lesion, thereby exacerbating brain injury. This review describes how the roles of glial cells and circulating leukocytes are a double-edged sword for neuroinflammation by focusing on their detrimental and protective effects in ischemic stroke. Here, we will focus on underlying characterize of glial cells and leukocytes under inflammation after ischemic stroke. PMID:27790058

  1. Endovascular therapy in children with acute ischemic stroke: review and recommendations.

    PubMed

    Ellis, Michael J; Amlie-Lefond, Catherine; Orbach, Darren B

    2012-09-25

    This review provides a summary of the currently available data pertaining to the interventional management of acute ischemic stroke in children. The literature is scarce and is lacking much-needed prospective trials. No study in the literature on the well-established systemic or local thrombolysis trials has included children. Mechanical thrombectomy trials using clot retriever devices have also excluded patients younger than 18 years. The current review is limited to case series of interventional acute ischemic stroke therapy in children and the potential future of endovascular ischemic stroke therapy in this patient population. Recommendations in this review represent the opinion of the authors, based on review of the limited literature covering endovascular acute ischemic stroke therapy in children.

  2. Recovery of slow-5 oscillations in a longitudinal study of ischemic stroke patients

    PubMed Central

    La, C.; Nair, V.A.; Mossahebi, P.; Stamm, J.; Birn, R.; Meyerand, M.E.; Prabhakaran, V.

    2016-01-01

    Functional networks in resting-state fMRI are identified by characteristics of their intrinsic low-frequency oscillations, more specifically in terms of their synchronicity. With advanced aging and in clinical populations, this synchronicity among functionally linked regions is known to decrease and become disrupted, which may be associated with observed cognitive and behavioral changes. Previous work from our group has revealed that oscillations within the slow-5 frequency range (0.01–0.027 Hz) are particularly susceptible to disruptions in aging and following a stroke. In this study, we characterized longitudinally the changes in the slow-5 oscillations in stroke patients across two different time-points. We followed a group of ischemic stroke patients (n = 20) and another group of healthy older adults (n = 14) over two visits separated by a minimum of three months (average of 9 months). For the stroke patients, one visit occurred in their subacute window (10 days to 6 months after stroke onset), the other took place in their chronic window (> 6 months after stroke). Using a mid-order group ICA method on 10-minutes eyes-closed resting-state fMRI data, we assessed the frequency distributions of a component's representative time-courses for differences in regards to slow-5 spectral power. First, our stroke patients, in their subacute stage, exhibited lower amplitude slow-5 oscillations in comparison to their healthy counterparts. Second, over time in their chronic stage, those same patients showed a recovery of those oscillations, reaching near equivalence to the healthy older adult group. Our results indicate the possibility of an eventual recovery of those initially disrupted network oscillations to a near-normal level, providing potentially a biomarker for stroke recovery of the cortical system. This finding opens new avenues in infra-slow oscillation research and could serve as a useful biomarker in future treatments aimed at recovery. PMID:27077023

  3. Pathophysiology, treatment, and animal and cellular models of human ischemic stroke.

    PubMed

    Woodruff, Trent M; Thundyil, John; Tang, Sung-Chun; Sobey, Christopher G; Taylor, Stephen M; Arumugam, Thiruma V

    2011-01-25

    Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to

  4. 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

  5. Thrombolysis and thrombectomy in patients treated with dabigatran with acute ischemic stroke: Expert opinion.

    PubMed

    Diener, H C; Bernstein, R; Butcher, K; Campbell, B; Cloud, G; Davalos, A; Davis, S; Ferro, J M; Grond, M; Krieger, D; Ntaios, G; Slowik, A; Touzé, E

    2017-01-01

    Systemic thrombolysis with rt-PA is contraindicated in patients with acute ischemic stroke anticoagulated with dabigatran. This expert opinion provides guidance on the use of the specific reversal agent idarucizumab followed by rt-PA and/or thrombectomy in patients with ischemic stroke pre-treated with dabigatran. The use of idarucizumab followed by rt-PA is covered by the label of both drugs.

  6. [The effect of cerebrolysin in dosage 50 ml on the volume of lesion in ischemic stroke].

    PubMed

    Shamalov, N A; Stakhovskaia, L V; Burenchev, D V; Kichuk, I V; Tvorogova, T V; Botsina, A Iu; Smychkov, A S; Kerbikov, O B; Moessler, H; Novak, P; Skvortsova, V I

    2010-01-01

    The purpose of this randomized, double-blind, placebo-controlled study was to assess safety and efficacy of cerebrolysin used in dosage 50 ml in acute ischemic stroke. Forty-seven patients with ischemic stroke, aged 45-85 years, who were admitted to a clinical unit within the first 12 h after stroke onset were included in the study. A quantitative time-related MRI analysis of the dynamics of neurological deficit revealed the more rapid decrease of stroke volume to the 28th day in the group treated with cerebrolysin (45.4% versus 43.6% in the placebo-group (p < 0.05)). No side-effects of treatment with cerebrolysin was found. The results of this prospective, randomized, placebo-controlled study suggest the positive effect of cerebrolysin on the dynamics of volume lesion in patients with ischemic stroke.

  7. Comparative risk of ischemic stroke among users of clopidogrel together with individual proton pump inhibitors

    PubMed Central

    Bilker, Warren B.; Brensinger, Colleen M.; Flockhart, David A.; Freeman, Cristin P.; Kasner, Scott E.; Kimmel, Stephen E.; Hennessy, Sean

    2015-01-01

    Background and Purpose There is controversy and little information concerning whether individual proton pump inhibitors (PPIs) differentially alter the effectiveness of clopidogrel in reducing ischemic stroke risk. We therefore aimed to elucidate the risk of ischemic stroke among concomitant users of clopidogrel and individual PPIs. Methods We conducted a propensity score-adjusted cohort study of adult new users of clopidogrel, using 1999–2009 Medicaid claims from 5 large states. Exposures were defined by prescriptions for esomeprazole, lansoprazole, omeprazole, rabeprazole and pantoprazole—with pantoprazole serving as the referent. The endpoint was hospitalization for acute ischemic stroke, defined by International Classification of Diseases 9th Revision Clinical Modification codes in the principal position on inpatient claims, within 180 days of concomitant therapy initiation. Results Among 325,559 concomitant users of clopidogrel and a PPI, we identified 1,667 ischemic strokes for an annual incidence of 2.4% (95% confidence interval: 2.3–2.5). Adjusted hazard ratios for ischemic stroke vs. pantoprazole were: 0.98 (0.82–1.17) for esomeprazole; 1.06 (0.92–1.21) for lansoprazole; 0.98 (0.85–1.15) for omeprazole; and 0.85 (0.63–1.13) for rabeprazole. Conclusions PPIs of interest did not increase the rate of ischemic stroke among clopidogrel users when compared to pantoprazole, a PPI thought to be devoid of the potential to interact with clopidogrel. PMID:25657176

  8. Association between matrix metalloproteinase gene polymorphisms and development of ischemic stroke.

    PubMed

    Hao, Yunhua; Tian, Shihong; Sun, Min; Zhu, Yuanjian; Nie, Zhiyu; Yang, Shujuan

    2015-01-01

    We investigated the association between MMP2 rs243865, MMP3 rs3025058 and MMP9 rs3918242 polymorphisms and development of ischemic stroke in a Chinese population. Between January 2012 and May 2014, a total of 317 patients with ischemic stroke and 317 health control subjects were enrolled into our study. The MMP2 rs243865, MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By multivariate logistic regression analysis, we found that individuals carrying with the CC genotype and the TC+CC genotype of MMP9 rs3918242 were associated with a significantly increased risk of ischemic stroke when compared with the TT genotype, and the ORs (95% CI) was 5.47 (2.64-12.38) and 1.55 (1.08-2.24), respectively. The TC+CC genotype of MMP9 rs3918242 was associated with an elevated risk of ischemic stroke in tobacco smokers, and the OR (95% CI) was 2.03 (1.11-3.74). In conclusion, our study suggests that MMP9 rs3918242 polymorphism is correlated with an elevated risk of ischemic stroke, and this gene polymorphism has interaction with tobacco smoking in the risk of ischemic stroke.

  9. Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

    PubMed

    Mestriner, Régis Gemerasca; Miguel, Patrícia Maidana; Bagatini, Pamela Brambilla; Saur, Lisiani; Boisserand, Lígia Simões Braga; Baptista, Pedro Porto Alegre; Xavier, Léder Leal; Netto, Carlos Alexandre

    2013-05-01

    Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults.

  10. Increased risk of posterior circulation infarcts among ischemic stroke patients with cervical spondylosis

    PubMed Central

    Chen, Chih-Chi; Chung, Chia-Ying; Lee, Tsong-Hai; Chang, Wei-Han; Tang, Simon FT; Pei, Yu-Cheng

    2015-01-01

    Background Cervical spondylosis is one of the extrinsic factors causing vertebral artery stenosis. Several case studies have reported compression of the vertebral artery induced by cervical osteophytes that has resulted in posterior circulation infarcts (POCI). However, to the best of our knowledge, no studies have yet analyzed differences in the risk factors and stroke subtypes between ischemic stroke patients with cervical spondylosis and those without. Purpose In the case-controlled study reported here, we analyzed the risk factors and stroke subtypes in ischemic stroke patients with and without cervical spondylosis. Characteristics in all the recruited patients with POCI and non-POCI were further compared to extract other risk factors that could predict the occurrence of POCI. Methods and patients We filtered out ischemic stroke patients with cervical spondylosis (“Stroke+C” group) by International Classification of Diseases, Ninth Revision codes. We analyzed the data of 38 subjects in the Stroke+C group and 152 sex- and age-comparable ischemic stroke patients without cervical spondylosis (“Stroke−C” group). We recorded the demographic characteristics including sex and age, and stroke risk factors, including diabetes mellitus, hypertension, heart disease, hyperlipidemia, and smoking habits. The stroke classifications were defined by the Oxford Community Stroke Project classification. All subjects were further categorized into POCI or non-POCI groups. The ultrasound findings of the vertebral arteries (extracranial and intracranial) in the Stroke+C group were also recorded. Results More patients in the Stroke+C group tended to have POCI (34.2%) than patients in the Stroke−C group (17.5%) (odds ratio [OR] =2.41, P<0.05). Furthermore, hypertension (OR=3.41, P<0.01) and cervical spondylosis (OR=2.41, P<0.05) were two independent risk factors for POCI in ischemic stroke patients. Conclusion Ischemic stroke patients with cervical spondylosis are more prone

  11. Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats.

    PubMed

    Wang, X; Zhang, M; Yang, S-D; Li, W-B; Ren, S-Q; Zhang, J; Zhang, F

    2014-08-22

    Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-α (PKC-α), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-α and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (p<0.05). The over-expression of mGluR5 and NR2B mRNA was also inhibited by pre-ischemic exercise (p<0.05). In summary, exercise preconditioning ameliorated brain damage after ischemic stroke, which might be involved in two signal pathways: PKC-α-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate.

  12. Ischemic stroke incidence in Santa Coloma de Gramenet (ISISCOG), Spain. A community-based study

    PubMed Central

    Alzamora, María Teresa; Sorribes, Marta; Heras, Antonio; Vila, Nicolás; Vicheto, Marisa; Forés, Rosa; Sánchez-Ojanguren, José; Sancho, Amparo; Pera, Guillem

    2008-01-01

    Background In Spain, stroke is one of the major causes of death and the main cause of severe disability in people over 65 years. We analyzed the incidence of ischemic stroke, stroke subtypes, case fatality and disability at 90 days after the event in a Spanish population. Methods A prospective community-based register of ischemic strokes was established in Santa Coloma de Gramenet (Barcelona) [116,220 inhabitants of all ages, according to the municipal census of December 31,2001], from January 1 to December 31, 2003. Standard definitions and case finding methods were used to identify all cases in all age groups. Every patient underwent a complete clinical evaluation and systematic tests including neuroimaging (CT/MRI) and vascular studies (carotid duplex ultrasound intra and extracranial and MR angiography). Results Over a one year period, 196 ischemic strokes were registered [107 men; median age = 76 years (range 39–98)], being the first event in 159 patients (81.1%) and a recurrent stroke in 37 (18.9%). After age-adjustment to the European population, the incidence of ischemic stroke per 100,000 inhabitants was 172 (95% CI, 148–196); 219 (176–261) in men and 133 (105–160) in women, with an annual incidence for first ischemic stroke of 139 (118–161); 165 (128–201) in men and 115 (89–140) in women. The incidence of stroke increased with age. Stroke subtypes (TOAST classification criteria) were lacunar in 28.8%, atherothrombotic in 18.6%, cardioembolic in 26.6% and undetermined in 26.0% of patients. At 90 days, the case-fatality was 12%, and among survivors, moderate-to-severe disability was present in 45 % at 3 months. Conclusion This prospective community-based study shows one of the lowest incidences of stroke in Europe, as well as one of the lowest case fatality and disability rates at 90 days after stroke. PMID:18371212

  13. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association.

    PubMed

    Furie, Karen L; Kasner, Scott E; Adams, Robert J; Albers, Gregory W; Bush, Ruth L; Fagan, Susan C; Halperin, Jonathan L; Johnston, S Claiborne; Katzan, Irene; Kernan, Walter N; Mitchell, Pamela H; Ovbiagele, Bruce; Palesch, Yuko Y; Sacco, Ralph L; Schwamm, Lee H; Wassertheil-Smoller, Sylvia; Turan, Tanya N; Wentworth, Deidre

    2011-01-01

    The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.

  14. Is cirrhosis associated with lower odds of ischemic stroke: A nationwide analysis?

    PubMed Central

    Goyal, Abhinav; Chatterjee, Kshitij; Shah, Nishi; Singh, Shailender

    2016-01-01

    AIM To determine the association between cirrhosis and ischemic stroke in a large nationally representative sample. METHODS A retrospective cross-sectional study of all hospitalized patients during 2012 and 2013 in the United States was performed using the National Inpatient Sample database. Hospitalizations with acute stroke, cirrhosis and other risk factors were identified using ICD-9-CM codes. RESULTS There were a total of 72082638 hospitalizations in the United States during the years 2012 and 2013. After excluding hospitalizations with missing demographic variables, that there were a total of 1175210 (1.6%) out of these were for acute ischemic stroke. Cirrhosis was present among 5605 (0.4%) cases of ischemic stroke. Mean age among the cirrhotic and non-cirrhotic groups with ischemic stroke were 66.4 and 70.5 years, respectively. Prevalence of risk factors among the two groups was also calculated. After adjusting for various known risk factors the odds of having an ischemic stroke (OR = 0.28, P < 0.001) were 72% lower in cirrhotics compared to non-cirrhotics. CONCLUSION Our study suggests that in a large, nationally representative sample of the United States population, cirrhosis is associated with a lower likelihood of stroke. PMID:28050237

  15. miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke

    PubMed Central

    Yao, Shengtao; Tang, Bo; Li, Gang; Fan, Ruiming; Cao, Fang

    2016-01-01

    Ischemic stroke is one of the leading causes of brain disease, with high morbidity, disability, and mortality. MicroRNAs (miRNAs) have been identified as vital gene regulators in various types of human diseases. Accumulating evidence has suggested that aberrant expression of miRNAs play critical roles in the pathologies of ischemic stroke. Yet, the precise mechanism by which miRNAs control cerebral ischemic stroke remains unclear. In the present study, we explored whether miR-455 suppresses neuronal death by targeting TRAF3 in cerebral ischemic stroke. The expression levels of miR-455 and TRAF3 were detected by quantitative real-time polymerase chain reaction and Western blot. The role of miR-455 in cell death caused by oxygen–glucose deprivation (OGD) was assessed using Cell Counting Kit-8 (CCK-8) assay. The influence of miR-455 on infarct volume was evaluated in mouse brain after middle cerebral artery occlusion (MCAO). Bioinformatics softwares and luciferase analysis were used to find and confirm the targets of miR-455. The results showed that the expression levels of miR-455 significantly decreased in primary neuronal cells subjected to OGD and mouse brain subjected to MCAO. In addition, forced expression of miR-455 inhibited neuronal death and weakened ischemic brain infarction in focal ischemia-stroked mice. Furthermore, TRAF3 was proved to be a direct target of miR-455, and miR-455 could negatively suppress TRAF3 expression. Biological function analysis showed that TRAF3 silencing displayed the neuroprotective effect in ischemic stroke and could enhance miR-455-induced positive impact on ischemic injury both in vitro and in vivo. Taken together, miR-455 played a vital role in protecting neuronal cells from death by downregulating TRAF3 protein expression. These findings may represent a novel latent therapeutic target for cerebral ischemic stroke. PMID:27980410

  16. [The combined effects of family history of cardiovascular disease and overweight on ischemic stroke incidence among the Mongolian population].

    PubMed

    Tian, Y F; Zhang, J H; Lu, H M; Liu, Y Y; Zhou, Y P; Lu, Q; Buren, Rbt; Zhang, Y H

    2016-09-06

    Objective: To investigate the cumulative effect of family history of cardiovascular disease(CVD)and overweight on ischemic stroke events in the Mongolian population. Methods: Study participants were recruited from 32 villages from May 2002 to August 2012 in Kezuohou Banner(county)and Naiman Banner in Inner Mongolia, China. Among 3 457 Mongolian people aged ≥20 years old living in these villages, 2 589 were selected to participate in this study. None of the participants had chronic kidney disease, malignant tumor, thyroid disease or adrenalopathy, or acute infectious disease. The 2 589 participants were followed for a mean of 9.2 years. Six participants were lost to follow up, resulting in a follow-up rate of 99.8%. Information collected included demographic characteristics, lifestyle risk factors, alcohol consumption, cigarette smoking, history of disease, family history of CVD, and physical examination. Ischemic stroke incidence information was collected during follow-up. All participants were categorized into four subgroups according to family history of CVD and overweight status. Cox proportional hazards models were used to estimate the hazard ratios(HR)and 95% CI of ischemic stroke events among subgroups, compared with the subgroup with no family history of CVD and body mass index(BMI)<24 kg/m(2)(the reference group). Results: Among 2 589 participants, 76 ischemic stroke events occurred after follow-up, and 8 were excluded because of lack of key data. Finally, 2 581 participants were included in the analysis, and the incidence density was 323/100 000 person-years. The cumulative incidence rates of ischemic stroke were 2.48%, 1.86%, 6.67% and 9.00% in the no family history of CVD and BMI <24 kg/m(2), no family history of CVD and BMI ≥24 kg/m(2), family history of CVD and BMI <24 kg/m(2) and family history of CVD and BMI ≥ 24 kg/m(2) subgroups, respectively. Using the Cox proportional hazards model, after further adjustment for age, gender, smoking

  17. Traditional Chinese Patent Medicine for Acute Ischemic Stroke

    PubMed Central

    Zhang, Xin; Liu, Xue-Ting; Kang, De-Ying

    2016-01-01

    Abstract The aim of the study is to conduct an overview of systematic reviews (SRs) to provide a contemporary review of the evidence for delivery of Traditional Chinese Patent Medicine (TCPMs) for patients with acute ischemic stroke. SRs were assessed for quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the Oxman-Guyatt Overview Quality Assessment Questionnaire (OQAQ). We assessed the quality of the evidence of high methodological quality (an AMSTAR score ≥9 or an OQAQ score ≥7) for reported outcomes using the GRADE (the Grading of Recommendations Assessment, Development and Evaluation) approach. (1) Dan Shen agents: tiny trends toward the improvement in different neurological outcomes (RR = 1.16, 1.10, 1.23, 1.08, 1.12); (2) Mailuoning: a tiny trend toward improvement in the neurological outcome (RR = 1.18); (3) Ginkgo biloba: tiny trends toward improvement in the neurological outcome (RR = 1.18, MD = 0.81); (4) Dengzhanhua: a tiny trend toward an improvement in neurological (RR = 1.23); (5) Acanthopanax: a small positive (RR = 1.17, 1.31) result on neurological improvement reported; (6) Chuanxiong-type preparations: neurological functional improved (MD = 2.90);(7) Puerarin: no better effect on the rate of death or disability (OR = 0.81, 95% CI 0.35–1.87); (8) Milk vetch: no better effect on the rate of death (OR = 0.66, 95% CI: 0.11–2.83);(9) Qingkailing: rate of death reduced (OR = 0.66, 95% CI: 0.11–2.83). Limitations in the methodological quality of the RCTs, inconsistency and imprecision led to downgrading of the quality of the evidence, which varied by review and by outcome. Consequently, there are currently only weak evidences to support those TCPMs. The 9 TCPMs may be effective in the treatment of acute ischemic stroke, as the GRADE approach indicated a weak recommendation for those TCPMs’ usage. PMID:27015174

  18. Neurohormonal activation in ischemic stroke: effects of acute phase disturbances on long-term mortality.

    PubMed

    Anne, Mäkikallio; Juha, Korpelainen; Timo, Mäkikallio; Mikko, Tulppo; Olli, Vuolteenaho; Kyösti, Sotaniemi; Heikki, Huikuri; Vilho, Myllylä

    2007-08-01

    A stress response consisting of elevated levels of cortisol and catecholamines is common after acute stroke. The plasma levels of natriuretic peptides are known to be elevated after ischemic stroke, but the relations of these neurohormonal systems in the acute phase of stroke and their impact on long-term prognosis have not been studied previously. A series of 51 consecutive patients (mean age 68+/-11 years) with an ischemic first-ever stroke underwent a comprehensive clinical investigation, scoring of their neurologic deficit by Scandinavian Stroke Scale (SSS), Barthel Index (BI) and Modified Ranking Scale (MRS) as well as measurements of plasma cortisol, norepinephrine, epinephrine, ACTH and atrial (N-ANP) and brain (N-BNP) natriuretic peptides on the 2nd and 7th days after ischemic stroke. The patients were followed up for 44+/-21 months. Higher levels of cortisol, ACTH and natriuretic peptides were observed in the stroke patients who died (n=22) during the follow-up than in the stroke survivors. Cortisol levels associated significantly with the 2nd and 7th day N-ANP and N-BNP levels, catecholamine levels (r= 0.55 - 0.94, p<0.01 for all) and measures of neurologic deficit (r= 0.36 - -0.44, p<0.05). High acute phase cortisol levels assessed either in the morning (RR=5.4, p<0.05) or in the evening (RR=5.8, p<0.05) predicted long-term mortality after stroke in multivariate analysis. Activation of the hypothalamus-pituitary-adrenal axis in ischemic stroke is associated with elevated levels of natriuretic peptides. High cortisol and natriuretic peptide values predict long-term mortality after ischemic stroke, suggesting that this profound neurohumoral disturbance is prognostically unfavourable.

  19. Polymorphism of Nitric Oxide Synthase 1 Affects the Clinical Phenotypes of Ischemic Stroke in Korean Population

    PubMed Central

    Yoo, Seung Don; Yun, Dong Hwan; Kim, Hee-Sang; Kim, Su Kang; Kim, Dong Hwan; Chon, Jinmann; Je, Goun; Kim, Yoon-Seong; Chung, Joo-Ho; Chung, Seung Joon; Yeo, Jin Ah

    2016-01-01

    Objective To investigate whether four single nucleotide polymorphisms (SNPs) rs2293054 [Ile734Ile], rs1047735 [His902His], rs2293044 [Val1353Val], rs2682826 (3'UTR) of nitric oxide synthase 1 (NOS1) are associated with the development and clinical phenotypes of ischemic stroke. Methods We enrolled 120 ischemic stroke patients and 314 control subjects. Ischemic stroke patients were divided into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ≥6) and Modified Barthel Index (MBI, <60 and ≥60). SNPStats, SNPAnalyzer, and HelixTree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. Multiple logistic regression models were performed to analyze genetic data. Results No SNPs of the NOS1 gene were found to be associated with ischemic stroke. However, in an analysis of clinical phenotypes, we found that rs2293054 was associated with the NIHSS scores of ischemic stroke patients in codominant (p=0.019), dominant (p=0.007), overdominant (p=0.033), and log-additive (p=0.0048) models. Also, rs2682826 revealed a significant association in the recessive model (p=0.034). In allele frequency analysis, we also found that the T alleles of rs2293054 were associated with lower NIHSS scores (p=0.007). Respectively, rs2293054 had a significant association in the MBI scores of ischemic stroke in codominant (p=0.038), dominant (p=0.031), overdominant (p=0.045), and log-additive (p=0.04) models. Conclusion These results suggest that NOS1 may be related to the clinical phenotypes of ischemic stroke in Korean population. PMID:26949676

  20. Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke

    PubMed Central

    Yamashiro, Kazuo; Tanaka, Ryota; Urabe, Takao; Ueno, Yuji; Yamashiro, Yuichiro; Nomoto, Koji; Takahashi, Takuya; Tsuji, Hirokazu; Asahara, Takashi; Hattori, Nobutaka

    2017-01-01

    The role of metabolic diseases in ischemic stroke has become a primary concern in both research and clinical practice. Increasing evidence suggests that dysbiosis is associated with metabolic diseases. The aim of this study was to investigate whether the gut microbiota, as well as concentrations of organic acids, the major products of dietary fiber fermentation by the gut microbiota, are altered in patients with ischemic stroke, and to examine the association between these changes and host metabolism and inflammation. We analyzed the composition of the fecal gut microbiota and the concentrations of fecal organic acids in 41 ischemic stroke patients and 40 control subjects via 16S and 23S rRNA-targeted quantitative reverse transcription (qRT)-PCR and high-performance liquid chromatography analyses, respectively. Multivariable linear regression analysis was subsequently performed to evaluate the relationships between ischemic stroke and bacterial counts and organic acid concentrations. Correlations between bioclinical markers and bacterial counts and organic acids concentrations were also evaluated. Although only the bacterial counts of Lactobacillus ruminis were significantly higher in stroke patients compared to controls, multivariable analysis showed that ischemic stroke was independently associated with increased bacterial counts of Atopobium cluster and Lactobacillus ruminis, and decreased numbers of Lactobacillus sakei subgroup, independent of age, hypertension, and type 2 diabetes. Changes in the prevalence of Lactobacillus ruminis were positively correlated with serum interleukin-6 levels. In addition, ischemic stroke was associated with decreased and increased concentrations of acetic acid and valeric acid, respectively. Meanwhile, changes in acetic acid concentrations were negatively correlated with the levels of glycated hemoglobin and low-density lipoprotein cholesterol, whereas changes in valeric acid concentrations were positively correlated with the

  1. Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages

    PubMed Central

    Weiner, Daniel E.; Dad, Taimur

    2015-01-01

    Summary Cerebrovascular disease and stroke are very common at all stages of chronic kidney disease (CKD), likely representing both shared risk factors as well as synergy among risk factors. More subtle ischemic brain lesions may be particularly common in the CKD population, with subtle manifestations including cognitive impairment. For individuals with nondialysis CKD, the prevention, approach to, diagnosis, and management of stroke is similar to the general, non-CKD population. For individuals with end-stage renal disease, far less is known regarding the prevention of stroke. Stroke prophylaxis using warfarin in dialysis patients with atrial fibrillation in particular remains of uncertain benefit. End-stage renal disease patients can be managed aggressively in the setting of acute stroke. Outcomes after stroke at all stages of CKD are poor, and improving these outcomes should be the subject of future clinical trials. PMID:26355250

  2. Upper Extremity Motion Assessment in Adult Ischemic Stroke Patients: A 3-D Kinematic Model

    DTIC Science & Technology

    2001-10-25

    Botox , motion analysis, hemiplegia, stroke I. INTRODUCTION Recovery from ischemic stroke has been explained by patients learning new skills, by...University and the Medical College of Wisconsin and to Allergan, Inc.(Irvine, CA), makers of BOTOX ®, for their sponsorship. REFERENCES [1] Gracies

  3. Positron emission tomography in minor ischemic stroke using oxygen-15 steady-state technique

    SciTech Connect

    Pozzilli, C.; Itoh, M.; Matsuzawa, T.; Fukuda, H.; Abe, Y.; Sato, T.; Takeda, S.; Ido, T.

    1987-04-01

    A study with positron emission tomography (PET) was performed on 10 patients with ischemic stroke and mild disability. The patients underwent cerebral angiography, x-ray computed tomography (CT) scan and regional cerebral measurements of CBF, CMRO2, oxygen extraction ratio (OER), and cerebral blood volume (CBV). Only minor arterial involvement was detected by angiography. In all patients, PET images of functional defects were more extensive than the corresponding CT hypodensity, and there were statistically significant reductions in CBF, CMRO2, and CBF/CBV ratio as compared with control subjects. Half of the regions analyzed in the affected hemisphere demonstrated a disruption of the normal coupling between CBF and CMRO2 as reflected by OER values significantly higher or lower than those of the corresponding region of the contralateral hemisphere. The pathophysiological pattern of high OER combined with a reduction in CBF proportionally greater than the reduction in CMRO2 was particularly indicative of regional chronic hemodynamic compromise in these patients.

  4. The Role of Arginase 1 in Post-Stroke Immunosuppression and Ischemic Stroke Severity.

    PubMed

    Petrone, Ashley B; O'Connell, Grant C; Regier, Michael D; Chantler, Paul D; Simpkins, James W; Barr, Taura L

    2016-04-01

    A balanced immune system response plays an important role in acute ischemic stroke (AIS) recovery. Our laboratory has previously identified several immune-related genes, including arginase 1 (ARG1), with altered expression in human AIS patients. The neutrophil-lymphocyte ratio (NLR) may be a marker of the degree of immune dysregulation following AIS; however, the molecular mechanisms that may mediate the NLR are unknown. The purpose of this study was to (1) examine the relationship between ARG1, NLR, and AIS severity and (2) to utilize principal component analysis (PCA) to statistically model multiple gene expression changes following AIS. AIS patients and stroke-free control subjects were recruited, and blood samples were collected from AIS patients within 24 h of stroke symptom onset. White blood cell differentials were obtained at this time to calculate the NLR. Gene expression was measured using real-time PCR. PCA with varimax rotation was used to develop composite variables consisting of a five-gene profile. ARG1 was positively correlated with NLR (r = 0.57, p = 0.003), neutrophil count (r = 0.526, p = 0.007), NIHSS (r = 0.607, p = 0.001), and infarct volume (r = 0.27, p = 0.051). PCA identified three principal components that explain 84.4 % of variation in the original patient gene dataset comprised of ARG1, LY96, MMP9, s100a12, and PC1 was a significant explanatory variable for NIHSS (p < 0.001) and NLR (p = 0.005). Our study suggests a novel relationship between ARG1, NLR, and stroke severity, and the NLR is an underutilized clinically available biomarker to monitor the post-stroke immune response.

  5. Adjuvant Chinese Herbal Products for Preventing Ischemic Stroke in Patients with Atrial Fibrillation

    PubMed Central

    Muo, Chih-Hsin; Chiu, Hsienhsueh Elley; Liu, Chun-Ting

    2016-01-01

    Objective Chinese herbal products (CHPs) are widely used for atrial fibrillation (AF) in Taiwan. We investigated the effect of adjuvant CHPs in preventing ischemic stroke in patients with AF. Methods Taiwanese patients in the Health Insurance Database newly diagnosed with AF during 2000–2011 were enrolled. Medication treatment with/without CHPs was administered within 7 days after the AF diagnosis. The clinical endpoint was an ischemic stroke. The Chi-square test, Fisher’s exact test, and Student t test were used to examine differences between the traditional Chinese medicine (TCM) and non-TCM cohorts. Cox proportional hazard regression was used to assess the risk for ischemic stroke between two cohorts. Results Three hundred and eleven patients underwent TCM treatment and 1715 patients did not. Compared to non-TCM users, TCM users had a lower incidence of stroke (12.59% vs. 1.93%, respectively) and lower risk of stroke [CHA2DS2-VASc score = 0–2 (hazard ratio = 0.20; 95% confidence interval = 0.06–0.65)]. Compared to non-TCM users, the stroke risk was significantly lower in TCM users with AF who were female or younger than 65 years, but not in males, people more than 65 years old, or people with comorbidities. Compared to TCM users, non-TCM users who received conventional treatment had a higher ischemic stroke risk. The risk for AF-related hospitalization was significantly lower in TCM users (0.64%) than in non-TCM users (38.1%). Conclusions Users of TCM with AF have a lower risk of new-onset ischemic stroke. Therefore, adjuvant CHP therapy may have a protective effect and may be used in AF patients to prevent ischemic stroke. PMID:27428543

  6. Acute ischemic stroke in a child with cyanotic congenital heart disease due to non-compliance of anticoagulation

    PubMed Central

    Mohammad, Misbahuddin; James, Anish F.; Qureshi, Raheel S.; Saraf, Sapan; Ahluwalia, Tina; Mukherji, Joy Dev; Kole, Tamorish

    2012-01-01

    BACKGROUND: Stroke is a common presentation in geriatric patients in emergency department but rarely seen in pediatric patients. In case of acute ischemic stroke in pediatric age group, management is different from that of adult ischemic stroke where thrombolysis is a good op. METHODS: We report a case of a 17-year-old male child presenting in emergency with an episode of acute ischemic stroke causing left hemiparesis with left facial weakness and asymmetry. The patient suffered from cyanotic congenital heart disease for which he had undergone Fontan operation previously. He had a history of missing his daily dose of warfarin for last 3 days prior to the stroke. RESULTS: The patient recovered from acute ischemic stroke without being thrombolyzed. CONCLUSION: In pediatric patients, acute ischemic stroke usually is evolving and may not require thrombolysis. PMID:25215056

  7. Statin Prescription Adhered to Guidelines for Patients Hospitalized due to Acute Ischemic Stroke or Transient Ischemic Attack

    PubMed Central

    Hong, Keun-Sik; Oh, Mi Sun; Choi, Hye-Yeon; Cho, A-Hyun; Kwon, Hyung-Min; Yu, Kyung-Ho; Bae, Hee-Joon; Lee, Juneyoung

    2013-01-01

    Background and Purpose Secondary stroke prevention guidelines recommend statins for the management of dyslipidemia in ischemic stroke and transient ischemic attack (TIA). This study assessed the guideline-based statin prescription (GBSP) rate in Korea and the associated physician and patient factors. Methods A survey was conducted to assess Korean neurologists' knowledge of and attitude toward the current dyslipidemia management guidelines. The characteristics and discharge statin prescription for all consecutive patients with acute ischemic stroke or TIA treated by participating neurologists during the 6 months prior to the survey were abstracted. Using algorithms to determine GBSP, we assessed the rate and independent factors of GBSP. Results Of the 174 participating neurologists, 79 (45.4%) were categorized as a higher-level knowledge group. For the 4407 patients (mean age, 66.4 years; female, 42.5%; 90.6% with ischemic stroke and 9.4% with TIA) enrolled in this study, the GBSP rate at discharge was 78.6%. The GBSP rate increased significantly with increasing physician knowledge level (test for trend, p<0.0001), and was higher among patients treated by the higher-level knowledge group than for those treated by the lower-level knowledge group (81.6% vs. 74.7%; unadjusted p<0.0001 and adjusted p=0.045). Other independent factors associated with a higher GBSP rate were hypercholesterolemia and higher low-density lipoprotein cholesterol level, while those associated with a lower GBSP rate were cardioembolism, undetermined etiology due to negative or incomplete work-up, other determined etiology, and TIA presentation. Conclusions More than three-quarters of acute ischemic stroke survivors and TIA patients receive a GBSP at discharge, and this proportion would be further improved by improving the knowledge of dyslipidemia management guidelines among neurologists. PMID:24285962

  8. Developing drug strategies for the neuroprotective treatment of acute ischemic stroke.

    PubMed

    Tuttolomondo, Antonino; Pecoraro, Rosaria; Arnao, Valentina; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

    2015-01-01

    Developing new treatment strategies for acute ischemic stroke in the last twenty years has offered some important successes, but also several failures. Most trials of neuroprotective therapies have been uniformly negative to date. Recent research has reported how excitatory amino acids act as the major excitatory neurotransmitters in the cerebral cortex and hippocampus. Furthermore, other therapeutic targets such as free radical scavenger strategies and the anti-inflammatory neuroprotective strategy have been evaluated with conflicting data in animal models and human subjects with acute ischemic stroke. Whereas promising combinations of neuroprotection and neurorecovery, such as citicoline, albumin and cerebrolysin have been tested with findings worthy of further evaluation in larger randomized clinical trials. Understanding the complexities of the ischemic cascade is essential to developing pharmacological targets for acute ischemic stroke in neuroprotective or flow restoration therapeutic strategies.

  9. Ischemic stroke as a rare manifestation of aluminum phosphide poisoning: a case report.

    PubMed

    Abedini, Mahmoud; Fatehi, Farzad; Tabrizi, Nasim

    2014-01-01

    Aluminum phosphide (AlP) is a solid fumigant which is widely used for a suicide attempt in Iran. Although neurologic symptoms are commonly reported, cerebrovascular stenosis is rare in AlP poisoning. We described ischemic stroke as a delayed complication of AlP intoxication. A 30-year-old man was admitted because of sudden onset left side hemiplegia, 11 days after intentional ingestion of three rice tablets. Investigations revealed in situ thrombosis in right middle cerebral artery (MCA) while other causes of stroke in young adults were excluded. Ischemic stroke should be considered as a delayed complication of AlP intoxication even after the acute phase of intoxication.

  10. [Clinical and pathogenetical peculiarities and treatment policy in ischemic stroke of elderly and old age].

    PubMed

    Gafurov, B G; Alikulova, N A

    2004-01-01

    The data on randomized study of 2 groups of patients with ischemic brain hemisphere stroke of elderly and old (over 70 years) as well as middle (under 60 years) age are presented. In elderly and old age, stroke develops on the basis of common affection of major vessels, with a great role of the "steal syndrome" in its pathogenesis. In authors' opinion, in treatment of ischemic stroke of elderly and old age attention should be paid to metabolic therapy, in particular to using high dosages of Cerebrolysin. Basing on clinical and paraclinical study, efficacy of this medication is revealed.

  11. Painless legs and moving toes as an initial presentation of ischemic stroke.

    PubMed

    Oh, Se Mi; Yoon, Won Tae; Kim, Ji Youn; Shin, Hee-Young; Lee, Won Yong

    2009-05-01

    Painless legs and moving toes is an unusual syndrome, which has not previously been reported as an initial presentation of ischemic stroke. We encountered a 78-year-old woman who developed dysarthria and involuntary movement of her left toes that was clinically regarded as painless legs and moving toes. These symptoms appeared abruptly and simultaneously as the initial symptoms of stroke, and improved gradually with conservative management by intravenous hydration for a month. We suggest that, in our case, a cortical brain lesion caused by ischemic stroke might be associated with the development of painless legs and moving toes.

  12. Atrial fibrillation is a predictor of in-hospital mortality in ischemic stroke patients

    PubMed Central

    Ong, Cheung-Ter; Wong, Yi-Sin; Wu, Chi-Shun; Su, Yu-Hsiang

    2016-01-01

    Background/purpose In-hospital mortality rate of acute ischemic stroke patients remains between 3% and 18%. For improving the quality of stroke care, we investigated the factors that contribute to the risk of in-hospital mortality in acute ischemic stroke patients. Materials and methods Between January 1, 2007, and December 31, 2011, 2,556 acute ischemic stroke patients admitted to a stroke unit were included in this study. Factors such as demographic characteristics, clinical characteristics, comorbidities, and complications related to in-hospital mortality were assessed. Results Of the 2,556 ischemic stroke patients, 157 received thrombolytic therapy. Eighty of the 2,556 patients (3.1%) died during hospitalization. Of the 157 patients who received thrombolytic therapy, 14 (8.9%) died during hospitalization. History of atrial fibrillation (AF, P<0.01) and stroke severity (P<0.01) were independent risk factors of in-hospital mortality. AF, stroke severity, cardioembolism stroke, and diabetes mellitus were independent risk factors of hemorrhagic transformation. Herniation and sepsis were the most common complications of stroke that were attributed to in-hospital mortality. Approximately 70% of in-hospital mortality was related to stroke severity (total middle cerebral artery occlusion with herniation, basilar artery occlusion, and hemorrhagic transformation). The other 30% of in-hospital mortality was related to sepsis, heart disease, and other complications. Conclusion AF is associated with higher in-hospital mortality rate than in patients without AF. For improving outcome of stroke patients, we also need to focus to reduce serious neurological or medical complications. PMID:27418830

  13. Emergency EC-IC bypass for symptomatic atherosclerotic ischemic stroke.

    PubMed

    Horiuchi, Tetsuyoshi; Nitta, Junpei; Ishizaka, Shigetoshi; Kanaya, Kohei; Yanagawa, Takao; Hongo, Kazuhiro

    2013-10-01

    Previous studies have shown that extracranial-intracranial (EC-IC) bypass surgery has no preventive effect on subsequent ipsilateral ischemic stroke in patients with symptomatic atherosclerotic internal carotid occlusion and hemodynamic cerebral ischemia. A few studies have assessed whether an urgent EC-IC bypass surgery is an effective treatment for main trunk stenosis or occlusion in acute stage. The authors retrospectively reviewed 58 consecutive patients who underwent urgent EC-IC bypass for symptomatic internal carotid artery or the middle cerebral artery stenosis or occlusion between January 2003 and December 2011. Clinical characteristics and neuroimagings were evaluated and analyzed. Based on preoperative angiogram, responsible lesions were the internal carotid artery in 19 (32.8%) patients and the middle cerebral artery in 39 (67.2%). No hemorrhagic complication occurred. Sixty-nine percent of patients showed improvement of neurological function after surgery, and 74.1% of patients had favorable outcome. Unfavorable outcome was associated with insufficient collateral flow and new infarction after bypass surgery.

  14. Evolution of endovascular mechanical thrombectomy for acute ischemic stroke

    PubMed Central

    Przybylowski, Colin J; Ding, Dale; Starke, Robert M; Durst, Christopher R; Crowley, R Webster; Liu, Kenneth C

    2014-01-01

    Acute ischemic stroke (AIS) is a common medical problem associated with significant morbidity and mortality worldwide. A small proportion of AIS patients meet eligibility criteria for intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator, and its efficacy for large vessel occlusion is poor. Therefore, an increasing number of patients with AIS are being treated with endovascular mechanical thrombectomy when IVT is ineffective or contraindicated. Rapid advancement in catheter-based and endovascular device technology has led to significant improvements in rates of cerebral reperfusion with these devices. Stentrievers and modern aspiration catheters have now surpassed earlier generation devices in the degree and rapidity of revascularization. This progress has been achieved with no concurrent increase in risk of major complications or mortality, both when used alone or in combination with IVT. The initial randomized controlled trials comparing endovascular therapy to IVT for AIS failed to show superior outcomes with endovascular treatment, but key limitations of each trial may limit the significance of these results to current practice. While endovascular devices and operator experience continue to evolve, we are optimistic that this will be accompanied by improvements in patient outcomes. This review highlights the major endovascular devices used in current practice and the trials which have investigated their efficacy. PMID:25405185

  15. Evolution of endovascular mechanical thrombectomy for acute ischemic stroke.

    PubMed

    Przybylowski, Colin J; Ding, Dale; Starke, Robert M; Durst, Christopher R; Crowley, R Webster; Liu, Kenneth C

    2014-11-16

    Acute ischemic stroke (AIS) is a common medical problem associated with significant morbidity and mortality worldwide. A small proportion of AIS patients meet eligibility criteria for intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator, and its efficacy for large vessel occlusion is poor. Therefore, an increasing number of patients with AIS are being treated with endovascular mechanical thrombectomy when IVT is ineffective or contraindicated. Rapid advancement in catheter-based and endovascular device technology has led to significant improvements in rates of cerebral reperfusion with these devices. Stentrievers and modern aspiration catheters have now surpassed earlier generation devices in the degree and rapidity of revascularization. This progress has been achieved with no concurrent increase in risk of major complications or mortality, both when used alone or in combination with IVT. The initial randomized controlled trials comparing endovascular therapy to IVT for AIS failed to show superior outcomes with endovascular treatment, but key limitations of each trial may limit the significance of these results to current practice. While endovascular devices and operator experience continue to evolve, we are optimistic that this will be accompanied by improvements in patient outcomes. This review highlights the major endovascular devices used in current practice and the trials which have investigated their efficacy.

  16. Stenting in the Treatment of Acute Ischemic Stroke: Literature Review

    PubMed Central

    Samaniego, Edgar A.; Dabus, Guilherme; Linfante, Italo

    2011-01-01

    Recanalization of acute large artery occlusions is a strong predictor of good outcome. The development of thrombectomy devices resulted in a significant improvement in recanalization rates compared to thrombolytics alone. However, clinical trials and registries with these thrombectomy devices in acute ischemic stroke (AIS) have shown recanalization rates in the range of 40–81%. The last decade has seen the development of nickel titanium self-expandable stents (SES). These stents, in contrast to balloon-mounted stents, allow better navigability and deployment in tortuous vessels and therefore are optimal for the cerebral circulation. SES were initially used for stent-assisted coil embolization of intracranial aneurysms and for treatment of intracranial stenosis. However, a few authors have recently reported feasibility of deployment of SES in AIS. The use of these devices yielded higher recanalization rates compared to traditional thrombectomy devices. Encouraged by these results, retrievable SES systems have been recently used in AIS. These devices offer the advantage of resheathing and retrieving of the stent even after full deployment. Some of these stents can also be detached in case permanent stent placement is needed. Retrievable SES are being used in Europe and currently tested in clinical trials in the United States. We review the recent literature in the use of stents for the treatment of AIS secondary to large vessel occlusion. PMID:22163225

  17. Tissue pertechnetate and iodinated contrast material ischemic stroke

    SciTech Connect

    Anderson, D.C.; Coss, D.T.; Jacobson, R.L.; Meyer, M.W.

    1980-11-01

    Isotope uptake during static radionuclide scanning and contrast enhancement during CT scanning, which may result from similar pathophysiologic mechanisms after ischemic infarction, were investigated in an animal model. Infarction was produced by transorbital occlusion of the middle cerebral artery in cats killed one, 2, 4, 8, or 16 days later. Sodium pertechnetate containing technetium-99m and 30% methylglucamine iothalamate labeled with I-125 were administered intravenously 60 and 15 min respectively prior to sacrifice. A coronal section through the infarct was parceled into 30 portions which were assayed for concentration of each isotope. Adjacent brain was prepared for histopathologic correlation. Concentrations of the 2 materials were highest in infarcted brain at 4 and 8 days. Strong positive correlation was found between tissue concentrations of the 2 materials in all brain samples. Elevated tissue levels correlated with necrosis, macrophage infiltration, and vascular hyperplasia. The results support the probability that radionuclide scan positivity and CT contrast enhancement reflect the same pathophysiologic development, probably extravasation of the respective labels, after schemic stroke.

  18. Astrocyte morphology after ischemic and hemorrhagic experimental stroke has no influence on the different recovery patterns.

    PubMed

    Mestriner, Régis Gemerasca; Saur, Lisiani; Bagatini, Pamela Brambilla; Baptista, Pedro Porto Alegre; Vaz, Sabrina Pereira; Ferreira, Kelly; Machado, Susane Alves; Xavier, Léder Leal; Netto, Carlos Alexandre

    2015-02-01

    Stroke, broadly subdivided into ischemic and hemorrhagic subtypes, is a serious health-care problem worldwide. Previous studies have suggested ischemic and hemorrhagic stroke could present different functional recovery patterns. However, little attention has been given to this neurobiological finding. Coincidently, astrocyte morphology could be related to improved sensorimotor recovery after skilled reaching training and modulated by physical exercise and environmental enrichment. Therefore, it is possible that astrocyte morphology might be linked to differential recovery patterns between ischemic and hemorrhagic stroke. Thus, we decided to compare long-term GFAP-positive astrocyte morphology after ischemic (IS, n=5), hemorrhagic (HS, n=5) and sham (S, n=5) stroke groups (induced by endothelin-1, collagenase type IV-S and salina, respectively). Our results showed ischemic and hemorrhagic stroke subtypes induced similar long-term GFAP-positive astrocyte plasticity (P>0.05) for all evaluated measures (regional and cellular optical density; astrocytic primary processes ramification and length; density of GFAP positive astrocytes) in perilesional sensorimotor cortex and striatum. These interesting negative results discourage similar studies focused on long-term plasticity of GFAP-positive astrocyte morphology and recovery comparison of stroke subtypes.

  19. Association between TNFRSF11B gene polymorphisms and history of ischemic stroke in Italian diabetic patients.

    PubMed

    Biscetti, Federico; Straface, Giuseppe; Giovannini, Silvia; Santoliquido, Angelo; Angelini, Flavia; Santoro, Luca; Porreca, Carlo Filippo; Pecorini, Giovanni; Ghirlanda, Giovanni; Flex, Andrea

    2013-01-01

    Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. The present study aimed to evaluate whether OPG gene (TNFRSF11B) polymorphisms are involved in ischemic stroke in an Italian population with diabetes. Participants in a retrospective case-control study included 364 diabetic patients (180 males, 184 females) with history of ischemic stroke and 492 diabetic subjects without history of ischemic stroke (252 males, 240 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism. We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were significantly (34.1 vs. 9.5 %, P < 0.0001; 30.8 vs. 6.3 %, P < 0.0001 and 26.4 vs. 11.6 % P < 0.0001, respectively) and independently (adjusted OR 5.15 [3.46-7.68], OR 6.63 [4.26-10.31], and OR 3.03 [2.04-4.50], respectively) associated with history of ischemic stroke. We also found that these three polymorphisms act synergistically in patients with stroke history. The TNFRSF11B gene polymorphisms studied are associated with history of ischemic stroke and synergistic effects between these genotypes might be potential markers for cerebrovascular disorders.

  20. KALRN Rare and Common Variants and Susceptibility to Ischemic Stroke in Chinese Han Population.

    PubMed

    Dang, Meizheng; Wang, Zhenzhen; Zhang, Ruyou; Li, Xiaoying; Peng, Yanqing; Han, Xuesong; Sun, Litao; Tian, Jiawei

    2015-09-01

    Stroke is the second most common cause of mortality worldwide, and it is a major cause of physical disability. Several genome-wide association studies have yielded numerous common variants which increase the risk of ischemic stroke, including the Kalirin-coding gene, KALRN. KALRN strongly associates with early-onset coronary artery disease and atherosclerosis and plays an important role in stroke in the European population. In this study, we analyzed four KALRN gene SNPs in 503 ischemic stroke patients and 493 control subjects, separating the patients into separate research groups based on comorbidity with hypertension or diabetes and stroke type (atherosis or lacunar and combination type). We found a rare variant of KALRN, rs11712619, that associated with lacunar stroke in the northern Chinese Han population with an average-risk allele frequency 0.009 (OR 2.95, 95 % CI 1.08-8.01, p = 0.028). However, after adjusting for relevant factors, including sex, age, body mass index, dyslipidemia, alcohol consumption, and smoking, this association was not evident. Additionally, the KALRN variant rs6438833 was associated with ischemic stroke, ischemic stroke comorbid with diabetes, and lacunar stroke after adjusting for the relevant factors (p = 0.046, p = 0.019 and p = 0.046, respectively), which remained significant after 10,000 permutation procedure test (p' = 0.047, p' = 0.018 and p' = 0.048, respectively). The association of these rare and common variants of KALRN with ischemic stroke in northern Chinese Han population offers insight for potential therapeutic research.

  1. Clinical presentation and imaging characteristics of occult lung cancer associated ischemic stroke.

    PubMed

    Mai, Hui; Xia, Jun; Wu, Yongjun; Ke, Junlong; Li, Junliang; Pan, Jiangang; Chen, Wubiao; Shao, Yiming; Yang, Zhi; Luo, Saihua; Sun, Yonghua; Zhao, Bin; Li, Longxuan

    2015-02-01

    We investigated the clinical and imaging characteristics of initial and recurrent strokes in patients with occult lung cancer associated ischemic stroke (OLCA-stroke). A retrospective review of all ischemic stroke patients with occult lung cancer in the absence of conventional stroke etiologies between 2005 and 2013 was conducted. We compared the initial and recurrent lesion patterns on diffusion-weighted MRI in patients with OLCA-stroke, with respect to vascular territory involved, number and size of lesions, clinical presentation, cancer subtypes, recurrences and fatalities, and outcome of survivors. Thirteen patients with confirmed OLCA-stroke were identified. All had elevated D-dimer levels, six had central lung cancer and seven had peripheral lung cancer. Eight (62%) had adenocarcinoma, and nine (69%) had metastasis. Ten (77%) patients had multiple lesions in multiple vascular territories. Twelve (92%) patients suffered recurrent strokes. Multiple small and large disseminated lesions in multiple vascular territories were more frequent in recurrent strokes in comparison with initial strokes. The middle cerebral artery was most frequently involved in recurrent strokes, followed by the posterior circulation territory and anterior cerebral artery, which were of similar frequency as initial strokes. Overall, 58% of patients had their first recurrent stroke within the first month, and 69% had a poor outcome, especially for those with multiple recurrent strokes and metastases. Occult cancer should be considered in the setting of multiple and recurrent embolic strokes within the short term in the absence of conventional stroke etiologies. The severity of malignancy and cancer treatments and stroke influenced the recurrences and outcome.

  2. Efficacy of telemedicine for thrombolytic therapy in acute ischemic stroke: a meta-analysis.

    PubMed

    Zhai, Yun-kai; Zhu, Wei-jun; Hou, Hong-li; Sun, Dong-xu; Zhao, Jie

    2015-04-01

    The aim of this study was to assess the benefits of telemedicine in the delivery of thrombolytic therapy for patients with acute ischemic stroke. We performed a meta-analysis using combinations of the following terms: telestroke, telemedicine, tissue plasminogen activator/t-PA, and acute ischemic stroke. The primary outcome was favorable outcome based on the modified Rankin score. Secondary outcomes were incidence of symptomatic intracranial hemorrhage and overall mortality. We found no significant difference in favorable outcome between the telemedicine and control groups, and no significant difference was found between these groups in the rate of symptomatic intracranial hemorrhage or overall mortality. Patients with acute ischemic stroke who were treated with intravenous thrombolysis had similar outcomes regardless of whether telemedicine was used or they were treated in-person at a medical facility. Telemedicine can be used to support hospitals with limited experience in administering thrombolytic therapy for stroke.

  3. Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with ischemic stroke in the Eastern Chinese Han population.

    PubMed

    Lv, Q-Q; Lu, J; Sun, H; Zhang, J-S

    2015-04-27

    The association between the MTHFR genetic polymorphism and ischemic stroke has been reported by a number of investigators. However, the results have been controversial and conflicting. The aim of this study was to explore the association between the MTHFR variants C677T and A1298C and the risk of ischemic stroke in an Eastern Chinese Han population. A total of 199 patients with ischemic stroke and 241 controls were recruited. Genotyping of the MTHFR C677T and A1298C polymorphisms was carried out using the Taqman 7900HT Sequence Detection System. The overall estimates (odds ratio: OR) for the allele (C) and genotype (AC+CC) of the A1298C polymorphism were 1.57 [95% confidence interval (CI) = 1.16-2.10], and 2.36 (95%CI = 1.39-4.00), respectively, establishing significant association of the MTHFR A1298C polymorphism with ischemic stroke. In contrast, there were no statistically significant differences compared to controls between MTHFR C677T polymorphic variants in the association ischemic stroke risk. Furthermore, haplotype-based analysis demonstrated that compared with the C-677-A-1298 haplotype, the C-677-C-1298 and T-677-C-1298 haplotypes showed significant increased risk of ischemic stroke (OR = 1.56; 95%CI = 1.07- 2.2; P = 0.02; OR = 1.76; 95%CI = 1.17-2.65; P < 0.01, respectively). We concluded that the A1298C polymorphism and the haplotypes C-677-C-1298 and T-677-C-1298 in MTHFR might modulate the risk of ischemic stroke in the Eastern Chinese Han population.

  4. Lesion segmentation from multimodal MRI using random forest following ischemic stroke.

    PubMed

    Mitra, Jhimli; Bourgeat, Pierrick; Fripp, Jurgen; Ghose, Soumya; Rose, Stephen; Salvado, Olivier; Connelly, Alan; Campbell, Bruce; Palmer, Susan; Sharma, Gagan; Christensen, Soren; Carey, Leeanne

    2014-09-01

    Understanding structure-function relationships in the brain after stroke is reliant not only on the accurate anatomical delineation of the focal ischemic lesion, but also on previous infarcts, remote changes and the presence of white matter hyperintensities. The robust definition of primary stroke boundaries and secondary brain lesions will have significant impact on investigation of brain-behavior relationships and lesion volume correlations with clinical measures after stroke. Here we present an automated approach to identify chronic ischemic infarcts in addition to other white matter pathologies, that may be used to aid the development of post-stroke management strategies. Our approach uses Bayesian-Markov Random Field (MRF) classification to segment probable lesion volumes present on fluid attenuated inversion recovery (FLAIR) MRI. Thereafter, a random forest classification of the information from multimodal (T1-weighted, T2-weighted, FLAIR, and apparent diffusion coefficient (ADC)) MRI images and other context-aware features (within the probable lesion areas) was used to extract areas with high likelihood of being classified as lesions. The final segmentation of the lesion was obtained by thresholding the random forest probabilistic maps. The accuracy of the automated lesion delineation method was assessed in a total of 36 patients (24 male, 12 female, mean age: 64.57±14.23yrs) at 3months after stroke onset and compared with manually segmented lesion volumes by an expert. Accuracy assessment of the automated lesion identification method was performed using the commonly used evaluation metrics. The mean sensitivity of segmentation was measured to be 0.53±0.13 with a mean positive predictive value of 0.75±0.18. The mean lesion volume difference was observed to be 32.32%±21.643% with a high Pearson's correlation of r=0.76 (p<0.0001). The lesion overlap accuracy was measured in terms of Dice similarity coefficient with a mean of 0.60±0.12, while the contour

  5. Detection of Early Ischemic Changes in Noncontrast CT Head Improved with "Stroke Windows".

    PubMed

    Mainali, Shraddha; Wahba, Mervat; Elijovich, Lucas

    2014-01-01

    Introduction. Noncontrast head CT (NCCT) is the standard radiologic test for patients presenting with acute stroke. Early ischemic changes (EIC) are often overlooked on initial NCCT. We determine the sensitivity and specificity of improved EIC detection by a standardized method of image evaluation (Stroke Windows). Methods. We performed a retrospective chart review to identify patients with acute ischemic stroke who had NCCT at presentation. EIC was defined by the presence of hyperdense MCA/basilar artery sign; sulcal effacement; basal ganglia/subcortical hypodensity; and loss of cortical gray-white differentiation. NCCT was reviewed with standard window settings and with specialized Stroke Windows. Results. Fifty patients (42% females, 58% males) with a mean NIHSS of 13.4 were identified. EIC was detected in 9 patients with standard windows, while EIC was detected using Stroke Windows in 35 patients (18% versus 70%; P < 0.0001). Hyperdense MCA sign was the most commonly reported EIC; it was better detected with Stroke Windows (14% and 36%; P < 0.0198). Detection of the remaining EIC also improved with Stroke Windows (6% and 46%; P < 0.0001). Conclusions. Detection of EIC has important implications in diagnosis and treatment of acute ischemic stroke. Utilization of Stroke Windows significantly improved detection of EIC.

  6. Hyperhomocysteinemia, Folateo and B12 Vitamin in Iranian Patients with Acute Ischemic Stroke

    PubMed Central

    Omrani, Hoseinali Qeilichnia; Qabai, Mojdeh; Chaman, Reza; Fard, Hamed Amiri; Qaffarpoor, Majid

    2011-01-01

    BACKGROUND The objective of this study was to evaluate the association of some factors such as serum levels of homocysteine, folate and B12 vitamin with stroke in acute ischemic stroke patients. METHODS In this case control study, serum levels of homocysteine, folate and B12 vitamin in 93 patients with acute ischemic stroke admitted to Imam Khomeini Hospital between September 2008 and January 2010, and 93 healthy controls were measured. Cerebrovascular risk factors including age, sex, hypertension, hyperlipidemia, smoking, diabetes mellitus, alcohol consumption, coronary artery disease and obesity were recorded. The results were compared between the case and control groups. RESULTS The mean ± standard deviation (SD) of fasting total homocysteine (tHcy) level in acute ischemic stroke patients was 20.58 ± 19.6 µmol/l, which was significantly higher than that of control group being 14.11 ± 9.5 µmol/l (P = 0.002). 39 (41.9%) stroke cases and 25 (26.8%) controls had hyperhomocysteinemia. There were no significant relationships between tHcy, folate and B12 vitamin levels with the above mentioned cerebrovascular risk factors except for smoking (p> 0.05). No significant difference in B12 vitamin and folate levels between patients and healthy controls were detected (P> 0.05). CONCLUSION Hyperhomocysteinemia is common in Iranian patients with acute ischemic stroke and might play a role as an independent risk factor in stroke. PMID:22577454

  7. Vagus Nerve Stimulation in Ischemic Stroke: Old Wine in a New Bottle

    PubMed Central

    Cai, Peter Y.; Bodhit, Aakash; Derequito, Roselle; Ansari, Saeed; Abukhalil, Fawzi; Thenkabail, Spandana; Ganji, Sarah; Saravanapavan, Pradeepan; Shekar, Chandana C.; Bidari, Sharatchandra; Waters, Michael F.; Hedna, Vishnumurthy Shushrutha

    2014-01-01

    Vagus nerve stimulation (VNS) is currently Food and Drug Administration-approved for treatment of both medically refractory partial-onset seizures and severe, recurrent refractory depression, which has failed to respond to medical interventions. Because of its ability to regulate mechanisms well-studied in neuroscience, such as norepinephrine and serotonin release, the vagus nerve may play an important role in regulating cerebral blood flow, edema, inflammation, glutamate excitotoxicity, and neurotrophic processes. There is strong evidence that these same processes are important in stroke pathophysiology. We reviewed the literature for the role of VNS in improving ischemic stroke outcomes by performing a systematic search for publications in Medline (1966–2014) with keywords “VNS AND stroke” in subject headings and key words with no language restrictions. Of the 73 publications retrieved, we identified 7 studies from 3 different research groups that met our final inclusion criteria of research studies addressing the role of VNS in ischemic stroke. Results from these studies suggest that VNS has promising efficacy in reducing stroke volume and attenuating neurological deficits in ischemic stroke models. Given the lack of success in Phase III trials for stroke neuroprotection, it is important to develop new therapies targeting different neuroprotective pathways. Further studies of the possible role of VNS, through normally physiologically active mechanisms, in ischemic stroke therapeutics should be conducted in both animal models and clinical studies. In addition, recent advent of a non-invasive, transcutaneous VNS could provide the potential for easier clinical translation. PMID:25009531

  8. Objective Ventricle Segmentation in Brain CT with Ischemic Stroke Based on Anatomical Knowledge

    PubMed Central

    Qian, Xiaohua; Lin, Yuan; Zhao, Yue; Yue, Xinyan

    2017-01-01

    Ventricle segmentation is a challenging technique for the development of detection system of ischemic stroke in computed tomography (CT), as ischemic stroke regions are adjacent to the brain ventricle with similar intensity. To address this problem, we developed an objective segmentation system of brain ventricle in CT. The intensity distribution of the ventricle was estimated based on clustering technique, connectivity, and domain knowledge, and the initial ventricle segmentation results were then obtained. To exclude the stroke regions from initial segmentation, a combined segmentation strategy was proposed, which is composed of three different schemes: (1) the largest three-dimensional (3D) connected component was considered as the ventricular region; (2) the big stroke areas were removed by the image difference methods based on searching optimal threshold values; (3) the small stroke regions were excluded by the adaptive template algorithm. The proposed method was evaluated on 50 cases of patients with ischemic stroke. The mean Dice, sensitivity, specificity, and root mean squared error were 0.9447, 0.969, 0.998, and 0.219 mm, respectively. This system can offer a desirable performance. Therefore, the proposed system is expected to bring insights into clinic research and the development of detection system of ischemic stroke in CT. PMID:28271071

  9. Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction.

    PubMed

    Cho, Yunkyung; Kim, Jung O; Lee, Jeong Han; Park, Hye Mi; Jeon, Young Joo; Oh, Seung Hun; Bae, Jinkun; Park, Young Seok; Kim, Ok Joon; Kim, Nam Keun

    2015-01-01

    Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke.

  10. Inducible Glutamate Oxaloacetate Transaminase as a Therapeutic Target Against Ischemic Stroke

    PubMed Central

    Khanna, Savita; Briggs, Zachary

    2015-01-01

    Abstract Significance: Glutamate serves multi-faceted (patho)physiological functions in the central nervous system as the most abundant excitatory neurotransmitter and under pathological conditions as a potent neurotoxin. Regarding the latter, elevated extracellular glutamate is known to play a central role in ischemic stroke brain injury. Recent Advances: Glutamate oxaloacetate transaminase (GOT) has emerged as a new therapeutic target in protecting against ischemic stroke injury. Oxygen-sensitive induction of GOT expression and activity during ischemic stroke lowers glutamate levels at the stroke site while sustaining adenosine triphosphate levels in brain. The energy demands of the brain are among the highest of all organs underscoring the need to quickly mobilize alternative carbon skeletons for metabolism in the absence of glucose during ischemic stroke. Recent work builds on the important observation of Hans Krebs that GOT-mediated metabolism of glutamate generates tri-carboxylic acid (TCA) cycle intermediates in brain tissue. Taken together, outcomes suggest GOT may enable the transformative switch of otherwise excitotoxic glutamate into life-sustaining TCA cycle intermediates during ischemic stroke. Critical Issues: Neuroprotective strategies that focus solely on blocking mechanisms of glutamate-mediated excitotoxicity have historically failed in clinical trials. That GOT can enable glutamate to assume the role of a survival factor represents a paradigm shift necessary to develop the overall significance of glutamate in stroke biology. Future Directions: Ongoing efforts are focused to develop the therapeutic significance of GOT in stroke-affected brain. Small molecules that target induction of GOT expression and activity in the ischemic penumbra are the focus of ongoing studies. Antioxid. Redox Signal. 22, 175–186. PMID:25343301

  11. Phosphodiesterase 4D polymorphisms associate with the short-term outcome in ischemic stroke

    PubMed Central

    Song, Yan-li; Wang, Chun-juan; Wu, Yi-ping; Lin, Jie; Wang, Peng-lian; Du, Wan-liang; Liu, Li; Lin, Jin-xi; Wang, Yi-long; Wang, Yong-jun; Liu, Gai-fen

    2017-01-01

    It has been demonstrated that phosphodiesterase 4D (PDE4D) genetic polymorphism is associated with ischemic stroke. However, the association between PDE4D gene and prognosis after ischemic stroke remains unknown. We consecutively enrolled ischemic stroke patients admitted to Beijing Tiantan Hospital from October 2009 to December 2013. Clinical, laboratory and imaging data upon admission were collected. All patients were followed up 3 months after stroke onset. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the associations of genetic polymorphisms with 3-month outcome after ischemic stroke and different subtypes, under various genetic models. A total of 1447 patients were enrolled, and 3-month follow-up data were obtained from 1388 (95.92%). Multivariate regression analysis showed that SNP87 of PDE4D gene was associated with increased risk of unfavorable outcome after total ischemic stroke (OR = 1.47, 95%CI 1.12–1.93), as well as stroke due to large-artery atherosclerosis (OR = 1.49, 95%CI 1.04–2.11) and small-artery occlusion (OR = 1.76, 95%CI 1.05–2.96) under a recessive model. No association between SNP83 genotype and poor outcome was found. Overall, this study demonstrated that the TT genotype of SNP87 in PDE4D was associated with increased risk of poor outcome after total ischemic stroke, large-artery atherosclerosis and small-artery occlusion, in a Chinese population. PMID:28225001

  12. Effect of statin use on clinical outcomes in ischemic stroke patients with atrial fibrillation

    PubMed Central

    Wu, Yi-Ling; Saver, Jeffrey L.; Chen, Pei-Chun; Lee, Jiann-Der; Wang, Hui-Hsuan; Rao, Neal M.; Lee, Meng; Ovbiagele, Bruce

    2017-01-01

    Abstract It remains unclear whether statin therapy should be applied to ischemic stroke patients with atrial fibrillation. The objective of this study was to clarify whether statin therapy can influence the prognosis in recent ischemic stroke patients with atrial fibrillation. We identified ischemic stroke patients with atrial fibrillation between 2001 and 2011 from Taiwan National Health Insurance Database. Patients not treated with statins during the first 90 days after the index stroke were matched to patients treated with statins in the first 90 days in a 2:1 ratio on the basis of age, sex, hypertension, diabetes mellitus, ischemic heart disease, heart failure, estimated National Institutes of Health Stroke Scale, use of anticoagulant, and year of their entry into the cohort. The primary outcome was the first event of recurrent stroke, and the secondary outcome was in-hospital death. A total of 1546 atrial fibrillation patients with statin therapy in the first 90 days poststroke and 3092 matched atrial fibrillation nonstatin controls were enrolled for this analysis. During the median 2.4-year follow-up, the risk of recurrent stroke was not different between subjects receiving versus not receiving statin therapy (hazard ratios = 1.01, 95% confidence interval 0.88 to 1.15). However, patients with atrial fibrillation receiving statin therapy had a reduced risk for death during any hospitalization throughout the long-term follow-up period (hazard ratios = 0.74, 95% confidence interval 0.61 to 0.89). Among ischemic stroke patients with atrial fibrillation, statin therapy initiated during the acute to subacute poststroke stage did not alter the rate of stroke recurrence but was associated with a decreased rate of in-hospital death. PMID:28151869

  13. Risk of Ischemic Stroke after Intracranial Hemorrhage in Patients with Atrial Fibrillation

    PubMed Central

    Lerario, Michael P.; Gialdini, Gino; Lapidus, Daniel M.; Shaw, Mesha M.; Navi, Babak B.; Merkler, Alexander E.; Lip, Gregory Y. H.; Healey, Jeff S.; Kamel, Hooman

    2015-01-01

    Background We aimed to estimate the risk of ischemic stroke after intracranial hemorrhage in patients with atrial fibrillation. Materials and Methods Using discharge data from all nonfederal acute care hospitals and emergency departments in California, Florida, and New York from 2005 to 2012, we identified patients at the time of a first-recorded encounter with a diagnosis of atrial fibrillation. Ischemic stroke and intracranial hemorrhage were identified using validated diagnosis codes. Kaplan-Meier survival statistics and Cox proportional hazard analyses were used to evaluate cumulative rates of ischemic stroke and the relationship between incident intracranial hemorrhage and subsequent stroke. Results Among 2,084,735 patients with atrial fibrillation, 50,468 (2.4%) developed intracranial hemorrhage and 89,594 (4.3%) developed ischemic stroke during a mean follow-up period of 3.2 years. The 1-year cumulative rate of stroke was 8.1% (95% CI, 7.5–8.7%) after intracerebral hemorrhage, 3.9% (95% CI, 3.5–4.3%) after subdural hemorrhage, and 2.0% (95% CI, 2.0–2.1%) in those without intracranial hemorrhage. After adjustment for the CHA2DS2-VASc score, stroke risk was elevated after both intracerebral hemorrhage (hazard ratio [HR], 2.8; 95% CI, 2.6–2.9) and subdural hemorrhage (HR, 1.6; 95% CI, 1.5–1.7). Cumulative 1-year rates of stroke ranged from 0.9% in those with subdural hemorrhage and a CHA2DS2-VASc score of 0, to 33.3% in those with intracerebral hemorrhage and a CHA2DS2-VASc score of 9. Conclusions In a large, heterogeneous cohort, patients with atrial fibrillation faced a substantially heightened risk of ischemic stroke after intracranial hemorrhage. The risk was most marked in those with intracerebral hemorrhage and high CHA2DS2-VASc scores. PMID:26701759

  14. Increased Circulating Exosomal miRNA-223 Is Associated with Acute Ischemic Stroke

    PubMed Central

    Chen, Yajing; Song, Yaying; Huang, Jun; Qu, Meijie; Zhang, Yu; Geng, Jieli; Zhang, Zhijun; Liu, Jianrong; Yang, Guo-Yuan

    2017-01-01

    Recent studies have demonstrated that exosomal microRNAs (miRNAs) are novel biomarkers and therapeutic targets for various diseases including vascular disease. However, specific exosomal miRNAs expression in stroke patients has not been reported yet. Here, we explored whether circulating exosomal miRNAs can serve as potential biomarkers for the diagnosis of acute ischemic stroke and discussed the potential for clinical application. Blood samples were collected from acute ischemic stroke patients within the first 72 h (n = 50). Circulating exosomes were exacted by Exoquick exosome isolation kit and characterized by transmission electron microscopy. Western blot was performed to assess the expression of exosomal protein makers. Exosomal miRNA-223 (miR-223) was detected by RT-PCR assay. The relationship between the expression levels of miR-223 and National Institutes of Health Stroke Scale (NIHSS) scores, brain infarct volume, and neurological outcomes were analyzed. Circulating exosomes were isolated and the size of vesicles ranged between 30 and 100 nm. The identification of exosomes was further confirmed by the detection of specific exosomal protein markers CD9, CD63, and Tsg101. Exosomal miR-223 in acute ischemic stroke patients was significantly upregulated compared to control group (p < 0.001). Exosomal miR-223 level was positively correlated with NIHSS scores (r = 0.31, p = 0.03). Exosomal miR-223 expression in stroke patients with poor outcomes was higher than those with good outcomes (p < 0.05). Increased exosomal miR-223 was associated with acute ischemic stroke occurrence, stroke severity, and short-term outcomes. Future studies with large sample are needed to assess the clinical application of exosomal miR-223 as a novel biomarker for ischemic stroke diagnosis. PMID:28289400

  15. Effect of statin use on clinical outcomes in ischemic stroke patients with atrial fibrillation.

    PubMed

    Wu, Yi-Ling; Saver, Jeffrey L; Chen, Pei-Chun; Lee, Jiann-Der; Wang, Hui-Hsuan; Rao, Neal M; Lee, Meng; Ovbiagele, Bruce

    2017-02-01

    It remains unclear whether statin therapy should be applied to ischemic stroke patients with atrial fibrillation. The objective of this study was to clarify whether statin therapy can influence the prognosis in recent ischemic stroke patients with atrial fibrillation.We identified ischemic stroke patients with atrial fibrillation between 2001 and 2011 from Taiwan National Health Insurance Database. Patients not treated with statins during the first 90 days after the index stroke were matched to patients treated with statins in the first 90 days in a 2:1 ratio on the basis of age, sex, hypertension, diabetes mellitus, ischemic heart disease, heart failure, estimated National Institutes of Health Stroke Scale, use of anticoagulant, and year of their entry into the cohort. The primary outcome was the first event of recurrent stroke, and the secondary outcome was in-hospital death.A total of 1546 atrial fibrillation patients with statin therapy in the first 90 days poststroke and 3092 matched atrial fibrillation nonstatin controls were enrolled for this analysis. During the median 2.4-year follow-up, the risk of recurrent stroke was not different between subjects receiving versus not receiving statin therapy (hazard ratios = 1.01, 95% confidence interval 0.88 to 1.15). However, patients with atrial fibrillation receiving statin therapy had a reduced risk for death during any hospitalization throughout the long-term follow-up period (hazard ratios = 0.74, 95% confidence interval 0.61 to 0.89).Among ischemic stroke patients with atrial fibrillation, statin therapy initiated during the acute to subacute poststroke stage did not alter the rate of stroke recurrence but was associated with a decreased rate of in-hospital death.

  16. Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patients

    PubMed Central

    Rosa, Alexandra; Fonseca, Benedita V; Krug, Tiago; Manso, Helena; Gouveia, Liliana; Albergaria, Isabel; Gaspar, Gisela; Correia, Manuel; Viana-Baptista, Miguel; Simões, Rita Moiron; Pinto, Amélia Nogueira; Taipa, Ricardo; Ferreira, Carla; Fontes, João Ramalho; Silva, Mário Rui; Gabriel, João Paulo; Matos, Ilda; Lopes, Gabriela; Ferro, José M; Vicente, Astrid M; Oliveira, Sofia A

    2008-01-01

    Background The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk. Methods We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk. Results Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45–0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41–7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13–7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect. Conclusion Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample. PMID:18593462

  17. A lower baseline glomerular filtration rate predicts high mortality and newly cerebrovascular accidents in acute ischemic stroke patients

    PubMed Central

    Dong, Kai; Huang, Xiaoqin; Zhang, Qian; Yu, Zhipeng; Ding, Jianping; Song, Haiqing

    2017-01-01

    Abstract Chronic kidney disease (CKD) is gradually recognized as an independent risk factor for cardiovascular and cardio-/cerebrovascular disease. This study aimed to examine the association of the estimated glomerular filtration rate (eGFR) and clinical outcomes at 3 months after the onset of ischemic stroke in a hospitalized Chinese population. Totally, 972 patients with acute ischemic stroke were enrolled into this study. Modified of Diet in Renal Disease (MDRD) equations were used to calculate eGFR and define CKD. The site and degree of the stenosis were examined. Patients were followed-up for 3 months. Endpoint events included all-cause death and newly ischemic events. The multivariate logistic model was used to determine the association between renal dysfunction and patients’ outcomes. Of all patients, 130 patients (13.4%) had reduced eGFR (<60 mL/min/1.73 m2), and 556 patients had a normal eGFR (≥90 mL/min/1.73 m2). A total of 694 patients suffered from cerebral artery stenosis, in which 293 patients only had intracranial artery stenosis (ICAS), 110 only with extracranial carotid atherosclerotic stenosis (ECAS), and 301 with both ICAS and ECAS. The patients with eGFR <60 mL/min/1.73m2 had a higher proportion of death and newly ischemic events compared with those with a relatively normal eGFR. Multivariate analysis revealed that a baseline eGFR <60 mL/min/1.73 m2 increased the risk of mortality by 3.089-fold and newly ischemic events by 4.067-fold. In further analysis, a reduced eGFR was associated with increased rates of mortality and newly events both in ICAS patients and ECAS patients. However, only an increased risk of newly events was found as the degree of renal function deteriorated in ICAS patients (odds ratio = 8.169, 95% confidence interval = 2.445–14.127). A low baseline eGFR predicted a high mortality and newly ischemic events at 3 months in ischemic stroke patients. A low baseline eGFR was also a strong independent

  18. [Management of ischemic strokes derived from intraventricular thrombi: report of two cases].

    PubMed

    Oberreuter, Gerardo; Silva, Natalia; Caba, Sheila; Morales, Marcelo; Nieto, Elena; Guevara, Carlos

    2014-09-01

    The origin of 20% of ischemic strokes is a left ventricular thrombus. We report two patients with strokes originating from cardiac thrombi, treated in two different ways. A 42-year-old diabetic man admitted with a left parietal and occipital stroke. An echocardiogram showed a left ventricular thrombus. The patient was subjected to a surgical cardiac revascularization procedure and left ventricular thrombectomy. The postoperative evolution was uneventful and the patient was discharged on oral anticoagulation. On ambulatory follow up, no neurological deterioration was evidenced. A 38-year-old male admitted with an acute ischemic stroke, was subjected to thrombolysis with human plasminogen activator. An echocardiogram showed a left ventricular thrombus, considered the cause of the stroke. The patient was anticoagulated with heparin and discharged ten days after admission with oral anticoagulation. A new echocardiogram performed one month later, did not show the left ventricular thrombus.

  19. Hyperpolarized 129Xe magnetic resonance imaging of a rat model of transient Ischemic Stroke

    NASA Astrophysics Data System (ADS)

    Walvick, Ronn P.; Bastan, Birgul; Reno, Austin; Mansour, Joey; Sun, Yanping; Zhou, Xin; Mazzani, Mary; Fisher, Marc; Sotak, Christopher H.; Albert, Mitchell S.

    2009-02-01

    Ischemic stroke accounts for nearly 80% of all stroke cases. Although proton diffusion and perfusion magnetic resonance imaging (MRI) are the gold standards in ischemic stroke diagnostics, the use of hyperpolarized 129Xe MRI has a potential role to contribute to the diagnostic picture. The highly lipophilic hyperpolarized 129Xe can be non-invasively delivered via inhalation into the lungs where it is dissolved into the blood and delivered to other organs such as the brain. As such, we expect hyperpolarized 129Xe to act as a perfusion tracer which will result in a signal deficit in areas of blood deprived tissue. In this work, we present imaging results from an animal model of transient ischemic stroke characterized through 129Xe MRI. In this model, a suture is used to occlude the middle cerebral artery (MCA) in the rat brain, thus causing an ischemic event. After a period of MCA occlusion, the suture can then be removed to reperfuse the ischemic area. During the ischemic phase of the stroke, a signal void was observed in the MCA territory; which was subsequently restored by normal 129Xe MRI signal once perfusion was reinstated. Further, a higher resolution one-dimensional chemical shift image shows a sharp signal drop in the area of ischemia. Validation of ischemic damage was shown through both proton diffusion-weighted MRI (DWI) and by 2,3,5-triphenyltetrazoliumchloride (TTC) staining. The results show the potential of 129Xe to act as a perfusion tracer; information that may add to the diagnostic and prognostic utility of the clinical picture of stroke.

  20. Association of Serum Calcium Levels with Infarct Size in Acute Ischemic Stroke: Observations from Northeast India

    PubMed Central

    Borah, Meghna; Dhar, Sriparna; Gogoi, Dipankar Mall; Ruram, Alice Abraham

    2016-01-01

    Background: Calcium is known to be major mediator in ischemic neuronal cell death. Recent studies have shown that elevated serum calcium levels at admission in patients with stroke have been associated with less severe clinical deficits and with better outcomes. Aim: The aim of this to determine the correlation between serum calcium (total, corrected, and ionized) and infarct size (IS) in patients with acute ischemic stroke. Materials and Methods: Data were collected from 61 patients presenting with acute ischemic stroke from May 2015 to April 2016 at a tertiary care institute in Northeast India. Only patients aged ≥40 years and diagnosed as having acute ischemic cerebrovascular stroke with clinical examination and confirmed by a computed tomography scan were included in the study. Serum calcium levels (total, albumin corrected, and ionized) were collapsed into quartiles, and these quartile versions were used for calculating correlation. Pearson's correlation coefficient was used for comparing calcium levels with IS. Results: Total calcium, albumin-corrected calcium, and ionized calcium had a statistically significant negative correlation with IS with r = −0.578, −0.5396, and −0.5335, respectively. Total and ionized calcium showed a significant negative correlation with IS across all four quartiles. Albumin-corrected calcium levels showed a significant negative correlation with IS only across the lowest and highest quartiles. Conclusion: The findings in our study suggest that serum calcium can be used as a prognostic indicator in ischemic stroke as its levels directly correlates with the IS. PMID:28163502

  1. Plasma C-Reactive Protein and Clinical Outcomes after Acute Ischemic Stroke: A Prospective Observational Study

    PubMed Central

    Matsuo, Ryu; Ago, Tetsuro; Hata, Jun; Wakisaka, Yoshinobu; Kuroda, Junya; Kuwashiro, Takahiro; Kitazono, Takanari; Kamouchi, Masahiro

    2016-01-01

    Background and Purpose Although plasma C-reactive protein (CRP) is elevated in response to inflammation caused by brain infarction, the association of CRP with clinical outcomes after acute ischemic stroke remains uncertain. This study examined whether plasma high-sensitivity CRP (hsCRP) levels at onset were associated with clinical outcomes after acute ischemic stroke independent of conventional risk factors and acute infections after stroke. Methods We prospectively included 3653 patients with first-ever ischemic stroke who had been functionally independent and were hospitalized within 24 h of onset. Plasma hsCRP levels were measured on admission and categorized into quartiles. The association between hsCRP levels and clinical outcomes, including neurological improvement, neurological deterioration, and poor functional outcome (modified Rankin scale ≥3 at 3 months), were investigated using a logistic regression analysis. Results Higher hsCRP levels were significantly associated with unfavorable outcomes after adjusting for age, sex, baseline National Institutes of Health Stroke Scale score, stroke subtype, conventional risk factors, intravenous thrombolysis and endovascular therapy, and acute infections during hospitalization (multivariate-adjusted odds ratios [95% confidence interval] in the highest quartile versus the lowest quartile as a reference: 0.80 [0.65–0.97] for neurological improvement, 1.72 [1.26–2.34] for neurological deterioration, and 2.03 [1.55–2.67] for a poor functional outcome). These associations were unchanged after excluding patients with infectious diseases occurring during hospitalization, or those with stroke recurrence or death. These trends were similar irrespective of stroke subtypes or baseline stroke severity, but more marked in patients aged <70 years (Pheterogeneity = 0.001). Conclusions High plasma hsCRP is independently associated with unfavorable clinical outcomes after acute ischemic stroke. PMID:27258004

  2. Shared genetic susceptibility of vascular-related biomarkers with ischemic and recurrent stroke

    PubMed Central

    Williams, Stephen R.; Hsu, Fang-Chi; Keene, Keith L.; Chen, Wei-Min; Nelson, Sarah; Southerland, Andrew M.; Madden, Ebony B.; Coull, Bruce; Gogarten, Stephanie M.; Furie, Karen L.; Dzhivhuho, Godfrey; Rowles, Joe L.; Mehndiratta, Prachi; Malik, Rainer; Dupuis, Josée; Lin, Honghuang; Seshadri, Sudha; Rich, Stephen S.; Sale, Michèle M.

    2016-01-01

    Objective: To investigate the genetic contributors to cerebrovascular disease and variation in biomarkers of ischemic stroke. Methods: The Vitamin Intervention for Stroke Prevention Trial (VISP) was a randomized, controlled clinical trial of B vitamin supplementation to prevent recurrent stroke, myocardial infarction, or death. VISP collected baseline measures of C-reactive protein (CRP), fibrinogen, creatinine, prothrombin fragments F1+2, thrombin-antithrombin complex, and thrombomodulin prior to treatment initiation. Genome-wide association scans were conducted for these traits and follow-up replication analyses were performed. Results: We detected an association between CRP single nucleotide polymorphisms (SNPs) and circulating CRP levels (most associated SNP, rs2592902, p = 1.14 × 10−9) in 2,100 VISP participants. We discovered a novel association for CRP level in the AKR1D1 locus (rs2589998, p = 7.3 × 10−8, approaching genome-wide significance) that also is an expression quantitative trait locus for CRP gene expression. We replicated previously identified associations of fibrinogen with SNPs in the FGB and LEPR loci. CRP-associated SNPs and CRP levels were significantly associated with risk of ischemic stroke and recurrent stroke in VISP as well as specific stroke subtypes in METASTROKE. Fibrinogen levels but not fibrinogen-associated SNPs were also found to be associated with recurrent stroke in VISP. Conclusions: Our data identify a genetic contribution to inflammatory and hemostatic biomarkers in a stroke population. Additionally, our results suggest shared genetic contributions to circulating CRP levels measured poststroke and risk for incident and recurrent ischemic stroke. These data broaden our understanding of genetic contributors to biomarker variation and ischemic stroke risk, which should be useful in clinical risk evaluation. PMID:26718567

  3. Neuropsychiatric Symptom Clusters in Stroke and Transient Ischemic Attack by Cognitive Status and Stroke Subtype: Frequency and Relationships with Vascular Lesions, Brain Atrophy and Amyloid

    PubMed Central

    Wong, Adrian; Lau, Alexander Y. L.; Yang, Jie; Wang, Zhaolu; Liu, Wenyan; Lam, Bonnie Y. K.; Au, Lisa; Shi, Lin; Wang, Defeng; Chu, Winnie C. W.; Xiong, Yun-yun; Lo, Eugene S. K.; Law, Lorraine S. N.; Leung, Thomas W. H.; Lam, Linda C. W.; Chan, Anne Y. Y.; Soo, Yannie O. Y.; Leung, Eric Y. L.; Wong, Lawrence K. S.; Mok, Vincent C. T.

    2016-01-01

    Background The objectives of this study are 1) to examine the frequencies of neuropsychiatric symptom clusters in patients with stroke or transient ischemic attack (TIA) by cognitive level and stroke subtype; and 2) to evaluate effect of demographic, clinical, and neuroimaging measures of chronic brain changes and amyloid upon neuropsychiatric symptom clusters. Methods Hospital-based, cross-sectional study. 518 patients were administered the Neuropsychiatric Inventory (NPI) 3–6 months post index admission. NPI symptoms were classified into four symptom clusters (Behavioral Problems, Psychosis, Mood Disturbance & Euphoria) derived from a confirmatory factor analysis of the 12 NPI items. Multivariable logistic regression was used to determine independent associations between demographic, clinical and neuroimaging measures of chronic brain changes (white matter changes, old infarcts, whole brain atrophy, medial temporal lobe atrophy [MTLA] and frontal lobe atrophy [FLA]) with the presence of NPI symptoms and all symptom clusters except euphoria. 11C-Pittsburg Compound B Positron Emission Tomography (11C-PiB PET) was performed in 24 patients to measure amyloid retention for Alzheimer’s Disease (AD) pathology. Results 50.6% of the whole sample, including 28.7% cognitively normal and 66.7% of patients with mild cognitive symptoms, had ≥1 NPI symptoms. Frequencies of symptom clusters were largely similar between stroke subtypes. Compared to patients with cardioembolic stroke and intracranial haemorrhage, those with TIA had less frequent mood disturbance. Stroke severity at admission and MTLA were the most robust correlates of symptoms. FLA was associated with behavioral problems cluster only. Frequency of symptom clusters did not differ between patients with and without significant amyloid retention. Conclusion Frequency of neuropsychiatric symptoms increased with level of cognitive impairment but was largely similar between stroke subtypes. Stroke severity and MTLA

  4. Intraperitoneal administration of thioredoxin decreases brain damage from ischemic stroke.

    PubMed

    Wang, Bin; Tian, Shilai; Wang, Jiayi; Han, Feng; Zhao, Lei; Wang, Rencong; Ning, Weidong; Chen, Wei; Qu, Yan

    2015-07-30

    Recent studies demonstrate that Thioredixin (Trx) possesses a neuronal protective effect and closely relates to oxidative stress and apoptosis of cerebral ischemia injury. The present study was conducted to validate the neuroprotective effect of recombinant human Trx-1 (rhTrx-1) and its potential mechanisms against ischemia injury at middle cerebral artery occlusion (MCAO) in mice. rhTrx-1 was administrated intraperitoneally at a dose of 5, 10 and 20mg/kg 30 min before MCAO in mice, and its neuronal protective effect was evaluated by neurological deficit score, brain dry-wet weight, 2,3,5-triphenyltetrazolium chloride (TTC) staining. The protein carbonyl content and HO-1 were detected to investigate its potential anti-oxidative and anti-inflammatory property, and the anti-apoptotic ability of rhTrx-1 was assessed by casepase-3 and TUNEL staining. The results demonstrated that rhTrx-1 significantly improved neurological functions and reduced cerebral infarction and apoptotic cell death at 24h after MCAO. Moreover, rhTrx-1 resulted in a significant decrease in carbonyl contents and HO-1 against oxidative stress, which turned to be fast reduction during the first 24h and tended to be stable from 24h to 72h after MCAO. The study shows that rhTrx-1 exerts an neuroprotective effect in cerebral ischemia injury. The anti-oxidative, anti-apoptotic and anti-inflammatory properties of rhTrx-1 are more likely to succeed as a therapeutic approach to diminish oxidative stress-induced neuronal apoptotic cell death in acute ischemic stroke.

  5. Preventive Antibacterial Therapy in Acute Ischemic Stroke: A Randomized Controlled Trial

    PubMed Central

    Klehmet, Juliane; Rogge, Witold; Drenckhahn, Christoph; Göhler, Jos; Bereswill, Stefan; Göbel, Ulf; Wernecke, Klaus Dieter; Wolf, Tilo; Arnold, Guy; Halle, Elke; Volk, Hans-Dieter; Dirnagl, Ulrich; Meisel, Andreas

    2008-01-01

    Background Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients. Methods Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance. Findings On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections. Interpretation PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the

  6. Alberta Stroke Program Early CT Score in the Prognostication after Endovascular Treatment for Ischemic Stroke: A Meta-analysis

    PubMed Central

    Shin, Hee Shup; Park, Soonchan; Suh, Sang Hyun; Koh, Jun Seok; Choi, Hye-Yeon

    2017-01-01

    Purpose The Alberta Stroke Program Early CT Score (ASPECTS) was devised to quantify the extent of early ischemic changes in the middle cerebral artery territory on brain CT. We performed a systematic review and meta-analysis of studies that presented clinical outcomes and baseline ASPECTS in ischemic stroke patients managed with endovascular methods to validate the use of ASPECTS for risk prognostication. Materials and Methods We searched the MEDLINE, EMBASE, and Cochran databases for observational or interventional studies that reported clinical outcomes and baseline ASPECTS in ischemic stroke patients treated with endovascular methods. Data were pooled to perform a meta-analysis for comparisons of clinical outcomes between high and low ASPECTS patients. Results A meta-analysis of 13 studies (six observational and seven interventional) revealed favorable outcomes (mRS sore 0-2 at 90 days) for high baseline ASPECTS (odds ratio=2.22; 95% CI: 1.74-2.86). Conclusion High ASPECTS is a predictor of favorable outcome after endovascular therapy for ischemic stroke. PMID:28316866

  7. Sitting occupations are an independent risk factor for Ischemic stroke in North Indian population.

    PubMed

    Kumar, A; Prasad, M; Kathuria, P

    2014-10-01

    Stroke is a multi-factorial disease and is influenced by complex environmental interactions. The purpose of this case-control study was to determine the relationship of sitting occupations with ischemic stroke in the North Indian population. In a hospital-based case-control study, age- and sex-matched controls were recruited from the outpatient department and the neurology ward of All India Institute of Medical Sciences, New Delhi. Occupation along with other demographic and risk factor variables was measured in-person interview in standardized case record form. The multivariate logistic regression model was used to estimate the odds ratio associated with ischemic stroke. Two hundred and twenty-four people post-stroke and 224 control participants were recruited from the period of February 2009 to February 2012. Mean age of cases and controls was 53.47 ± 14 and 52.92 ± 13.4, respectively. The occupations which involve sitting at work were independently associated with the risk of ischemic stroke after adjustment for demographic and risk factor variables (OR 2.2, 95% CI 1.12-3.8). The result of this study has shown an independent association between the sitting occupations and ischemic stroke in North Indian population. The present study supports the workplace health initiative to implement workplace physical activity policy and encourages employee to reduce the amount of time they spend sitting throughout the day.

  8. Ischemic Stroke in Young Adults and Preexisting Psychiatric Disorders: A Nationwide Case-Control Study.

    PubMed

    Chiu, Yu-Chuan; Bai, Ya-Mei; Su, Tung-Ping; Chen, Tzeng-Ji; Chen, Mu-Hong

    2015-09-01

    Previous studies showed that psychiatric disorders such as major depression, bipolar disorders, and alcohol misuse are associated with an increased risk of ischemic stroke. However, the link between psychiatric disorders and stroke in the young population is rarely investigated. Using the Taiwan National Health Insurance Research Database, 2063 young adults aged between 18 and 45 years with ischemic stroke and 8252 age- and sex-matched controls were enrolled in our study between 1998 and 2011. Participants who had preexisting psychiatric disorders were identified. After adjusting for preexisting physical disorders and demographic data, patients with ischemic stroke had an increased risk of having preexisting psychiatric disorders, including bipolar disorder (odds ratio [OR]: 2.23, 95% confidence interval [CI]: 1.06∼4.67), unipolar depression (OR: 2.15, 95% CI: 1.62∼2.86), anxiety disorders (OR: 2.63, 95% CI: 1.87∼3.69), and alcohol use disorders (OR: 2.86, 95% CI: 1.79∼4.57). Young ischemic stroke (age ≥30 years) was related to the risk of preexisting unipolar depression (OR: 1.49, 95% CI: 1.05∼2.11), anxiety disorders (OR: 1.99, 95% CI: 1.33∼2.97), and alcohol use disorders (OR: 2.54, 95% CI: 1.55∼4.14); very young stroke (age <30 years) was only associated with the risk of preexisting unipolar depression (OR: 4.15, 95% CI: 1.47∼11.72). Patients who had experienced ischemic stroke at age younger than 45 years had a higher risk of having pre-existing bipolar disorder, unipolar depression, anxiety disorders, and alcohol use disorders than those who did not after adjusting for demographic data and stroke-related medical comorbidities.

  9. Chronic metformin treatment improves post-stroke angiogenesis and recovery after experimental stroke

    PubMed Central

    Venna, Venugopal Reddy; Li, Jun; Hammond, Matthew D.; Mancini, Nickolas S.; McCullough, Louise D.

    2014-01-01

    Metformin is currently the first-line treatment drug for type 2 diabetes. Metformin is a well-known activator of AMP-activated protein kinase (AMPK). In experimental studies, metformin has been shown to exert direct vascular effects by increasing vascular endothelial growth factor expression and improving microvascular density. As stroke is the leading cause of long-term disability and angiogenesis is implicated as an important mechanism in functional recovery, we hypothesized that chronic metformin treatment would improve post-stroke functional recovery by enhancing functional microvascular density. For this study, C57BL/6N male mice were subjected to a 60-min middle cerebral artery occlusion, and were given 50 mg/kg/day metformin beginning 24 h post-stroke for 3 weeks. Behavioral recovery was assessed using adhesive-tape removal and the apomorphine-induced turning test. The role of angiogenesis was assessed by counting vessel branch points from fluorescein-conjugated lectin-perfused brain sections. Importantly even if metformin treatment was initiated 24 h after injury it enhanced recovery and significantly improved stroke-induced behavioral deficits. This recovery occurred in parallel with enhanced angiogenesis and with restoration of endogenous cerebral dopaminergic tone and revascularization of ischemic tissue. We assessed if the effects on recovery and angiogenesis were mediated by AMPK. When tested in AMPK α-2 knockout mice, we found that metformin treatment did not have the same beneficial effects on recovery and angiogenesis, suggesting that metformin-induced angiogenic effects are mediated by AMPK. The results from this study suggest that metformin mediates post-stroke recovery by enhancing angiogenesis, and these effects are mediated by AMPK signaling. PMID:24649970

  10. Deep vein thrombosis after ischemic stroke: rationale for a therapeutic trial

    SciTech Connect

    Bornstein, N.M.; Norris, J.W.

    1988-11-01

    Deep venous thrombosis (DVT) in the legs occurs in 23% to 75% of patients with acute ischemic stroke, and pulmonary embolism accounts for about 5% of deaths. New heparinoid substances, lacking the hazards of more established anticoagulants, raise the question of DVT prophylaxis for these patients. Two hundred fifty consecutive acute ischemic stroke patients were evaluated for the presence of DVT of the legs in a feasibility study for a trial of low-molecular-weight heparin prophylaxis. Forty-nine patients were found suitable for the study, of whom 11 (22.5%) developed DVT. All patients underwent clinical examination, I-125 fibrinogen leg scanning, and impedance plethysmography. Five patients were sufficiently alert and without serious neurologic deficits to justify DVT prophylaxis. Recent advances in noninvasive diagnostic techniques to detect DVT early and the development of relatively safe heparinoid compounds increase the need for a prophylactic study in patients with ischemic stroke.

  11. [Comparative aspects of using neuroprotectors in the management of patients with ischemic stroke].

    PubMed

    Ershov, V I

    2011-01-01

    Comparative efficacy of neuroprotective preparations: actovegin, cerebrolysin and ceraxon was studied in 73 patients in the most acute phase of ischemic stroke. A control group included 33 patients in the most acute phase of ischemic stroke who received only basic treatment without neuroprotectors. Patient's state was assessed with the NIHSS, the original scale of E.I. Gusev and V.I. Skvortsova and the Barthel index. Ceraxon in daily dosage 2 g and cerebrolysin in daily dosage 10 ml during 10 days after the development of ischemic stroke led to the significantly better regression of neurological symptoms to the 21st day of disease compared to the control group. Barthel index scores did not differ in the groups studied.

  12. Cost - effectiveness analysis of the antiplatelet treatment administered on ischemic stroke patients using goal programming approach

    NASA Astrophysics Data System (ADS)

    Rajendran, Rasvini; Zainuddin, Zaitul Marlizawati; Idris, Badrisyah

    2014-09-01

    There are numerous ways to prevent or treat ischemic stroke and each of these competing alternatives is associated with a different effectiveness and a cost. In circumstances where health funds are budgeted and thus fixed, cost-effectiveness analysis (CEA) can provide information on how to comprehend the largest health gains with that limited fund as CEA is used to compare different strategies for preventing or treating a single disease. The most common medications for ischemic stroke are the anti-platelet drugs. While some drugs are more effective than others, they are also more expensive. This paper will thus assess the CEA of anti-platelet drug available for ischemic stroke patients using goal programming (GP) approach subject to in-patients days and patients' quality-of-life. GP presents a way of striving towards several objectives simultaneously whereby in this case we will consider minimizing the cost and maximizing the effectiveness.

  13. Acute ischemic stroke after cardiac catheterization: the protamine low-dose recombinant tissue plasminogen activator pathway.

    PubMed

    Guevara, Carlos; Quijada, Alonso; Rosas, Carolina; Bulatova, Katya; Lara, Hugo; Nieto, Elena; Morales, Marcelo

    2016-05-20

    Intravenous thrombolysis is the preferred treatment for acute ischemic stroke; however, it remains unestablished in the area of cardiac catheterization. We report three patients with acute ischemic stroke after cardiac catheterization. After reversing the anticoagulant effect of unfractionated heparin with protamine, all of the patients were successfully off-label thrombolyzed with reduced doses of intravenous recombinant tissue plasminogen activator (0.6 mg/kg). This dose was preferred to reduce the risk of symptomatic cerebral or systemic bleeding. The sequential pathway of protamine recombinant tissue plasminogen activator at reduced doses may be safer for reducing intracranial or systemic bleeding events, whereas remaining efficacious for the treatment of acute ischemic stroke after cardiac catheterization.

  14. Current recommendations for endovascular interventions in the treatment of ischemic stroke.

    PubMed

    Appelboom, Geoffrey; Strozyk, Dorothea; Meyers, Philip M; Higashida, Randall T

    2010-07-01

    Ischemic stroke remains one of the leading cause of adult death and disability in the United States. Reperfusion of the occluded vessel is the standard of care in the setting of acute ischemic stroke according to established guidelines. Since the introduction of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in the late 1990s, significant advances have been made in methods to deliver thrombolytic agents and in devices for mechanical recanalization of occluded vessels. Furthermore, improvements in patient selection contribute to achievement of good clinical outcomes after endovascular therapy. This article summarizes findings from recent clinical trials and presents evidence-based guidelines for endovascular interventions in the treatment of ischemic stroke.

  15. Forced Arterial Suction Thrombectomy Using Distal Access Catheter in Acute Ischemic Stroke

    PubMed Central

    Lee, Ho-Cheol; Kang, Dong-Hun; Hwang, Yang-Ha; Kim, Yong-Sun

    2017-01-01

    Historical innovations in mechanical thrombectomy devices and strategies for ischemic stroke have resulted in improved angiographic outcomes and better clinical outcomes. Various devices have been used, but the two most common approaches are aspiration thrombectomy and stent-retrieval thrombectomy. Aspiration thrombectomy has advanced from the traditional Penumbra system to forced arterial suction thrombectomy and a direct aspiration first-pass technique. Newer generation aspiration catheters with flexible distal tips and a larger bore have demonstrated faster and better recanalization relative to older devices. Recently, several species of distal access catheters have similar structural characteristics to the Penumbra reperfusion catheter. Therefore, we used the distal access catheter for forced arterial suction thrombectomy in three patients with acute ischemic stroke. In each case, we achieved fast and complete recanalization without significant complications. Forced arterial suction thrombectomy using a distal access catheter might provide another option for mechanical thrombectomy in patients with acute ischemic stroke. PMID:28316869

  16. [Effect of low frequency magnetic fields used in magnetotherapy and magnetostimulation on the rehabilitation results of patients after ischemic stroke].

    PubMed

    Woldańska-Okońska, Marta; Czernicki, Jan

    2007-01-01

    New methods of rehabilitation should be introduced in order to reduce disability resulting from stroke. During the twelve months of follow-up, effect of low frequency magnetic field (If mf) on the course of patient rehabilitation following ischemic stroke was evaluated on in-patient (acute and subacute period of the stroke) and outpatient (chronic period) basis with the use of Mathew et al's and Barthel's scales. Lf mf (20 procedures of 20-min. duration) of magnetotherapy (I group--placebo, II--group 5.6 mT induction, 10 Hz frequency and sinusoidal shape, III group--2.8 mT induction, 10 Hz frequency and sinusoidal shape) and magnetostimulation (IV group--M1P1 program of Viofor JPS system, 16 min a day) was applied as early as in the subacute period of the stroke (1-8 weeks). The data obtained were presented in the form of percentage changes in the pain levels as well as in the form of the arithmetical mean and standard deviation (X +/- SD). The ANOVA test was used for a statistical evaluation of the data obtained in the tests. The results obtained indicate beneficial effects of If mf in the III and IV group of patients in the Barthel's scale and Mathew scale, which were observed during the examination 12 months after the stroke. The recommended doses of If mf seem to be adequate to obtain therapeutic effects and may be used in the early period of rehabilitation. The neurological and functional improvement persisted for a long-period of the out-patient treatment, which was confirmed during the control examination 12 months after the ischemic stroke. As no adverse effects (which could be attributed to If mf), were observed, this method of physical therapy can be recognized as a safe one and worth making popular in clinical practice.

  17. Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models.

    PubMed

    Nathaniel, Thomas I; Williams-Hernandez, Ashley; Hunter, Anan L; Liddy, Caroline; Peffley, Dennis M; Umesiri, Francis E; Imeh-Nathaniel, Adebobola

    2015-05-01

    The treatment and prevention of hypoxic/ischemic brain injury in stroke patients remain a severe and global medical issue. Numerous clinical studies have resulted in a failure to develop chemical neuroprotection for acute, ischemic stroke. Over 150 estimated clinical trials of ischemic stroke treatments have been done, and more than 200 drugs and combinations of drugs for ischemic and hemorrhagic strokes have been developed. Billions of dollars have been invested for new scientific breakthroughs with only limited success. The revascularization of occluded cerebral arteries such as anti-clot treatments of thrombolysis has proven effective, but it can only be used in a 3-4.5h time frame after the onset of a stroke, and not for every patient. This review is about novel insights on how to resist tissue hypoxia from unconventional animal models. Ability to resist tissue hypoxia is an extraordinary ability that is not common in many laboratory animals such as rat and mouse models. For example, we can learn from a naked mole-rat, Chrysemys picta, how to actively regulate brain metabolic activity to defend the brain against fluctuating oxygen tension and acute bouts of oxidative stress following the onset of a stroke. Additionally, a euthermic arctic ground squirrel can teach us how the brain of a stroke patient can remain well oxygenated during tissue hypoxia with no evidence of cellular stress. In this review, we discuss how these animals provide us with a system to gain insight into the possible mechanisms of tissue hypoxia/ischemia. This issue is of clinical significance to stroke patients. We describe specific physiological and molecular adaptations employed by different animals' models of hypoxia tolerance in aquatic and terrestrial environments. We highlight how these adaptations might provide potential clues on strategies to adapt for the clinical management of tissue hypoxia during conditions such as stroke where oxygen demand fails to match the supply.

  18. [Analysis of a disturbance of trace element balance in patients with ischemic stroke with arterial hypertension].

    PubMed

    Kuramshina, D B; Novikova, L B; Nikonov, A A; Torshin, I Iu; Gromova, O A

    2012-01-01

    Disturbance of trace element balance increases the risk of cerebrovascular disease and, above all, ischemic stroke (IS). A comparative analysis of clinical and demographic parameters and trace element composition of hair was performed in the group of 30 ischemic stroke patients with arterial hypertension (AH) and 30 stroke patients without hypertension (mean age 55±7 years). The stroke patients with hypertension were characterized by the elevated body mass index (28.5±4.1 kg/m2, AI, 26.0±2.9 kg/m2, p=0.006), higher incidence of coronary heart disease (p=0.04). Alcohol consumption more than 3 drinks a week was associated with a 5-fold increase of the risk of stroke with hypertension (95% CI 1.0-27, p=0.035). The results revealed a number of statistically significant differences in trace element profile in the studied groups of patients: deficits of essential magnesium, manganese, cobalt, copper, zinc, a statistically significant increase in sodium levels, toxic and conditionally toxic trace elements (cadmium, mercury, bismuth, barium, etc.). One of the probable factors that lead to the accumulation of toxic trace elements in stroke patients is the increased consumption of alcohol including that of substandard quality. The data obtained also show the feasibility of implementing screening programs to assess micronutrient status (including trace elements) for early detection of pathological abnormalities in the elemental homeostasis that might lead to an increased risk of ischemic stroke and hypertension.

  19. Metabolic syndrome, platelet activation and the development of transient ischemic attack or thromboembolic stroke.

    PubMed

    van Rooy, Mia-Jeanne; Pretorius, Etheresia

    2015-03-01

    Stroke is the second most common cause of mortality in the world today, where transient ischemic attack (TIA) is a period of focal ischemia, the symptoms of which resemble a thromboembolic stroke. Contrary to stroke, TIA symptoms typically last less than one hour and necrosis is absent. Stroke is often preceded by TIA, making it an important predictor of future ischemic events. The causal role of atherosclerosis in the development of TIA is well established, however, research indicates that the atherosclerotic process begins years earlier with the development of metabolic syndrome, which affects approximately 45% of the adult population worldwide. Metabolic syndrome is present if three or more of the following is present: increased waist circumference, increased triglycerides, decreased HDL, increased fasting glucose and hypertension. This syndrome causes systemic inflammation that activates the coagulation system and may cause the formation of pathological thrombi. The role of platelets in stroke has been studied and platelet activation pathways identified. ADP and thromboxane A(2) are the most common activators of platelets in normal physiology. Several pharmacological treatments have been employed to prevent the activation of platelets, the most common of which include aspirin and P2Y(12)-inhibitors. Although treatment is administered strokes and subsequent TIAs are very common in individuals that suffered an initial event. This indicates that research needs to be done in order to elucidate new therapeutic targets, but also to better treat ischemic events to not only decrease the amount of recurring events but also decrease stroke mortality worldwide.

  20. 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

  1. Engineering triiodothyronine (T3) nanoparticle for use in ischemic brain stroke.

    PubMed

    Mdzinarishvili, Alexander; Sutariya, Vijaykumar; Talasila, Phani K; Geldenhuys, Werner J; Sadana, Prabodh

    2013-08-01

    A potential means of pharmacological management of ischemic stroke is rapid intervention using potent neuroprotective agents. Thyroid hormone (T3) has been shown to protect against ischemic damage in middle cerebral artery occlusion (MCAO) model of ischemic brain stroke. While thyroid hormone is permeable across the blood-brain barrier, we hypothesized that efficacy of thyroid hormone in ischemic brain stroke can be enhanced by encapsulation in nanoparticulate delivery vehicles. We tested our hypothesis by generating poly-(lactide-co-glycolide)-polyethyleneglycol (PLGA-b-PEG) nanoparticles that are either coated with glutathione or are not coated. We have previously reported that glutathione coating of PLGA-PEG nanoparticles is an efficient means of brain targeted drug delivery. Encapsulation of T3 in PLGA-PEG delivery vehicle resulted in particles that were in the nano range and exhibited a zeta potential of -6.51 mV (uncoated) or -1.70 mV (coated). We observed that both glutathione-coated and uncoated nanoparticles are taken up in cells wherein they stimulated the expression of thyroid hormone response element driven reporter robustly. In MCAO model of ischemic stroke, significant benefit of administering T3 in nanoparticulate form was observed over injection of a T3 solution. A 34 % decrease in tissue infarction and a 59 % decrease in brain edema were seen upon administration of T3 solution in MCAO stroke model. Corresponding measurements for uncoated T3 nanoparticles were 51 % and 68 %, whereas for the glutathione coated were 58 % and 75 %. Our study demonstrates that using nanoparticle formulations can significantly improve the efficacy of neuroprotective drugs in ischemic brain stroke.

  2. Differentiating the effects of characteristics of PM pollution on mortality from ischemic and hemorrhagic strokes.

    PubMed

    Lin, Hualiang; Tao, Jun; Du, Yaodong; Liu, Tao; Qian, Zhengmin; Tian, Linwei; Di, Qian; Zeng, Weilin; Xiao, Jianpeng; Guo, Lingchuan; Li, Xing; Xu, Yanjun; Ma, Wenjun

    2016-03-01

    Though increasing evidence supports significant association between particulate matter (PM) air pollution and stroke, it remains unclear what characteristics, such as particle size and chemical constituents, are responsible for this association. A time-series model with quasi-Poisson function was applied to assess the association of PM pollution with different particle sizes and chemical constituents with mortalities from ischemic and hemorrhagic strokes in Guangzhou, China, we controlled for potential confounding factors in the model, such as temporal trends, day of the week, public holidays, meteorological factors and influenza epidemic. We found significant association between stroke mortality and various PM fractions, such as PM10, PM2.5 and PM1, with generally larger magnitudes for smaller particles. For the PM2.5 chemical constituents, we found that organic carbon (OC), elemental carbon (EC), sulfate, nitrate and ammonium were significantly associated with stroke mortality. The analysis for specific types of stroke suggested that it was hemorrhagic stroke, rather than ischemic stroke, that was significantly associated with PM pollution. Our study shows that various PM pollution fractions are associated with stroke mortality, and constituents primarily from combustion and secondary aerosols might be the harmful components of PM2.5 in Guangzhou, and this study suggests that PM pollution is more relevant to hemorrhagic stroke in the study area, however, more studies are warranted due to the underlying limitations of this study.

  3. Pathophysiology, treatment, and animal and cellular models of human ischemic stroke

    PubMed Central

    2011-01-01

    Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to

  4. Complex Roles of Microglial Cells in Ischemic Stroke Pathobiology: New Insights and Future Directions

    PubMed Central

    Guruswamy, Revathy; ElAli, Ayman

    2017-01-01

    Ischemic stroke constitutes the major cause of death and disability in the industrialized world. The interest in microglia arose from the evidence outlining the role of neuroinflammation in ischemic stroke pathobiology. Microglia constitute the powerhouse of innate immunity in the brain. Microglial cells are highly ramified, and use these ramifications as sentinels to detect changes in brain homeostasis. Once a danger signal is recognized, cells become activated and mount specialized responses that range from eliminating cell debris to secreting inflammatory signals and trophic factors. Originally, it was suggested that microglia play essentially a detrimental role in ischemic stroke. However, recent reports are providing evidence that the role of these cells is more complex than what was originally thought. Although these cells play detrimental role in the acute phase, they are required for tissue regeneration in the post-acute phases. This complex role of microglia in ischemic stroke pathobiology constitutes a major challenge for the development of efficient immunomodulatory therapies. This review aims at providing an overview regarding the role of resident microglia and peripherally recruited macrophages in ischemic pathobiology. Furthermore, the review will highlight future directions towards the development of novel fine-tuning immunomodulatory therapeutic interventions. PMID:28245599

  5. Management of ischemic stroke in Central and Eastern Europe.

    PubMed

    Budincevic, Hrvoje; Tiu, Cristina; Bereczki, Daniel; Kõrv, Janika; Tsiskaridze, Alexander; Niederkorn, Kurt; Czlonkowska, Anna; Demarin, Vida

    2015-10-01

    Stroke is one of the leading causes of disability in Europe. Central and Eastern European countries have the highest incidence and mortality rates through Europe. The improvements in stroke prevention and treatment in Central and Eastern European countries did not completely reach the quality parameters present in Western European countries. We present features of current management of stroke in Central and Eastern European countries.

  6. Atrial myxoma: a rare cause of ischemic stroke.

    PubMed

    Negi, R C; Chauhan, Vivek; Sharma, Brij; Bhardwaj, Rajeev; Thakur, Surinder

    2013-04-01

    Arial myxoma can present as stroke and should be considered as a differential diagnosis of stroke in young individuals. We present here a 42 years female who presented with sudden loss of conciousness. After extensive work up for young stroke, left atrial myxoma was detected and tumor was removed surgically and histopathological report was consistent with the atrial myxoma.

  7. Association of TOMM40 and SLC22A4 polymorphisms with ischemic stroke

    PubMed Central

    YAMASE, YUICHIRO; HORIBE, HIDEKI; UEYAMA, CHIKARA; FUJIMAKI, TETSUO; OGURI, MITSUTOSHI; KATO, KIMIHIKO; ARAI, MASAZUMI; WATANABE, SACHIRO; YAMADA, YOSHIJI

    2015-01-01

    Recent genome-wide association studies (GWASs) and their meta-analyses have identified various genes and loci underlying the predisposition to ischemic stroke or coronary artery disease in Caucasian populations. Given that ischemic stroke and coronary artery disease may have a shared genetic architecture, certain polymorphisms may confer genetic susceptibility to these two diseases. The aim of the present study was to examine the possible association of ischemic stroke with 29 single-nucleotide polymorphisms (SNPs) previously identified by the meta-analyses of GWASs as susceptibility loci for coronary artery disease. The study population comprised 3,187 Japanese individuals, including 894 subjects with ischemic stroke and 2,293 controls. The genotypes for the 29 SNPs of the 28 genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ2 test between subjects with ischemic stroke and controls revealed that rs9319428 (G→A) of the fms-related tyrosine kinase 1 gene (P=0.0471), rs2075650 (G→A) of the translocase of outer mitochondrial membrane 40 homolog gene (TOMM40, P=0.0102) and rs273909 (T→C) of the solute carrier family 22, member 4 gene (SLC22A4, P=0.0097) were significantly (P<0.05) associated with the prevalence of ischemic stroke. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, smoking status and the prevalence of hypertension, diabetes mellitus and dyslipidemia revealed that rs2075650 of TOMM40 (P=0.0443; recessive model; odds ratio=0.50) and rs273909 of SLC22A4 (P=0.0123; dominant model; odds ratio=0.45) were significantly associated with ischemic stroke with the minor G and C allele, respectively, being protective against this condition. TOMM40 and SLC22A4 may thus be susceptibility loci for ischemic stroke in Japanese individuals. PMID:26171154

  8. 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.

  9. Fibrinogen nitrotyrosination after ischemic stroke impairs thrombolysis and promotes neuronal death.

    PubMed

    Ill-Raga, Gerard; Palomer, Ernest; Ramos-Fernández, Eva; Guix, Francesc X; Bosch-Morató, Mònica; Guivernau, Biuse; Tajes, Marta; Valls-Comamala, Victòria; Jiménez-Conde, Jordi; Ois, Angel; Pérez-Asensio, Fernando; Reyes-Navarro, Mario; Caballo, Carolina; Gil-Gómez, Gabriel; Lopez-Vilchez, Irene; Galan, Ana M; Alameda, Francesc; Escolar, Gines; Opazo, Carlos; Planas, Anna M; Roquer, Jaume; Valverde, Miguel A; Muñoz, Francisco J

    2015-03-01

    Ischemic stroke is an acute vascular event that compromises neuronal viability, and identification of the pathophysiological mechanisms is critical for its correct management. Ischemia produces increased nitric oxide synthesis to recover blood flow but also induces a free radical burst. Nitric oxide and superoxide anion react to generate peroxynitrite that nitrates tyrosines. We found that fibrinogen nitrotyrosination was detected in plasma after the initiation of ischemic stroke in human patients. Electron microscopy and protein intrinsic fluorescence showed that in vitro nitrotyrosination of fibrinogen affected its structure. Thromboelastography showed that initially fibrinogen nitrotyrosination retarded clot formation but later made the clot more resistant to fibrinolysis. This result was independent of any effect on thrombin production. Immunofluorescence analysis of affected human brain areas also showed that both fibrinogen and nitrotyrosinated fibrinogen spread into the brain parenchyma after ischemic stroke. Therefore, we assayed the toxicity of fibrinogen and nitrotyrosinated fibrinogen in a human neuroblastoma cell line. For that purpose we measured the activity of caspase-3, a key enzyme in the apoptotic pathway, and cell survival. We found that nitrotyrosinated fibrinogen induced higher activation of caspase 3. Accordingly, cell survival assays showed a more neurotoxic effect of nitrotyrosinated fibrinogen at all concentrations tested. In summary, nitrotyrosinated fibrinogen would be of pathophysiological interest in ischemic stroke due to both its impact on hemostasis - it impairs thrombolysis, the main target in stroke treatments - and its neurotoxicity that would contribute to the death of the brain tissue surrounding the infarcted area.

  10. Next-generation antithrombotics in ischemic stroke: preclinical perspective on ‘bleeding-free antithrombosis'

    PubMed Central

    Kraft, Peter; De Meyer, Simon F; Kleinschnitz, Christoph

    2012-01-01

    The present antithrombotic drugs used to treat or prevent ischemic stroke have significant limitations: either they show only moderate efficacy (platelet inhibitors), or they significantly increase the risk for hemorrhages (thrombolytics, anticoagulants). Although most strokes are caused by thrombotic or embolic vessel occlusions, the pathophysiological role of platelets and coagulation is largely unclear. The introduction of novel transgenic mouse models and specific coagulation inhibitors facilitated a detailed analysis of molecular pathways mediating thrombus formation in models of acute ischemic stroke. Prevention of early platelet adhesion to the damaged vessel wall by blocking platelet surface receptors glycoprotein Ib alpha (GPIbα) or glycoprotein VI (GPVI) protects from stroke without provoking bleeding complications. In addition, downstream signaling of GPIbα and GPVI has a key role in platelet calcium homeostasis and activation. Finally, the intrinsic coagulation cascade, activated by coagulation factor XII (FXII), has only recently been identified as another important mediator of thrombosis in cerebrovascular disease, thereby disproving established concepts. This review summarizes the latest insights into the pathophysiology of thrombus formation in the ischemic brain. Potential clinical merits of novel platelet inhibitors and anticoagulants as powerful and safe tools to combat ischemic stroke are discussed. PMID:22805877

  11. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study

    PubMed Central

    Timm, Fanny P; Houle, Timothy T; Grabitz, Stephanie D; Lihn, Anne-Louise; Stokholm, Janne B; Eikermann-Haerter, Katharina; Nozari, Ala; Kurth, Tobias

    2017-01-01

    Objective To evaluate whether patients with migraine are at increased risk of perioperative ischemic stroke and whether this may lead to an increased hospital readmission rate. Design Prospective hospital registry study. Setting Massachusetts General Hospital and two satellite campuses between January 2007 and August 2014. Participants 124 558 surgical patients (mean age 52.6 years; 54.5% women). Main outcome measures The primary outcome was perioperative ischemic stroke occurring within 30 days after surgery in patients with and without migraine and migraine aura. The secondary outcome was hospital readmission within 30 days of surgery. Exploratory outcomes included post-discharge stroke and strata of neuroanatomical stroke location. Results 10 179 (8.2%) patients had any migraine diagnosis, of whom 1278 (12.6%) had migraine with aura and 8901 (87.4%) had migraine without aura. 771 (0.6%) perioperative ischemic strokes occurred within 30 days of surgery. Patients with migraine were at increased risk of perioperative ischemic stroke (adjusted odds ratio 1.75, 95% confidence interval 1.39 to 2.21) compared with patients without migraine. The risk was higher in patients with migraine with aura (adjusted odds ratio 2.61, 1.59 to 4.29) than in those with migraine without aura (1.62, 1.26 to 2.09). The predicted absolute risk is 2.4 (2.1 to 2.8) perioperative ischemic strokes for every 1000 surgical patients. This increases to 4.3 (3.2 to 5.3) for every 1000 patients with any migraine diagnosis, 3.9 (2.9 to 5.0) for migraine without aura, and 6.3 (3.2 to 9.5) for migraine with aura.Patients with migraine had a higher rate of readmission to hospital within 30 days of discharge (adjusted odds ratio 1.31, 1.22 to 1.41). Conclusions Surgical patients with a history of migraine are at increased risk of perioperative ischemic stroke and have an increased 30 day hospital readmission rate. Migraine should be considered in the risk assessment for perioperative

  12. Absolute and Relative Contraindications to IV rt-PA for Acute Ischemic Stroke

    PubMed Central

    Rabinstein, Alejandro A.

    2015-01-01

    Most of the contraindications to the administration of intravenous (IV) recombinant tissue plasminogen activator (rtPA) originated as exclusion criteria in major stroke trials. These were derived from expert consensus for the National Institute of Neurological Disorders and Stroke (NINDS) trial. Despite the fact that the safety and efficacy of IV rtPA has been repeatedly confirmed in large international observational studies over the past 20 years, most patients with acute ischemic stroke disappointingly still do not receive thrombolytic treatment. Some of the original exclusion criteria have proven to be unnecessarily restrictive in real-world clinical practice. It has been suggested that application of relaxed exclusion criteria might increase the IV thrombolysis rate up to 20% with comparable outcomes to thrombolysis with more conventional criteria. We review the absolute and relative contraindications to IV rtPA for acute ischemic stroke, discussing the underlying rationale and evidence supporting these exclusion criteria. PMID:26288669

  13. 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.

  14. Successful Intra-Arterial Thrombolysis for Acute Ischemic Stroke in the Immediate Postpartum Period: Case Report

    SciTech Connect

    Mendez, Jose C. Masjuan, J.; Garcia, N.; Lecinana, M. de

    2008-01-15

    Stroke in pregnancy and the puerperium is a rare but potentially devastating event. We present the case of a previously healthy woman who underwent a cesarean delivery and experienced a middle cerebral artery thrombosis in the immediate postpartum period that was subsequently lysed with intra-arterial urokinase. The patient made a complete neurologic recovery. To the best of our knowledge, this is the first reported case of successful intra-arterial thrombolysis for ischemic stroke in the postpartum period.

  15. [The experience with endolumbar application of cerebrolysin in hemispheric ischemic stroke].

    PubMed

    Vilenskiĭ, B S; Odinak, M M; Shirokov, E A; Vozniuk, I A; Semenova, G M; Grinevich, T V

    2000-01-01

    The purpose of the investigation was to evaluate the efficiency of therapy of patients with hemispheric ischemic stroke with cerebrolysin (C) (using two different regimens of its injections) versus placebo. One endolumbar C injection (5 ml) made in the first 12 hours of stroke and after the subsequent therapy with dropwise C injections (10 ml) significantly enhanced the efficiency of therapy and improved the functional recovery of patients was observed 12 hours following.

  16. The Association of Lesion Location and Sleep Related Breathing Disorder in Patients with Acute Ischemic Stroke

    PubMed Central

    Teuber, Anja; Wersching, Heike; Young, Peter; Dittrich, Ralf; Ritter, Martin; Dziewas, Rainer; Minnerup, Jens

    2017-01-01

    Background and aims Sleep related breathing disorders (SRBD) are common in patients with ischemic stroke and are associated with poor outcome. SRBD after stroke were assumed to be a direct consequence of injury of specific central nervous system structures. However, whether specific locations of ischemic infarcts cause SRBD is yet unknown. We therefore investigated the association of ischemic lesion location with SRBD. Methods Patients with acute ischemic stroke treated on our stroke unit were included in a prospective observational study. All patients underwent magnetic resonance imaging (MRI) and polygraphy in the acute phase after stroke. SRBD was defined by an apnea—hypopnea index (AHI) ≥10. MRI were evaluated using standardized maps to depict voxel-wise probability distribution of infarction for patients with and without SRBD. Groups were compared using logistic regression analysis. Results Of 142 patients included, 86 (59%) had a SRBD. Age, body mass index and prevalence of arterial hypertension were significantly higher in patients with SRBD. There was no statistically significant association between any lesion location and SRBD. Conclusion We found no association of lesion location and SRBD in stroke patients, whereas established risk factors for SRBD, known from general population, were significantly associated with SRBD. Given the high prevalence of SRBD in stroke patients, these findings suggest that cerebral ischemia facilitates the occurrence of SRBD in patients with pre-existing risk factors rather than causing it by damaging specific central nervous system structures. Our findings can be used to identify stroke patients who might benefit from polygraphy screening. PMID:28135315

  17. The Role of Ethnicity, Sex and Language on Delay to Hospital Arrival for Acute Ischemic Stroke

    PubMed Central

    Smith, Melinda A.; Lisabeth, Lynda D.; Bonikowski, Frank; Morgenstern, Lewis B.

    2010-01-01

    Background and Purpose Use of emergency medical services (EMS) has been shown to decrease transport and triage times for stroke. Mexican Americans and women experience a large stroke burden. The objective of this study was to compare time to hospital arrival and EMS use for stroke care by ethnicity, sex and language preference among Mexican American and non-Hispanic white ischemic stroke patients. Methods The Brain Attack Surveillance in Corpus Christi (BASIC) project is a population-based study in South Texas. All stroke cases were identified by active or passive surveillance and validated by neurologists. Logistic regression models assessing time to hospital arrival and EMS use were analyzed. Results There were 1,134 ischemic stroke cases ascertained between January 1, 2000 and December 31, 2006. Mexican Americans were less likely than non-Hispanic whites to arrive by EMS (OR: 0.6, 95% CI 0.4, 0.8). Men were more likely than women to present to the hospital within 3 hours (OR: 0.7, 95% CI 0.5, 0.9); language was not associated with study outcomes. Conclusions Sex and ethnic differences in hospital presentation were found in this community. There is a need to promote an urgent response to stroke symptoms, especially in groups that experience the greatest stroke burden. PMID:20339124

  18. Antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke: a critical review.

    PubMed

    O'Donnell, Martin J; Hankey, Graeme J; Eikelboom, John W

    2008-05-01

    For patients with ischemic stroke or transient ischemic attack caused by atherothromboembolism, immediate and long-term aspirin reduces the relative risk of recurrent stroke, MI, and death attributable to vascular causes. Oral anticoagulation is not more effective than aspirin. Long-term clopidogrel reduces the relative risk of stroke, MI, or vascular death by about 9% (0.3% to 16.5%) compared with aspirin. Any long-term benefits of clopidogrel combined with aspirin, compared with aspirin or clopidogrel alone, appear to be offset by increased major bleeding. The combination of aspirin and extended-release dipyridamole reduces the relative odds of stroke, MI, or vascular death by about 18% (odds ratio 0.82, 0.74 to 0.91) compared with aspirin alone without causing more bleeding. Cilostazole reduces the risk of stroke, MI, or vascular death by 39% compared to placebo. A large clinical trial comparing clopidogrel with the combination of aspirin and dipyridamole, in >20 000 patients with recent (<120 days) atherothrombotic ischemic stroke, is expected to report in 2008. Emerging antiplatelet therapies presently being evaluated for secondary prevention of atherothromboembolism include other P(2)Y(12) ADP receptor antagonists (prasugrel, cangrelor, AZD 6140), thromboxane receptor antagonists (eg, S18886 - terutroban), and thrombin receptor (PAR-1) antagonists (eg, SCH530348).

  19. Why emergency XeCT-CBF should become routine in acute ischemic stroke before thrombolytic therapy.

    PubMed

    Meyer, J S; Rauch, G M

    2000-02-01

    Intravenous thrombolytic therapy using recombinant tissue plasminogen activator (rtpa) has been approved for the treatment of acute ischemic stroke in the USA, if treatment is initiated within 3-hours (NINDS tpa Stroke Study Group) but not 6 hours (ECASS II) after time of onset. Favorable outcome in the placebo arm was much higher than expected possibly because patients with TIA's are likely to be included as progressive ischemic stroke subjects when a brief 3-6 hours duration of stroke is defined as the therapeutic window. Yonas' group at the University of Pittsburg demonstrated that adding stable xenon inhalation to routine CT scanning performed during emergency screening of acute stroke, predicted which cases became irreversibly infarcted if thrombolytic therapy was not administered within a few hours of stroke onset, since non-contrasted CT scans are usually normal this early. Adding a few minutes for inhalation of 26% xenon is justified in order to measure LCBF values which predict size, severity and volumes of impending cerebral infarctions and rule out TIA's which have relatively normal CT-CBF values. CT-CBF measures provide positive indications for thrombolytic therapy. This is not possible by MRI and SPECT methods which are not sufficiently quantitative to discern LCBF values persistently below ischemic thresholds of 16 mls/100 gm/min, thereby predicting impending infarction.

  20. Homocysteine, heat shock proteins, genistein and vitamins in ischemic stroke--pathogenic and therapeutic implications.

    PubMed

    Banecka-Majkutewicz, Zyta; Sawuła, Wojciech; Kadziński, Leszek; Węgrzyn, Alicja; Banecki, Bogdan

    2012-01-01

    Stroke is one of the most devastating neurological conditions, with an approximate worldwide mortality of 5.5 million annually and loss of 44 million disability-adjusted life-years. The etiology of stroke is often unknown; it has been estimated that the etiology and pathophysiology remains unexplained in more than 40% of stroke cases. The conventional stroke risk factors, including hypertension, diabetes mellitus, smoking, and cardiac diseases, do not fully account for the risk of stroke, and stroke victims, especially young subjects, often do not have any of these factors. It is very likely that inflammation, specific genetic predispositions and traditional risk factors interact with each other and may together increase the risk of stroke. Inflammatory and immune responses play important roles in the course of ischemic stroke. Hyperhomocysteinemia (hcy) is considered a modifiable risk factor for stroke, possibly through an atherogenic and prothrombotic mechanism. Both genetic and environmental factors (e.g., dietary intake of folic acid and B vitamins) affect homocysteine level. Identification of the role of hcy as a modifiable risk factor for stroke and of HSPs as regulators of the immune response may lead to more effective prevention and treatment of stroke through dietary and pharmacological intervention. Dietary modification may also include supplementation with novel preventive compounds, such as the antioxidative isoflavones--genistein or daidzein.

  1. A Low Baseline Glomerular Filtration Rate Predicts Poor Clinical Outcome at 3 Months after Acute Ischemic Stroke

    PubMed Central

    Kim, Hyung Jik; Kim, Jwa-Kyung; Oh, Mi Sun; Kim, Sung Gyun; Yu, Kyung-Ho

    2015-01-01

    Background and Purpose Chronic kidney disease (CKD) is an established risk factor for numerous cardiovascular diseases including stroke. The relationship between the baseline estimated glomerular filtration rate (eGFR) and clinical 3-month outcomes in patients with acute ischemic stroke were evaluated in this study. Methods This was a prospective cohort study involving a hospital-based stroke registry; 1373 patients with acute ischemic stroke were enrolled. Patients were divided into the following four groups according their eGFR (calculated using the CKD Epidemiology Collaboration equations): ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. The primary endpoint of poor functional outcome was defined as 3-month death or dependency (modified Rankin Scale score ≥3); secondary endpoints were neurological deterioration (increase in National Institutes of Health Stroke Severity score of ≥4 at discharge compared to baseline) during hospitalization and in-hospital mortality. Results The overall eGFR was 84.5±20.8 mL/min/1.73 m2 (mean±SD). The distribution of baseline renal impairment was as follows: 1,218, 82, 40, and 33 patients had eGFRs of ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. At 3 months after the stroke, 476 (34.7%) patients exhibited poor functional outcome. Furthermore, a poor functional outcome occurred more frequently with increasingly advanced stages of CKD (rates of 31.9%, 53.7%, 55.0%, and 63.6% for CKD stages 1/2, 3a, 3b, and 4/5, respectively; p<0.001). Multivariate analysis revealed that a baseline eGFR of <30 mL/min/1.73m2 increased the risk of a poor functional outcome by 2.37-fold (p=0.047). In addition, baseline renal dysfunction was closely associated with neurological deterioration during hospitalization and with in-hospital mortality. Conclusions A low baseline eGFR was strongly predictive of both poor functional outcome at 3 months after ischemic stroke and neurological deterioration/mortality during hospitalization. PMID

  2. Detailed Analysis of Gene Polymorphisms Associated with Ischemic Stroke in South Asians

    PubMed Central

    Yadav, Sunaina; Hasan, Nazeeha; Marjot, Thomas; Khan, Muhammad S.; Prasad, Kameshwar; Bentley, Paul; Sharma, Pankaj

    2013-01-01

    The burden of stroke is disproportionately high in the South Asian subcontinent with South Asian ethnicity conferring a greater risk of ischemic stroke than European ancestry regardless of country inhabited. While genes associated with stroke in European populations have been investigated, they remain largely unknown in South Asians. We conducted a comprehensive meta-analysis of known genetic polymorphisms associated with South Asian ischemic stroke, and compared effect size of the MTHFR C677T-stroke association with effect sizes predicted from homocysteine-stroke association. Electronic databases were searched up to August 2012 for published case control studies investigating genetic polymorphisms associated with ischemic stroke in South Asians. Pooled odds ratios (OR) for each gene-disease association were calculated using a random-effects model. We identified 26 studies (approximately 2529 stroke cases and 2881 controls) interrogating 33 independent genetic polymorphisms in 22 genes. Ten studies described MTHFR C677T (108 with TT genotype and 2018 with CC genotype) -homocysteine relationship and six studies (735 stroke cases and 713 controls) described homocysteine-ischemic stroke relationship. Risk association ORs were calculated for ACE I/D (OR 5.00; 95% CI, 1.17–21.37; p = 0.03), PDE4D SNP 83 (OR 2.20; 95% CI 1.21–3.99; p = 0.01), PDE4D SNP 32 (OR 1.57; 95% CI 1.01–2.45, p = 0.045) and IL10 G1082A (OR 1.44; 95% CI, 1.09–1.91, p = 0.01). Significant association was observed between elevated plasma homocysteine levels and MTHFR/677 TT genotypes in healthy South Asians (Mean difference (ΔX) 5.18 µmol/L; 95% CI 2.03–8.34: p = 0.001). Our results demonstrate that the genetic etiology of ischemic stroke in South Asians is broadly similar to the risk conferred in Europeans, although the dataset is considerably smaller and warrants the same clinical considerations for risk profiling. PMID:23505425

  3. Relationship between weather conditions and admissions for ischemic stroke and subarachnoid hemorrhage

    PubMed Central

    Tarnoki, Adam D.; Türker, Acar; Tarnoki, David L.; İyisoy, Mehmet S; Szilagyi, Blanka K.; Duong, Hoang; Miskolczi, Laszlo

    2017-01-01

    Aim To assess impacts of different weather conditions on hospitalizations of patients with ischemic strokes and subarachnoid hemorrhages (SAH) in South Florida. Methods Diagnostic data of patients with spontaneous SAH and strokes were recorded between June 2010 and July 2013. Daily synchronous forecast charts were collected from the National Weather Service and the whole data were matched prospectively. The incidence rate ratio (IRR) was calculated. Results Increased incidence rate of ischemic stroke was consistent with the daily lowest and highest air pressure (IRR 1.03, P = 0.128 and IRR 0.98, P = 0.380, respectively), highest air temperature (IRR 0.99, P = 0.375), and presence of hurricanes or storms (IRR 0.65, P = 0.054). Increased incidence of SAH cases was consistent with daily lowest and highest air pressure (IRR 0.87, P < 0.001 and IRR 1.08, P = 0.019, respectively) and highest air temperature (IRR 0.98, P < 0.001). Presence of hurricanes and/or tropical storms did not influence the frequency of SAH. We found no relationship between the presence of fronts and the admissions for ischemic stroke or SAH. Conclusion Higher number of ischemic stroke and SAH cases can be expected with the daily lowest and highest air pressure, highest air temperature. Presence of hurricanes or tropical storms increased the risk of ischemic stroke but not the SAH. These findings can help to develop preventive health plans for cerebrovascular diseases. PMID:28252876

  4. Difference in the Location and Risk Factors of Cerebral Microbleeds According to Ischemic Stroke Subtypes

    PubMed Central

    Kim, Bum Joon; Yoon, Youngshin; Sohn, Hoyon; Kang, Dong-Wha; Kim, Jong S.; Kwon, Sun U.

    2016-01-01

    Background and Purpose The location of cerebral microbleeds (CMBs) may differ according to ischemic stroke subtype, and the underlying pathomechanism may differ by their location. Here, we investigated the characteristics of CMBs according to various ischemic stroke subtypes to verify this issue. Methods Patients with acute ischemic stroke were consecutively included. The presence of CMBs was determined by gradient echo image sequence. The distribution of CMBs was classified as deep, lobar, or diffuse (both deep and lobar). The prevalence, risk factors, and distribution of CMBs were compared among patients with different stroke subtypes. Factors associated with the distribution of CMBs were investigated. Results Among the 1033 patients included in this study, ischemic stroke subtypes were classified as large artery atherosclerosis (LAA; n=432), small vessel occlusion (SVO; n=304), and cardioembolism (CE; n=297). The prevalence of CMBs was highest in patients with SVO (40.5%), followed by CE (33.0%) and LAA (24.8%; P<0.001). The locations of CMBs was different according to subtype (P=0.004). CE [odds ratio (OR)=1.85 (1.02-3.34); P=0.042] and the use of antithrombotics [OR=1.80 (1.10-2.94); P=0.019] were associated with lobar CMBs, and old age [OR=1.02 (1.00-1.04); P=0.015] and hypertension [OR=1.61 (1.08-2.40); P=0.020] were associated with deep CMBs. Conclusions CMBs were frequently located in the lobar area in patients with CE. Previous use of antithrombotic agents is associated with lobar CMBs. The pathogenic mechanism of CMB may differ according to ischemic stroke subtype and location. PMID:27733027

  5. Effect of educational television commercial on pre-hospital delay in patients with ischemic stroke.

    PubMed

    Nishijima, Haruo; Kon, Tomoya; Ueno, Tatsuya; Haga, Rie; Yamazaki, Keishi; Yagihashi, Kei; Funamizu, Yukihisa; Arai, Akira; Suzuki, Chieko; Nunomura, Jin-ichi; Baba, Masayuki; Tomiyama, Masahiko

    2016-01-01

    Administering intravenous recombinant tissue plasminogen activator (r-tPA) within 4.5 h or endovascular procedures within 8 h of ischemic stroke onset may reduce the risk of disability. The effectiveness of media campaigns to raise stroke awareness and shorten pre-hospital delay is unclear. We studied 1144 consecutive ischemic stroke patients at Aomori Prefectural Central Hospital, Japan, between March 2010 and February 2014. From March 2012, the government sponsored an educational campaign based on a television commercial to improve knowledge of stroke symptoms and encourage ambulance calls for facial palsy, arm palsy, or speech disturbance. For the 544 and 600 patients admitted before and during the intervention, respectively, we recorded the National Institutes of Health Stroke Scale score, stroke type, the time when patients or bystanders recognized stroke symptoms, and hospital arrival time. Pre-hospital delay, as the time interval from awareness of stroke to hospital arrival, was categorized as 0-3, 3-6, and 6+ h. The mean pre-hospital delay was shorter (12.0 vs 13.5 h; P = 0.0067), the proportion of patients arriving within 3 h was larger (55.7 vs 46.5 %; P = 0.0021), and the proportion arriving after 6 h was smaller (32.7 vs 39.5 %; P = 0.0162) in the intervention group than in the pre-intervention group. There was no significant difference in the proportion of patients treated with r-tPA (6 and 7.5 % of the intervention and pre-intervention groups, respectively). A television-based public education campaign potentially reduced pre-hospital delay for ischemic stroke patients, but the r-tPA treatment rate was unchanged.

  6. Association of the Single Nucleotide Polymorphisms in microRNAs 130b, 200b, and 495 with Ischemic Stroke Susceptibility and Post-Stroke Mortality

    PubMed Central

    Choi, Gun Ho; Ko, Ki Han; Kim, Jung Oh; Oh, Seung Hun; Park, Young Seok

    2016-01-01

    The microRNA (miRNA) is a small non-coding RNA molecule that modulates gene expression at the posttranscriptional level. Platelets have a crucial role in both hemostasis and thrombosis, a condition that can occlude a cerebral artery and cause ischemic stroke. miR-130b, miR-200b, and miR-495 are potential genetic modulators involving platelet production and activation. We hypothesized that single nucleotide polymorphisms (SNPs) in these miRNAs might potentially contribute to the susceptibility to ischemic stroke and post-stroke mortality. This study included 523 ischemic stroke patients and 400 control subjects. We investigated the association of three miRNA SNPs (miR-130bT>C, miR-200bT>C, and miR-495A>C) with ischemic stroke prevalence and post-stroke mortality. In the multivariate logistic regression, there was no statistically significant difference in the distribution of miR-130bT>C, miR-200bT>C, or miR-495A>C between the ischemic stroke and control groups. In the subgroup analysis based on ischemic stroke subtype, the miR-200b CC genotype was less frequently found in the large-artery atherosclerosis stroke subtype compared with controls (TT+CT vs CC; adjusted odds ratio for CC, 0.506; 95% confidence interval, 0.265–0.965). During a mean follow-up period of 4.80 ± 2.11 years after stroke onset, there were 106 all-cause deaths among the 523 stroke patients. Multivariate Cox regression analysis did not find a significant association between post-stroke mortality and three miRNA SNPs. Our findings suggest that the functional SNP of miR-200b might be responsible for the susceptibility to large-artery atherosclerotic stroke. PMID:27603512

  7. Predicting value of cerebrospinal fluid proinflammatory factors in acute phase of ischemic stroke.

    PubMed

    Beridze, M; Shakarishvili, R

    2006-03-01

    Study purposed to establish the correlation between proinflammatory cytokines' initial CSF levels and neurological outcome on 7th day of acute ischemic stroke. 58 patients with acute ischemic stroke have been investigated. Neurological impairment assessed in 48 hours and on 7th day of stroke applying the international scales NIHSS and GCS. Patients divided into two groups: with severe stroke (GCS>9, NIHSS>15) and stroke with moderate severity (GCS=14,15; NIHSS=10-15). On 7th day increase of NIHSS score and decrease of GCS score at least 1 point was considered as deterioration and decrease of NIHSS score and increase of GCS score at least 1 point was considered as amelioration. CSF levels of proinflamatory cytokines determined using the enzyme-linked immunosorbent assay (ELISA). Control consisted with 15 patients, which were taken CSF in relation with vertebral discopathies. Means calculated by t-paired test. Pearson correlation and multivariate logistic regression were used. In 48 hours of stroke onset the CSF levels of interleukine-1beta (IL-1beta), interleukine-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were elevated compared to control. Statistical differences were not found between groups regarding the initial CSF levels of IL-1beta and TNF-alpha (p<0,5), while the significant statistical differences were found in regard with IL-6 CSF levels (p<0,05) between groups and against control. Significant positive correlation was found between initial CSF IL-6 levels and ischemic lesion size and neurological outcome at 1 week as well (r=+0,48 p<0,05 and r=+0,54 p<0,01 respectively). Thus, the IL-6 CSF levels in acute stage of ischemic stroke might be considered as the relatively stable prognostic indicator of clinical course of the disease.

  8. Torsade de pointes indicates early neurologic damage in acute ischemic stroke.

    PubMed

    Huang, Li-Yen; Lin, Wei-Shiang; Lin, Wen-Yu; Cheng, Cheng-Chung; Cheng, Shu-Meng; Tsai, Tsung-Neng

    2013-12-01

    Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia that is related to QT prolongation. Although QT prolongation is commonly seen in acute stroke, TdP is rare. We report the case of a 78-year-old woman with ischemic stroke who presented with TdP as the initial manifestation of early neurologic deterioration. We hypothesized that an increase in intracranial pressure may result in neurohormonal activation, QT prolongation, and then myocardial damage, leading to TdP. We highlight that new onset of TdP in a patient with stroke may reflect neurologic deterioration, requiring further evaluation and specific intervention.

  9. A Family History of Stroke Is Associated with Increased Intima-Media Thickness in Young Ischemic Stroke - The Norwegian Stroke in the Young Study (NOR-SYS)

    PubMed Central

    Øygarden, Halvor; Fromm, Annette; Sand, Kristin Modalsli; Kvistad, Christopher Elnan; Eide, Geir Egil; Thomassen, Lars; Naess, Halvor; Waje-Andreassen, Ulrike

    2016-01-01

    Background and Purpose Positive family history (FH+) of cardiovascular disease (CVD) is a risk factor for own CVD. We aimed to analyze the effect of different types of FH (stroke, coronary heart disease (CHD), peripheral artery disease (PAD) on carotid intima-media thickness (cIMT) in young and middle-aged ischemic stroke patients. Methods First-degree FH of CVD was assessed in ischemic stroke patients ≤ 60y using a standardized interview. Carotid ultrasound was performed and far wall cIMT in three carotid artery segments was registered, representing the common carotid (CCA-IMT), carotid bifurcation (BIF-IMT) and the internal carotid artery (ICA-IMT). Measurements were compared between FH+ and FH negative groups and stepwise backward regression analyses were performed to identify factors associated with increased cIMT. Results During the study period 382 patients were enrolled, of which 262 (68%) were males and 233 (61%) reported FH of CVD. Regression analyses adjusting for risk factors revealed age as the most important predictor of cIMT in all segments. The association between FH+ and cIMT was modified by age (p = 0.014) and was significant only regarding ICA-IMT. FH+ was associated with increased ICA-IMT in patients aged < 45y (p = 0.001), but not in patients ≥ 45y (p = 0.083). The association with ICA-IMT was present for a FH of stroke (p = 0.034), but not a FH+ of CHD or PAD. Conclusions FH of stroke is associated with higher ICA-IMT in young ischemic stroke patients. Subtyping of cardiovascular FH is important to investigate heredity in young ischemic stroke patients. Trial Registration ClinicalTrials.gov NCT01597453 PMID:27504830

  10. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and susceptibility to ischemic stroke: a meta-analysis.

    PubMed

    Li, Pingping; Qin, Chao

    2014-02-10

    Associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and ischemic stroke have been reported (Ariyaratnam et al., 2007; Banerjee et al., 2007; Casas et al., 2004), but the results of these studies are inconsistent. To investigate the possible associations between the MTHFR gene polymorphism and ischemic stroke, we performed a meta-analysis. Nineteen case-control studies associated with MTHFR gene C667T involving 2223 cases and 2936 controls were included. Heterogeneity among studies was evaluated with I(2) and Egger's test and an inverted funnel plot was used to assess publication bias. Odds ratio (OR) was observed to identify the associations. Statistically significant association with ischemic stroke was identified for allele T polymorphism of MTHFR [fixed-effects OR=1.28, 95% confidence interval (95% CI): 1.17-1.40, P<0.00001] and marginally significant association was detected with genotype CT of MTHFR (fixed-effects OR=1.13, 95% CI: 1.01-127, P=0.04) and genotype TT of MTHFR (fixed-effects OR=1.43, 95% CI: 1.20-1.70, P<0.001). The results suggested that the MTHFR C667T genetic polymorphism was significantly associated with increased risk of ischemic stroke.

  11. Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study

    PubMed Central

    Wu, Ping; Zhou, Yu-mei; Zeng, Fang; Li, Zheng-jie; Luo, Lu; Li, Yong-xin; Fan, Wei; Qiu, Li-hua; Qin, Wei; Chen, Lin; Bai, Lin; Nie, Juan; Zhang, San; Xiong, Yan; Bai, Yu; Yin, Can-xin; Liang, Fan-rong

    2016-01-01

    Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment (r = –0.609, P = 0.047) and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale (r = –0.737, P = 0.010). Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients. PMID:27857744

  12. Clinical factors associated with statins prescription in acute ischemic stroke patients: findings from the Lombardia Stroke Registry

    PubMed Central

    2014-01-01

    Background Statins, due to their well-established pleiotropic effects, have noteworthy benefits in stroke prevention. Despite this, a significant proportion of high-risk patients still do not receive the recommended therapeutic regimens, and many others discontinue treatment after being started on them. The causes of non-adherence to current guidelines are multifactorial, and depend on both physicians and patients. The aim of this study is to identify the factors influencing statin prescription at Stroke Unit (SU) discharge. Methods This study included 12,750 patients enrolled on the web-based Lombardia Stroke Registry (LRS) from July 2009 to April 2012 and discharged alive, with a diagnosis of ischemic stroke or transient ischemic attack (TIA) and without contra-indication to statin therapy. By logistic regression analysis and classification trees, we evaluated the impact of demographic data, risk factors, tPA treatment, in-hospital procedures and complications on statin prescription rate at discharge. Results We observed a slight increase in statins prescription during the study period (from 39.1 to 43.9%). Lower age, lower stroke severity and prestroke disability, the presence of atherothrombotic/lacunar risk factors, a diagnosis of non-cardioembolic stroke, tPA treatment, the absence of in-hospital complications, with the sole exception of hypertensive fits and hyperglycemia, were the patient-related predictors of adherence to guidelines by physicians. Overall, dyslipidemia appears as the leading factor, while TOAST classification does not reach statistical significance. Conclusions In our region, Lombardia, adherence to guidelines in statin prescription at Stroke Unit discharge is very different from international goals. The presence of dyslipidemia remains the main factor influencing statin prescription, while the presence of well-defined atherosclerotic etiopathogenesis of stroke does not enhance statin prescription. Some uncertainties about the risk

  13. Outdoor air pollution, subtypes and severity of ischemic stroke – a small-area level ecological study

    PubMed Central

    2014-01-01

    Background Evidence linking outdoor air pollution and incidence of ischemic stroke subtypes and severity is limited. We examined associations between outdoor PM10 and NO2 concentrations modeled at a fine spatial resolution and etiological and clinical ischemic stroke subtypes and severity of ischemic stroke. Methods We used a small-area level ecological study design and a stroke register set up to capture all incident cases of first ever stroke (1995–2007) occurring in a defined geographical area in South London (948 census output areas; population of 267839). Modeled PM10 and NO2 concentrations were available at a very fine spatial scale (20 meter by 20 meter grid point resolution) and were aggregated to output area level using postcode population weighted averages. Ischemic stroke was classified using the Oxford clinical classification, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) etiological classification, National Institutes of Health Stroke Scale (NIHSS) score and a pragmatic clinical severity classification based on Glasgow coma score, ability to swallow, urinary continence and death <2 days of stroke onset. Results Mean (SD) concentrations were 25.1 (1.2) ug/m3 (range 23.3-36.4) for PM10 and 41.4 (3.0) ug/m3 (range 35.4-68.0) for NO2. There were 2492 incident cases of ischemic stroke. We found no evidence of association between these pollutants and the incidence of ischemic stroke subtypes classified using the Oxford and TOAST classifications. We found no significant association with stroke severity using NIHSS severity categories. However, we found that outdoor concentrations of both PM10 and NO2 appeared to be associated with increased incidence of mild but not severe ischemic stroke, classified using the pragmatic clinical severity classification. For mild ischemic stroke, the rate ratio in the highest PM10 category by tertile was 1.20 (1.05-1.38) relative to the lowest category. The rate ratio in the highest NO2 category was 1.22 (1

  14. Epigenetic Regulation of Oxidative Stress in Ischemic Stroke

    PubMed Central

    Zhao, Haiping; Han, Ziping; Ji, Xunming; Luo, Yumin

    2016-01-01

    The prevalence and incidence of stroke rises with life expectancy. However, except for the use of recombinant tissue-type plasminogen activator, the translation of new therapies for acute stroke from animal models into humans has been relatively unsuccessful. Oxidative DNA and protein damage following stroke is typically associated with cell death. Cause-effect relationships between reactive oxygen species and epigenetic modifications have been established in aging, cancer, acute pancreatitis, and fatty liver disease. In addition, epigenetic regulatory mechanisms during stroke recovery have been reviewed, with focuses mainly on neural apoptosis, necrosis, and neuroplasticity. However, oxidative stress-induced epigenetic regulation in vascular neural networks following stroke has not been sufficiently explored. Improved understanding of the epigenetic regulatory network upon oxidative stress may provide effective antioxidant approaches for treating stroke. In this review, we summarize the epigenetic events, including DNA methylation, histone modification, and microRNAs, that result from oxidative stress following experimental stroke in animal and cell models, and the ways in which epigenetic changes and their crosstalk influence the redox state in neurons, glia, and vascular endothelial cells, helping us to understand the foregone and vicious epigenetic regulation of oxidative stress in the vascular neural network following stroke. PMID:27330844

  15. Case Report of False-Negative Diffusion-Weighted Image of Brain Magnetic Resonance Imaging (MRI) in Acute Ischemic Stroke

    PubMed Central

    Chang, Wei-Lun; Lai, Ji-Ching; Chen, Rong-Fu; Hu, Han-Hwa; Pan, Chau-Shiung

    2017-01-01

    Patient: Male, 75 Final Diagnosis: Acute ischemic stroke Symptoms: Dizziness • unsteady gait Medication: — Clinical Procedure: None Specialty: Radiology Objective: Challenging differential diagnosis Background: Acute ischemic stroke is a major cause of mortality and morbidity in Taiwan. Diffusion-weighted image (DWI) is a sensitive and common strategy used for imaging acute ischemic stroke. Case report: We present a case of a negative DWI MRI for detecting acute ischemic stroke in a clinical setting. A 75-year-old male had a DWI performed after onset of symptoms suggesting acute ischemic stroke. The initial DWI result was negative at 72 hours of presentation. The neurological symptoms of the patient persisted and DWI was repeated. After 14 days, the DWI data confirmed and demonstrated an acute ischemic stroke. The delay in DWI confirmation, from symptom onset until DWI diagnosis, was 336 hours. Conclusions: DWI may not have 100% sensitivity and accuracy in early stages of acute ischemic stroke. The time course to the development of abnormalities detected by DWI may be longer than anticipated. PMID:28111452

  16. Comparison of neurological clinical manifestation in patients with hemorrhagic and ischemic stroke

    PubMed Central

    Ojaghihaghighi, Seyedhossein; Vahdati, Samad Shams; Mikaeilpour, Akram; Ramouz, Ali

    2017-01-01

    BACKGROUND: Cerebrovascular accident (CVA) is the third leading cause of death and disability in developed countries. Anyone suspected of having a stroke should be taken immediately to a medical facility for diagnosis and treatment. The symptoms that follow a stroke aren’t significant and depend on the area of the brain that has been affected and the amount of tissue damaged. Parameters for predicting long-term outcome in such patients have not been clearly delineated, therefore the aim of this study was to investigate this possibility and to test a system that might practicably be used routinely to aid management and predict outcomes of individual stroke patients. METHODS: A descriptive hospital-based study of the neurological symptoms and signs of 503 patients with ischemic stroke, including severe headache, seizure, eye movement disorder, pupil size, Glasgow Coma Scale (GCS), agitation were analyzed in this study. RESULTS: In the current study, dilated pupils, agitation, acute onset headache, lower GCS score, seizure, and eye gaze impairment had significantly higher prevalence in hemorrhagic stroke patients (P<0.001). However, the rate of gradual progressive headache is significantly higher in ischemic stroke patients (P<0.001). CONCLUSION: Although this result provides reliable indicators for discrimination of stroke types, imaging studies are still the gold standard modality for diagnosis. PMID:28123618

  17. Cortical thickness and metabolite concentration in chronic stroke and the relationship with motor function

    PubMed Central

    Jones, Paul W.; Borich, Michael R.; Vavsour, Irene; Mackay, Alex; Boyd, Lara A.

    2016-01-01

    Introduction Hemiparesis is one of the most prevalent chronic disabilities after stroke. Biochemical and structural magnetic resonance imaging approaches may be employed to study the neural substrates underpinning upper-extremity (UE) recovery after chronic stroke. Objective The purposes of this study were to 1) quantify anatomical and metabolic differences in the precentral gyrus, and 2) test the relationships between anatomical and metabolic differences, and hemiparetic arm function in individuals in the chronic stage of stroke recovery. Our hypotheses were: 1) the Stroke group would exhibit reduced precentral gyrus cortical thickness and lower concentrations of total N-acetylaspartate (tNAA) and glutamate+glutamine (Glx) in the ipsilesional motor cortex; and 2) that each of these measures would be associated with UE motor function after stroke. Methods Seventeen individuals with chronic (>6 months) subcortical ischemic stroke and eleven neurologically healthy controls were recruited. Single voxel proton magnetic resonance spectroscopy (H1MRS) was performed to measure metabolite concentrations of tNAA and Glx in the precentral gyrus in both ipsilesional and contralesional hemispheres. Surface-based cortical morphometry was used to quantify precentral gyral thickness. Upper-extremity motor function was assessed using the Wolf Motor Function Test (WMFT). Results Results demonstrated significantly lower ipsilesional tNAA and Glx concentrations and precentral gyrus thickness in the Stroke group. Ipsilesional tNAA and Glx concentration and precentral gyrus thickness was significantly lower in the ipsilesional hemisphere in the Stroke group. Parametric correlation analyses revealed a significant positive relationship between precentral gyrus thickness and tNAA concentration bilaterally. Multivariate regression analyses revealed that ipsilesional concentrations of tNAA and Glx predicted the largest amount of variance in WMFT scores. Cortical thickness measures alone did

  18. Carnosine protects the brain of rats and Mongolian gerbils against ischemic injury: after-stroke-effect.

    PubMed

    Dobrota, Dusan; Fedorova, Tatiana; Stvolinsky, Sergey; Babusikova, Eva; Likavcanova, Katarina; Drgova, Anna; Strapkova, Adriana; Boldyrev, Alexander

    2005-10-01

    Carnosine, a specific constituent of excitable tissues of vertebrates, exhibits a significant antioxidant protecting effect on the brain damaged by ischemic-reperfusion injury when it was administered to the animals before ischemic episode. In this study, the therapeutic effect of carnosine was estimated on animals when this drug was administered intraperitoneally (100 mg/kg body weight) after ischemic episode induced by experimental global brain ischemia. Treatment of the animals with carnosine after ischemic episode under long-term (7-14 days) reperfusion demonstrated its pronounced protective effect on neurological symptoms and animal mortality. Carnosine also prevented higher lipid peroxidation of brain membrane structures and increased a resistance of neuronal membranes to the in vitro induced oxidation. Measurements of malonyl dialdehyde (MDA) in brain homogenates showed its increase in the after brain stroke animals and decreased MDA level in the after brain stroke animals treated with carnosine. We concluded that carnosine compensates deficit in antioxidant defense system of brain damaged by ischemic injury. The data presented demonstrate that carnosine is effective in protecting the brain in the post-ischemic period.

  19. [Pulmonary function in chronic ischemic cardiopathy].

    PubMed

    Martínez Guerra, M L; Gómez González, A; Fernández Bonetti, P; Martínez Ríos, M A

    1983-01-01

    Twenty patients with heart disease were prospectively studied. Seven of them had an old myocardial infarction and thirteen, ischemic symptoms without infarction. Pulmonary function was studied focusing on small airway disease and gas exchange abnormalities. Our results showed that a mild degree of abnormality exists as reflected by bronchial obstruction with origin in small airways, V/Q disturbed and hypoxemia. In 88% these seem to be related to left ventricular disfunction. Twenty four hours after pulmonary function test all patients underwent left heart catheterization with coronarography and ventriculography.

  20. The Taxonomy Statistic Uncovers Novel Clinical Patterns in a Population of Ischemic Stroke Patients

    PubMed Central

    Tukiendorf, Andrzej; Kaźmierski, Radosław; Michalak, Sławomir

    2013-01-01

    In this paper, we describe a simple taxonomic approach for clinical data mining elaborated by Marczewski and Steinhaus (M-S), whose performance equals the advanced statistical methodology known as the expectation-maximization (E-M) algorithm. We tested these two methods on a cohort of ischemic stroke patients. The comparison of both methods revealed strong agreement. Direct agreement between M-S and E-M classifications reached 83%, while Cohen’s coefficient of agreement was κ = 0.766(P < 0.0001). The statistical analysis conducted and the outcomes obtained in this paper revealed novel clinical patterns in ischemic stroke patients. The aim of the study was to evaluate the clinical usefulness of Marczewski-Steinhaus’ taxonomic approach as a tool for the detection of novel patterns of data in ischemic stroke patients and the prediction of disease outcome. In terms of the identification of fairly frequent types of stroke patients using their age, National Institutes of Health Stroke Scale (NIHSS), and diabetes mellitus (DM) status, when dealing with rough characteristics of patients, four particular types of patients are recognized, which cannot be identified by means of routine clinical methods. Following the obtained taxonomical outcomes, the strong correlation between the health status at moment of admission to emergency department (ED) and the subsequent recovery of patients is established. Moreover, popularization and simplification of the ideas of advanced mathematicians may provide an unconventional explorative platform for clinical problems. PMID:23875000

  1. Program to Diagnose Probability of Aspiration Pneumonia in Patients with Ischemic Stroke

    PubMed Central

    Pinto, Gisele; Zétola, Viviane; Lange, Marcos; Gomes, Guilherme; Nunes, Maria Cristina; Hirata, Gisela; Lagos-Guimarães, Hellen Nataly

    2014-01-01

    Introduction Stroke is a major cause of death and disability worldwide, with a strong economic and social impact. Approximately 40% of patients show motor, language, and swallowing disorders after stroke. Objective To evaluate the use of software to infer the probability of pneumonia in patients with ischemic stroke. Methods Prospective and cross-sectional study conducted in a university hospital from March 2010 to August 2012. After confirmation of ischemic stroke by computed axial tomography, a clinical and flexible endoscopic evaluation of swallowing was performed within 72 hours of onset of symptoms. All patients received speech therapy poststroke, and the data were subsequently analyzed by the software. The patients were given medical treatment and speech therapy for 3 months. Results The study examined 52 patients with a mean age of 62.05 ± 13.88 years, with 23 (44.2%) women. Of the 52 patients, only 3 (5.7%) had a probability of pneumonia between 80 and 100% as identified by the software. Of all patients, 32 (61.7%) had pneumonia probability between 0 and 19%, 5 (9.5%) between 20 and 49%, 3 (5.8%) between 50 and 79%, and 12 (23.0%) between 80 and 100%. Conclusion The computer program indicates the probability of patient having aspiration pneumonia after ischemic stroke. PMID:25992100

  2. Increased Blood Pressure Variability Is Associated with Worse Neurologic Outcome in Acute Anterior Circulation Ischemic Stroke

    PubMed Central

    Bennett, Alicia; Stoddard, Gregory J.; Smith, Gordon; Wang, Haimei; Wold, Jana; Chung, Lee; Tirschwell, David L.; Majersik, Jennifer J.

    2016-01-01

    Background. Although research suggests that blood pressure variability (BPV) is detrimental in the weeks to months after acute ischemic stroke, it has not been adequately studied in the acute setting. Methods. We reviewed acute ischemic stroke patients from 2007 to 2014 with anterior circulation stroke. Mean blood pressure and three BPV indices (standard deviation, coefficient of variation, and successive variation) for the intervals 0–24, 0–72, and 0–120 hours after admission were correlated with follow-up modified Rankin Scale (mRS) in ordinal logistic regression models. The correlation between BPV and mRS was further analyzed by terciles of clinically informative stratifications. Results. Two hundred and fifteen patients met inclusion criteria. At all time intervals, increased systolic BPV was associated with higher mRS, but the relationship was not significant for diastolic BPV or mean blood pressure. This association was strongest in patients with proximal stroke parent artery vessel occlusion and lower mean blood pressure. Conclusion. Increased early systolic BPV is associated with worse neurologic outcome after ischemic stroke. This association is strongest in patients with lower mean blood pressure and proximal vessel occlusion, often despite endovascular or thrombolytic therapy. This hypothesis-generating dataset suggests potential benefit for interventions aimed at reducing BPV in this patient population. PMID:27974991

  3. Effect of prior medical treatments on ischemic stroke severity and outcome

    PubMed Central

    Sacco, Simona; Toni, Danilo; Bignamini, Angelo A.; Zaninelli, Augusto; Gensini, Gian Franco; Carolei, Antonio

    Summary Antiplatelets, antihypertensives, and statins might reduce the severity of the event or improve outcome in patients who, despite prior medical treatment, have a stroke. We evaluated, in patients who had an ischemic stroke, the effect, on stroke severity and outcome, of prior treatment with antiplatelets, antihypertensives, and statins, used either alone or in a three-drug combination. Stroke in Italy and Related Impact on Outcome (SIRIO) was a prospective, nationwide, multicenter, hospital-based, observational study that included patients aged ≥18 years with acute ischemic stroke. We studied 2,529 acute ischemic stroke patients from the SIRIO population: 887 were antiplatelet users, 1,497 antihypertensive users, 231 statin users, and 138 three-drug combination users prior to the index event. The adjusted logistic regression analysis showed an association between prior treatment with statins and good functional outcome at discharge, while prior treatment with antiplatelets, antihypertensives or the three-drug combination did not influence severity or outcome. The absolute probability of a good functional outcome was 46.3% (95% CI: 40.3%–53.2%) in statin users and 36.7% (95% CI: 34.7%–38.7%) in non-users of statins; the absolute risk difference was 9.6% (95% CI: 2.9%–16.4%; p=0.004). Prior treatment with antiplatelets, antihypertensives, or the three-drug combination did not influence stroke severity or outcome, while prior treatment with statins did not influence stroke severity but was associated with a better functional outcome. PMID:22152434

  4. Perinatal ischemic stroke: a five-year retrospective study in a level-III maternity

    PubMed Central

    Machado, Virgínia; Pimentel, Sónia; Pinto, Filomena; Nona, José

    2015-01-01

    Objective To study the incidence, clinical presentation, risk factors, imaging diagnosis, and clinical outcome of perinatal stroke. Methods Data was retrospectively collected from full-term newborns admitted to the neonatal unit of a level III maternity in Lisbon with cerebral stroke, from January 2007 to December 2011. Results There were 11 cases of stroke: nine were arterial ischemic stroke and two were cerebral venous sinus thrombosis. We estimated an incidence of arterial ischemic stroke of 1.6/5,000 births and of cerebral venous sinus thrombosis of 7.2/100,000 births. There were two cases of recurrent stroke. Eight patients presented with symptoms while the remaining three were asymptomatic and incidentally diagnosed. The most frequently registered symptoms (8/11) were seizures; in that, generalized clonic (3/8) and focal clonic (5/8). Strokes were more commonly left-sided (9/11), and the most affected artery was the left middle cerebral artery (8/11). Transfontanelle ultrasound was positive in most of the patients (10/11), and stroke was confirmed by cerebral magnetic resonance in all patients. Electroencephalographic recordings were carried out in five patients and were abnormal in three (focal abnormalities n=2, burst-suppression pattern n=1). Eight patients had previously identified risk factors for neonatal stroke which included obstetric and neonatal causes. Ten patients were followed up at outpatients setting; four patients developed motor deficits and one presented with epilepsy. Conclusions Although a modest and heterogeneous sample, this study emphasizes the need for a high level of suspicion when it comes to neonatal stroke, primarily in the presence of risk factors. The prevalence of neurological sequelae in our series supports the need of long-term follow-up and early intervention strategies. PMID:25993071

  5. Detection of crossed cerebellar diaschisis in hyperacute ischemic stroke using arterial spin-labeled MR imaging

    PubMed Central

    Kang, Koung Mi; Sohn, Chul-Ho

    2017-01-01

    Background and purpose Arterial spin-labeling (ASL) was recently introduced as a noninvasive method to evaluate cerebral hemodynamics. The purposes of this study were to assess the ability of ASL imaging to detect crossed cerebellar diaschisis (CCD) in patients with their first unilateral supratentorial hyperacute stroke and to identify imaging or clinical factors significantly associated with CCD. Materials and methods We reviewed 204 consecutive patients who underwent MRI less than 8 hours after the onset of stroke symptoms. The inclusion criteria were supratentorial abnormality in diffusion-weighted images in the absence of a cerebellar or brain stem lesion, bilateral supratentorial infarction, subacute or chronic infarction, and MR angiography showing vertebrobasilar system disease. For qualitative analysis, asymmetric cerebellar hypoperfusion in ASL images was categorized into 3 grades. Quantitative analysis was performed to calculate the asymmetric index (AI). The patients’ demographic and clinical features and outcomes were recorded. Univariate and multivariate analyses were also performed. Results A total of 32 patients met the inclusion criteria, and 24 (75%) presented CCD. Univariate analyses revealed more frequent arterial occlusions, higher diffusion-weighted imaging (DWI) lesion volumes and higher initial NIHSS and mRS scores in the CCD-positive group compared with the CCD-negative group (all p < .05). The presence of arterial occlusion and the initial mRS scores were related with the AI (all p < .05). Multivariate analyses revealed that arterial occlusion and the initial mRS scores were significantly associated with CCD and AI. Conclusion ASL imaging could detect CCD in 75% of patients with hyperacute infarction. We found that CCD was more prevalent in patients with arterial occlusion, larger ischemic brain volumes, and higher initial NIHSS and mRS scores. In particular, vessel occlusion and initial mRS score appeared to be significantly related

  6. 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.

  7. 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

  8. Predicting Discharge Mortality after Acute Ischemic Stroke Using Balanced Data

    PubMed Central

    Ho, King Chung; Speier, William; El-Saden, Suzie; Liebeskind, David S.; Saver, Jeffery L.; Bui, Alex A. T.; Arnold, Corey W.

    2014-01-01

    Several models have been developed to predict stroke outcomes (e.g., stroke mortality, patient dependence, etc.) in recent decades. However, there is little discussion regarding the problem of between-class imbalance in stroke datasets, which leads to prediction bias and decreased performance. In this paper, we demonstrate the use of the Synthetic Minority Over-sampling Technique to overcome such problems. We also compare state of the art machine learning methods and construct a six-variable support vector machine (SVM) model to predict stroke mortality at discharge. Finally, we discuss how the identification of a reduced feature set allowed us to identify additional cases in our research database for validation testing. Our classifier achieved a c-statistic of 0.865 on the cross-validated dataset, demonstrating good classification performance using a reduced set of variables. PMID:25954451

  9. Is Intravenous Heparin a Contraindication for TPA in Ischemic Stroke?

    PubMed Central

    Deol, Nisha; Tolly, Renee; Manocha, Rohan; Naseer, Maliha

    2017-01-01

    There are approximately 2 million cardiac catheterizations that occur every year in the United States and with an aging population this number continues to rise. Adverse events due to this procedure occur at low rates and include stroke, arrhythmia, and myocardial infarctions. Due to the high volume of procedures there are a growing number of adverse events. Stroke after cardiac catheterization (SCC) has an incidence between 0.27 and 0.5% and is one of the most debilitating complications leading to high rates of mortality and morbidity. Given the relatively uncommon clinical setting of stroke after cardiac catheterization, treatment protocols regarding the use of IV or IA thrombolysis have not been adequately developed. Herein, we describe a case of a 39-year-old male who developed a stroke following a cardiac catheterization where IV thrombolysis was utilized although the patient was on heparin prior to cardiac catheterization. PMID:28261510

  10. Methylene blue treatment in experimental ischemic stroke: a mini review

    PubMed Central

    Jiang, Zhao; Duong, Timothy Q

    2016-01-01

    Stroke is a leading cause of death and long-term disability. Methylene blue, a drug grandfathered by the Food and Drug Administration with a long history of safe usage in humans for treating methemoglobinemia and cyanide poisoning, has recently been shown to be neuroprotective in neurodegenerative diseases and brain injuries. The goal of this paper is to review studies on methylene blue in experimental stroke models. PMID:27042692

  11. The Economic Burden of Ischemic Stroke and Major Hemorrhage in Medicare Beneficiaries with Nonvalvular Atrial Fibrillation: A Retrospective Claims Analysis

    PubMed Central

    Fitch, Kathryn; Broulette, Jonah; Kwong, Winghan Jacqueline

    2014-01-01

    Background Understanding the economic implications of oral anticoagulation therapy requires careful consideration of the risks and costs of stroke and major hemorrhage. The majority of patients with atrial fibrillation (AF) are aged ≥65 years, so focusing on the Medicare population is reasonable when discussing the risk for stroke. Objective To examine the relative economic burden associated with stroke and major hemorrhage among Medicare beneficiaries who are newly diagnosed with nonvalvular atrial fibrillation (NVAF). Methods This study was a retrospective analysis of a 5% sample of Medicare claims data for patients with NVAF from 2006 to 2008. Patients with NVAF without any claims of AF during the 12 months before the first (index) claim for AF in 2007 (baseline period) were identified and were classified into 4 cohorts during a 12-month follow-up period after the index date. These cohorts included (1) no claims for ischemic stroke or major hemorrhage (without stroke or hemorrhage); (2) no claims for ischemic stroke and ≥1 claims for major hemorrhage (hemorrhage only); (3) ≥1 claims for ischemic stroke and no major hemorrhage claims (stroke only); and (4) ≥1 claims each for ischemic stroke and for major hemorrhage (stroke and hemorrhage). The 1-year mean postindex total all-cause healthcare costs adjusted by the Centers for Medicare & Medicaid Services Hierarchical Condition Categories (HCC) score were compared among the study cohorts. Results: Of the 9455 eligible patients included in this study, 3% (N = 261) of the patients had ischemic stroke claims only, 3% (N = 276) had hemorrhage claims only, and <1% (N = 13) had both during the follow-up period. The unadjusted follow-up healthcare costs were $63,781 and $64,596 per patient for the ischemic stroke only and the hemorrhage only cohorts, respectively, compared with $35,474 per patient for those without hemorrhage or stroke claims. After adjustment for HCC risk score, the mean incremental costs for

  12. 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

  13. ISLES 2015 - A public evaluation benchmark for ischemic stroke lesion segmentation from multispectral MRI.

    PubMed

    Maier, Oskar; Menze, Bjoern H; von der Gablentz, Janina; Häni, Levin; Heinrich, Mattias P; Liebrand, Matthias; Winzeck, Stefan; Basit, Abdul; Bentley, Paul; Chen, Liang; Christiaens, Daan; Dutil, Francis; Egger, Karl; Feng, Chaolu; Glocker, Ben; Götz, Michael; Haeck, Tom; Halme, Hanna-Leena; Havaei, Mohammad; Iftekharuddin, Khan M; Jodoin, Pierre-Marc; Kamnitsas, Konstantinos; Kellner, Elias; Korvenoja, Antti; Larochelle, Hugo; Ledig, Christian; Lee, Jia-Hong; Maes, Frederik; Mahmood, Qaiser; Maier-Hein, Klaus H; McKinley, Richard; Muschelli, John; Pal, Chris; Pei, Linmin; Rangarajan, Janaki Raman; Reza, Syed M S; Robben, David; Rueckert, Daniel; Salli, Eero; Suetens, Paul; Wang, Ching-Wei; Wilms, Matthias; Kirschke, Jan S; Krämer, Ulrike M; Münte, Thomas F; Schramm, Peter; Wiest, Roland; Handels, Heinz; Reyes, Mauricio

    2017-01-01

    Ischemic stroke is the most common cerebrovascular disease, and its diagnosis, treatment, and study relies on non-invasive imaging. Algorithms for stroke lesion segmentation from magnetic resonance imaging (MRI) volumes are intensely researched, but the reported results are largely incomparable due to different datasets and evaluation schemes. We approached this urgent problem of comparability with the Ischemic Stroke Lesion Segmentation (ISLES) challenge organized in conjunction with the MICCAI 2015 conference. In this paper we propose a common evaluation framework, describe the publicly available datasets, and present the results of the two sub-challenges: Sub-Acute Stroke Lesion Segmentation (SISS) and Stroke Perfusion Estimation (SPES). A total of 16 research groups participated with a wide range of state-of-the-art automatic segmentation algorithms. A thorough analysis of the obtained data enables a critical evaluation of the current state-of-the-art, recommendations for further developments, and the identification of remaining challenges. The segmentation of acute perfusion lesions addressed in SPES was found to be feasible. However, algorithms applied to sub-acute lesion segmentation in SISS still lack accuracy. Overall, no algorithmic characteristic of any method was found to perform superior to the others. Instead, the characteristics of stroke lesion appearances, their evolution, and the observed challenges should be studied in detail. The annotated ISLES image datasets continue to be publicly available through an online evaluation system to serve as an ongoing benchmarking resource (www.isles-challenge.org).

  14. Proximal Arterial Occlusion in Acute Ischemic Stroke with Low NIHSS Scores Should Not Be Considered as Mild Stroke

    PubMed Central

    Kim, Joon-Tae; Park, Man-Seok; Chang, Jane; Lee, Ji Sung; Choi, Kang-Ho; Cho, Ki-Hyun

    2013-01-01

    Background Untreated acute mild stroke patients have substantial 90-day disability rates and worse outcomes than those who are treated with thrombolysis. There is little information regarding which patients with acute mild stroke will benefit from thrombolysis. We sought to investigate factors that are associated with early neurological deterioration (END) and poor prognosis in patients with acute mild stroke. Methods This was a retrospective study of consecutively registered patients with acute mild stroke (NIHSS ≤3) at our tertiary stroke center between October 2008 and December 2011. END was defined as an increase in NIHSS ≥2 points between hospital days 0 and 5. Modified Rankin Scale (mRS) scores of 0–1 at 90 days post-stroke were defined as favorable outcomes. Results A total of 378 (mean age, 65.9±13.0 years) patients were included in this study. END occurred in 55 patients (14.6%). IV-thrombolysis was performed in only 9 patients. Symptomatic arterial occlusion on the initial MRA was independently associated with END (OR, 2.206; 95% CI, 1.219–3.994; p = 0.009) by multivariate logistic regression. Of the 119 patients with symptomatic arterial occlusion, ICA occlusion was independently associated with END (OR, 8.606; 95% CI, 2.312–32.043; p = 0.001). Conclusions This study demonstrates that symptomatic arterial occlusion may be an important predictor of END in patients with acute mild stroke. It may therefore be important to consider that acute ischemic stroke with symptomatic arterial occlusion and low NIHSS scores may not represent mild stroke in acute periods. PMID:23976971

  15. Antithrombotic Management of Patients with Nonvalvular Atrial Fibrillation and Ischemic Stroke or Transient Ischemic Attack: Executive Summary of the Korean Clinical Practice Guidelines for Stroke

    PubMed Central

    Jung, Keun-Hwa; Kim, Young Dae; Park, Jong-Moo; Hong, Keun-Sik; Rha, Joung-Ho; Kwon, Sun U.; Bae, Hee-Joon; Heo, Ji Hoe; Lee, Byung-Chul; Yoon, Byung-Woo

    2015-01-01

    Cardioembolic stroke related to nonvalvular atrial fibrillation is associated with a high recurrence rate and high mortality and morbidity. In this population, therefore, optimal anticoagulant therapy is required to prevent the occurrence of second stroke. Oral anticoagulant, warfarin has been traditionally used, but it is greatly limited by its narrow efficacy window, complex pharmacokinetics, and multiple drug interactions, thus requiring frequent blood monitoring. Recently, oral anticoagulants targeted for a specific coagulation component have been newly developed and tested in large clinical trials. Dabigatran, direct thrombin inhibitor, and rivaroxaban, apixaban, and edoxaban, inhibitors of factor Xa harbor great merits of rapid action time, short half-life, stable plasma concentration, and little drug interaction. Recently, large randomized clinical trials and meta-analyses have been published to show the efficacy and safety of the new oral anticoagulants compared with warfarin. Based on the results from recent clinical trials, we revised recommendations to apply optimal anticoagulant therapy in patients with nonvalvular atrial fibrillation and ischemic stroke or transient ischemic attack. PMID:26060808

  16. The Relationship between Ischemic Stroke Patients with and without Retroflex Tongue: A Retrospective Study

    PubMed Central

    Huang, Yung-Sheng; Sun, Mu-Chien; Chen, Yu-Liang; Chiang, John Y.

    2017-01-01

    Background. Patients suffering from stroke exhibit different levels of capability in retroflex tongues, in our clinical observation. This study aims to derive the association of tongue retroflexibility with the degree of severity for stroke patients. Methods. All ischemic stroke patients were collected from August 2010 to July 2013 in the Stroke Center, Changhua Christian Hospital, Taiwan. All participants underwent medical history collection and clinical examination, including tongue images captured by ATDS. Statistical analysis was performed to compare the differences of ischemic stroke patients with and without retroflex tongue. Result. Among the total of 308 cases collected, 123 patients cannot retroflex their tongues, that is, the non-RT group. The length of stay in the non-RT group, 32.0 ± 21.5, was longer than those of the RT counterparts, 25.9 ± 14.4 (p value: 0.007). The NIHSS on admission, 14.1 ± 7.8 versus 8.9 ± 5.2, was higher and the Barthel Index upon admission, 18.6 ± 20.7 and 35.0 ± 24.2, was lower for the non-RT patients than that of the RT counterparts. Also, the non-RT patients account for 60.2% and 75.6% for Barthel Index ≤ 17 and NIHSS ≥ 9, respectively. Conclusion. The stroke patients in non-RT group showed significantly poor prognosis and were more serious in the degree of severity and level of autonomy than RT group, indicating that the ability to maneuver tongue retroflex can serve as a simple, reliable, and noninvasive means for the prognosis of ischemic stroke patients. PMID:28367222

  17. Weather as physiologically equivalent was not associated with ischemic stroke onsets in Vienna, 2004-2010.

    PubMed

    Ferrari, Julia; Shiue, Ivy; Seyfang, Leonhard; Matzarakis, Andreas; Lang, Wilfried

    2015-06-01

    Stroke rates were found to have seasonal variations. However, previous studies using air temperature, humidity, or air pressure separately were not adequate, and the study catchment was not clearly drawn. Therefore, here we proposed to use a thermal index called physiologically equivalent temperature (PET) that incorporates air temperature, humidity, wind speed, cloud cover, air pressure and radiation flux from a biometeorological approach to estimate the effect of weather as physiologically equivalent on ischemic stroke onsets in an Austrian population. Eight thousand four hundred eleven stroke events in Vienna registered within the Austrian Stroke Unit Register from January 1, 2004 to December 31, 2010 were included and were correlated with the weather data, obtained from the Central Institute for Meteorology and Geodynamics in the same area and study time period and calculated as PET (°C). Statistical analysis involved Poisson regression modeling. The median age was 74 years, and men made up 49 % of the entire population. Eighty percent had hypertension while 25.4 % were current smokers. Of note, 26.5 % had diabetes mellitus, 28.9 % had pre-stroke, and 11.5 % had pre-myocardial infarction. We have observed that onsets were higher on the weekdays than on the weekend. However, we did not find any significant association between PETs and ischemic stroke onsets by subtypes in Vienna. We did not observe any significant associations between PETs and ischemic stroke onsets by subtypes in Vienna. Hospital admission peaks on the weekdays might be due to hospital administration reasons.

  18. Determinants of outcome in patients eligible for thrombolysis for ischemic stroke

    PubMed Central

    Caso, Valeria; Paciaroni, Maurizio; Venti, Michele; Palmerini, Francesco; Silvestrelli, Giorgio; Milia, Paolo; Biagini, Sergio; Agnelli, Giancarlo

    2007-01-01

    Objectives Eligibility criteria for thrombolysis in ischemic stroke have been clearly defined. However, not all eligible patients benefit from this treatment. This study aimed to assess the determinants for clinical outcome in consecutive, eligible patients with ischemic stroke treated with thrombolysis in a single-center study. Methods Consecutive patients with ischemic stroke were treated with tissue plasminogen activator (t-PA) following the established eligibility National Institute of Neurological Disorders and Stroke (NINDS) and European Stroke Initiative (EUSI) criteria. Risk factors including blood pressure and pre-treatment glycemia were properly managed. Death and disability at 3 months were the study outcomes. Disability was evaluated by the Rankin-scale. Favorable outcome was defined as 0–2 and adverse outcome as 3–6 including death. Results Seventy-eight patients were included in the study in a single stroke unit. The mean age was 70.9 ± 13.2 years (range 36–94). Follow-up at 3 months was completed in 73 patients. A favorable outcome was observed in 37 patients (50%) and adverse outcome in 36 (36%). Nine patients (12.3%) died within 3 months. The presence of an occluded carotid artery was a strong predictor for adverse outcome (p < 0.0001). A low NIH Stroke Scale-Score (NIHSS) at admission was a associated with a favorable outcome, while history of diabetes mellitus led to an unfavorable outcome. Conclusion Among patients eligible for thrombolysis, many do not benefit from this treatment. These include patients with carotid occlusion and diabetes. PMID:18078026

  19. Assessment and provision of rehabilitation among patients hospitalized with acute ischemic stroke in China: Findings from the China National Stroke Registry II.

    PubMed

    Bettger, Janet Prvu; Li, Zixiao; Xian, Ying; Liu, Liping; Zhao, Xingquan; Li, Hao; Wang, Chunxue; Wang, Chunjuan; Meng, Xia; Wang, Anxin; Pan, Yuesong; Peterson, Eric D; Wang, Yilong; Wang, Yongjun

    2017-04-01

    Background Stroke rehabilitation improves functional recovery among stroke patients. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation among patients with acute ischemic stroke. Aims We examined the frequency and determinants of an assessment for rehabilitation among acute ischemic stroke patients from the China National Stroke Registry II. Methods Data for 19,294 acute ischemic stroke patients admitted to 219 hospitals from June 2012 to January 2013 were analyzed. The multivariable logistic regression model with the generalized estimating equation method accounting for in-hospital clustering was used to identify patient and hospital factors associated with having a rehabilitation assessment during the acute hospitalization. Results Among 19,294 acute ischemic stroke patients, 11,451 (59.4%) were assessed for rehabilitation. Rates of rehabilitation assessment varied among 219 hospitals (IQR 41.4% vs 81.5%). In the multivariable analysis, factors associated with increased likelihood of a rehabilitation assessment ( p < 0.05) included disability prior to stroke, higher NIHSS on admission, receipt of a dysphagia screen, deep venous thrombosis prophylaxis, carotid vessel imaging, longer length of stay, and treatment at a hospital with a higher number of hospital beds (per 100 units). In contrast, patients with a history of atrial fibrillation and hospitals with higher number of annual stroke discharges (per 100 patients) were less likely to receive rehabilitation assessment during the acute stroke hospitalization. Conclusions Rehabilitation assessment among acute ischemic stroke patients was suboptimal in China. Rates varied considerably among hospitals and support the need to improve adherence to recommended care for stroke survivors.

  20. Antigen-specific immune reactions to ischemic stroke

    PubMed Central

    Urra, Xabier; Miró, Francesc; Chamorro, Angel; Planas, Anna M.

    2014-01-01

    Brain proteins are detected in the cerebrospinal fluid (CSF) and blood of stroke patients and their concentration is related to the extent of brain damage. Antibodies against brain antigens develop after stroke, suggesting a humoral immune response to the brain injury. Furthermore, induced immune tolerance is beneficial in animal models of cerebral ischemia. The presence of circulating T cells sensitized against brain antigens, and antigen presenting cells (APCs) carrying brain antigens in draining lymphoid tissue of stroke patients support the notion that stroke might induce antigen-specific immune responses. After stroke, brain proteins that are normally hidden from the periphery, inflammatory mediators, and danger signals can exit the brain through several efflux routes. They can reach the blood after leaking out of the damaged blood-brain barrier (BBB) or following the drainage of interstitial fluid to the dural venous sinus, or reach the cervical lymph nodes through the nasal lymphatics following CSF drainage along the arachnoid sheaths of nerves across the nasal submucosa. The route and mode of access of brain antigens to lymphoid tissue could influence the type of response. Central and peripheral tolerance prevents autoimmunity, but the actual mechanisms of tolerance to brain antigens released into the periphery in the presence of inflammation, danger signals, and APCs, are not fully characterized. Stroke does not systematically trigger autoimmunity, but under certain circumstances, such as pronounced systemic inflammation or infection, autoreactive T cells could escape the tolerance controls. Further investigation is needed to elucidate whether antigen-specific immune events could underlie neurological complications impairing recovery from stroke. PMID:25309322

  1. Rapid weather changes are associated with increased ischemic stroke risk: a case-crossover study.

    PubMed

    Rakers, Florian; Schiffner, Rene; Rupprecht, Sven; Brandstädt, Antje; Witte, Otto W; Walther, Mario; Schlattmann, Peter; Schwab, Matthias

    2016-02-01

    Observational studies focusing on absolute meteorological values suggest an association between meteorological parameters and stroke risk but these results are inconsistent and conflicting. Since changes in weather can provoke atrial fibrillation, we examined the association between rapid weather changes and stroke risk in 1694 patients with determinable onset of stroke symptoms in a case-crossover study in central Germany. Days one to three before stroke onset were classified as hazard periods and day seven as the respective control period. Risk of ischemic stroke in relation to 24 h differences in mean ambient temperature, relative humidity and atmospheric pressure was determined. The association between temperature and stroke risk appears to be close to linear with an increase in stroke risk of 11 % (odds ratio 1.11, 95 % confidence interval 1.01-1.22) for each 2.9 °C temperature decrease over 24 h. In individuals with a higher cardiovascular risk, stroke risk increased by 30 % (1.30, 1.06-1.61). Risk for cardioembolic strokes increased by 26 % (1.26, 1.06-1.50). Rapid positive or negative changes in relative humidity (>5 %) and atmospheric pressure (>10 hPa) increased stroke risk by a maximum of 30 % (1.30, 1.02-1.66) and 63 % (1.63, 1.10-2.42). In individuals with a higher cardiovascular risk, rapid changes in atmospheric pressure were associated with a four-times higher stroke risk (4.56, 1.26-16.43). Our results suggest that rapid decreases in ambient temperature and rapid changes in relative humidity and atmospheric pressure increase stroke risk under temperate climate conditions. Individuals with a high cardiovascular risk profile seem to be at greater risk.

  2. Multi-Center Prediction of Hemorrhagic Transformation in Acute Ischemic Stroke using Permeability Imaging Features

    PubMed Central

    Scalzo, Fabien; Alger, Jeffry R.; Hu, Xiao; Saver, Jeffrey L.; Dani, Krishna A.; Muir, Keith W.; Demchuk, Andrew M.; Coutts, Shelagh B.; Luby, Marie; Warach, Steven; Liebeskind, David S.

    2013-01-01

    Permeability images derived from magnetic resonance (MR) perfusion images are sensitive to blood-brain barrier derangement of the brain tissue and have been shown to correlate with subsequent development of hemorrhagic transformation (HT) in acute ischemic stroke. This paper presents a multi-center retrospective study that evaluates the predictive power in terms of HT of six permeability MRI measures including contrast slope (CS), final contrast (FC), maximum peak bolus concentration (MPB), peak bolus area (PB), relative recirculation (rR), and percentage recovery (%R). Dynamic T2*-weighted perfusion MR images were collected from 263 acute ischemic stroke patients from four medical centers. An essential aspect of this study is to exploit a classifier-based framework to automatically identify predictive patterns in the overall intensity distribution of the permeability maps. The model is based on normalized intensity histograms that are used as input features to the predictive model. Linear and nonlinear predictive models are evaluated using a crossvalidation to measure generalization power on new patients and a comparative analysis is provided for the different types of parameters. Results demonstrate that perfusion imaging in acute ischemic stroke can predict HT with an average accuracy of more than 85% using a predictive model based on a nonlinear regression model. Results also indicate that the permeability feature based on the percentage of recovery performs significantly better than the other features. This novel model may be used to refine treatment decisions in acute stroke. PMID:23587928

  3. [Amantadine sulfate (PK-Merz) in the treatment of ischemic stroke: a clinical-experimental study].

    PubMed

    Khasanova, D R; Saĭkhunov, M V; Kitaeva, E A; Khafiz'ianova, R Kh; Islaamov, R R; Demin, T V

    2009-01-01

    A rat model of big brain ischemia with the middle brain artery occlusion was used for the study of amantadine sulfate (PK-Merz) effect on the expression of Hsp70 measured with immunohistochemical method and Western blot 12 h and 4 days after surgery. The neuroprotective effect of PK-Merz associated with the enhancement of Hsp70 expression in ischemic stroke in rats. To confirm the multivector neuroprotective action of the drug, a comparative study of clinical effectiveness of PK-Merz and magnesium sulfate was carried out in 40 patients (20 patients in each group) in the most acute period of atherothrombotic and cardioembolic strokes. Patients treated with PK-Merz exhibited the more significant restoration of consciousness and better dynamics (regress) of neurological deficit with the most intensive restoration of neurological deficit in the first day that allows to recommend the use of amantadine sulfate in the first hours of ischemic stroke and for the prevention of reperfusion damage in recanalisation therapy of ischemic stroke.

  4. A male Fabry disease patient treated with intravenous thrombolysis for acute ischemic stroke.

    PubMed

    Saarinen, Jukka T; Sillanpää, Niko; Kantola, Ilkka

    2015-02-01

    The use of intravenous thrombolytic therapy for acute ischemic stroke is associated with improved outcomes. Fabry disease is an X-linked glycosphingolipid storage disease with vascular endothelial deposits. Affected males with the classic phenotype develop renal, cardiac, and cerebrovascular disease and die prematurely. However, Fabry disease is rare in young men with first ischemic stroke of undetermined cause. We report a 38-year-old man with acute aphasia and a left M2 segment of the middle cerebral artery thrombus with no recanalization who was finally diagnosed with Fabry disease after left ventricular hypertrophy of undetermined cause had been identified. A gene test revealed a R227X mutation typical of Fabry disease with the classical phenotype. To our knowledge our patient is the first reported male Fabry patient who was given intravenous thrombolytic therapy and the first reported Fabry patient who received intravenous thrombolytic therapy between 3 and 4.5 hours of the symptom onset. Despite favorable prognostic indicators on admission imaging, our patient suffered a significant stroke and had an unfavorable clinical outcome. Fortunately, the episode was not complicated by intracranial hemorrhage. Further studies are needed to evaluate the efficacy and safety of intravenous thrombolytic therapy in treating patients with Fabry disease and acute ischemic stroke.

  5. Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke.

    PubMed

    Zhang, Chunling; Chopp, Michael; Cui, Yisheng; Wang, Lei; Zhang, Ruilan; Zhang, Li; Lu, Mei; Szalad, Alexandra; Doppler, Edith; Hitzl, Monika; Zhang, Zheng Gang

    2010-11-15

    Cerebrolysin is a peptide preparation mimicking the action of neurotrophic factors and has beneficial effects on neurodegenerative diseases and stroke. The present study investigated the effect of Cerebrolysin on neurogenesis in a rat model of embolic middle cerebral artery occlusion (MCAo). Treatment with Cerebrolysin at doses of 2.5 and 5 ml/kg significantly increased the number of bromodeoxyuridine-positive (BrdU(+)) subventricular zone (SVZ) neural progenitor cells and doublecortin (DCX) immunoreactivity (migrating neuroblasts) in the ipsilateral SVZ and striatal ischemic boundary 28 days after stroke when the treatment was initiated 24 hr after stroke. The treatment also reduced TUNEL(+) cells by ∼50% in the ischemic boundary. However, treatment with Cerebrolysin at a dose of 2.5 ml/kg initiated at 24 and 48 hr did not significantly reduce infarct volume but substantially improved neurological outcomes measured by an array of behavioral tests 21 and 28 days after stroke. Incubation of SVZ neural progenitor cells from ischemic rats with Cerebrolysin dose dependently augmented BrdU(+) cells and increased the number of Tuj1(+) cells (a marker of immature neurons). Blockage of the PI3K/Akt pathway abolished Cerebrolysin-increased BrdU(+) cells. Moreover, Cerebrolysin treatment promoted neural progenitor cell migration. Collectively, these data indicate that Cerebrolysin treatment when initiated 24 and 48 hr after stroke enhances neurogenesis in the ischemic brain and improves functional outcome and that Cerebrolysin-augmented proliferation, differentiation, and migration of adult SVZ neural progenitor cells contribute to Cerebrolysin-induced neurogenesis, which may be related to improvement of neurological outcome. The PI3K/Akt pathway mediates Cerebrolysin-induced progenitor cell proliferation.

  6. Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke

    PubMed Central

    Zhang, Chunling; Chopp, Michael; Cui, Yisheng; Wang, Lei; Zhang, Ruilan; Zhang, Li; Lu, Mei; Szalad, Alexandra; Doppler, Edith; Hitzl, Monika; Zhang, Zheng Gang

    2011-01-01

    Cerebrolysin is a peptide preparation mimicking the action of neurotrophic factors and has beneficial effects on neurodegenerative diseases and stroke. The present study investigated the effect of Cerebrolysin on neurogenesis in a rat model of embolic middle cerebral artery occlusion (MCAo). Treatment with Cerebrolysin at doses of 2.5 and 5 ml/kg significantly increased the number of bromodeoxyuridine positive (BrdU+) subventricular zone (SVZ) neural progenitor cells and doublecortin (DCX) immunoreactivity (migrating neuroblasts) in the ipsilateral SVZ and striatal ischemic boundary 28 days after stroke when the treatment was initiated 24h after stroke. The treatment also reduced TUNEL+ cells by ~50% in the ischemic boundary. However, treatment with Cerebrolysin at a dose of 2.5 ml/kg initiated at 24 and 48h did not significantly reduce infarct volume, but substantially improved neurological outcomes measured by an array of behavioral tests 21 and 28 days after stroke. Incubation of SVZ neural progenitor cells from ischemic rats with Cerebrolysin dose dependently augmented BrdU+ cells and increased the number of Tuj1+ cells (a marker of immature neurons). Blockage of the PI3K/Akt pathway abolished Cerebrolysin-increased BrdU+ cells. Moreover, Cerebrolysin treatment promoted neural progenitor cell migration. Collectively, these data indicate that Cerebrolysin treatment when initiated 24 and 48h after stroke enhances neurogenesis in the ischemic brain and improves functional outcome and that Cerebrolysin-augmented proliferation, differentiation, and migration of adult SVZ neural progenitor cells contribute to Cerebrolysin-induced neurogenesis, which may be related to improvement of neurological outcome. The PI3K/Akt pathway mediates Cerebrolysin-induced progenitor cell proliferation. PMID:20857512

  7. Role of brain natriuretic peptide as a novel prognostic biomarker in acute ischemic stroke

    PubMed Central

    Menon, Bindu; Ramalingam, Krishnana; Conjeevaram, Jyoti; Munisusmitha, K.

    2016-01-01

    Aim: We investigated to study the prognostic importance of brain natriuretic peptide (BNP) in ischemic stroke. Materials and Methods: We prospectively enrolled 100 patients with acute ischemic stroke and measured plasma BNP levels and compared with age- and sex-matched healthy controls. Risk factors, biochemical parameters, lipid profile, carotid and vertebral Doppler, imaging, and cardiac evaluation were done. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score on admission and functional disability by Barthel Index (BI) at 3 months. Ischemic stroke subtype was classified according to the Oxfordshire Community Stroke Project (OCSP). Data were entered in MS Excel, and appropriate statistical analysis was done using the SPSS software version 21.0. A P = 0.05 was considered as significant. Results: Mean age of patients was 55.17 ± 11.37 years with a male:female ratio 3:1. OCSP showed total anterior circulation infarct (TACI) 35, partial anterior circulation infarct 9, lacunar infarct 12, and posterior circulation infarct 44. NIHSS on admission was average 10 ± 7 and BI was 57 ± 30. BNP in patients (435 ng/ml) was very high as compared to controls (<60 ng/ml) (P < 0.001). There was a positive correlation between age and BNP (R2 = 0.34; P < 0.00); NIHSS and BNP (R2 = 0.255; P < 0.01), negative correlation between BI and BNP (R2 = −0.064; P < 0.01). Mean BNP levels across the OCSP showed higher values in TACI (F = 4.609 P = 0.005). Regression analysis showed that BNP can predict BI which was statistically significant. Conclusion: Plasma BNP levels was significantly elevated in patients with ischemic stroke. Our study concludes that high BNP levels are seen in large anterior circulation stroke and is a predictor for the poor functional outcome at 3 months. Determination of BNP levels as a biomarker could be helpful in predicting the outcome in stroke patients. PMID:27994354

  8. Polyhydroxylated fullerene nanoparticles attenuate brain infarction and oxidative stress in rat model of ischemic stroke

    PubMed Central

    Vani, Javad Rasouli; Mohammadi, Mohammad Taghi; Foroshani, Mahsa Sarami; Jafari, Mahvash

    2016-01-01

    Oxidative stress is the common underlying mechanism of damage in ischemic stroke. Therefore, we aimed to evaluate the possible protective effects of polyhydroxylated fullerene derivatives on brain infarction and oxidative/nitrosative stress in a rat model of ischemic stroke. The experiment was performed by four groups of rats (each; n=12); Sham, Control ischemia, and ischemic treatment groups (Pretreatment and Posttreatment). Brain ischemia was induced by 90 min middle cerebral artery occlusion (MCAO) followed by 24 hours reperfusion. Rats received fullerene nanoparticles at dose of 1 mg/kg 30 min before MCAO and immediately after beginning of reperfusion. Infarct volume, contents of malondialdehyde (MDA), glutathione (GSH) and nitrate as well as superoxide dismutase (SOD) activity were assessed 24 hours after termination of MCAO. Brain infarct volume was 310 ± 21 mm3 in control group. Administration of fullerene nanoparticles before and after MCAO significantly decreased the infarct volume by 53 % (145 ± 45 mm3) and 81 % (59 ± 13 mm3), respectively. Ischemia also enhanced MDA and nitrate contents of ischemic hemispheres by 45 % and 25 % , respectively. Fullerene nanoparticles considerably reduced the MDA and nitrate contents of ischemic hemispheres before MCAO by 58 % and 17 % , respectively, and after MCAO by 38 % and 21 % , respectively. Induction of MCAO significantly decreased GSH content (19 % ) and SOD activity (52 % ) of ischemic hemispheres, whereas fullerene nanoparticles increased the GSH content and SOD activity of ischemic hemispheres by 19 % and 52 % before MCAO, respectively, and 21 % and 55 % after MCAO, respectively. Our findings indicate that fullerene nanoparticles, as a potent scavenger of free radicals, protect the brain cells against ischemia/reperfusion injury and inhibit brain oxidative/nitrosative damage. PMID:27540350

  9. Implementing diagnostic reasoning to differentiate Todd's paralysis from acute ischemic stroke.

    PubMed

    Brosinski, Carmen M

    2014-01-01

    Emergency department clinicians with limited resources are relied upon to deliver safe and timely patient care. Clinicians rely on cognitive biases such as anchoring, availability, and premature closure based on experience and quick mental algorithms to streamline medical data and arrive at a diagnosis. Although this is a time-saving and efficient method in the management of uncomplicated illnesses, it can result in a wrong diagnosis when managing patients with complicated presentations such as a stroke or a stroke mimic. Two conditions that present similarly, making it difficult to differentiate between them, are Todd's paralysis (a stroke mimic seen in selected patients with epilepsy) and acute ischemic stroke. However, by clinical reasoning, clinicians can formulate an accurate diagnosis while avoiding diagnostic biases. Incorporating clinical reasoning into the diagnostic process consists of gathering pertinent data, performing a diagnostic time-out, and arriving at a diagnosis reflective of data findings.

  10. Translational strategies for neuroprotection in ischemic stroke - focusing on Acid Sensing Ion Channel 1a

    PubMed Central

    O'Bryant, Zaven; Vann, Kiara T.; Xiong, Zhi-Gang

    2014-01-01

    Ischemic stroke contributes to the majority of brain injuries and remains to be a leading cause of death and long-term disability. Despite the devastating pathology and high incidence of disease, there remain only few treatment options (tPA and endovascular procedures), which may be hampered by time dependent administration among a variety of other factors. Promising research of glutamate receptor antagonists has been unsuccessful in clinical trial. But, the mechanism by which glutamate receptors initiate injury by excessive calcium overload has spurred investigation of new and potentially successful candidates for stroke therapy. Acid sensing ion channels (ASICs) may contribute to poor stroke prognosis due to localized drop in brain pH, resulting in excessive calcium overload, independent of glutamate activation. Accumulating studies targeting ASICs have underscored the importance of understanding inhibition, regulation, desensitization and trafficking of this channel and its role in disease. This review will discuss potential directions in translational ASIC research for future stroke therapies. PMID:24390970

  11. Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke

    PubMed Central

    Turner, Renée J.; Sharp, Frank R.

    2016-01-01

    Numerous studies have documented increases in matrix metalloproteinases (MMPs), specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB), increased risk of hemorrhagic complications, and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA) treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke. PMID:26973468

  12. Association of Apolipoprotein C3 Genetic Polymorphisms with the Risk of Ischemic Stroke in the Northern Chinese Han Population

    PubMed Central

    Wang, Yanzhe; Yin, Xiaoyu; Li, Lei; Deng, Shumin; He, Zhiyi

    2016-01-01

    The apolipoprotein C3 (APOC3) gene, which is a member of the APOA1/C3/A4/A5 gene cluster, plays a crucial role in lipid metabolism. Dyslipidemia is an important risk factor for ischemic stroke. In the present study, we performed a hospital-based case—control study of 895 ischemic stroke patients and 883 control subjects to examine the effects of four APOC3 single nucleotide polymorphisms (SNPs) (rs2854116, rs2854117, rs4520 and rs5128) on the risk of ischemic stroke in a northern Chinese Han population. The SNaPshot Multiplex sequencing assay was used for SNP genotyping, and the potential association of genotype distributions and allele frequencies with ischemic stroke was analyzed statistically. Compared with the GG genotype, the CC+GC genotype of rs5128 was significantly associated with an increased risk in females (adjusted OR = 3.38, 95% CI = 1.82–6.28, P <0.01) after all of the risk factors were adjusted for with logistic regression analyses. A similar relationship was found between the rs4520 polymorphism and ischemic stroke risk in Han Chinese women. Under a recessive genetic model, the TT+TC genotypes of this variant increased ischemic stroke risk (adjusted OR = 2.05; 95% CI = 1.28–3.29; P <0.01). Haplotype analysis revealed that in males, the T-C-T-C haplotype of rs2854116-rs2854117-rs4520-rs5128 was significantly more frequent in the ischemic stroke group than in the control group (OR = 1.49, 95% CI = 1.18–1.87, P<0.01). The results of our study indicate that the APOC3 polymorphisms contribute to ischemic stroke susceptibility in females in the northern Chinese Han population. PMID:27690381

  13. Thrombin induces ischemic LTP (iLTP): implications for synaptic plasticity in the acute phase of ischemic stroke

    PubMed Central

    Stein, Efrat Shavit; Itsekson-Hayosh, Zeev; Aronovich, Anna; Reisner, Yair; Bushi, Doron; Pick, Chaim G.; Tanne, David; Chapman, Joab; Vlachos, Andreas; Maggio, Nicola

    2015-01-01

    Acute brain ischemia modifies synaptic plasticity by inducing ischemic long-term potentiation (iLTP) of synaptic transmission through the activation of N-Methyl-D-aspartate receptors (NMDAR). Thrombin, a blood coagulation factor, affects synaptic plasticity in an NMDAR dependent manner. Since its activity and concentration is increased in brain tissue upon acute stroke, we sought to clarify whether thrombin could mediate iLTP through the activation of its receptor Protease-Activated receptor 1 (PAR1). Extracellular recordings were obtained in CA1 region of hippocampal slices from C57BL/6 mice. In vitro ischemia was induced by acute (3 minutes) oxygen and glucose deprivation (OGD). A specific ex vivo enzymatic assay was employed to assess thrombin activity in hippocampal slices, while OGD-induced changes in prothrombin mRNA levels were assessed by (RT)qPCR. Upon OGD, thrombin activity increased in hippocampal slices. A robust potentiation of excitatory synaptic strength was detected, which occluded the ability to induce further LTP. Inhibition of either thrombin or its receptor PAR1 blocked iLTP and restored the physiological, stimulus induced LTP. Our study provides important insights on the early changes occurring at excitatory synapses after ischemia and indicates the thrombin/PAR1 pathway as a novel target for developing therapeutic strategies to restore synaptic function in the acute phase of ischemic stroke. PMID:25604482

  14. Nonstenotic Culprit Plaque: The Utility of High-Resolution Vessel Wall MRI of Intracranial Vessels after Ischemic Stroke

    PubMed Central

    de Havenon, Adam; Yuan, Chun; Tirschwell, David; Hatsukami, Thomas; Anzai, Yoshimi; Becker, Kyra; Sultan-Qurraie, Ali; Mossa-Basha, Mahmud

    2015-01-01

    Intracranial atherosclerotic disease (ICAD) accounts for 9–15% of ischemic stroke in the United States. Although highly stenotic ICAD accounts for most of the strokes, it is assumed that nonstenotic ICAD (nICAD) can result in stroke, despite being missed on standard luminal imaging modalities. We describe a patient with nICAD who suffered recurrent thromboembolic stroke and TIA but had a negative conventional stroke workup. As a result, they were referred for high-resolution magnetic resonance imaging (HR-MRI) of the arterial vessel wall, which identified a nonstenotic plaque with multiple high-risk features, identifying it as the etiology of the patient's thromboembolic events. The diagnosis resulted in a transition from anticoagulation to antiplatelet therapy, after which the patient's clinical events resolved. HR-MRI is an imaging technique that has the potential to guide medical management for patients with ischemic stroke, particularly in cryptogenic stroke. PMID:26346855

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

    PubMed Central

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

    2013-01-01

    Background and purpose 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. Methods 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. Results 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. Conclusion 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. PMID:24293992

  16. Pathophysiology and Treatments of Oxidative Injury in Ischemic Stroke: Focus on the Phagocytic NADPH Oxidase 2

    PubMed Central

    Carbone, Federico; Teixeira, Priscila Camillo; Braunersreuther, Vincent; Mach, François; Vuilleumier, Nicolas

    2015-01-01

    Abstract Significance: Phagocytes play a key role in promoting the oxidative stress after ischemic stroke occurrence. The phagocytic NADPH oxidase (NOX) 2 is a membrane-bound enzyme complex involved in the antimicrobial respiratory burst and free radical production in these cells. Recent Advances: Different oxidants have been shown to induce opposite effects on neuronal homeostasis after a stroke. However, several experimental models support the detrimental effects of NOX activity (especially the phagocytic isoform) on brain recovery after stroke. Therapeutic strategies selectively targeting the neurotoxic ROS and increasing neuroprotective oxidants have recently produced promising results. Critical Issues: NOX2 might promote carotid plaque rupture and stroke occurrence. In addition, NOX2-derived reactive oxygen species (ROS) released by resident and recruited phagocytes enhance cerebral ischemic injury, activating the inflammatory apoptotic pathways. The aim of this review is to update evidence on phagocyte-related oxidative stress, focusing on the role of NOX2 as a potential therapeutic target to reduce ROS-related cerebral injury after stroke. Future Directions: Radical scavenger compounds (such as Ebselen and Edaravone) are under clinical investigation as a therapeutic approach against stroke. On the other hand, NOX inhibition might represent a promising strategy to prevent the stroke-related injury. Although selective NOX inhibitors are not yet available, nonselective compounds (such as apocynin and fasudil) provided encouraging results in preclinical studies. Whereas additional studies are needed to better evaluate this therapeutic potential in human beings, the development of specific NOX inhibitors (such as monoclonal antibodies, small-molecule inhibitors, or aptamers) might further improve brain recovery after stroke. Antioxid. Redox Signal. 23, 460–489. PMID:24635113

  17. [Diagnosis and potential treatment of antiphospholipid syndrome-related mainly on ischemic stroke].

    PubMed

    Okuma, Hirohisa; Kitagawa, Yasuhisa

    2013-11-01

    Antiphospholipid syndrome (APS) was defined in 2006 by an international consensus as an autoimmune disease that manifests clinically as recurrent thrombotic complications or fetal loss and serologically as elevated plasma levels of antiphospholipid antibodies (aPLs). aPLs are a heterogeneous group of antibodies directed against anionic phospholipids, phospholipid-binding plasma proteins, and phospholipid-protein complexes. Standard ELISA for anticardiolipin (aCL) and anti-β2-glycoprotein I antibodies and clotting assays for lupus anticoagulant (LA) are recommended for detecting aPLs. Phosphatidylserine-dependent anti-prothrombin antibody (aPS/PT) assay may also be useful as a confirmatory test for APS. aPLs are an independent risk factor for initial occurence of ischemic stroke, especially in young adults. APS patients with thrombotic stroke frequently have other, often conventional, vascular risk factors. Guidelines issued in 2011 by the American Heart Association and American Stroke Association recommended antiplatelet therapy for patients with cryptogenic ischemic stroke or TIA and who test positive for aPL. In contrast, oral anticoagulants with a target international normalized ratio (INR) of 2.0-3.0 are recommended for patients with ischemic stroke who meet all the criteria for APS. Recently, 3 new anticoagulants for stroke prevention, dabigatran, rivaroxaban, and apixaban, have been studied in phase 3 clinical trials in patients with atrial fibrillation. However, optimal treatment for catastrophic APS is unknown. Current treatment guidelines emphasize the importance of early diagnosis and recommend aggressive therapies to avoid a fatal outcome. Combinations of high doses of intravenous heparin, steroids, and immunoglobulins and/or repeated plasma exchanges can be considered as treatments of choice for this severe condition.

  18. Intranasal Delivery of Apelin-13 Is Neuroprotective and Promotes Angiogenesis After Ischemic Stroke in Mice.

    PubMed

    Chen, Dongdong; Lee, Jinhwan; Gu, Xiaohuan; Wei, Ling; Yu, Shan Ping

    2015-01-01

    Apelin is a peptide originally isolated from bovine stomach tissue extracts and identified as an endogenous ligand of the APJ receptor; recent work showed that apelin ameliorates the ischemic injury in the heart and the brain. Being an analogue to the angiotensin II receptor, the apelin/APJ signaling may mediate angiogenesis process. We explored the noninvasive intranasal brain delivery method and investigated therapeutic effects of apelin-13 in a focal ischemic stroke model of mice. Intranasal administration of apelin-13 (4 mg/kg) was given 30 min after the onset of stroke and repeated once daily. Three days after stroke, mice received apelin-13 had significantly reduced infarct volume and less neuronal death in the penumbra. Western blot analyses showed upregulated levels of apelin, apelin receptor APLNR, and Bcl-2 and decreased caspase-3 activation in the apelin-13-treated brain. The proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1β, and chemokine monocyte chemoattractant protein-1 mRNA increased in the ischemic brain, which were significantly attenuated by apelin-13. Apelin-13 remarkably reduced microglia recruitment and activation in the penumbra according to morphological features of Iba-1-positive cells 3 days after ischemia. Apelin-13 significantly increased the expression of angiogenic factor vascular endothelial growth factor and matrix metalloproteinase-9 14 days after stroke. Angiogenesis illustrated by collagen IV + /5-bromo-2'-deoxyuridin + colabeled cells was significantly increased by the apelin-13 treatment 21 days after stroke. Finally, apelin-13 promoted the local cerebral blood flow restoration and long-term functional recovery. This study demonstrates a noninvasive intranasal delivery of apelin-13 after stroke, suggesting that the reduced inflammatory activities, decreased cell death, and increased angiogenesis contribute to the therapeutic benefits of apelin-13.

  19. Forebrain neuronal specific ablation of p53 gene provide protection in a cortical ischemic stroke model

    PubMed Central

    Filichia, Emily; Shen, Hui; Zhou, Xiaofei; Qi, Xin; Jin, Kevin; Greig, Nigel; Hoffer, Barry; Luo, Yu

    2016-01-01

    Cerebral ischemic injury involves death of multiple cell types at the ischemic sites. As a key regulator of cell death, the p53 gene has been implicated in the regulation of cell loss in stroke. Less focal damage is found in stroke animals pre-treated with a p53 inhibitor or in traditional p53 knockout (ko) mice. However, whether the p53 gene plays a direct role in regulating neuronal cell death is unknown. In this study, in contrast to the global inhibition of p53 function by pharmacological inhibitors and in traditional p53 ko mice, we utilized a neuronal specific conditional ko mouse line (CamcreTRP53 loxP/loxP) to achieve forebrain neuronal specific deletion of p53 and examined the role of the p53 gene in ischemia-induced cell death in neurons. Expression of p53 after stroke is examined using immunohistochemical method and outcome of stroke is examined by analysis of infarction size and behavioral deficits caused by stroke. Our data showed that p53 expression is upregulated in the ischemic region in neuronal cells in wildtype (wt) mice but not in CamcreTRP53 loxP/loxP ko mice. Deletion of the p53 gene in forebrain neurons results in a decreased infarction area in ko mice. Locomotor behavior, measured in automated activity chambers, showed that CamcreTRP53 loxP/loxP ko mice have less locomotor deficits compared to wt mice after MCAo. We conclude that manipulation of p53 expression in neurons may lead to unique therapeutic development in stroke. PMID:25779964

  20. Intranasal Delivery of Apelin-13 Is Neuroprotective and Promotes Angiogenesis After Ischemic Stroke in Mice

    PubMed Central

    Chen, Dongdong; Lee, Jinhwan; Gu, Xiaohuan; Wei, Ling

    2015-01-01

    Apelin is a peptide originally isolated from bovine stomach tissue extracts and identified as an endogenous ligand of the APJ receptor; recent work showed that apelin ameliorates the ischemic injury in the heart and the brain. Being an analogue to the angiotensin II receptor, the apelin/APJ signaling may mediate angiogenesis process. We explored the noninvasive intranasal brain delivery method and investigated therapeutic effects of apelin-13 in a focal ischemic stroke model of mice. Intranasal administration of apelin-13 (4 mg/kg) was given 30 min after the onset of stroke and repeated once daily. Three days after stroke, mice received apelin-13 had significantly reduced infarct volume and less neuronal death in the penumbra. Western blot analyses showed upregulated levels of apelin, apelin receptor APLNR, and Bcl-2 and decreased caspase-3 activation in the apelin-13-treated brain. The proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1β, and chemokine monocyte chemoattractant protein-1 mRNA increased in the ischemic brain, which were significantly attenuated by apelin-13. Apelin-13 remarkably reduced microglia recruitment and activation in the penumbra according to morphological features of Iba-1-positive cells 3 days after ischemia. Apelin-13 significantly increased the expression of angiogenic factor vascular endothelial growth factor and matrix metalloproteinase-9 14 days after stroke. Angiogenesis illustrated by collagen IV + /5-bromo-2′-deoxyuridin + colabeled cells was significantly increased by the apelin-13 treatment 21 days after stroke. Finally, apelin-13 promoted the local cerebral blood flow restoration and long-term functional recovery. This study demonstrates a noninvasive intranasal delivery of apelin-13 after stroke, suggesting that the reduced inflammatory activities, decreased cell death, and increased angiogenesis contribute to the therapeutic benefits of apelin-13. PMID:26391329

  1. Association of Geographical Factors With Administration of Tissue Plasminogen Activator for Acute Ischemic Stroke

    PubMed Central

    Kunisawa, Susumu; Morishima, Toshitaka; Ukawa, Naoto; Ikai, Hiroshi; Otsubo, Tetsuya; Ishikawa, Koichi B.; Yokota, Chiaki; Minematsu, Kazuo; Fushimi, Kiyohide; Imanaka, Yuichi

    2013-01-01

    Background Intravenous tissue plasminogen activator (tPA) is an effective treatment for acute ischemic stroke if administered within a few hours of stroke onset. Because of this time restriction, tPA administration remains infrequent. Ambulance use is an effective strategy for increasing tPA administration but may be influenced by geographical factors. The objectives of this study are to investigate the relationship between tPA administration and ambulance use and to examine how patient travel distance and population density affect tPA utilization. Methods and Results We analyzed administrative claims data from 114 194 acute ischemic stroke cases admitted to 603 hospitals between July 2010 and March 2012. Mixed‐effects logistic regression models of patients nested within hospitals with a random intercept were generated to analyze possible predictive factors (including patient characteristics, ambulance use, and driving time from home to hospital) of tPA administration for different population density categories to investigate differences in these factors in various regional backgrounds. Approximately 5.1% (5797/114 194) of patients received tPA. The composition of baseline characteristics varied among the population density categories, but adjustment for covariates resulted in all factors having similar associations with tPA administration in every category. The administration of tPA was associated with patient age and severity of stroke symptoms, but driving time showed no association. Ambulance use was significantly associated with tPA administration even after adjustment for covariates. Conclusion The association between ambulance use and tPA administration suggests the importance of calling an ambulance for suspected stroke. Promoting ambulance use for acute ischemic stroke patients may increase tPA use. PMID:24045119

  2. Urine specific gravity as a predictor of early neurological deterioration in acute ischemic stroke.

    PubMed

    Lin, L C; Fann, W C; Chou, M H; Chen, H W; Su, Y C; Chen, J C

    2011-07-01

    We previously found that a blood urea nitrogen/creatinine (BUN/Cr) ratio>15 is an independent predictor of early neurological deterioration after acute ischemic stroke, which suggests that dehydration may be a cause of early deterioration. The aim of this study was to determine whether urine specific gravity, which is another indicator of hydration status and one that is more easily obtained, is also an independent predictor of early deterioration or stroke-in-evolution (SIE). Demographic and clinical data were recorded at admission from patients with acute ischemic stroke who were prospectively enrolled from October 2007 to June 2010. We compared patients with and without stroke-in-evolution (based on an increase of 3 points or more points on the National Institutes of Health Stroke Scale within 3 days). Univariate and multivariate statistical analyses were carried out. A total of 317 patients (43 SIE and 274 non-SIE) were enrolled; the first 196 patients comprised the cohort of our previous study. The only two independent predictors of early deterioration or SIE were BUN/Cr>15 and urine specific gravity>1.010. After adjusting for age and gender, patients with a urine specific gravity>1.010 were 2.78 times more likely to develop SIE (95% CI=1.11-6.96; P=0.030). Urine specific gravity may be useful as an early predictor of early deterioration in patients with acute ischemic stroke. Patients with urine specific gravity ≤ 1.010 therefore may have a reduced likelihood of early neurological deterioration.

  3. Obesity and ischemic stroke modulate the methylation levels of KCNQ1 in white blood cells.

    PubMed

    Gómez-Úriz, Ana M; Milagro, Fermín I; Mansego, María L; Cordero, Paúl; Abete, Itziar; De Arce, Ana; Goyenechea, Estíbaliz; Blázquez, Vanessa; Martínez-Zabaleta, Maite; Martínez, José Alfredo; López De Munain, Adolfo; Campión, Javier

    2015-03-01

    Obesity and stroke are multifactorial diseases in which genetic, epigenetic and lifestyle factors are involved. The research aims were, first, the description of genes with differential epigenetic regulation obtained by an 'omics' approach in patients with ischemic stroke and, second, to determine the importance of some regions of these selected genes in biological processes depending on the body mass index. A case-control study using two populations was designed. The first population consisted of 24 volunteers according to stroke/non-stroke and normal weight/obesity conditions. The second population included 60 stroke patients and 55 controls classified by adiposity. DNA from the first population was analyzed with a methylation microarray, showing 80 cytosine-guanine dinucleotides (CpG) sites differentially methylated in stroke and 96 CpGs in obesity, whereas 59 CpGs showed interaction. After validating these data by MassArray Epityper, the promoter region of peptidase M20 domain containing 1 (PM20D1) gene was significantly hypermethylated in stroke patients. One CpG site at Caldesmon 1 (CALD1) gene showed an interaction between stroke and obesity. Two CpGs located in the genes Wilms' tumor 1 (WT1) and potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) were significantly hypermethylated in obese patients. In the second population, KCNQ1 was also hypermethylated in the obese subjects. Two CpGs of this gene were subsequently validated by methylation-sensitive high-resolution melting. Moreover, KCNQ1 methylation levels were associated with plasma KCNQ1 protein concentrations. In conclusion, obesity induced changes in the KCNQ1 methylation pattern which were also dependent on stroke. Furthermore, the epigenetic marks differentially methylated in the stroke patients were dependent on the previous obese state. These DNA methylation patterns could be used as future potential stroke biomarkers.

  4. Induction of pluripotent stem cells transplantation therapy for ischemic stroke.

    PubMed

    Jiang, Mei; Lv, Lei; Ji, Haifeng; Yang, Xuelian; Zhu, Wei; Cai, Liying; Gu, Xiaju; Chai, Changfeng; Huang, Shu; Sun, Jian; Dong, Qiang

    2011-08-01

    Stroke can cause permanent neurological damage, complications, and even death. However, there is no treatment exists to restore its lost function. Human embryonic stems transplantation therapy was a novel and potential therapeutic approach for stroke. However, as we have seen, the ethical controversy pertains to embryonic stem cell research. Human induced pluripotent stem cells (iPSCs) are the latest generation of stem cells that may be a solution to the controversy of using embryonic cells. In our study, we generated iPSCs from adult human fibroblasts by introduction of four defined transcription factors (Oct4, Sox2, Nanog, and Lin-28). And then, we investigated the efficacy of iPSCs transplantation therapy for stroke on the animal models of middle cerebral artery occlusion. Surprisingly, we found that transplanted iPSCs migrated to injured brain areas, and differentiated into neuron-like cells successfully. After 4-16 days iPSCs grafting, sensorimotor function of rats has been improved significantly. In one word, we may prove that iPSCs therapy in stroke to be an effective form of treatment.

  5. Circulating damage marker profiles support a neuroprotective effect of erythropoietin in ischemic stroke patients.

    PubMed

    Ehrenreich, Hannelore; Kästner, Anne; Weissenborn, Karin; Streeter, Jackson; Sperling, Swetlana; Wang, Kevin K; Worthmann, Hans; Hayes, Ronald L; von Ahsen, Nico; Kastrup, Andreas; Jeromin, Andreas; Herrmann, Manfred

    2011-01-01

    The German Multicenter EPO Stroke Trial, which investigated safety and efficacy of erythropoietin (EPO) treatment in ischemic stroke, was formally declared a negative study. Exploratory subgroup analysis, however, revealed that patients not receiving thrombolysis most likely benefited from EPO during clinical recovery, a result demonstrated in the findings of the Göttingen EPO Stroke Study. The present work investigated whether the positive signal on clinical outcome in this patient subgroup was mirrored by respective poststroke biomarker profiles. All patients of the German Multicenter EPO Stroke Trial nonqualifying for thrombolysis were included if they (a) were treated per protocol and (b) had at least two of the five follow-up blood samples for circulating damage markers drawn (n = 163). The glial markers S100B and glial fibrillary acid protein (GFAP) and the neuronal marker ubiquitin C-terminal hydrolase (UCH-L1) were measured by enzyme-linked immunosorbent assay in serum on d 1, 2, 3, 4 and 7 poststroke. All biomarkers increased poststroke. Overall, EPO-treated patients had significantly lower concentrations (area under the curve) over 7 d of observation, as reflected by the composite score of all three markers (Cronbach α = 0.811) and by UCH-L1. S100B and GFAP showed a similar tendency. To conclude, serum biomarker profiles, as an outcome measure of brain damage, corroborate an advantageous effect of EPO in ischemic stroke. In particular, reduction in the neuronal damage marker UCH-L1 may reflect neuroprotection by EPO.

  6. Thromboembolic ischemic stroke and the presence of necrotic platelets: a scanning electron microscopy investigation.

    PubMed

    Pretorius, Etheresia; Engelbrecht, Mia-Jeanne; Duim, Wiebren

    2012-02-01

    Stroke is one of the most debilitating diseases worldwide, with its occurrence increasing in Western societies. Central to the pathogenesis of thromboembolic stroke is the involvement of platelets. During thromboembolic events, nucleated cells undergo cell death, and platelets are also affected by parameters causing these incidents. Particularly, initiation of necrotic cell death at sites of vascular injury may play an important role in inducing inflammatory and repair processes. In the current research, the authors investigate whether a changed platelet ultrastructure is visible in thromboembolic stroke and whether it might be visible in platelets as apoptosis or necrosis. Therefore, in the current investigation, the authors study smears of platelet-rich plasma (PRP) from thromboembolic ischemic stroke patients to investigate whether a changed morphology is visible in distressed platelets. Scanning electron microscopy is used and platelets are viewed at up to 200,000× machine magnification. Results indicate that thromboembolic ischemic stroke causes membrane tears and swollen platelets, and this is indicative of necrosis. It is therefore concluded that this morphology might be due to the pro-coagulant activity characteristic of the disease.

  7. [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)].

    PubMed

    Gusev, E I; Skvortsova, V I; Miasoedov, N F; Nezavibat'ko, V N; Zhuravleva, E Iu; Vanichkin, A V

    1997-01-01

    Efficiency of Semax (synthetic derivative of ACTH-4-10) was studied in 30 patients in acute period of hemispherical ischemic stroke. Control group consisted of 80 patients with the strokes analogous in severity and location of the damages and which were treated by conventional therapy. Different clinical rating scales were used for both objectivization of the severity of the patients' state and estimation of the degree of neurological defect. The control of Semax influence on the functional state of the brain included monitoring of EEG with mapping, repeated analysis of somatosensory evoked potentials and their mapping. It was established that including of Semax in combined intensive therapy of acute ischemic stroke had some influence on the rate of restoration of the damaged neurological functions in terms of increasing the regress of general cerebral and focal, especially motor disorders. The most effective daily doses were 12 mg for patients with strokes of moderate severity and 18 mg for patients with severe strokes (treatment course--5 and 10 days).

  8. Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke

    PubMed Central

    Lioutas, Vasileios-Arsenios; Alfaro-Martinez, Freddy; Bedoya, Francisco; Chung, Chen-Chih; Pimentel, Daniela A.; Novak, Vera

    2016-01-01

    Treatment options for stroke remain limited. Neuroprotective therapies, in particular, have invariably failed to yield the expected benefit in stroke patients, despite robust theoretical and mechanistic background and promising animal data. Insulin and insulin-like growth factor 1 (IGF-1) play a pivotal role in critical brain functions, such as energy homeostasis, neuronal growth, and differentiation. They may exhibit neuroprotective properties in acute ischemic stroke based upon their vasodilatory, anti-inflammatory and antithrombotic effects, as well as improvements of functional connectivity, neuronal metabolism, neurotransmitter regulation, and remyelination. Intranasally administered insulin has demonstrated a benefit for prevention of cognitive decline in older people, and IGF-1 has shown potential benefit to improve functional outcomes in animal models of acute ischemic stroke. The intranasal route presents a feasible, tolerable, safe, and particularly effective administration route, bypassing the blood–brain barrier and maximizing distribution to the central nervous system (CNS), without the disadvantages of systemic side effects and first-pass metabolism. This review summarizes the neuroprotective potential of intranasally administered insulin and IGF-1 in stroke patients. We present the theoretical background and pathophysiologic mechanisms, animal and human studies of intranasal insulin and IGF-1, and the safety and feasibility of intranasal route for medication administration to the CNS. PMID:26040423

  9. Different impairment of immune and inflammation functions in short and long-term after ischemic stroke

    PubMed Central

    Li, Wen-Xing; Qi, Fei; Liu, Jia-Qian; Li, Gong-Hua; Dai, Shao-Xing; Zhang, Tao; Cheng, Fei; Liu, Dahai; Zheng, Song Guo

    2017-01-01

    Ischemic stroke therapy and prognosis outcomes largely depend on the time periods after symptom onset. This study aims to explore the difference of global gene expression profiles and impairment of biological functions between short-term and long-term after stroke onset. We compared three short-term (3 h, 5 h and 24 h) and a long-term (6-month) gene expression levels by a multi-platform microarray data integration method. RankProd was used to calculate the differentially expressed genes between stroke patients and controls. DAVID Bioinformatics Resources was utilized to determine affected biological functions. Consensus cluster and hierarchical cluster methods were employed to compare the gene expression patterns of the commonly biological functions among these four time course groups. The results showed that severe impairment of inflammation and immune related functions in 5 h and 24 h after symptom onset. However, these functions were less affected in the 3 h and the 6-month groups. In addition, several key genes (CCL20, THBS1, EREG, and IL6 et al.) were dramatically down-regulated in 5 h and 24 h groups, whereas these genes showed no change or even a slight contrary expression in 3 h or 6-month groups. This study has identified the large differences of altered immune and inflammation functions based on gene levels between short and long-term after stroke onset. The findings provide valuable insight into the clinical practice and prognosis evaluation of ischemic stroke. PMID:28337302

  10. A Young Woman with Ischemic Stroke: Should We Pay More Attention to Varicella Zoster Infection?

    PubMed Central

    Borbinha, Cláudia; Marto, João Pedro; Calado, Sofia; Viana-Baptista, Miguel

    2016-01-01

    Ischemic and hemorrhagic stroke are recognized complications of Varicella zoster virus (VZV) infections, although uncommon and poorly documented. The authors report the case of a 31-year-old woman admitted with acute ischemic stroke of the right posterior cerebral artery and a history of a thoracic rash 1 month before. Aspirin and simvastatin were prescribed, but the patient suffered a stepwise deterioration the following days, with new areas of infarction on brain imaging. Despite no evidence of cardiac or large vessel embolic sources, anticoagulation was started empirically 6 days after stroke onset. One week later, symptomatic hemorrhagic transformation occurred. The diagnosis of VZV vasculopathy was then considered, and treatment with acyclovir and prednisolone was started with no further vascular events. Cerebrospinal fluid analysis and digital subtraction angiography findings corroborated the diagnosis. The patient was discharged to the rehabilitation center with a modified Rankin scale (mRS) score of 4. On the 6-month follow-up, she presented only a slight disability (mRS score 2). In conclusion, VZV vasculopathy needs to be considered in young adults with stroke. A high index of suspicion and early treatment seem to be important to minimize morbidity and mortality. Anticoagulation should probably be avoided in stroke associated with VZV vasculopathy. PMID:27504091

  11. Pilot study of the safety of starting administration of low-dose aspirin and cilostazol in acute ischemic stroke.

    PubMed

    Fujita, Keishi; Komatsu, Yoji; Sato, Naoaki; Higuchi, Osamu; Kujiraoka, Yuji; Kamezaki, Takao; Suzuki, Kensuke; Matsumura, Akira

    2011-01-01

    Progressive stroke is a serious problem due to the associated morbidity and mortality. Aspirin is recommended for acute ischemic stroke, but does not reduce the frequency of stroke progression. No standard treatment has been approved for the prevention of stroke progression. Cilostazol, which reduces platelet aggregation about 3 hours after single administration, does not increase the frequency of bleeding events when compared with aspirin or a placebo. Moreover, the combination of 100 mg aspirin and 200 mg cilostazol does not increase the frequency of bleeding events compared with only 100 mg aspirin, and thus is expected to prevent stroke progression with a high degree of safety. The present study investigated the safety of this combination of two drugs administered at the above concentrations in 54 patients with acute ischemic stroke within 48 hours of stroke onset. Modified National Institutes of Health Stroke Scale (NIHSS) measurements were performed at baseline and again on day 4 to 7. Progressive stroke was defined as an increase greater than or equal to 1 point on NIHSS. Patient scores on the modified Rankin Scale (mRS) were evaluated at baseline and 3 months after enrollment. Stroke progression occurred in 11.1% of the patients. The percentages of patients with mRS score from 0 to 2 were 42.6% and 75% at baseline and 3 months, respectively. No symptomatic intracranial hemorrhage or major extracranial hemorrhage occurred. These results suggest that administration of aspirin and cilostazol is safe for acute ischemic stroke.

  12. Role of Vitamin D in the Outcome of Ischemic Stroke- A Randomized Controlled Trial

    PubMed Central

    Balasubramanian, Prakash

    2017-01-01

    Introduction Vitamin D deficiency has reached epidemic proportions in India with prevalence rates of 70-100% in the general population. Low vitamin D levels are associated with worse outcomes in ischemic strokes. The outcome of stroke after vitamin D replenishment has not been much studied. Aim To compare the stroke outcome between patients receiving vitamin D supplementation and patients without vitamin D supplementation by Scandinavian Stroke Scale (SSS) and thus, to assess the long term outcome of ischemic stroke patients with low vitamin D level by supplementation of vitamin D. Materials and Methods This is a non blinded randomized controlled trial conducted in ischemic stroke patients. The patients were divided into two groups (A and B) where Group A received a single dose of 6 lac IU of Cholecalciferol Intramascular (IM) injection and Group B were not given vitamin D. Finally 30 patients in each group were analyzed. SSS was applied to evaluate the stroke severity at the onset and at the follow up after three months in both groups. The difference in SSS was analyzed using SPSS software. Independent t-test was applied and p-value < 0.05 was taken as significant. Results Mean±SD of vitamin D levels in Group A and Group B were 17.98±3.81ng/ml and 18.44±4.69 ng/ml respectively. Mean±SD of SSS at time of admission and after three months for Group A was 32.50±11.61 and 38.89±8.34; and for Group B 35.82±8.56 and 38.32±7.10. The difference in SSS from time of admission and after three months, in Group A (6.39±4.56) and Group B (2.50±2.20) were analyzed statistically and found to be highly significant (p<0.001). Conclusion The results showed that there is a significant improvement in the stroke outcome after three months in those patients who were supplemented with vitamin D. Thus screening for vitamin D deficiency in stroke patients is essential and vitamin D replenishment will improve the stroke outcome. PMID:28384856

  13. Treatment Strategies for Acute Ischemic Stroke Caused by Carotid Artery Occlusion

    PubMed Central

    Li, Wei; Yin, Qin; Xu, Gelin; Liu, Xinfeng

    2016-01-01

    Background: Acute ischemic stroke caused by internal carotid artery (ICA) occlusion usually has a poor prognosis, especially the T occlusion cases without functional collaterals. The efficacy of intravenous (IV) or intra-arterial (IA) thrombolysis with recombinant tissue plasminogen activator (rt-PA) remains ambiguous in these patients. Eendovascular recanalization of the occluded carotid has been attempted in recent years as a potential strategy. However, the different etiologies of ICA occlusion pose a significant challenge to neurointerventionists. Recently, several endovascular evolvements have been reported in treating carotid occlusion-related stroke. This review summarizes the current status of treatment for acute ICA occlusion. PMID:27781043

  14. Successful Escape of Acute Ischemic Stroke Patients from Hospital to Home: Clinical Note

    PubMed Central

    Tei, Hideaki

    2012-01-01

    I describe four patients who successfully escaped from the hospital to their own home during the acute phase of ischemic stroke. This is a very rare phenomenon (seen in 0.35% of 1150 consecutive patients with first ischemic stroke within 24 h after onset), but the patients had rather uniform clinical characteristics. All were male, around 60 years old, had moderate to severe aphasia (Wernicke’s in 2 patients, Broca's in 1, and transcortical motor in 1), and cerebral infarction of the left middle cerebral artery territory. None had significant motor weakness, hemispatial neglect, or hemianopia at the time of escape. Overall functional outcome was good for all but one patient, but aphasia persisted in three. Although none of the four patients sustained serious injury during the escape, patients with such clinical characteristics must be managed cautiously to prevent serious consequences. PMID:22425726

  15. [Investigation of mechanisms of neuro-protective effect of semax in acute period of ischemic stroke].

    PubMed

    Miasoedova, N F; Skvortsova, V I; Nasonov, E L; Zhuravleva, E Iu; Grivennikov, I A; Arsen'eva, E L; Sukhanov, I I

    1999-01-01

    Semax is the first domestic nootropic drug of an unexhausted type from the group of neuropeptides. In experimental studies it showed angioprotective, antihypoxic and neurotrophic activity in the doses 100-150 micrograms/kg. A combined clinical-electrophysiologic study revealed its high efficiency in acute ischemic stroke. A clinical trial was performed of immunobiochemical mechanisms of neuroprotective properties of Semax in acute period of ischemic stroke. A retrospective comparative clinicoimmunobiochemical analysis provided objective data on the molecular level on activating influence of Semax on antiinflammatory postischemic reactions in the brain. Shifting neuromediatory balance toward a prevalence of the antiinflammatory agents (interleukin-10, tumor necrosis factor-alpha) over the factors maintaining the inflammation (interleukin-8, C-reactive protein).

  16. Mild Sensory Stimulation Completely Protects the Adult Rodent Cortex from Ischemic Stroke

    PubMed Central

    Chen-Bee, Cynthia H.; Frostig, Ron D.

    2010-01-01

    Despite progress in reducing ischemic stroke damage, complete protection remains elusive. Here we demonstrate that, after permanent occlusion of a major cortical artery (middle cerebral artery; MCA), single whisker stimulation can induce complete protection of the adult rat cortex, but only if administered within a critical time window. Animals that receive early treatment are histologically and behaviorally equivalent to healthy controls and have normal neuronal function. Protection of the cortex clearly requires reperfusion to the ischemic area despite permanent occlusion. Using blood flow imaging and other techniques we found evidence of reversed blood flow into MCA branches from an alternate arterial source via collateral vessels (inter-arterial connections), a potential mechanism for reperfusion. These findings suggest that the cortex is capable of extensive blood flow reorganization and more importantly that mild sensory stimulation can provide complete protection from impending stroke given early intervention. Such non-invasive, non-pharmacological intervention has clear translational potential. PMID:20585659

  17. Bioactive components of Chinese herbal medicine enhance endogenous neurogenesis in animal models of ischemic stroke

    PubMed Central

    Li, Ji-Huang; Chen, Zi-Xian; Zhang, Xiao-Guang; Li, Yan; Yang, Wen-Ting; Zheng, Xia-Wei; Chen, Shuang; Lu, Lin; Gu, Yong; Zheng, Guo-Qing

    2016-01-01

    Abstract Background: Chinese herbal medicine (CHM) has been used to treat stroke for thousands of years. The objective of the study is to assess the current evidence for bioactive components of CHM as neurogenesis agent in animal models of ischemic stroke. Methods: We searched PubMed, China National Knowledge Infrastructure, WanFang Database, and VIP Database for Chinese Technical Periodicals published from the inception up to November 2015. The primary measured outcome was one of neurogenesis biomarker, including Bromodeoxyuridine (BrdU), Nestin, doublecortin (DCX), polysialylated form of the neural cell adhesion molecule (PSA-NCAM), neuronal nuclear antigen (NeuN), and glial fibrillary acidic protein (GFAP). Results: Thirty eligible studies were identified. The score of quality assessment ranged from 2 of 10 to 7 of 10. Compared with controls, 10 studies conducting neurobehavioral evaluation showed significant effects on bioactive components of CHM for improving neurological deficits score after ischemic insults (P < 0.01 or P < 0.05); 6 studies in Morris water-maze test showed bioactive components of CHM significantly decreased escape latency and increased residence time (P < 0.05); 5 studies demonstrated that bioactive components of CHM significantly reduced infarct volume after ischemic stroke (P < 0.05); 25 of 26 studies showed that bioactive components of CHM significantly increased the expression of BrdU and/or Nestin markers in rats/mice brain after ischemic injury (P < 0.05, or P < 0.01); 4 of 5 studies for promoting the expression of PSA-NCAM or DCX biomarker (P < 0.05); 5 studies for improving the expression of NeuN biomarker (P < 0.05); 6 of 7 studies for promoting the expression of GFAP biomarker in brain after ischemic stroke (P < 0.05). Conclusion: The findings suggest that bioactive components of CHM may improve neurological function, reduce infarct volume, and promote endogenous neurogenesis, including

  18. Metabolic syndrome associated with ischemic stroke among the Mexican Hispanic population in the El Paso/US-Mexico border region.

    PubMed

    Osborn, Michael F; Miller, Charles C; Badr, Ahmed; Zhang, Jun

    2014-07-01

    The Hispanic population carries a disproportionate burden of stroke compared with the non-Hispanic White population. Most studies have been conducted on Caribbean Hispanics, indicating a need to better understand the characteristics of stroke and its prevalence among the Hispanic populations of Mexican descent. In this report, data were collected in the El Paso/US-Mexico border region, where 82% of the population is Mexican Hispanic, through a retrospective study of ischemic stroke from 2005-2010. Odds ratios (ORs), 95% confidence intervals, logistic regression, and multivariate analysis of the ORs adjusted for other variables, were used to analyze the effects of various risk factors on ischemic stroke. The metabolic syndrome and its components, specifically hypertension, diabetes, and dyslipidemia appeared to be strongly associated with ischemic stroke in the Mexican Hispanic population. Mexican Hispanic ischemic stroke patients were nearly 7 times more likely to have this syndrome, compared with Mexican Hispanic controls from the National Health and Nutrition Examination Survey. Likewise, the patients were nearly 40 times more likely to have hypertension and 11 times more likely to have diabetes. Efforts to prevent ischemic stroke and limit its impact in the Mexican Hispanic population should focus on controlling hypertension and diabetes.

  19. Ischemic Stroke: From Next Generation Sequencing and GWAS to Community Genomics?

    PubMed

    Black, Michael; Wang, Wenzhi; Wang, Wei

    2015-08-01

    Stroke is a major cause of mortality and morbidity in both the developed and developing world. Next generation sequencing (NGS) and multi-omics integrative biology research offer new opportunities in the way we research and understand stroke. These biotechnologies also signal a shift from genetics to genomics of stroke, which is highlighted in this review. Stroke is a focal neurological deficit resulting from disruption of the cerebral blood supply. There are two main types of common stroke, ischemic stroke (IS), which comprises 80% of cases, and hemorrhagic stroke (HS) that accounts for about 20% of cases. IS is a complex multi-factorial disease with multiple environmental and genomic determinants. We discuss here IS from genomics and bioinformatics perspectives, including the highlights of the genome wide association studies (GWAS), NGS progress to date, and exome studies. While both 'common variant, common disease' and 'rare variant, common disease' approaches need to be assessed in tandem, future studies into IS omics should also consider pedigree and/or community based sampling to take account of the complex diversity of IS genetics. We conclude by presenting an example of such community genomics research from China in an extended pedigree sample, and the ways in which the intersection of genomics and global society can usefully inform our understanding of IS pathophysiology and potential preventive medicine interventions in the future.

  20. MRI of the pharynx in ischemic stroke patients with and without obstructive sleep apnea

    PubMed Central

    Brown, Devin L.; Bapuraj, J. Rajiv; Mukherji, Suresh K.; Chervin, Ronald D.; Concannon, Maryann; Helman, Joseph I.; Lisabeth, Lynda D.

    2010-01-01

    Background Obstructive sleep apnea (OSA) is common after stroke and associated with poor stroke outcomes. Whether OSA after acute stroke is caused by anatomic, physiologic, or both etiologies has not been studied. We therefore used brain magnetic resonance imaging (MRI) scans to assess oropharyngeal anatomy in stroke patients with and without OSA. Methods Patients within 7 days of ischemic stroke underwent nocturnal polysomnography. Sagittal T1-weighted MRI performed for clinical purposes was used to measure retropalatal distance, soft palatal length, soft palatal thickness, retroglossal space, and tongue length. Nasopharyngeal area and high retropharyngeal area were measured from axial T2-weighted images, and lateral pharyngeal wall thickness from coronal T1-weighted images. Results Among 27 subjects, 18 (67%) had OSA (apnea/hypopnea index (AHI) ≥5). Demographics, vascular risk factors, and stroke severity were similar in the two groups. Median retropalatal distance was shorter in subjects with OSA (Wilcoxon rank-sum test, p= 0.03). Shorter retropalatal distance was associated with higher AHI (linear regression, p=0.04). None of the other morphological characteristics differed. Conclusions Anatomic difference between awake acute stroke patients with and without OSA shows that the sleep disorder cannot be attributed solely to sleep, sleeping position, or changes in neuromuscular control that are specific to the sleep state. PMID:20466584

  1. [Course of free radical processes and prognosis of ischemic and hemorrhagic stroke].

    PubMed

    Silina, E V; Rumiantseva, S A; Bolevich, S B; Men'shova, N I

    2011-01-01

    A study of free radical processes (FRP) markers in 381 patients with ischemic and hemorrhagic stroke revealed the importance of oxidant stress that was most severe in patients with large volumes of stroke. Intensification of FRP consists in the reduction or inversion of oxygen FRP activity and increase in lipid free radical FRP that last till the patient discharge from a hospital. FRP indicators are early prognostic markers of stroke course and outcome. An inverse correlation between the level of anti peroxide plasma activity (APA) and the dynamics of the increase in stroke lesion from 1 to 20 days, and direct correlation between malondialdehyde (MDA) titer and the risk of hemorrhagic transformation and growth of the lesion from 5 to 20 days of disease were revealed. The results indicate that inclusion of antoixidant therapy should be conducted as early as possible after stroke using high doses of drugs in severe cases. The high efficacy of antioxidant cytoflavin in a daily dose of 20 ml in patients with stroke of different character and severity was shown. The positive effect of cytoflavin on FRP markers was accompanied by the improvement of clinical and morphological presentations and stroke outcome.

  2. Relationship Between Carotid Stenosis and Infarct Volume in Ischemic Stroke Patients

    PubMed Central

    Alagöz, Aybala Neslihan; Acar, Bilgehan Atılgan; Acar, Türkan; Karacan, Alper; Demiryürek, Bekir Enes

    2016-01-01

    Background Stroke is a serious health problem all over the world. Ischemia causes 85% of strokes and 75% of these ischemic strokes occur within the area supplied by the internal carotid artery (ICA). Material/Methods This study included 47 acute stroke patients who were in the large-artery atherosclerosis group according to Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification and who had an infarct in the area supplied by the internal carotid artery. We sought to determine whether there was a significant correlation between the infarct volume of the patients as measured by diffusion-weighted magnetic resonance imaging (DW MRI), their National Institutes of Health Stroke Scale (NIHSS), and degree of carotid stenosis as identified by carotid computed tomography angiography (CTA). Results A significant correlation was observed between the percentage of carotid artery stenosis and infarct volume (p<0.001). In addition, there was a significant positive correlation between the NIHSS and infarct volume; the correlation was of moderate strength (r=0.366, p=0.001). Conclusions Our findings indicate that the percentage of carotid artery stenosis could be useful in predicting the infarct volume of the stroke. PMID:27984560

  3. Effect of IMOD™ on the inflammatory process after acute ischemic stroke: a randomized clinical trial

    PubMed Central

    2013-01-01

    Background and purpose of the study Considering the role of inflammation in acute cerebrovascular accidents, anti-inflammatory treatment has been considered as an option in cerebrovascular diseases. Regarding the properties of Setarud (IMOD™) in immune regulation, the aim of the present study was to evaluate the role of this medication in treating patients with acute ischemic stroke. Methods In this randomized clinical trial, 99 patients with their first ever acute ischemic stroke were divided into two groups of IMOD™ (n = 49) and control (n = 50). The control group underwent routine treatment and the intervention group underwent routine treatment plus daily intermittent infusion of IMOD™ (250mg on the first day and then 375mg into DW5% serum during a 30-minute period for 7 days). The serum levels of inflammatory markers were evaluated on the first day (baseline) and on 4th and 7th days. Data were analyzed and the results were compared. Results and major conclusion 58 males (58.6%) and 41 females (41.4%) with a mean age of 67.00 ± 8.82 years, who had their first ever stroke attack, were enrolled in this trial. Treatment with IMOD™ showed a decreasing trend in IL-6 levels compared to the control group (p = 0.04). In addition, the treatment resulted in the control of increasing serum levels of hsCRP after 7 days compared to the control group (p = 0.02). There was an insignificant decrease in TNF-α and IL-1 levels in the IMOD™ group. Considering the prominent role of inflammation after an ischemic cerebral damage, it appears that treatment with IMOD™ improves the inflammatory profile. Therefore, IMOD™ (Setarud) might be considered as a therapeutic option in the acute ischemic stroke. However, future studies are necessary on its long-term results and clinical efficacy. PMID:23514014

  4. Pacemaker lead malpositioning led to subsequent ischemic strokes despite antiplatelet and anticoagulation therapy

    PubMed Central

    2014-01-01

    Pacemaker lead malpositioning may lead to severe clinical adverse events. Rarely, cases of inadvertent placement of a lead into the left ventricle are reported in the literature. We herein report a case of pacemaker lead malpositioning into the left ventricle via a persistent foramen ovale in a male caucasian patient. After this procedural adverse event, the patient suffered from two ischemic strokes despite antiplatelet and anticoagulation therapy. PMID:24650169

  5. Minocycline-preconditioned neural stem cells enhance neuroprotection after ischemic stroke in rats.

    PubMed

    Sakata, Hiroyuki; Niizuma, Kuniyasu; Yoshioka, Hideyuki; Kim, Gab Seok; Jung, Joo Eun; Katsu, Masataka; Narasimhan, Purnima; Maier, Carolina M; Nishiyama, Yasuhiro; Chan, Pak H

    2012-03-07

    Transplantation of neural stem cells (NSCs) offers a novel therapeutic strategy for stroke; however, massive grafted cell death following transplantation, possibly due to a hostile host brain environment, lessens the effectiveness of this approach. Here, we have investigated whether reprogramming NSCs with minocycline, a broadly used antibiotic also known to possess cytoprotective properties, enhances survival of grafted cells and promotes neuroprotection in ischemic stroke. NSCs harvested from the subventricular zone of fetal rats were preconditioned with minocycline in vitro and transplanted into rat brains 6 h after transient middle cerebral artery occlusion. Histological and behavioral tests were examined from days 0-28 after stroke. For in vitro experiments, NSCs were subjected to oxygen-glucose deprivation and reoxygenation. Cell viability and antioxidant gene expression were analyzed. Minocycline preconditioning protected the grafted NSCs from ischemic reperfusion injury via upregulation of Nrf2 and Nrf2-regulated antioxidant genes. Additionally, preconditioning with minocycline induced the NSCs to release paracrine factors, including brain-derived neurotrophic factor, nerve growth factor, glial cell-derived neurotrophic factor, and vascular endothelial growth factor. Moreover, transplantation of the minocycline-preconditioned NSCs significantly attenuated infarct size and improved neurological performance, compared with non-preconditioned NSCs. Minocycline-induced neuroprotection was abolished by transfecting the NSCs with Nrf2-small interfering RNA before transplantation. Thus, preconditioning with minocycline, which reprograms NSCs to tolerate oxidative stress after ischemic reperfusion injury and express higher levels of paracrine factors through Nrf2 up-regulation, is a simple and safe approach to enhance the effectiveness of transplantation therapy in ischemic stroke.

  6. The current situation on vascular cognitive impairment after ischemic stroke in Changsha.

    PubMed

    Tu, Qiuyun; Ding, Binrong; Yang, Xia; Bai, Song; Tu, Junshi; Liu, Xiao; Wang, Ranran; Tao, Jinghua; Jin, Hui; Wang, Yiqun; Tang, Xiangqi

    2014-01-01

    The objectives of the study were to explore the prevalence and effects of vascular cognitive impairment (VCI) among ischemic stroke patients and to provide a basis for prevention and treatment strategies. A stratified cluster random sampling method was performed, and 689 ischemic stroke patients (over 40 years of age) were enrolled. All of the patients had received a neuropsychological assessment battery to assess cognitive function and self-designed questionnaires to collect relevant information. According to the cognitive status, the patients were divided into two groups, a case group and a control group. The caregivers of the patients were given a questionnaire concerning the awareness of and attitudes toward VCI. In this study, we determined that the prevalence of VCI was 41.8%. Aging, paraventricular white matter lesion (WML), macroangiopathy, high levels of alcohol, a lack of hobbies, and excessive sleep were risk factors for vascular cognitive impairment no dementia (VCIND). A high level of education, manual-work, low level of alcohol use, regular health checks, a vegetable-based diet, and more fruit and milk were protective factors for VCIND. Living alone, hyperlipidemia, transient ischemic attack, a family history of stroke, and brain atrophy were risk factors of vascular dementia (VD). A high educational level, a vegetable-based diet, and tea were protective factors for VD. The general public awareness of VCI was found to be insufficient, and there was a prejudice toward and lack of funding for the care of VCI patients. The prevalence of VCI is high in ischemic stroke patients, and there are different impact factors at different stages. Despite the high prevalence of VCI, the general public awareness is limited. Appropriate prevention measures should be developed to reduce the prevalence of VCI.

  7. Optimal Combination Treatment and Vascular Outcomes in Recent Ischemic Stroke Patients by Premorbid Risk Level

    PubMed Central

    Park, Jong-Ho; Ovbiagele, Bruce

    2015-01-01

    Background Optimal combination of secondary stroke prevention treatment including antihypertensives, antithrombotic agents, and lipid modifiers is associated with reduced recurrent vascular risk including stroke. It is unclear whether optimal combination treatment has a differential impact on stroke patients based on level of vascular risk. Methods We analyzed a clinical trial dataset comprising 3680 recent non-cardioembolic stroke patients aged ≥35 years and followed for 2 years. Patients were categorized by appropriateness level 0 to III depending on the number of the drugs prescribed divided by the number of drugs potentially indicated for each patient (0=none of the indicated medications prescribed and III=all indicated medications prescribed [optimal combination treatment]). High-risk was defined as having a history of stroke or coronary heart disease (CHD) prior to the index stroke event. Independent associations of medication appropriateness level with a major vascular event (stroke, CHD, or vascular death), ischemic stroke, and all-cause death were analyzed. Results Compared with level 0, for major vascular events, the HR of level III in the low-risk group was 0.51 (95% CI: 0.20–1.28) and 0.32 (0.14–0.70) in the high-risk group; for stroke, the HR of level III in the low-risk group was 0.54 (0.16–1.77) and 0.25 (0.08–0.85) in the high-risk group; and for all-cause death, the HR of level III in the low-risk group was 0.66 (0.09–5.00) and 0.22 (0.06–0.78) in the high-risk group. Conclusion Optimal combination treatment is related to a significantly lower risk of future vascular events and death among high-risk patients after a recent non-cardioembolic stroke. PMID:26044963

  8. Crossed Cerebellar Atrophy of the Lateral Cerebellar Nucleus in an Endothelin-1-Induced, Rodent Model of Ischemic Stroke

    PubMed Central

    Chan, Hugh H.; Cooperrider, Jessica L.; Park, Hyun-Joo; Wathen, Connor A.; Gale, John T.; Baker, Kenneth B.; Machado, Andre G.

    2017-01-01

    Crossed cerebellar diaschisis (CCD) is a functional deficit of the cerebellar hemisphere resulting from loss of afferent input consequent to a lesion of the contralateral cerebral hemisphere. It is manifested as a reduction of metabolism and blood flow and, depending on severity and duration, it can result in atrophy, a phenomenon known as crossed cerebellar atrophy (CCA). While CCA has been well-demonstrated in humans, it remains poorly characterized in animal models of stroke. In this study we evaluated the effects of cerebral cortical ischemia on contralateral cerebellar anatomy using an established rodent model of chronic stroke. The effects of cortical ischemia on the cerebellar hemispheres, vermis and deep nuclei were characterized. Intracortical microinjections of endothelin-1 (ET-1) were delivered to the motor cortex of Long Evans rats to induce ischemic stroke, with animals sacrificed 6 weeks later. Naive animals served as controls. Cerebral sections and cerebellar sections including the deep nuclei were prepared for analysis with Nissl staining. Cortical ischemia was associated with significant thickness reduction of the molecular layer at the Crus 1 and parafloccular lobule (PFL), but not in fourth cerebellar lobule (4Cb), as compared to the ipsilesional cerebellar hemisphere. A significant reduction in volume and cell density of the lateral cerebellar nucleus (LCN), the rodent correlate of the dentate nucleus, was also noted. The results highlight the relevance of corticopontocerebellar (CPC) projections for cerebellar metabolism and function, including its direct projections to the LCN. PMID:28261086

  9. Perioperative Atrial Fibrillation and the Long-term Risk of Ischemic Stroke

    PubMed Central

    Gialdini, Gino; Nearing, Katherine; Bhave, Prashant D.; Bonuccelli, Ubaldo; Iadecola, Costantino; Healey, Jeff S.; Kamel, Hooman

    2014-01-01

    IMPORTANCE Clinically apparent atrial fibrillation increases the risk of ischemic stroke. In contrast, perioperative atrial fibrillation may be viewed as a transient response to physiological stress, and the long-term risk of stroke after perioperative atrial fibrillation is unclear. OBJECTIVE To examine the association between perioperative atrial fibrillation and the long-term risk of stroke. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using administrative claims data on patients hospitalized for surgery (as defined by surgical diagnosis related group codes), and discharged alive and free of documented cerebrovascular disease or preexisting atrial fibrillation from nonfederal California acute care hospitals between 2007 and 2011. Patients undergoing cardiac vs other types of surgery were analyzed separately. MAIN OUTCOMES AND MEASURES Previously validated diagnosis codes were used to identify ischemic strokes after discharge from the index hospitalization for surgery. The primary predictor variable was atrial fibrillation newly diagnosed during the index hospitalization, as defined by previously validated present-on-admission codes. Patients were censored at postdischarge emergency department encounters or hospitalizations with a recorded diagnosis of atrial fibrillation. RESULTS Of 1 729 360 eligible patients, 24 711 (1.43%; 95% CI, 1.41%–1.45%) had new-onset perioperative atrial fibrillation during the index hospitalization and 13 952 (0.81%; 95% CI, 0.79%–0.82%) experienced a stroke after discharge. In a Cox proportional hazards analysis accounting for potential confounders, perioperative atrial fibrillation was associated with subsequent stroke both after noncardiac and cardiac surgery. Type of SurgeryCumulative Rate of Stroke 1 Year AfterHospitalization, % (95% CI)Hazard Ratio (95% CI)PerioperativeAtrial FibrillationNo PerioperativeAtrial FibrillationNoncardiac1.47 (1.24–1.75)0.36 (0.35–0.37)2.0 (1.7–2.3)Cardiac0.99 (0.81–1

  10. Worse Neurological State During Acute Ischemic Stroke is Associated with a Decrease in Serum Albumin Levels.

    PubMed

    Bielewicz, Joanna; Kurzepa, Jacek; Czekajska-Chehab, Elżbieta; Kamieniak, Piotr; Daniluk, Beata; Bartosik-Psujek, Halina; Rejdak, Konrad

    2016-04-01

    High serum albumin levels during ischemic stroke (IS) decrease the risk of a poor outcome. This study aimed to determine whether serum albumin levels within the first days after IS correlate with radiological and biochemical markers of brain tissue damage. Fifty-six IS patients were enrolled into the study. Neurological examinations were based on the National Institute of Health Stroke Scale. Serum albumin levels and S100BB were evaluated using commercially available ELISA kits. The albumin decrease index (ADI) was calculated as the difference between serum albumin levels measured on days 1 and 10 of IS. All parameters were estimated on the 1st, 3rd, 5th, and 10th days of IS, and the volume of ischemic focus was measured on the 10th day. Mean serum albumin levels were decreased during acute IS. There were correlations between the ADI and mean S100BB serum levels (r = 0.36, p < 0.05), the volume of ischemic focus (r = 0.39, p < 0.05), and the patients' neurological state when measured on day 10 of IS (r = 0.59, p < 0.001). A decrease in serum albumin levels during the acute phase of IS corresponds to a worse neurological state as a result of a large ischemic focus with intense catabolic processes.

  11. Intracranial transplantation of monocyte-derived multipotential cells enhances recovery after ischemic stroke in rats.

    PubMed

    Hattori, Hidenori; Suzuki, Shigeaki; Okazaki, Yuka; Suzuki, Norihiro; Kuwana, Masataka

    2012-02-01

    Cell transplantation has emerged as a potential therapy to reduce the neurological deficits caused by ischemic stroke. We previously reported a primitive cell population, monocyte-derived multipotential cells (MOMCs), which can differentiate into mesenchymal, neuronal, and endothelial lineages. In this study, MOMCs and macrophages were prepared from rat peripheral blood and transplanted intracranially into the ischemic core of syngeneic rats that had undergone a left middle cerebral artery occlusion procedure. Neurological deficits, as evaluated by the corner test, were less severe in the MOMC-transplanted rats than in macrophage-transplanted or mock-treated rats. Histological evaluations revealed that the number of microvessels that had formed in the ischemic boundary area by 4 weeks after transplantation was significantly greater in the MOMC-transplanted rats than in the control groups. The blood vessel formation was preceded by the appearance of round CD31(+) cells, which we confirmed were derived from the transplanted MOMCs. Small numbers of bloodvessels incorporating MOMC-derived endothelial cells expressing a mature endothelial marker RECA-1 were detected at 4 weeks after transplantation. In addition, MOMCs expressed a series of angiogenic factors, including vascular endothelial growth factor, angiopoetin-1, and placenta growth factor (PlGF). These findings provide evidence that the intracranial delivery of MOMCs enhances functional recovery by promoting neovascularization in a rat model for ischemic stroke.

  12. Nitric oxide donors as neuroprotective agents after an ischemic stroke-related inflammatory reaction.

    PubMed

    Godínez-Rubí, Marisol; 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.

  13. [Blood cell aggregation and oxidative stress in pathogenesis of ischemic stroke].

    PubMed

    Fedorova, T F; Aleksandrov, M V; Sokolovskiĭ, V V; Papaian, L P; Mashkova, N P

    2004-01-01

    Rheologic properties of blood cells and a state of oxidative-reductive processes and blood systems have been studied in 75 patients in acute period of ischemic stroke. The signs of oxidative stress development and simultaneous augmentation of blood cells aggregation were found. Shifts of redox-equilibrium in thiol-disulfide and ascorbate oxidative-reductive blood systems and cells aggregation dependence on their state were detected. An interrelation of oxidative processes and blood cells aggregation with clinical course severity and outcome was revealed. The authors discuss possible mechanisms for blood cells aggregation in oxidative stress. Including of antioxidants in the pathogenetic therapy and their earlier usage reduce essentially the intensity of oxidative stress and blood cells aggregation and promote neurological symptoms regress. The results obtained allow considering antioxidant treatment as a pathogenic modality for prevention and treatment of ischemic stroke. Clinico-laboratory correlations suggest a pathogenic role of oxidative stress in ischemic stroke as a factor augmenting aggregation processes and promoting intravascular thrombogenesis.

  14. 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

  15. A specific dietary intervention to restore brain structure and function after ischemic stroke

    PubMed Central

    Wiesmann, Maximilian; Zinnhardt, Bastian; Reinhardt, Dirk; Eligehausen, Sarah; Wachsmuth, Lydia; Hermann, Sven; Dederen, Pieter J; Hellwich, Marloes; Kuhlmann, Michael T; Broersen, Laus M; Heerschap, Arend; Jacobs, Andreas H; Kiliaan, Amanda J

    2017-01-01

    Occlusion of the middle cerebral artery (MCAo) is among the most common causes of ischemic stroke in humans. Cerebral ischemia leads to brain lesions existing of an irreversibly injured core and an ischemic boundary zone, the penumbra, containing damaged but potentially salvageable tissue. Using a transient occlusion (30 min) of the middle cerebral artery (tMCAo) mouse model in this cross-institutional study we investigated the neurorestorative efficacy of a dietary approach (Fortasyn) comprising docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium as therapeutic approach to counteract neuroinflammation and impairments of cerebral (structural+functional) connectivity, cerebral blood flow (CBF), and motor function. Male adult C57BL/6j mice were subjected to right tMCAo using the intraluminal filament model. Following tMCAo, animals were either maintained on Control diet or switched to the multicomponent Fortasyn diet. At several time points after tMCAo, behavioral tests, and MRI and PET scanning were conducted to identify the impact of the multicomponent diet on the elicited neuroinflammatory response, loss of cerebral connectivity, and the resulting impairment of motor function after experimental stroke. Mice on the multicomponent diet showed decreased neuroinflammation, improved functional and structural connectivity, beneficial effect on CBF, and also improved motor function after tMCAo. Our present data show that this specific dietary intervention may have beneficial effects on structural and functional recovery and therefore therapeutic potential after ischemic stroke. PMID:28255345

  16. Cofilin as a Promising Therapeutic Target for Ischemic and Hemorrhagic Stroke.

    PubMed

    Alhadidi, Qasim; Bin Sayeed, Muhammad Shahdaat; Shah, Zahoor A

    2016-02-01

    Neurovascular unit (NVU) is considered as a conceptual framework for investigating the mechanisms as well as developing therapeutic targets for ischemic and hemorrhagic stroke. From a molecular perspective, oxidative stress, excitotoxicity, inflammation, and disruption of the blood brain barrier are broad pathophysiological frameworks on the basis on which potential therapeutic candidates for ischemic and hemorrhagic stroke could be discussed. Cofilin is a potent actin-binding protein that severs and depolymerizes actin filaments in order to generate the dynamics of the actin cytoskeleton. Although studies of the molecular mechanisms of cofilin-induced reorganization of the actin cytoskeleton have been ongoing for decades, the multicellular functions of cofilin and its regulation in different molecular pathways are expanding beyond its primary role in actin cytoskeleton. This review focuses on the role of cofilin in oxidative stress, excitotoxicity, inflammation, and disruption of the blood brain barrier in the context of NVU as well as how and why cofilin could be studied further as a potential target for ischemic and hemorrhagic stroke.

  17. Dynamic functional cerebral blood volume responses to normobaric hyperoxia in acute ischemic stroke

    PubMed Central

    Wu, Ona; Lu, Jie; Mandeville, Joseph B; Murata, Yoshihiro; Egi, Yasu; Dai, Guangping; Marota, John J; Diwan, Izzuddin; Dijkhuizen, Rick M; Kwong, Kenneth K; Lo, Eng H; Singhal, Aneesh B

    2012-01-01

    Studies suggest that neuroprotective effects of normobaric oxygen (NBO) therapy in acute stroke are partly mediated by hemodynamic alterations. We investigated cerebral hemodynamic effects of repeated NBO exposures. Serial magnetic resonance imaging (MRI) was performed in Wistar rats subjected to focal ischemic stroke. Normobaric oxygen-induced functional cerebral blood volume (fCBV) responses were analyzed. All rats had diffusion-weighted MRI (DWI) lesions within larger perfusion deficits, with DWI lesion expansion after 3 hours. Functional cerebral blood volume responses to NBO were spatially and temporally heterogeneous. Contralateral healthy tissue responded consistently with vasoconstriction that increased with time. No significant responses were evident in the acute DWI lesion. In hypoperfused regions surrounding the acute DWI lesion, tissue that remained viable until the end of the experiment showed relative preservation of mean fCBV at early time points, with some rats showing increased fCBV (vasodilation); however, these regions later exhibited significantly decreased fCBV (vasoconstriction). Tissue that became DWI abnormal by study-end initially showed marginal fCBV changes that later became moderate fCBV reductions. Our results suggest that a reverse-steal hemodynamic effect may occur in peripheral ischemic zones during NBO treatment of focal stroke. In addition, CBV responses to NBO challenge may have potential as an imaging marker to distinguish ischemic core from salvageable tissues. PMID:22739619

  18. Left ventricular geometry and white matter lesions in ischemic stroke patients.

    PubMed

    Butenaerts, Demian; Chrzanowska-Wasko, Joanna; Slowik, Agnieszka; Dziedzic, Tomasz

    2016-06-01

    Abnormal left ventricular (LV) geometry is associated with extracardiac organ damage in patients with hypertension. The aim of this study was to determine the relationship between LV geometry and white matter lesions (WMLs) in ischemic stroke patients. We retrospectively analyzed data from 155 patients (median age 62; 49.8% male) with mild ischemic stroke (median National Institutes of Health Stroke Scale score 4) who underwent brain magnetic resonance imaging and echocardiography. Patients were categorized into four groups: normal LV geometry, concentric remodeling, eccentric left ventricular hypertrophy (LVH) and concentric LVH. WMLs were graded using the Fazekas scale on fluid-attenuated inversion recovery images. Extensive WMLs were defined as a Fazekas score > 2. Extensive WMLs were more prevalent in patients with concentric LVH, eccentric LVH and concentric remodeling than in those with normal LV geometry. After adjusting for hypertension, age, diabetes mellitus, hypercholesterolemia, glomerular filtration rate and ischemic heart disease, patients with concentric remodeling [odds ratio (OR) 3.94, 95% confidence interval (CI) 1.26-12.31, p = 0.02] and those with concentric LVH (OR 3.69, 95% CI 1.24-10.95, p = 0.02), but not patients with eccentric LVH (OR 2.44, 95% CI 0.72-8.29, p = 0.15), had higher risk of extensive WMLs than patients with normal LV geometry.

  19. Association between Ischemic Stroke and Iron-Deficiency Anemia: A Population-Based Study

    PubMed Central

    Chang, Yen-Liang; Hung, Shih-Han; Ling, Wells; Lin, Herng-Ching

    2013-01-01

    Background Very little is known about the relationship between non-sickle cell anemia and stroke. The purpose of this study is to evaluate the association of iron-deficiency anemia (IDA) with stroke based on a nationwide coverage database in Taiwan. Methods The case-control study subjects were obtained from the Taiwanese Longitudinal Health Insurance Database 2000. We included 51,093 subjects with stroke as cases and randomly selected 153,279 controls (3 controls per case) in this study.Separate conditional logistic regression analyses were used to calculate the odds ratio (OR) for having been previously diagnosed with IDA between cases and controls.We further analyzed the association between stroke and IDA by stroke subtype. Results Results showed that 3,685 study subjects (1.81%) had been diagnosed with IDA prior to the index date; of those subjects, 1,268 (2.48%) were cases and 2,417 (1.58%) were controls (p<0.001). Conditional logistic regression shows that the OR of having previously received an IDA diagnosis among cases was 1.49 (95% CI: 1.39~1.60; p < 0.01) that of controls after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, atrial fibrillation, heart failure, hyperlipidemia, tobacco use disorder, and alcohol abuse/alcohol dependency syndrome. Furthermore, the adjusted OR of prior IDA for cases with ischemic stroke was found to be 1.45 (95% CI: 1.34~1.58) compared to controls. However, we did not find any significant relationship between IDA and subarachnoid/intracerebral hemorrhage even adjusting for other confounding factors (OR=1.17, 95% CI=0.97~1.40). Conclusion There is a significant association between prior IDA and ischemic stroke. PMID:24349404

  20. The Association of Body Mass Index and Mortality after Acute Ischemic Stroke

    PubMed Central

    Skolarus, Lesli E.; Sanchez, Brisa N.; Levine, Deborah A; Baek, Jonggyu; Kerber, Kevin A.; Morgenstern, Lewis B.; Smith, Melinda A.; Lisabeth, Lynda D.

    2015-01-01

    Background The prevalence of severe obesity is rising in the US. Although mild to moderately elevated Body Mass Index (BMI) is associated with reduced mortality after acute ischemic stroke, less is known about severe obesity. Methods and Results Acute ischemic stroke patients (n=1,791) aged ≥45 years were identified from the bi-ethnic population-based Brain Attack Surveillance in Corpus Christi (BASIC) study from June 1, 2005 to December 31, 2010. Median follow-up was 660 days. BMI was abstracted from the medical record. Survival was estimated by BMI category (underweight normal-weight, overweight, class 1 obesity, class 2 obesity, and severe obesity) using Kaplan-Meier methods. Hazard ratios for the relationship between BMI modeled continuously and mortality were estimated from Cox regression models after adjusting for patient factors. The median BMI was 27.1 kg/m2 (interquartile range, 23.7–31.2) and 56% were Mexican American. A total of 625 (35%) patients died during the study period. Persons with higher baseline BMI had longer survival in unadjusted analysis (P<0.01). After adjusting for demographics, stroke severity, stroke and mortality risk factors, the relationship between BMI and mortality was U-shaped. The lowest mortality risk was observed among patients with an approximate BMI of 35 kg/m2, whereas those with lower or higher BMI had higher mortality risk. Conclusions Severe obesity is associated with increased post-stroke mortality in middle-aged and older adults. Stroke patients with class 2 obesity had the lowest mortality risk. More research is needed to determine weight management goals among stroke survivors. PMID:24326935

  1. Comparative Effectiveness of Standard Care With IV Thrombolysis Versus Without IV Thrombolysis for Mild Ischemic Stroke

    PubMed Central

    Choi, Jay Chol; Jang, Min Uk; Kang, Kyusik; Park, Jong‐Moo; Ko, Youngchai; Lee, Soo‐Joo; Cha, Jae‐Kwan; Kim, Dae‐Hyun; Park, Sang Soon; Park, Tai Hwan; Lee, Kyung Bok; Lee, Jun; Kim, Joon‐Tae; Cho, Ki‐Hyun; Yu, Kyung‐Ho; Oh, Mi‐Sun; Lee, Byung‐Chul; Cho, Yong‐Jin; Kim, Dong‐Eog; Lee, Ji Sung; Lee, Juneyoung; Gorelick, Philip B.; Bae, Hee‐Joon

    2015-01-01

    Background One third of patients presenting with initially mild strokes have unfavorable outcomes, and the efficacy of intravenous thrombolysis (IVT) in this population has not been proven. This study aimed to evaluate the comparative effectiveness of standard care with IVT versus without IVT in mild stroke patients. Methods and Results Using a multicenter stroke registry database, we identified patients with acute ischemic stroke who presented within 4.5 hours of symptom onset and had initial National Institutes of Health Stroke Scale scores ≤5. Multivariable logistic analysis and propensity score matching were used to adjust for baseline imbalances between the patients who did and did not receive IVT. Adjusted odds ratios and 95% CIs of IVT were estimated for 3‐month modified Rankin Scale scores of 0 to 1 and symptomatic. Of 13 117 patients with stroke who were hospitalized between April 2008 and May 2012, 1386 met the eligibility criteria, and 194 (14.0%) were treated with IVT. For a modified Rankin Scale of 0 to 1 at 3 months, the adjusted odds ratios were 1.96 (95% CI, 1.28 to 3.00; P=0.002) by multivariable logistic analysis and 1.68 (1.10 to 2.56; P=0.02) by propensity score matching analysis, respectively. There was a statistically nonsignificant excess of symptomatic hemorrhagic transformation (odds ratios=3.76 [0.95 to 16.42; P=0.06] and 4.81 [0.84 to 49.34; P=0.09]), respectively. Conclusions In this observational registry‐based study, standard care with IVT is more effective than not receiving IVT in mild ischemic stroke patients, and there is a statistically nonsignificant risk of symptomatic hemorrhagic transformation. PMID:25628404

  2. Plasma thrombin-cleaved osteopontin as a potential biomarker of acute atherothrombotic ischemic stroke.

    PubMed

    Ozaki, Saya; Kurata, Mie; Kumon, Yoshiaki; Matsumoto, Shirabe; Tagawa, Masahiko; Watanabe, Hideaki; Ohue, Shiro; Higaki, Jitsuo; Ohnishi, Takanori

    2017-01-01

    We investigated whether thrombin-cleaved osteopontin N-terminal is useful as a blood biomarker of acute atherothrombotic ischemic stroke. Acute ischemic stroke patients were prospectively evaluated with brain magnetic resonance imaging and cardiac evaluations for etiological diagnosis according to the Trial of Org 10172 in Acute Stroke Treatment classification. They were divided into the atherothrombotic and non-atherothrombotic groups. Thrombin-cleaved osteopontin N-terminal, osteopontin, matrix metalloproteinase-9, S100B, C-reactive protein and D-dimer levels were measured from blood samples collected at admission. After excluding patients who met the exclusion criteria or had stroke of other/undetermined etiology, 60 of the 100 patients initially enrolled were included in the final analysis. The ischemic stroke subtypes were atherothrombotic (n=28, 46.7%), cardioembolic (n=19, 31.7%) and lacunar (n=13, 21.7%). Thrombin-cleaved osteopontin N-terminal and matrix metalloproteinase-9 levels were significantly higher in the atherothrombotic than in the non-atherothrombotic group (median (interquartile range): 5.83  (0.0-8.6 ) vs. 0.0  (0.0-3.3) pmol l(-1), P=0.03 and 544   (322-749 ) vs. 343   (254-485) ng ml(-1), P=0.01, respectively). After adjustment for the prevalence of hypertension, diabetes and dyslipidemia, thrombin-cleaved osteopontin N-terminal levels of >5.47 pmol l(-1) (odds ratio, 16.81; 95% confidence interval, 3.53-80.10) and matrix metalloproteinase-9 levels of >605.5 ng ml(-1) (6.59; 1.77-24.60) were identified as independent predictors of atherothrombosis. Within 3 h from stroke onset, only thrombin-cleaved osteopontin N-terminal independently predicted atherothrombosis and thus may add valuable, time-sensitive diagnostic information in the early evaluation of ischemic stroke, especially the atherothrombotic subtype.

  3. Early Sitting in Ischemic Stroke Patients (SEVEL): A Randomized Controlled Trial

    PubMed Central

    Herisson, Fanny; Godard, Sophie; Volteau, Christelle; Le Blanc, Emilie; Guillon, Benoit; Gaudron, Marie

    2016-01-01

    Background Extended immobility has been associated with medical complications during hospitalization. However no clear recommendations are available for mobilization of ischemic stroke patients. Objective As early mobilization has been shown to be feasible and safe, we tested the hypothesis that early sitting could be beneficial to stroke patient outcome. Methods This prospective multicenter study tested two sitting procedures at the acute phase of ischemic stroke, in a randomized controlled fashion (clinicaltrials.org registration number NCT01573299). Patients were eligible if they were above 18 years of age and showed no sign of massive infarction or any contra-indication for sitting. In the early-sitting group, patients were seated out of bed at the earliest possible time but no later than one calendar day after stroke onset, whereas the progressively-sitting group was first seated out of bed on the third calendar day after stroke onset. Primary outcome measure was the proportion of patients with a modified Rankin score [0–2] at 3 months post stroke. Secondary outcome measures were a.) prevalence of medical complications, b.) length of hospital stay, and c.) tolerance to the procedure. Results One hundred sixty seven patients were included in the study, of which 29 were excluded after randomization. Data from 138 patients, 63 in the early-sitting group and 75 in the progressively-sitting group were analyzed. There was no difference regarding outcome of people with stroke, with a proportion of Rankin [0–2] score at 3 months of 76.2% and 77.3% of patients in the early- and progressive-sitting groups, respectively (p = 0.52). There was also no difference between groups for secondary outcome measures, and the procedure was well tolerated in both arms. Conclusion Due to a slow enrollment, fewer patients than anticipated were available for analysis. As a result, we can only detect beneficial/detrimental effects of +/- 15% of the early sitting procedure on stroke

  4. Searching for patent foramen ovale in a 44-year-old female patient after ischemic stroke – diagnostic problems

    PubMed Central

    Kralisz, Paweł; Bachórzewska-Gajewska, Hanna; Dobrzycki, Sławomir

    2016-01-01

    Patent foramen ovale (PFO) is associated with the occurrence of cryptogenic strokes in young patients. Transesophageal echocardiography with contrast is the established standard in PFO diagnostics. We present the case of a 44-year-old female patient after ischemic stroke, in whom PFO was not detected by echocardiography; the defect was ultimately diagnosed by right heart catheterization. PMID:27516797

  5. Decreased oxygen saturation in asymmetrically prominent cortical veins in patients with cerebral ischemic stroke.

    PubMed

    Xia, Shuang; Utriainen, David; Tang, Jin; Kou, Zhifeng; Zheng, Gang; Wang, Xuesong; Shen, Wen; Haacke, E Mark; Lu, Guangming

    2014-12-01

    Decreased oxygen saturation in asymmetrically prominent cortical veins (APCV) seen in ischemic stroke has been hypothesized to correlate with an increase of de-oxygenated hemoglobin. Our goal is to quantify magnetic susceptibility to define APCV by establishing a cutoff above which the deoxyhemoglobin levels are considered abnormal. A retrospective study was conducted on 26 patients with acute ischemic stroke in one cerebral hemisphere that exhibited APCV with 30 age- and sex-matched healthy controls. Quantitative susceptibility mapping (QSM) was used to calculate the magnetic susceptibility of the cortical veins. A paired t-test was used to compare the susceptibility of the cortical veins in the left and right hemispheres for healthy controls as well as in the contralateral hemisphere for stroke patients with APCV. The change in oxygen saturation in the APCV relative to the contralateral side was calculated after thresholding the susceptibility using the mean plus two standard deviations of the contralateral side for each individual. The thresholded susceptibility value of the APCVs in the stroke hemisphere was 254±48 ppb which was significantly higher (p<0.05) than that in the contralateral hemisphere (123±12 ppb) and in healthy controls (125±8 ppb). There was a decrease of oxygen saturation in the APCV ranging from 16% to 44% relative to the veins of the contralateral hemisphere. In conclusion, APCV seen in SWI correspond to reduced levels of oxygen saturation and these abnormal veins can be identified using a susceptibility threshold on the QSM data.

  6. Clinical implication of hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator.

    PubMed

    Ho, Bo-Lin; Chen, Chien-Fu; Lin, Ruey-Tay; Liu, Ching-Kuan; Chao, A-Ching

    2016-11-01

    To determine the clinical implications of hemorrhagic transformation (HT) after thrombolysis, 241 eligible patients receiving alteplase for acute ischemic stroke were studied. HT was classified, according to the European Cooperative Acute Stroke Study criteria, as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH). Symptomatic intracranial hemorrhage (SICH) was defined according to the National Institute of Neurological Disorders and Stroke study. A novel classification, clinically significant intracranial hemorrhage (CSICH) was defined as HTs associated with an unfavorable clinical outcome (modified Rankin Scale 5-6) at 3 months. For all subtypes of HT, we found that patients receiving alteplase were more often in the standard-dose group (0.90 ± 0.02 mg/kg) than in the lower dose group (0.72 ± 0.07 mg/kg). PH and SICH were related to an unfavorable clinical outcome, while HI was not. There was a positive trend between age and CSICH in patients receiving the standard dose (P = 0.0101), and between alteplase dose and CSICH in patients ≥70 years old (P = 0.0228). All PHs (including asymptomatic PHs) and symptomatic HIs have been found to be associated with unfavorable outcome, and for this reason defined as CSICH. Independent predictors of CSICH were age ≥70 years and the standard dose of alteplase. Further studies of thrombolysis for ischemic stroke with different doses of alteplase are warranted.

  7. Modulation of Cardiac Autonomic Dysfunction in Ischemic Stroke following Ayurveda (Indian System of Medicine) Treatment

    PubMed Central

    Jaideep, Sriranjini Sitaram; Nagaraja, Dindagur; Pal, Pramod Kumar; Sudhakara, D.; Talakad, Sathyaprabha N.

    2014-01-01

    Objectives. Cardiac autonomic dysfunction in stroke has implications on morbidity and mortality. Ayurveda (Indian system of medicine) describes stroke as pakshaghata. We intended to study the effect of Ayurveda therapies on the cardiac autonomic dysfunction. Methods. Fifty patients of ischemic stroke (middle cerebral artery territory) (mean age 39.26 ± 9.88 years; male 43, female 7) were recruited within one month of ictus. All patients received standard allopathic medications as advised by neurologist. In addition, patients were randomized to receive physiotherapy (Group I) or Ayurveda treatment (Group II) for 14 days. Continuous electrocardiogram and finger arterial pressure were recorded for 15 min before and after treatments and analyzed offline to obtain heart rate and blood pressure variability and baroreflex sensitivity (BRS). Results were analysed by RMANOVA. Results. Patients in Group II showed statistically significant improvement in cardiac autonomic parameters. The standard deviation of normal to normal intervals,and total and low frequency powers were significantly enhanced (F = 8.16, P = 0.007, F = 9.73, P = 0.004, F = 13.51, and P = 0.001, resp.). The BRS too increased following the treatment period (F = 10.129, P = 0.004). Conclusions. The current study is the first to report a positive modulation of cardiac autonomic activity after adjuvant Ayurveda treatment in ischemic stroke. Further long term studies are warranted. PMID:24971149

  8. Advanced imaging to extend the therapeutic time window of acute ischemic stroke.

    PubMed

    Fisher, Marc; Albers, Gregory W

    2013-01-01

    Reperfusion therapy for acute stroke has evolved from the initial use of intravenous tissue plasminogen activator (tPA) within 3 hours of symptom onset to more recent guideline-recommended use up to 4.5 hours. In addition, endovascular therapy is increasingly utilized for stroke treatment and is typically initiated up to 8 hours after onset. Recent studies demonstrate that imaging of the ischemic penumbra with diffusion/perfusion magnetic resonance imaging (MRI) can identify subgroups of patients who are likely to improve following successful reperfusion (Target Mismatch profile) and others who are at increased risk for hemorrhage and poor clinical outcomes (Malignant profile). New data indicate that stent retriever devices provide better recanalization efficacy and clinical outcomes than the previously available mechanical thrombectomy devices. Going forward, we believe that the use of penumbral imaging with validated MRI techniques, as well as the currently less well-validated computed tomography (CT) perfusion approach, will maximize benefit and reduce the risk of adverse events and poor outcomes when used both early after stroke onset and at later time points. New trials that feature diffusion/perfusion MRI or CT perfusion-based patient selection for treatment with intravenous tPA and or endovascular therapies versus nonreperfused control groups are planned or in progress. We predict that these trials will confirm the hypothesis that penumbral imaging can enhance patient selection and extend the therapeutic time window for acute ischemic stroke.

  9. Paradigms and mechanisms of inhalational anesthetics mediated neuroprotection against cerebral ischemic stroke

    PubMed Central

    Wang, Hailian; Li, Peiying; Xu, Na; Zhu, Ling; Cai, Mengfei; Yu, Weifeng; Gao, Yanqin

    2016-01-01

    Cerebral ischemic stroke is a leading cause of serious long-term disability and cognitive dysfunction. The high mortality and disability of cerebral ischemic stroke is urging the health providers, including anesthesiologists and other perioperative professioners, to seek effective protective strategies, which are extremely limited, especially for those perioperative patients. Intriguingly, several commonly used inhalational anesthetics are recently suggested to possess neuroprotective effects against cerebral ischemia. This review introduces multiple paradigms of inhalational anesthetic treatments that have been investigated in the setting of cerebral ischemia, such as preconditioning, proconditioning and postconditioning with a variety of inhalational anesthetics. The pleiotropic mechanisms underlying these inhalational anesthetics-afforded neuroprotection against stroke are also discussed in detail, including the common pathways shared by most of the inhalational anesthetic paradigms, such as anti-excitotoxicity, anti-apoptosis and anti-inflammation. There are also distinct mechanisms involved in specific paradigms, such as preserving blood brain barrier integrity, regulating cerebral blood flow and catecholamine release. The ready availability of these inhalational anesthetics bedside and renders them a potentially translatable stroke therapy attracting great efforts for understanding of the underlying mechanisms. PMID:28217291

  10. The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke.

    PubMed

    Wu, Long-Jun; Wu, Gongxiong; Akhavan Sharif, M Reza; Baker, Amanda; Jia, Yonghui; Fahey, Frederic H; Luo, Hongbo R; Feener, Edward P; Clapham, David E

    2012-03-04

    Phagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. The voltage-gated proton channel Hv1 enables NOX function by compensating cellular loss of electrons with protons. Accordingly, we investigated whether NOX-mediated brain damage in stroke can be inhibited by suppression of Hv1. We found that mouse and human brain microglia, but not neurons or astrocytes, expressed large Hv1-mediated currents. Hv1 was required for NOX-dependent ROS generation in brain microglia in situ and in vivo. Mice lacking Hv1 were protected from NOX-mediated neuronal death and brain damage 24 h after stroke. These results indicate that Hv1-dependent ROS production is responsible for a substantial fraction of brain damage at early time points after ischemic stroke and provide a rationale for Hv1 as a therapeutic target for the treatment of ischemic stroke.

  11. Phase I and Phase II Therapies for Acute Ischemic Stroke: An Update on Currently Studied Drugs in Clinical Research

    PubMed Central

    Reis, Cesar; Akyol, Onat; Ho, Wing Mann; Araujo, Camila; Huang, Lei; Applegate II, Richard

    2017-01-01

    Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia onset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue perfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research of pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from restoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has become a promising approach, especially in animal research. The purpose of this article is to review completed and ongoing phases I and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and antineuroinflammatory drugs that may translate into more effective treatments. PMID:28286764

  12. Cortical Plasticity during Motor Learning and Recovery after Ischemic Stroke

    PubMed Central

    Hosp, Jonas A.; Luft, Andreas R.

    2011-01-01

    The motor system has the ability to adapt to environmental constraints and injury to itself. This adaptation is often referred to as a form of plasticity allowing for livelong acquisition of new movements and for recovery after stroke. We are not sure whether learning and recovery work via same or similar neural mechanisms. But, all these processes require widespread changes within the matrix of the brain. Here, basic mechanisms of these adaptations on the level of cortical circuitry and networks are reviewed. We focus on the motor cortices because their role in learning and recovery has been investigated more thoroughly than other brain regions. PMID:22135758

  13. Prediction of ischemic stroke in young Indians: is thrombophilia profiling a way out?

    PubMed

    Chatterjee, Tathagata; Gupta, Neha; Choudhry, Ved Prakash; Behari, Madhuri; Saxena, Renu; Ashraf, Mohammad Z

    2013-06-01

    Stroke in the young is attributed to the prevalence of thrombophilia, however, reports explaining the cause mechanisms from Indian populations are largely not known. The information about the association of inherited thrombophilia and occurrence of stroke is still missing. Therefore, we describe here 52 cases of young ischemic stroke of which 22 cases were of recurrent stroke and 30 cases of first episode stroke along with an equal number of healthy controls. Imaging techniques (CT/MRI/Doppler studies) were used to identify the type and location of infarcts among various regions of the brain. All the patients and controls were screened for hypercoagulable state by employing Pro C global test. Those tested positive for the latter were evaluated for conventional thrombophilic factors, activity levels of protein C and protein S, antithrombin III levels, plasma homocysteine levels and presence of activated protein C resistance, lupus anticoagulant, methylenetetrahydrofolate reductase (MTHFR C677T) and prothrombin G20210A polymorphisms. Out of 52 cases there were 22 cases of recurrent stroke and 30 cases of first ischemic stroke. Infarcts were single in 39 out of 52 cases and multiple in 13 cases. Among the different regions of brain internal capsule infarcts were seen in 13 of 52 (25%) cases, and cerebellum, basal ganglion and midbrain infarcts were seen in five cases (9.6%) each and remaining infarcts were in other anatomical regions of the brain. Left middle cerebral artery territory was involved in 17 of 52 (32.7%) cases. The prevalence of individual thrombophilia among cases ranged from 28.8% (15/52) for protein S and 11.5% (6/52) for protein C deficiencies respectively. All cases of protein C were protein S deficient. Five cases of protein C deficiency patients were of 25 years and younger as compared with one case in the at least 25 years age group. Plasma homocysteine levels were elevated in three cases (5.7%) as compared with normal levels in controls

  14. Progress in AQP Research and New Developments in Therapeutic Approaches to Ischemic and Hemorrhagic Stroke

    PubMed Central

    Previch, Lauren E.; Ma, Linlin; Wright, Joshua C.; Singh, Sunpreet; Geng, Xiaokun; Ding, Yuchuan

    2016-01-01

    Cerebral edema often manifests after the development of cerebrovascular disease, particularly in the case of stroke, both ischemic and hemorrhagic. Without clinical intervention, the influx of water into brain tissues leads to increased intracranial pressure, cerebral herniation, and ultimately death. Strategies to manage the development of edema constitute a major unmet therapeutic need. However, despite its major clinical significance, the mechanisms underlying cerebral water transport and edema formation remain elusive. Aquaporins (AQPs) are a class of water channel proteins which have been implicated in the regulation of water homeostasis and cerebral edema formation, and thus represent a promising target for alleviating stroke-induced cerebral edema. This review examines the significance of relevant AQPs in stroke injury and subsequently explores neuroprotective strategies aimed at modulating AQP expression, with a particular focus on AQP4, the most abundant AQP in the central nervous system. PMID:27438832

  15. Therapeutic outcomes of transplantation of amniotic fluid-derived stem cells in experimental ischemic stroke

    PubMed Central

    Tajiri, Naoki; Acosta, Sandra; Portillo-Gonzales, Gabriel S.; Aguirre, Daniela; Reyes, Stephanny; Lozano, Diego; Pabon, Mibel; Dela Peña, Ike; Ji, Xunming; Yasuhara, Takao; Date, Isao; Solomita, Marianna A.; Antonucci, Ivana; Stuppia, Liborio; Kaneko, Yuji; Borlongan, Cesar V.

    2014-01-01

    Accumulating preclinical evidence suggests the use of amnion as a source of stem cells for investigations of basic science concepts related to developmental cell biology, but also for stem cells’ therapeutic applications in treating human disorders. We previously reported isolation of viable rat amniotic fluid-derived stem (AFS) cells. Subsequently, we recently reported the therapeutic benefits of intravenous transplantation of AFS cells in a rodent model of ischemic stroke. Parallel lines of investigations have provided safety and efficacy of stem cell therapy for treating stroke and other neurological disorders. This review article highlights the need for investigations of mechanisms underlying AFS cells’ therapeutic benefits and discusses lab-to-clinic translational gating items in an effort to optimize the clinical application of the cell transplantation for stroke. PMID:25165432

  16. Review of technology development and clinical trials of transcranial laser therapy for acute ischemic stroke treatment

    NASA Astrophysics Data System (ADS)

    Catanzaro, Brian E.; Streeter, Jackson; de Taboada, Luis

    2010-02-01

    Stroke is the one of the leading causes of mortality in the United States, claiming 600,000 lives each year. Evidence suggests that near infrared (NIR) illumination has a beneficial effect on a variety of cells when these cells are exposed to adverse conditions. Among these conditions is the hypoxic state produced by acute ischemic stroke (AIS). To demonstrate the impact NIR Transcranial Laser Therapy (TLT) has on AIS in humans, a series of double blind, placebo controlled clinical trials were designed using the NeuroThera(R) System (NTS). The NTS was designed and developed to treat subjects non-invasively using 808 nm NIR illumination. TLT, as it applies to stroke therapy, and the NTS will be described. The results of the two clinical trials: NeuroThera(R) Safety and Efficacy Trial 1 (NEST-1) and NeuroThera(R) Safety and Efficacy Trial 2 (NEST-2) will be reviewed and discussed.

  17. Saturated Fat Consumption and Risk of Coronary Heart Disease and Ischemic Stroke: A Science Update.

    PubMed

    Nettleton, Joyce A; Brouwer, Ingeborg A; Geleijnse, Johanna M; Hornstra, Gerard

    2017-01-27

    At a workshop to update the science linking saturated fatty acid (SAFA) consumption with the risk of coronary heart disease (CHD) and ischemic stroke, invited participants presented data on the consumption and bioavailability of SAFA and their functions in the body and food technology. Epidemiological methods and outcomes were related to the association between SAFA consumption and disease events and mortality. Participants reviewed the effects of SAFA on CHD, causal risk factors, and surrogate risk markers. Higher intakes of SAFA were not associated with higher risks of CHD or stroke apparently, but studies did not take macronutrient replacement into account. Replacing SAFA by cis-polyunsaturated fatty acids was associated with significant CHD risk reduction, which was confirmed by randomized controlled trials. SAFA reduction had little direct effect on stroke risk. Cohort studies suggest that the food matrix and source of SAFA have important health effects.

  18. Polymorphism of the XRCC1 Gene Is Associated with Susceptibility and Short-Term Recovery of Ischemic Stroke

    PubMed Central

    He, Wei; Huang, Peng; Liu, Dinghua; Zhong, Lingling; Yu, Rongbin; Li, Jianan

    2016-01-01

    Background: Base excision repair (BER) is the primary DNA repair system with the ability to fix base lesions caused by oxidative damage. Genetic variants influencing the BER pathway may affect the susceptibility and the outcomes of ischemic stroke. Here, we examined how single nucleotide polymorphisms (SNPs) associated with BER impact susceptibility and short-term recovery of ischemic stroke. Methods: We selected 320 ischemic stroke patients and 303 controls. Then we genotyped SNPs of NEIL1 rs4462560, NEIL3 rs12645561 and XRCC1 rs25487 in both groups. Results: Polymorphism in XRCC1 rs25487 was significantly associated with reduced ischemic stroke (IS) risk (dominant model: OR = 0.53, 95% CI = 0.36–0.79, p = 0.002), a milder initial stroke (dominant model: OR = 0.57, 95% CI = 0.33–0.98, p = 0.043), and also a better short-term recovery (dominant model: OR = 0.57, 95% CI = 0.35–0.92, p = 0.022). No association was observed in the other two SNPs. Conclusions: Our study suggests that the genetic variant of XRCC1 rs25487 may contribute to the etiology of ischemic stroke. PMID:27763529

  19. Motor Imagery Cognitive Network after Left Ischemic Stroke: Study of the Patients during Mental Rotation Task

    PubMed Central

    Yan, Jing; Sun, Junfeng; Guo, Xiaoli; Jin, Zheng; Li, Yao; Li, Zhijun; Tong, Shanbao

    2013-01-01

    Although motor imagery could improve motor rehabilitation, the detailed neural mechanisms of motor imagery cognitive process of stroke patients, particularly from functional network perspective, remain unclear. This study investigated functional brain network properties in each cognitive sub-stage of motor imagery of stroke patients with ischemic lesion in left hemisphere to reveal the impact of stroke on the cognition of motor imagery. Both stroke patients and control subjects participated in mental rotation task, which includes three cognitive sub-stages: visual stimulus perception, mental rotation and response cognitive process. Event-related electroencephalograph was recorded and interdependence between two different cortical areas was assessed by phase synchronization. Both global and nodal properties of functional networks in three sub-stages were statistically analyzed. Phase synchronization of stroke patients significantly reduced in mental rotation sub-stage. Longer characteristic path length and smaller global clustering coefficient of functional network were observed in patients in mental rotation sub-stage which implied the impaired segregation and integration. Larger nodal clustering coefficient and betweenness in contralesional occipitoparietal and frontal area respectively were observed in patients in all sub-stages. In addition, patients also showed smaller betweenness in ipsilesional central-parietal area in response sub-stage. The compensatory effects on local connectedness and centrality indicated the neuroplasticity in contralesional hemisphere. The functional brain networks of stroke patients demonstrated significant alterations and compensatory effects during motor imagery. PMID:24167569

  20. The Relationship between C-Reactive Protein Level and Discharge Outcome in Patients with Acute Ischemic Stroke

    PubMed Central

    Geng, He-Hong; Wang, Xin-Wang; Fu, Rong-Li; Jing, Meng-Juan; Huang, Ling-Ling; Zhang, Qing; Wang, Xiao-Xiao; Wang, Pei-Xi

    2016-01-01

    Previous studies showed that C-reactive protein (CRP), an inflammatory marker, was associated with stroke severity and long-term outcome. However, the relationship between the acute-phase CRP level and discharge outcome has received little attention. We prospectively studied 301 patients with acute ischemic stroke (over a period of two weeks) from two hospital stroke wards and one rehabilitation department in Henan, China. Patients’ demographic and clinical data were collected and evaluated at admission. Poor discharge outcome was assessed in patients at discharge using the Modified Rankin Scale (MRS > 2). Multivariate logistic regression analysis was performed to determine the risk factors of poor discharge outcome after adjusting for potential confounders. Poor discharge outcome was observed in 78 patients (25.9%). Univariate analyses showed that factors significantly influencing poor discharge outcome were age, residence, recurrent acute ischemic stroke, coronary heart disease, the National Institutes of Health Stroke Scale (NIHSS) score at admission, non-lacunar stroke, time from onset of stroke to admission, CRP, TBIL (total bilirubin), direct bilirubin (DBIL), ALB (albumin), FIB (fibrinogen) and D-dimer (p < 0.05). After adjusting for age, residence, recurrent ischemic stroke, coronary heart disease, NIHSS score at admission, lacunar stroke, time from onset of stroke to admission, CRP, TBIL, DBIL, ALB, FIB and D-dimer, multivariate logistic regression analyses revealed that poor outcome at discharge was associated with recurrent acute ischemic stroke (OR, 2.115; 95% CI, 1.094–4.087), non-lacunar stroke (OR, 2.943; 95% CI, 1.436–6.032), DBIL (OR, 1.795; 95% CI, 1.311–2.458), and CRP (OR, 4.890; 95% CI, 3.063–7.808). In conclusion, the CRP level measured at admission was found to be an independent predictor of poor outcome at discharge. Recurrent acute ischemic stroke, non-lacunar stroke and DBIL were also significantly associated with discharge

  1. Advances in medical revascularisation treatments in acute ischemic stroke.

    PubMed

    Asadi, H; Yan, B; Dowling, R; Wong, S; Mitchell, P

    2014-01-01

    Urgent reperfusion of the ischaemic brain is the aim of stroke treatment and there has been ongoing research to find a drug that can promote vessel recanalisation more completely and with less side effects. In this review article, the major studies which have validated the use and safety of tPA are discussed. The safety and efficacy of other thrombolytic and anticoagulative agents such as tenecteplase, desmoteplase, ancrod, tirofiban, abciximab, eptifibatide, and argatroban are also reviewed. Tenecteplase and desmoteplase are both plasminogen activators with higher fibrin affinity and longer half-life compared to alteplase. They have shown greater reperfusion rates and improved functional outcomes in preliminary studies. Argatroban is a direct thrombin inhibitor used as an adjunct to intravenous tPA and showed higher rates of complete recanalisation in the ARTTS study with further studies which are now ongoing. Adjuvant thrombolysis techniques using transcranial ultrasound are also being investigated and have shown higher rates of complete recanalisation, for example, in the CLOTBUST study. Overall, development in medical therapies for stroke is important due to the ease of administration compared to endovascular treatments, and the new treatments such as tenecteplase, desmoteplase, and adjuvant sonothrombolysis are showing promising results and await further large-scale clinical trials.

  2. Early and intermediate prognosis of intravenous thrombolytic therapy in acute ischemic stroke subtypes according to the causative classification of stroke system

    PubMed Central

    Pashapour, Ali; Atalu, Abolfazl; Farhoudi, Mehdi; Taheraghdam, Ali-Akbar; Sadeghi Hokmabadi, Elyar; Sharifipour, Ehsan; NajafiNeshli, Mehdi

    2013-01-01

    Objectives: Intravenous thrombolytic therapy has established acceptable results in treating ischemic stroke. However, there is little information on treatment outcome especially in different subtypes. The aim of current study was to evaluate early and intermediate prognosis in intravenous thrombolytic therapy for acute ischemic stroke subtypes. Methodology: Forty eligible patients (57.5% male with mean age of 63.18±13.49 years) with definite ischemic stroke who were admitted to emergency department of Imam Reza University Hospital, in the first 180 minutes after occurrence received recombinant tissue plasminogen activator. All investigation findings were recorded and stroke subtypes were determined according to the Causative Classification of Stroke System. Stroke severity forms including modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) scores were recorded for all patients in first, seven and 90 days after stroke and disease outcome was evaluated. Results: The etiology of stroke was large artery atherosclerosis in 20%, cardio-aortic embolism in 45%, small artery occlusion in 17.5% and undetermined causes in 17.5%. NIHSS and mRS scores were significantly improved during time (P < 0.001 in both cases). Three months mortality rate was 25%. Among the etiologies, patients with small artery occlusion and then cardio-aortic embolism had lower NIHSS score at arrival (P = 0.04). Caplan-meier analysis showed that age, sex and symptom to needle time could predict disease outcome. Conclusion: Intravenous thrombolytic therapy is accompanied by good early and intermediate outcome in most patients with ischemic stroke. Small artery occlusion subtype had less disease severity and higher improvement. PMID:24353536

  3. Upside Down Crossed Cerebellar Diaschisis: Proposing Chronic Stimulation of the Dentatothalamocortical Pathway for Post-Stroke Motor Recovery

    PubMed Central

    Machado, Andre; Baker, Kenneth B.

    2012-01-01

    Background: Stroke remains the leading cause for long-term motor impairment in the industrialized world. New techniques are needed to improve outcomes. Objective: To propose chronic electrical stimulation of the dentatothalamocortical pathway as a method for enhancing cortical excitability and improving motor recovery following stroke. Method: In previous studies, motor evoked potentials were derived from intracortical microstimulation and used to index cortical excitability in rats undergoing continuous, asynchronous deep cerebellar stimulation. In a separate set of experiments, the effect of chronic deep cerebellar stimulation on motor recovery was tested in rats following large ischemic strokes. Results: Deep cerebellar stimulation modulated cortical excitability in a frequency-dependent fashion. Beta band stimulation yielded sustained increment in excitability and was associated with enhanced motor recovery compared to sham stimulation. Conclusion: Chronic deep cerebellar stimulation enhances recovery of motor function following large ischemic strokes in the rat, an effect that may be associated with increased cortical excitability. Given that deep brain stimulation is already a well established method, this new approach to motor recovery may be a viable option for human translation in stroke rehabilitation. PMID:22661933

  4. Antiplatelet therapy for preventing stroke in patients with chronic kidney disease.

    PubMed

    Kim, Suk Jae; Bang, Oh Young

    2013-01-01

    Chronic kidney disease (CKD), defined as reduced glomerular filtration rate and/or proteinuria, is a serious worldwide health problem. The incidence and prevalence of CKD are increasing with age, and patients with CKD are a population at very high risk for developing stroke. CKD may increase the risk for incident stroke independent of conventional stroke risk factors. A common pathological process including anemia, homocysteine, nitric oxide, oxidative stress, inflammation, and conditions promoting coagulation may be related to the development of stroke in the course of CKD. CKD can also serve as a marker of brain injury, because the cerebral microvascular system has similar hemodynamic features with the vascular beds of the kidney. CKD has been linked with markers of cerebral small artery disease including white matter lesions, lacunar infarctions, and cerebral microbleeds. CKD has been implicated with neurological deterioration during hospitalization, poor functional outcome, and hemorrhagic transformation in patients with acute stroke. Recurrence of stroke may also be higher in CKD patients compared with those having normal kidney function. However, there have been no specific recommendations for antiplatelet therapy in patients with ischemic stroke plus CKD. As CKD patients have distinct characteristics including high bleeding complications and poor response to antiplatelet agents, selecting and adjusting platelet aggregation inhibitors should be individualized. In addition, it should be noted that aspirin may aggravate renal dysfunction. Phosphodiesterase inhibitors restore endothelial dysfunction and may serve as a target for preventing stroke in CKD patients. Aside from antiplatelet therapy, other treatments including lipid control, blood pressure lowering, and renal transplantation are also important. Further studies are warranted for optimal treatment in stroke prevention in CKD patients.

  5. Hemorrhagic transformation and cerebral edema in acute ischemic stroke: Link to cerebral autoregulation

    PubMed Central

    Castro, Pedro; Azevedo, Elsa; Serrador, Jorge; Rocha, Isabel; Sorond, Farzaneh

    2017-01-01

    Background Hemorrhagic transformation and cerebral edema are feared complications of acute ischemic stroke but mechanisms are poorly understood and reliable early markers are lacking. Early assessment of cerebrovascular hemodynamics may advance our knowledge in both areas. We examined the relationship between dynamic cerebral autoregulation (CA) in the early hours post ischemia, and the risk of developing hemorrhagic transformation and cerebral edema at 24 h post stroke Methods We prospectively enrolled 46 patients from our center with acute ischemic stroke in the middle cerebral artery territory. Cerebrovascular resistance index was calculated. Dynamic CA was assessed by transfer function analysis (coherence, phase and gain) of the spontaneous blood flow velocity and blood pressure oscillations. Infarct volume, hemorrhagic transformation, cerebral edema, and white matter changes were collected from computed tomography performed at presentation and 24 h. Results At admission, phase was lower (worse CA) in patients with hemorrhagic transformation [6.6 ± 30 versus 45 ± 38°; adjusted odds ratio 0.95 (95% confidence internal 0.94–0.98), p = 0.023] and with cerebral edema [6.6 ± 30 versus 45 ± 38°, adjusted odds ratio 0.96 (0.92–0.999), p = 0.044]. Progression to edema was associated with lower cerebrovascular resistance (1.4 ± 0.2 versus 2.3 ± 1.5 mm Hg/cm/s, p = 0.033) and increased cerebral blood flow velocity (51 ± 25 versus 42 ± 17 cm/s, p = 0.033) at presentation. All hemodynamic differences resolved at 3 months Conclusions Less effective CA in the early hour post ischemic stroke is associated with increased risk of hemorrhagic transformation and cerebral edema, possibly reflecting breakthrough hyperperfusion and microvascular injury. Early assessment of dynamic CA could be useful in identifying individuals at risk for these complications. PMID:28017224

  6. Comparison of Statistical and Clinical Predictions of Functional Outcome after Ischemic Stroke

    PubMed Central

    Thompson, Douglas D.; Murray, Gordon D.; Sudlow, Cathie L. M.; Dennis, Martin; Whiteley, William N.

    2014-01-01

    Background To determine whether the predictions of functional outcome after ischemic stroke made at the bedside using a doctor’s clinical experience were more or less accurate than the predictions made by clinical prediction models (CPMs). Methods and Findings A prospective cohort study of nine hundred and thirty one ischemic stroke patients recruited consecutively at the outpatient, inpatient and emergency departments of the Western General Hospital, Edinburgh between 2002 and 2005. Doctors made informal predictions of six month functional outcome on the Oxford Handicap Scale (OHS). Patients were followed up at six months with a validated postal questionnaire. For each patient we calculated the absolute predicted risk of death or dependence (OHS≥3) using five previously described CPMs. The specificity of a doctor’s informal predictions of OHS≥3 at six months was good 0.96 (95% CI: 0.94 to 0.97) and similar to CPMs (range 0.94 to 0.96); however the sensitivity of both informal clinical predictions 0.44 (95% CI: 0.39 to 0.49) and clinical prediction models (range 0.38 to 0.45) was poor. The prediction of the level of disability after stroke was similar for informal clinical predictions (ordinal c-statistic 0.74 with 95% CI 0.72 to 0.76) and CPMs (range 0.69 to 0.75). No patient or clinician characteristic affected the accuracy of informal predictions, though predictions were more accurate in outpatients. Conclusions CPMs are at least as good as informal clinical predictions in discriminating between good and bad functional outcome after ischemic stroke. The place of these models in clinical practice has yet to be determined. PMID:25299053

  7. Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial

    PubMed Central

    Hill, Michael D.; Martin, Renee H.; Palesch, Yuko Y.; Moy, Claudia S.; Tamariz, Diego; Ryckborst, Karla J.; Jones, Elizabeth B.; Weisman, David; Pettigrew, Creed; Ginsberg, Myron D.

    2015-01-01

    Background Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial. Methods Ischemic stroke patients, aged 18–83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism. Results Among 830 patients, neurological and cardiopulmonary adverse events were not differentially associated with poor outcome between ALB and saline control subjects. The rate of symptomatic intracranial hemorrhage in the first 24h was low overall (2.9%, 24/830) but more common in the ALB treated subjects (RR = 2.4, CI95 1.01–5.8). The rate of pulmonary edema/CHF in the first 48h was 7.9% (59/830) and was more common among ALB treated subjects (RR = 10.7, CI95 4.3–26.6); this complication was expected and was satisfactorily managed with mandated diuretic administration and intravenous fluid guidelines. Troponin elevations in the first 48h were common, occurring without ECG change or cardiac symptoms in 52 subjects (12.5%). Conclusions ALB therapy was associated with an increase in symptomatic ICH and pulmonary edema/congestive heart failure but this did not affect final outcomes. Troponin elevation occurs routinely in the first 48 hours after acute ischemic stroke. Trial Registration ClincalTrials.gov NCT00235495 PMID:26325387

  8. Contralateral needling at unblocked collaterals for hemiplegia following acute ischemic stroke

    PubMed Central

    Gao, Huanmin; Li, Xugang; Gao, Xia; Ma, Benxu

    2013-01-01

    Hemiplegia caused by stroke indicates dysfunction of the network between the brain and limbs, namely collateral shock in the brain. Contralateral needling is the insertion of needles into acupoints on the relative healthy side of the body to treat diseases such as apoplexy. However, there is little well-designed and controlled clinical evidence for this practice. This study investigated whether contralateral needling could treat hemiplegia after acute ischemic stroke in 106 randomly selected patients with acute ischemic stroke. These patients were randomly assigned to three groups: 45 in the contralateral needling group, receiving acupuncture on the unaffected limbs; 45 in the tional acupuncture group, receiving acupuncture on the hemiplegic limbs; and 16 in the control group, receiving routine treatments without acupuncture. Acupuncture at acupoints Chize (LU5) in the upper limb and Jianliao (TE14) in the lower limb was performed for 45 minutes daily for 30 consecutive days. The therapeutic effective rate, Neurological Deficit Score, Modified Barthel Index and Fugl-Meyer Assessment were evaluated. The therapeutic effective rate of contralateral needling was higher than that of conventional acupuncture (46.67% vs. 31.11%, P < 0.05). The neurological deficit score of contralateral needling was significantly decreased compared with conventional acupuncture (P < 0.01). The Modified Barthel Index and Fugl-Meyer Assessment score of contralateral needling increased more significantly than those of conventional acupuncture (both P < 0.01). The present findings suggest that contralateral needling unblocks collaterals and might be more effective than conventional acupuncture in the treatment of hemiplegia following acute ischemic stroke. PMID:25206612

  9. Prevalence of Inadequate Blood Pressure Control Among Veterans After Acute Ischemic Stroke Hospitalization: A Retrospective Cohort

    PubMed Central

    Roumie, Christianne L.; Ofner, Susan; Ross, Joseph S.; Arling, Greg; Williams, Linda S.; Ordin, Diana L.; Bravata, Dawn M.

    2011-01-01

    Background Reducing blood pressure (BP) after stroke reduces risk for recurrent events. Our aim was to describe hypertension care among veterans with ischemic stroke including BP control by discharge and over the 6 months post stroke event. Methods and Results The Office of Quality and Performance Stroke Special Study included a systematic sample of veterans hospitalized for ischemic stroke in 2007. We examined BP control (<140/90 mmHg) at discharge excluding those who died, enrolled in hospice, or had unknown discharge disposition (N=3640, 3382 adjusted analysis). The second outcome was BP control (<140/90 mmHg) within 6-months post-stroke, excluding patients who died /readmitted within 30 days, lost to follow-up or did not have a BP recorded (N=2054, 1915 adjusted analysis). The population was white (62.7 %) and male (97.7%); 46.9% were <65 years of age; 29% and 37% had a history of cerebrovascular or cardiovascular disease, respectively. Among the 3640 stroke patients 1573(43%) had their last documented BP prior to discharge >140/90 mmHg. Black race (adjusted OR 0.77 [95% CI 0.65, 0.91]), diabetes (OR 0.73 [95% CI 0.62, 0.86]) and hypertension history (OR 0.51 [95% CI 0.42, 0.63]) were associated with lower odds for controlled BP at discharge. Of the 2054 stroke patients seen within 6 months from their index event, 673 (32.8%) remained uncontrolled. By 6 months post event, neither race nor diabetes was associated with BP control; whereas history of hypertension continued to have lower odds of BP control. For each 10 point increase in systolic BP > 140 mmHg at discharge, odds of BP control within 6 months post discharge decreased by 12% (95% CI (8%, 18%)). Conclusions BP values in excess of national guidelines are common after stroke. Forty three percent of patients were discharged with an elevated BP and 33% remained uncontrolled by 6 months. PMID:21693725

  10. Use of Antihypertensive Drugs and Ischemic Stroke Severity – Is There a Role for Angiotensin-II?

    PubMed Central

    Bots, Michiel L.; Selvarajah, Sharmini; Abdul Aziz, Zariah; Sidek, Norsima Nazifah; Spiering, Wilko; Kappelle, L. Jaap; Vaartjes, Ilonca

    2016-01-01

    Background The increase in angiotensin II (Ang II) formation by selected antihypertensive drugs is said to exhibit neuroprotective properties, but this translation into improvement in clinical outcomes has been inconclusive. We undertook a study to investigate the relationship between types of antihypertensive drugs used prior to a stroke event and ischemic stroke severity. We hypothesized that use of antihypertensive drugs that increase Ang II formation (Ang II increasers) would reduce ischemic stroke severity when compared to antihypertensive drugs that suppress Ang II formation (Ang II suppressors). Methods From the Malaysian National Neurology Registry, we included hypertensive patients with first ischemic stroke who presented within 48 hours from ictus. Antihypertensive drugs were divided into Ang II increasers (angiotensin-I receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics) and Ang II suppressors (angiotensin-converting-enzyme inhibitors (ACEIs) and beta blockers). We evaluated stroke severity during admission with the National Institute of Health Stroke Scale (NIHSS). We performed a multivariable logistic regression with the score being dichotomized at 15. Scores of less than 15 were categorized as less severe stroke. Results A total of 710 patients were included. ACEIs was the most commonly prescribed antihypertensive drug in patients using Ang II suppressors (74%) and CCBs, in patients prescribed with Ang II increasers at 77%. There was no significant difference in the severity of ischemic stroke between patients who were using Ang II increasers in comparison to patients with Ang II suppressors (OR: 1.32, 95%CI: 0.83–2.10, p = 0.24). Conclusion In our study, we found that use of antihypertensive drugs that increase Ang II formation was not associated with less severe ischemic stroke as compared to use of antihypertensive drugs that suppress Ang II formation. PMID:27846309

  11. Gene profiles and electrophysiology of doublecortin-expressing cells in the subventricular zone after ischemic stroke

    PubMed Central

    Shuang Liu, Xian; Chopp, Michael; Zhang, Xue Guo; Zhang, Rui Lan; Buller, Ben; Hozeska-Solgot, Ann; Gregg, Sara R; Zhang, Zheng Gang

    2009-01-01

    Stroke increases neuroblasts in the subventricular zone (SVZ) of the lateral ventricle and these neuroblasts migrate toward the ischemic boundary to replace damaged neurons. Using brain slices from the nonischemic adult rat and transgenic mice that expressed enhanced green fluorescent protein (EGFP) concomitantly with doublecortin (DCX), a marker for migrating neuroblasts, we recorded electrophysiological characteristics while simultaneously analyzing the gene expression in single SVZ cells. We found that SVZ cells expressing the DCX gene from the nonischemic rat had a mean resting membrane potential (RMP) of −30mV. DCX–EGFP-positive cells in the nonischemic SVZ of the transgenic mouse had a mean RMP of −25±7mV and did not exhibit Na+ currents, characteristic of immature neurons. However, DCX–EGFP-positive cells in the ischemic SVZ exhibited a hyperpolarized mean RMP of −54±18 mV and displayed Na+ currents, indicative of more mature neurons. Single-cell multiplex RT-PCR analysis revealed that DCX–EGFP-positive cells in the nonischemic SVZ of the transgenic mouse expressed high neural progenitor marker genes, Sox2 and nestin, but not mature neuronal marker genes. In contrast, DCX–EGFP-positive cells in the ischemic SVZ expressed tyrosine hydroxylase, a mature neuronal marker gene. Together, these data indicate that stroke changes gene profiles and the electrophysiology of migrating neuroblasts. PMID:18854839