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Showing papers on "Cerebral infarction published in 2009"


Journal ArticleDOI
TL;DR: Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset and there is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset.
Abstract: Summary Background Patients with space-occupying hemispheric infarctions have a poor prognosis, with case fatality rates of up to 80%. In a pooled analysis of randomised trials, surgical decompression within 48 h of stroke onset reduced case fatality and improved functional outcome; however, the effect of surgery after longer intervals is unknown. The aim of HAMLET was to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction. Methods Patients with space-occupying hemispheric infarction were randomly assigned within 4 days of stroke onset to surgical decompression or best medical treatment. The primary outcome measure was the modified Rankin scale (mRS) score at 1 year, which was dichotomised between good (0–3) and poor (4–6) outcome. Other outcome measures were the dichotomy of mRS score between 4 and 5, case fatality, quality of life, and symptoms of depression. Analysis was by intention to treat. This trial is registered, ISRCTN94237756. Findings Between November, 2002, and October, 2007, 64 patients were included; 32 were randomly assigned to surgical decompression and 32 to best medical treatment. Surgical decompression had no effect on the primary outcome measure (absolute risk reduction [ARR] 0%, 95% CI −21 to 21) but did reduce case fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction), DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke onset, surgical decompression reduced poor outcome (ARR 16%, −0·1 to 33) and case fatality (ARR 50%, 34 to 66). Interpretation Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset. The decision to perform the operation should depend on the emphasis patients and relatives attribute to survival and dependency. Funding Netherlands Heart Foundation.

761 citations


Journal ArticleDOI
TL;DR: Evidence is provided that good clinical outcome following angiographically successful reperfusion is significantly time-dependent, and at later times, angiographic reperfusions may be associated with a poor risk–benefit ratio in unselected patients.
Abstract: Background: Trials of IV recombinant tissue plasminogen activator (rt-PA) have demonstrated that longer times from ischemic stroke symptom onset to initiation of treatment are associated with progressively lower likelihoods of clinical benefit, and likely no benefit beyond 4.5 hours. How the timing of IV rt-PA initiation relates to timing of restoration of blood flow has been unclear. An understanding of the relationship between timing of angiographic reperfusion and clinical outcome is needed to establish time parameters for intraarterial (IA) therapies. Methods: The Interventional Management of Stroke pilot trials tested combined IV/IA therapy for moderate-to-severe ischemic strokes within 3 hours from symptom onset. To isolate the effect of time to angiographic reperfusion on clinical outcome, we analyzed only middle cerebral artery and distal internal carotid artery occlusions with successful reperfusion (Thrombolysis in Cerebral Infarction 2–3) during the interventional procedure ( Results: Among the 54 cases, only time to angiographic reperfusion and age independently predicted good clinical outcome after angiographic reperfusion. The probability of good clinical outcome decreased as time to angiographic reperfusion increased (unadjusted p = 0.02, adjusted p = 0.01) and approached that of cases without angiographic reperfusion within 7 hours. Conclusions: We provide evidence that good clinical outcome following angiographically successful reperfusion is significantly time-dependent. At later times, angiographic reperfusion may be associated with a poor risk–benefit ratio in unselected patients.

482 citations


Journal ArticleDOI
TL;DR: This review focuses on the ischemic cascade, which is a complex series of neurochemical processes that are unleashed by transient or permanent focal cerebral ischemia and involves cellular bioenergetic failure, excitotoxicity, oxidative stress, blood-brain barrier dysfunction, microvascular injury, hemostatic activation, post-ischemic inflammation and finally cell death of neurons, glial and endothelial cells.

475 citations


Journal ArticleDOI
01 Jun 2009-Stroke
TL;DR: Strokes are generally more severe in patients with HS within the first 3 months after stroke, and HS is associated with a considerable increase of mortality, which is specifically associated with the hemorrhagic nature of the lesion.
Abstract: Background and Purpose— Stroke patients with hemorrhagic (HS) and ischemic strokes were compared with regard to stroke severity, mortality, and cardiovascular risk factors. Methods— A registry started in 2001, with the aim of registering all hospitalized stroke patients in Denmark, now holds information for 39 484 patients. The patients underwent an evaluation including stroke severity (Scandinavian Stroke Scale), CT, and cardiovascular risk factors. They were followed-up from admission until death or censoring in 2007. Independent predictors of death were identified by means of a survival model based on 25 123 individuals with a complete data set. Results— Of the patients 3993 (10.1%) had HS. Stroke severity was almost linearly related to the probability of having HS (2% in patients with the mildest stroke and 30% in those with the most severe strokes). Factors favoring ischemic strokes vs HS were diabetes, atrial fibrillation, previous myocardial infarction, previous stroke, and intermittent arterial cl...

468 citations


Journal ArticleDOI
TL;DR: A variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated significantly with AF is identified, and this variant also associated with ischemic stroke and cardioembolic stroke in a combined analysis of five stroke samples.
Abstract: Daniel Gudbjartsson and colleagues report a genome-wide association study for atrial fibrillation, a condition associated with increased risk of stroke. They report a variant in ZFHX3 associated with atrial fibrillation as well as ischemic stroke. We expanded our genome-wide association study on atrial fibrillation (AF) in Iceland, which previously identified risk variants on 4q25, and tested the most significant associations in samples from Iceland, Norway and the United States. A variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated significantly with AF (odds ratio OR = 1.21, P = 1.4 × 10−10). This variant also associated with ischemic stroke (OR = 1.11, P = 0.00054) and cardioembolic stroke (OR = 1.22, P = 0.00021) in a combined analysis of five stroke samples.

450 citations


Journal ArticleDOI
01 Dec 2009-Stroke
TL;DR: Large vessel intracranial occlusion accounted for nearly half of acute ischemic strokes in unselected patients presenting to academic medical centers, and the presence of basilar and internal carotid terminus occlusions in addition to National Institutes of Health Stroke Scale and age independently predicted outcome.
Abstract: Background and Purpose— Acute ischemic stroke due to large vessel occlusion (LVO)—vertebral, basilar, carotid terminus, middle and anterior cerebral arteries—likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data have been reported on a cohort of unselected patients with stroke and with transient ischemic attack, the clinical impact of LVO has been difficult to quantify. Methods— The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, includ...

361 citations


Journal ArticleDOI
01 Sep 2009-Stroke
TL;DR: Most patients with proximal middle cerebral artery occlusion rapidly recruit sufficient collaterals and follow a clinical course similar to patients with no occlusions, but a subset with diminished collateral is at high risk for worsening.
Abstract: Background and Purpose— Despite the abundance of emerging multimodal imaging techniques in the field of stroke, there is a paucity of data demonstrating a strong correlation between imaging findings and clinical outcome. This study explored how proximal arterial occlusions alter flow in collateral vessels and whether occlusion or extent of collaterals correlates with prehospital symptoms of fluctuation and worsening since onset or predict in-hospital worsening. Methods— Among 741 patients enrolled in a prospective cohort study involving CT angiographic imaging in acute stroke, 134 cases with proximal middle cerebral artery occlusion and 235 control subjects with no occlusions were identified. CT angiography was used to identify occlusions and grade the extent of collateral vessels in the sylvian fissure and leptomeningeal convexity. History of symptom fluctuation or progressive worsening was obtained on admission. Results— Prehospital symptoms were unrelated to occlusion or collateral status. In cases, 37...

330 citations


Journal ArticleDOI
01 Apr 2009-Stroke
TL;DR: As patients with atrial fibrillation age, the relative efficacy of AP to prevent ischemic stroke appears to decrease, whereas it does not change for OAC, and the absolute benefit of OAC increases as patients get older.
Abstract: Background and Purpose - Stroke risk increases with age in patients who have nonvalvular atrial fibrillation. It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age. The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants (OAC) and antiplatelet (AP) therapy (including acetylsalicylic acid and triflusal) on ischemic stroke, serious bleeding, and vascular events in patients with atrial fibrillation. Methods - This is an analysis of the Atrial Fibrillation Investigators database, which contains patient level-data from randomized trials of stroke prevention in atrial fibrillation. We used Cox regression models with age as a continuous variable that controlled for sex, year of randomization, and history of cerebrovascular disease, diabetes, hypertension, and congestive heart failure. Outcomes included ischemic stroke, serious bleeding (intracranial hemorrhage or systemic bleeding requiring hospitalization, transfusion, or surgery), and cardiovascular events (ischemic stroke, myocardial infarction, systemic embolism, or vascular death). Results - The analysis included 8932 patients and 17 685 years of observation from 12 trials. Patient age increased risk of ischemic stroke (adjusted hazard ratio per decade increase 1.45; 95% CI, 1.26 to 1.66), serious bleeding (1.61; 1.47 to 1.77), and cardiovascular events (1.43; 1.33 to 1.53). Compared with placebo, OAC and AP significantly reduced the risk of ischemic stroke (OAC, 0.36; 0.29 to 0.45; AP, 0.81; 0.72 to 0.90) and cardiovascular outcomes (OAC, 0.59; 0.52 to 0.66; AP, 0.81; 0.75 to 0.88), whereas OAC increased risk of serious bleeding (1.56; 1.03 to 2.37). The relative benefit of OAC versus placebo or AP did not vary by patient age for any outcome. Compared with placebo, the relative benefit of AP for preventing ischemic stroke decreased significantly as patients aged (P=0.01). Conclusions - As patients with atrial fibrillation age, the relative efficacy of AP to prevent ischemic stroke appears to decrease, whereas it does not change for OAC. Because stroke risk increases with age, the absolute benefit of OAC increases as patients get older. © 2009 American Heart Association, Inc.

324 citations


Journal ArticleDOI
01 Jul 2009-Stroke
TL;DR: There is a strong association of high systolic BP after thrombolysis with poor outcome, whereas initiation of antihypertensive therapy in newly recognized moderate hypertension was associated with a favorable outcome.
Abstract: Background and Purpose— The optimal management of blood pressure (BP) in acute stroke remains unclear. For ischemic stroke treated with intravenous thrombolysis, current guidelines suggest pharmacological intervention if systolic BP exceeds 180 mm Hg. We determined retrospectively the association of BP and antihypertensive therapy with clinical outcomes after stroke thrombolysis. Methods— The SITS thrombolysis register prospectively recorded 11 080 treatments from 2002 to 2006. BP values were recorded at baseline, 2 hours, and 24 hours after thrombolysis. Outcomes were symptomatic (National Institutes of Health Stroke Scale score deterioration ≥4) intracerebral hemorrhage Type 2, mortality, and independence at (modified Rankin Score 0 to 2) 3 months. Patients were categorized by history of hypertension and antihypertensive therapy within 7 days after thrombolysis: Group 1, hypertensive treated with antihypertensives (n=5612); Group 2, hypertensive withholding antihypertensives (n=1573); Group 3, without history of hypertension treated with antihypertensives (n=995); and Group 4, without history of hypertension not treated with antihypertensives (n=2632). For 268 (2.4%) patients, these data were missing. Average systolic BP 2 to 24 hours after thrombolysis was categorized by 10-mm Hg intervals with 100 to 140 used as a reference. Results— In multivariable analysis, high systolic BP 2 to 24 hours after thrombolysis as a continuous variable was associated with worse outcome ( P <0.001) and as a categorical variable had a linear association with symptomatic hemorrhage and a U-shaped association with mortality and independence with systolic BP 141 to 150 mm Hg associated with most favorable outcomes. OR (95% CI) from multivariable analysis showed no difference in symptomatic hemorrhage (1.09 [0.83 to 1.51]; P =0.58) and independence (1.03 [0.93 to 1.10]; P =0.80) but lower mortality (0.82 [0.73 to 0.92]; P =0.0007) for Group 1 compared with Group 4. Group 2 had a higher symptomatic hemorrhage (1.86 [1.34 to 2.68]; P =0.0004) and mortality (1.62 [1.41 to 1.85]; P <0.0001) and lower independence (0.89 [0.80 to 0.99]; P =0.04) compared with Group 4. Group 3 had similar results as Group 1. Conclusions— There is a strong association of high systolic BP after thrombolysis with poor outcome. Withholding antihypertensive therapy up to 7 days in patients with a history of hypertension was associated with worse outcome, whereas initiation of antihypertensive therapy in newly recognized moderate hypertension was associated with a favorable outcome.

313 citations


Journal ArticleDOI
TL;DR: Arteriopathy is prevalent among children with arterial ischemic stroke, particularly those presenting in early school age, and those with a history of sickle cell disease, suggesting a possible role for infection in the pathogenesis of these lesions.
Abstract: Background— Cerebral arteriopathies, including an idiopathic focal cerebral arteriopathy of childhood (FCA), are common in children with arterial ischemic stroke and strongly predictive of recurrence. To better understand these lesions, we measured predictors of arteriopathy within a large international series of children with arterial ischemic stroke. Methods and Results— Between January 2003 and July 2007, 30 centers within the International Pediatric Stroke Study enrolled 667 children (age, 29 days to 19 years) with arterial ischemic stroke and abstracted clinical and radiographic data. Cerebral arteriopathy and its subtypes were defined using published definitions; FCA was defined as cerebral arterial stenosis not attributed to specific diagnoses such as moyamoya, arterial dissection, vasculitis, or postvaricella angiopathy. We used multivariate logistic regression techniques to determine predictors of arteriopathy and FCA among those subjects who received vascular imaging. Of 667 subjects, 525 had kn...

295 citations


Journal ArticleDOI
TL;DR: Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability, however, care must be taken when these results are interpreted and further evaluation in larger trials is needed.
Abstract: Summary Background Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for lowering blood pressure in patients who have had a stroke. Methods Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure [SBP] >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008. Findings 179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5–16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome—death or dependency at 2 weeks—occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1·03, 95% CI 0·80–1·33; p=0·82). There was no evidence of early neurological deterioration with active treatment (RR 1·22, 0·33–4·54; p=0·76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17–25] mm Hg vs 11 [5–17] mm Hg; p=0·004). No increase in serious adverse events was reported with active treatment (RR 0·91, 0·69–1·12; p=0·50) but 3-month mortality was halved (9·7% vs 20·3%, hazard ratio [HR] 0·40, 95% CI 0·2–1·0; p=0·05). Interpretation Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed. Funding UK National Health Service Research and Development Health Technology Assessment Programme.

Journal ArticleDOI
01 Dec 2009-Stroke
TL;DR: Final recanalization status represents the strongest predictor of clinical outcomes in patients undergoing thrombectomy, and supports the inclusion of internal carotid artery occlusions in future efficacy trials.
Abstract: Background and Purpose— The Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials evaluated the safety and efficacy of thrombectomy in the treatment of intracranial arterial occlusions within 8 hours of symptom onset. We sought to determine the predictors of clinical and angiographic outcomes in these patients. Methods— The trial cohorts were combined in a data set of 305 patients. Twenty-eight baseline variables were included in univariate and multivariate analyses to define the independent predictors of good outcomes (modified Rankin Scale score ≤2), mortality, and successful revascularization (Thrombolysis In Myocardial Ischemia 2 to 3 flow). Results— In the univariate analysis, final revascularization, baseline National Institutes of Health Stroke Scale, age, and systolic blood pressure were associated with both good outcomes and mortality at 90 days (P<0.0018 for all). In the multivariate analysis, final revascularization (OR, 20.4; 95% CI, 7.7 to 53.9; P<0.0001), baseline Na...

Journal ArticleDOI
01 Jun 2009-Stroke
TL;DR: In this paper, an acute diffusion-weighted imaging lesion volume >70 cm3 was found to predict poor outcome in patients with stroke, and the authors sought to determine if this threshold could identify patients treated with intra-arterial therapy who would do poorly despite reperfusion.
Abstract: Background and Purpose— Recent studies demonstrate that an acute diffusion-weighted imaging lesion volume >70 cm3 predicts poor outcome in patients with stroke. We sought to determine if this threshold could identify patients treated with intra-arterial therapy who would do poorly despite reperfusion. In patients with initial infarcts <70 cm3, we sought to determine what effect recanalization and time to recanalization had on infarct growth and functional outcome. Methods— We retrospectively studied 34 consecutive patients with anterior circulation stroke who underwent pretreatment diffusion-weighted imaging and perfusion-weighted imaging and subsequent intra-arterial therapy. Recanalization success and time to recanalization were recorded. Initial diffusion-weighted imaging and mean transit time lesion and final infarct volumes were determined. Patients were stratified based on initial infarct volume, recanalization status, and time to recanalization. Statistical tests were performed to assess difference...

Journal ArticleDOI
TL;DR: The best studied pathways of tPA neurotoxicity are discussed along with future directions for a safer use of t PA as a thrombolytic agent in the setting of acute ischemic stroke.

Journal ArticleDOI
01 Apr 2009-Stroke
TL;DR: TLT within 24 hours from stroke onset demonstrated safety but did not meet formal statistical significance for efficacy, however, all predefined analyses showed a favorable trend, consistent with the previous clinical trial (NEST-1).
Abstract: Background and Purpose—We hypothesized that transcranial laser therapy (TLT) can use near-infrared laser technology to treat acute ischemic stroke. The NeuroThera Effectiveness and Safety Trial–2 (NEST-2) tested the safety and efficacy of TLT in acute ischemic stroke. Methods—This double-blind, randomized study compared TLT treatment to sham control. Patients receiving tissue plasminogen activator and patients with evidence of hemorrhagic infarct were excluded. The primary efficacy end point was a favorable 90-day score of 0 to 2 assessed by the modified Rankin Scale. Other 90-day end points included the overall shift in modified Rankin Scale and assessments of change in the National Institutes of Health Stroke Scale score. Results—We randomized 660 patients: 331 received TLT and 327 received sham; 120 (36.3%) in the TLT group achieved favorable outcome versus 101 (30.9%), in the sham group (P0.094), odds ratio 1.38 (95% CI, 0.95 to 2.00). Comparable results were seen for the other outcome measures. Although no prespecified test achieved significance, a post hoc analysis of patients with a baseline National Institutes of Health Stroke Scale score of 16 showed a favorable outcome at 90 days on the primary end point (P0.044). Mortality rates and serious adverse events did not differ between groups with 17.5% and 17.4% mortality, 37.8% and 41.8% serious adverse events for TLT and sham, respectively. Conclusions—TLT within 24 hours from stroke onset demonstrated safety but did not meet formal statistical significance for efficacy. However, all predefined analyses showed a favorable trend, consistent with the previous clinical trial (NEST-1). Both studies indicate that mortality and adverse event rates were not adversely affected by TLT. A definitive trial with refined baseline National Institutes of Health Stroke Scale exclusion criteria is planned. (Stroke. 2009;40:1359-1364.)

Journal ArticleDOI
01 Jul 2009-Stroke
TL;DR: Treatment with tPA in the 3- to 4.5-hour time-window is beneficial and results in an increased rate of favorable outcome without adversely affecting mortality.
Abstract: Background and Purpose— The Third European Cooperative Acute Stroke Study (ECASS-3) demonstrated a benefit of treatment with intravenous tissue plasminogen activator (tPA) for acute stroke in the 3- to 4.5-hour time-window. Prior studies, however, have failed to demonstrate a significant benefit of tPA for patients treated beyond 3 hours. The purpose of this study was to produce reliable and precise estimates of the treatment effect of tPA by pooling data from all relevant studies. Methods— A metaanalysis was undertaken to determine the efficacy of tPA in the 3- to 4.5-hour time-window. The effect of tPA on favorable outcome and mortality was assessed. Results— The metaanalysis included data from patients treated in the 3- to 4.5-hour time-window in ECASS-1 (n=234), ECASS-2 (n=265), ECASS-3 (n=821) and The Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) (n=302). tPA treatment was associated with an increased chance of favorable outcome (odds ratio 1.31; 95% CI: 1.1...

Journal ArticleDOI
08 Oct 2009-Blood
TL;DR: It is reported that deficiency or reduction ofVWF reduces infarct volume up to 2-fold after focal cerebral ischemia in mice, thus showing the importance of VWF in stroke injury and suggesting that recombinant ADAMTS13 could be considered as a new therapeutic agent for prevention and/or treatment of stroke.

Journal ArticleDOI
01 Nov 2009-Stroke
TL;DR: This Food and Drug Administration-approved prospective pilot trial suggests primary intracranial stenting for acute stroke may be a valuable addition to the stroke treatment armamentarium.
Abstract: Background and Purpose— Acute revascularization is associated with improved outcomes in ischemic stroke patients. However, it is unclear which method of intraarterial intervention, if any, is ideal. Numerous case series and cardiac literature parallels suggest that acute stenting may yield high revascularization levels with low associated morbidity. We therefore conducted a Food and Drug Administration-approved prospective pilot trial to evaluate the safety of intracranial stenting for acute ischemic stroke. Methods— Eligibility criteria included presentation ≤8 hours after stroke onset, age 18 years or older, National Institutes of Health Stroke Scale score ≥8, angiographic demonstration of focal intracerebral artery occlusion ≤14 mm, and either contraindication to intravenous tissue plasminogen activator or failure to improve 1 hour after intravenous tissue plasminogen activator administration. Exclusion criteria included known hemorrhagic diathesis or coagulopathy, platelet count <100 000, intracranial...

Journal ArticleDOI
01 Aug 2009-Stroke
TL;DR: The proportion of patients with functional independence after stroke declines annually for up to 5 years, and these effects are greatest for those with Medicaid or no health insurance.
Abstract: Background and Purpose— Several factors predict functional status after stroke, but most studies have included hospitalized patients with limited follow-up. We hypothesized that patients with ischemic stroke experience functional decline over 5 years independent of recurrent stroke and other risk factors. Methods— In the population-based Northern Manhattan Study, patients ≥40 years of age with incident ischemic stroke were prospectively followed using the Barthel Index at 6 months and annually to 5 years. Baseline stroke severity was categorized as mild (National Institutes of Health Stroke Scale Results— Of 525 patients, mean age was 68.6±12.4 years, 45.5% were male, 54.7% Hispanic, 54.7% had Medicaid/no insurance, and 35.1% had moderate stroke. The proportion with Barthel Index ≥95 declined over time (OR, 0.91; 95% CI, 0.84 to 0.99). Changes in Barthel Index by insurance status were confirmed by a significant interaction term (β for interaction=−0.167, P =0.034); those with Medicaid/no insurance declined (OR, 0.84; P =0.003), whereas those with Medicare/private insurance did not (OR, 0.99; P =0.92). Conclusions— The proportion of patients with functional independence after stroke declines annually for up to 5 years, and these effects are greatest for those with Medicaid or no health insurance. This decline is independent of age, stroke severity, and other predictors of functional decline and occurs even among those without recurrent stroke or myocardial infarction.

Journal ArticleDOI
01 Apr 2009-Stroke
TL;DR: Age at natural menopause before age 42 was associated with increased ischemic stroke risk and future stroke studies with measures of endogenous hormones are needed to inform the underlying mechanisms so that novel prevention strategies for midlife women can be considered.
Abstract: Background and Purpose— Women have increased lifetime stroke risk and more disabling strokes compared with men. Insights into the association between menopause and stroke could lead to new prevention strategies for women. The objective of this study was to examine the association of age at natural menopause with ischemic stroke risk in the Framingham Heart Study. Methods— Participants included women who survived stroke-free until age 60, experienced natural menopause, did not use estrogen before menopause, and who had complete data (n=1430). Participants were followed until first ischemic stroke, death, or end of follow-up (2006). Age at natural menopause was self-reported. Cox proportional hazards models were used to examine the association between age at natural menopause (<42, 42 to 54, ≥55) and ischemic stroke risk adjusted for age, systolic blood pressure, atrial fibrillation, diabetes, current smoking, cardiovascular disease and estrogen use. Results— There were 234 ischemic strokes identified. Aver...

Journal ArticleDOI
TL;DR: The volume of leukoaraiosis is a predictor of clinical outcome after ischemic stroke and this relationship persists after adjustment for important prognostic factors including age, initial stroke severity, and infarct volume.
Abstract: Background: Leukoaraiosis (LA) is closely associated with aging, a major determinant of clinical outcome after ischemic stroke. In this study we sought to identify whether LA, independent of advancing age, affects outcome after acute ischemic stroke. Methods: LA volume was quantified in 240 patients with ischemic stroke and MRI within 24 hours of symptom onset. We explored the relationship between LA volume at admission and clinical outcome at 6 months, as assessed by the modified Rankin Scale (mRS). An ordinal logistic regression model was developed to analyze the independent effect of LA volume on clinical outcome. Results: Bivariate analyses showed a significant correlation between LA volume and mRS at 6 months ( r = 0.19, p = 0.003). Mean mRS was 1.7 ± 1.8 among those in the lowest (≤1.2 mL) and 2.5 ± 1.9 in the highest (>9.9 mL) quartiles of LA volume ( p = 0.01). The unfavorable prognostic effect of LA volume on clinical outcome was retained in the multivariable model ( p = 0.002), which included age, gender, stroke risk factors (hypertension, diabetes mellitus, atrial fibrillation), previous history of brain infarction, admission plasma glucose level, admission NIH Stroke Scale score, IV rtPA treatment, and acute infarct volume on MRI as covariates. Conclusions: The volume of leukoaraiosis is a predictor of clinical outcome after ischemic stroke and this relationship persists after adjustment for important prognostic factors including age, initial stroke severity, and infarct volume.

Journal ArticleDOI
TL;DR: Risk factors prior to initial stroke have a significant role in predicting stroke recurrence up to 10 years, and different predictors for stroke Recurrence were identified throughout the follow-up period.
Abstract: Background: Data estimating the risk of, and predictors for, long-term stroke recurrence are lacking. Methods: Data were collected from the population-based South London Stroke Register. Patients were followed up for a maximum of 10 years. Kaplan–Meier estimates and Cox proportional hazards models were used to assess the cumulative risk of and predictors for first stroke recurrence. Variables analysed included sociodemographic factors, stroke subtype (defined as cerebral infarction, intracerebral haemorrhage and subarachnoid haemorrhage), stroke severity markers and prior-to-stroke risk factors. Results: Between 1995 and 2004, 2874 patients with first-ever stroke were included. The mean follow-up period was 2.9 years. During 8311 person-years of follow-up, 303 recurrent events occurred. The cumulative risk of stroke recurrence at 1 year, 5 years and 10 years was 7.1%, 16.2% and 24.5% respectively. No differences in stroke recurrence were noted between the stroke subtypes. Factors increasing the risk of recurrence at 1 year were previous myocardial infarction (HR 1.73; 95% CI 1.08 to 2.78) and atrial fibrillation (HR 1.61; 95% CI 1.04 to 4.27); at 5 years, hypertension (HR 1.47; 95% CI 1.08 to 1.99) and atrial fibrillation (HR 1.79; 95% CI 1.29 to 2.49); and at 10 years, older age (p = 0.04), and hypertension (HR 1.38, 95% CI 1.04 to 1.82), myocardial infarction (HR 1.50, 95% CI 1.06 to 2.11) and atrial fibrillation (HR 1.51, 95% CI 1.09 to 2.09). Conclusions: Very-long-term risk of stroke recurrence is substantial. Different predictors for stroke recurrence were identified throughout the follow-up period. Risk factors prior to initial stroke have a significant role in predicting stroke recurrence up to 10 years.

Journal ArticleDOI
01 Mar 2009-Stroke
TL;DR: Intracranial placement of a self-expandable stent for acute ischemic stroke is feasible and seems to be safe to achieve sufficient recanalization.
Abstract: Background and Purpose— Stent placement has been applied in small case series as a rescue therapy in combination with different thrombolytic agents, percutaneous balloon angioplasty (PTA), and mechanical thromboembolectomy (MT) in acute stroke treatment. These studies report a considerable mortality and a high rate of intracranial hemorrhages when balloon-mounted stents were used. This study was performed to evaluate feasibility, efficacy, and safety of intracranial artery recanalization for acute ischemic stroke using a self-expandable stent. Methods— All patients treated with an intracranial stent for acute cerebral artery occlusion were included. Treatment comprised intraarterial thrombolysis, thromboaspiration, MT, PTA, and stent placement. Recanalization result was assessed by follow-up angiography immediately after stent placement. Complications related to the procedure and outcome at 3 months were assessed. Results— Twelve patients (median NIHSS 14, mean age 63 years) were treated with intracranial...

Journal ArticleDOI
TL;DR: The utility of DCS and NIRS to measure effects of head-of-bed positioning at 30 degrees, 15 degrees, 0 degrees, -5 degrees and 0 degrees angles in patients with acute ischemic stroke affecting frontal cortex and in controls is explored.
Abstract: "Diffuse correlation spectroscopy" (DCS) is a technology for non-invasive transcranial measurement of cerebral blood flow (CBF) that can be hybridized with "near-infrared spectroscopy" (NIRS). Taken together these methods hold potential for monitoring hemodynamics in stroke patients. We explore the utility of DCS and NIRS to measure effects of head-of-bed (HOB) positioning at 30 degrees , 15 degrees , 0 degrees , -5 degrees and 0 degrees angles in patients with acute ischemic stroke affecting frontal cortex and in controls. HOB positioning significantly altered CBF, oxy-hemoglobin (HbO(2)) and total-hemoglobin (THC) concentrations. Moreover, the presence of an ipsilateral infarct was a significant effect for all parameters. Results are consistent with the notion of impaired CBF autoregulation in the infarcted hemisphere.

Journal ArticleDOI
01 Feb 2009-Stroke
TL;DR: Low-dose glibenclamide has a strong beneficial effect on lesion volume and has a highly favorable therapeutic window in several models of ischemic stroke.
Abstract: Background and Purpose— Ischemia/hypoxia induces de novo expression of the sulfonylurea receptor 1-regulated NC(Ca-ATP) channel. In rodent models of ischemic stroke, early postevent administration of the sulfonylurea, glibenclamide, is highly effective in reducing edema, mortality, and lesion volume, and in patients with diabetes presenting with ischemic stroke, pre-event plus postevent use of sulfonylureas is associated with better neurological outcome. However, the therapeutic window for treatment with glibenclamide has not been studied. Methods— We examined the effect of low-dose (nonhypoglycemogenic) glibenclamide in 3 rat models of ischemic stroke, all involving proximal middle cerebral artery occlusion (MCAo): a thromboembolic model, a permanent suture occlusion model, and a temporary suture occlusion model with reperfusion (105 minutes occlusion, 2-day reperfusion). Treatment was started at various times up to 6 hours post-MCAo. Lesion volumes were measured 48 hours post-MCAo using 2,3,5-triphenylt...

Journal ArticleDOI
09 Apr 2009-Blood
TL;DR: This study indicates that VWF is critically involved in cerebral ischemia, and targeted inhibition of the GPIbalpha-VWF pathway might become a promising therapeutic option.

Journal ArticleDOI
01 Jan 2009-Stroke
TL;DR: It is demonstrated that blocking of B1R can diminish brain infarction and edema formation in mice and may open new avenues for acute stroke treatment in humans.
Abstract: Background and Purpose— Brain edema is detrimental in ischemic stroke and its treatment options are limited. Kinins are proinflammatory peptides that are released during tissue injury. The effects of kinins are mediated by 2 different receptors (B1 and B2 receptor [B1R and B2R]) and comprise induction of edema formation and release of proinflammatory mediators. Methods— Focal cerebral ischemia was induced in B1R knockout, B2R knockout, and wild-type mice by transient middle cerebral artery occlusion. Infarct volumes were measured by planimetry. Evan’s blue tracer was applied to determine the extent of brain edema. Postischemic inflammation was assessed by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. To analyze the effect of a pharmacological kinin receptor blockade, B1R and B2R inhibitors were injected. Results— B1R knockout mice developed significantly smaller brain infarctions and less neurological deficits compared to wild-type controls (16.8±4.7 mm3 vs 50.1±9.1 m...

Journal ArticleDOI
TL;DR: Admission PS measurement appears promising for distinguishing patients with acute stroke who are likely from those who are not likely to develop HT, and at stepwise multivariate analysis.
Abstract: Purpose: To determine whether admission computed tomography (CT) perfusion–derived permeability–surface area product (PS) maps differ between patients with hemorrhagic acute stroke and those with nonhemorrhagic acute stroke. Materials and Methods: This prospective study was institutional review board approved, and all participants gave written informed consent. Forty-one patients who presented with acute stroke within 3 hours after stroke symptom onset underwent two-phase CT perfusion imaging, which enabled PS measurement. Patients were assigned to groups according to whether they had hemorrhage transformation (HT) at follow-up magnetic resonance (MR) imaging and CT and/or whether they received tissue plasminogen activator (TPA) treatment. Clinical, demographic, and CT perfusion variables were compared between the HT and non-HT patient groups. Associations between PS and HT were tested at univariate and multivariate logistic regression analyses and receiver operating characteristic (ROC) analysis. Results...

Journal ArticleDOI
01 Jul 2009-Stroke
TL;DR: Differences of stroke lesion patterns in genders are paralleled by differences in etiology and risk factor profiles (women, cardioembolism; men, large and small vessel disease).
Abstract: Background and Purpose— Differences between women and men in relation to stroke are increasingly being recognized. Methods— From July 2004 until June 2007, 237 acute ischemic stroke (AIS) patients were treated with recombinant tissue plasminogen activator (rtPA) within 3 hours after onset of symptoms in our stroke unit. Baseline characteristics, etiology, CT/MRI stroke patterns, clinical outcome, and complications of women were compared to those of men. Results— Of 237 AIS patients (mean age 70.7 years), 111 (46.8%) were women and 126 (53.2%) were men. Women were older (P=0.001), but history of hyperlipidemia (P=0.03), smoking (P=0.03), and coronary heart disease (P<0.001) was less frequent than in men. Internal carotid artery disease occurred more often in men (P=0.02), whereas atrial fibrillation was observed more often in women (P=0.002). In men borderzone/small embolic and lacunar stroke was found more frequently (39.7 versus 27.2%), whereas women showed a higher percentage of large territorial stroke...

Journal ArticleDOI
01 Nov 2009-Stroke
TL;DR: Three-month outcomes of patients receiving low-dose intravenous recombinant tissue plasminogen activator therapy in the present study were similar to those from postmarketing surveys using 0.9 mg/kg alteplase.
Abstract: Background and Purpose— A retrospective, multicenter, observational study was conducted to document clinical outcomes and to identify outcome predictors in patients treated with low-dose intravenous recombinant tissue plasminogen activator (0.6 mg/kg alteplase), which was approved in Japan in 2005, within 3 hours of stroke onset. Methods— Consecutive patients with stroke treated with recombinant tissue plasminogen activator in 10 Japanese stroke centers were included. Results— A total of 600 patients (377 men, 72±12 years old) were studied. Median National Institutes of Health Stroke Scale scores decreased from 13 before recombinant tissue plasminogen activator to 8 at 24 hours later. Symptomatic intracerebral hemorrhage within 36 hours with a ≥1-point increase from the baseline National Institutes of Health Stroke Scale score developed in 23 patients (3.8%; 95% CI, 2.6% to 5.7%). At 3 months, 43 patients had died (7.2%; 5.4% to 9.5%), and 199 patients (33.2%; 29.5% to 37.0%) had a modified Rankin Scale s...