Objective: CHADS₂ and CHA₂DS₂-VASc scores are used to assess stroke risk in patients with atrial fibrillation (AF). We investigated whether these scores are associated with stroke outcome in non-AF stroke patients. Methods: Consecutive patients with acute first-ever ischemic stroke but without AF were classified into subgroups according to prestroke CHADS₂ and CHA₂DS₂-VASc scores and followed up for 5 years. The end points were death, stroke recurrence, and a composite of major cardiovascular events. Results: Among 1,756 patients (aged 67.2 ± 12.3 years, 68.2% males), there were 258 (14.7%), 617 (35.3%), and 878 (50.0%) patients with low, intermediate, and high CHADS₂ score, respectively. The corresponding figures for CHA₂DS₂-VASc subgroups were 110 (6.3%), 255 (14.5%), and 1,391 (79.2%). There were significant differences between CHADS₂ subgroups in 5-year mortality (log-rank test = 74.5, p < 0.0001), stroke recurrence (log-rank test = 12.3, p = 0.002), and cardiovascular events (log-rank test = 19.4, p < 0.001). Similarly, there were significant differences between CHA₂DS₂-VASc subgroups in 5-year mortality (log-rank test = 74.5, p < 0.0001), stroke recurrence (log-rank test = 10.6, p = 0.005), and cardiovascular events (log-rank test = 16.4, p < 0.001). Compared with the low-risk group, patients in intermediate- and high-risk CHADS₂ subgroups had higher 5-year mortality (hazard ratio [HR]: 2.22 [95% confidence interval {CI}: 1.78–2.77] and 3.66 [95% CI: 2.38–5.62], respectively), stroke recurrence (HR: 1.74 [95% CI: 1.09–2.79] and 1.71 [95% CI: 1.08–2.71], respectively), and cardiovascular events (HR: 1.78 [95% CI: 1.23–2.57] and 1.86 [95% CI: 1.30–2.67], respectively). Compared with the low-risk group, patients in the high-risk CHA₂DS₂-VASc subgroup also had higher 5-year mortality (HR: 3.56, 95% CI: 1.89–6.70), stroke recurrence (HR: 2.93, 95% CI: 1.30–6.61), and cardiovascular events (HR: 2.71, 95% CI: 1.49–4.95). Conclusions: Prestroke CHADS₂ and CHA₂DS₂-VASc scores predict long-term stroke outcomes in non-AF patients with acute ischemic stroke. These scores may provide a simple way of stroke prognostic risk stratification among non-AF stroke patients.

Background and Purpose—: To assess whether the combined analysis of all phase III trials of nonvitamin-K-antagonist (non-VKA) oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack shows a significant difference in efficacy or safety compared with warfarin. Methods—: We searched PubMed until May 31, 2012, for randomized clinical trials using the following search items: atrial fibrillation, anticoagulation, warfarin, and previous stroke or transient ischemic attack. Studies had to be phase III trials in atrial fibrillation patients comparing warfarin with a non-VKA currently on the market or with the intention to be brought to the market in North America or Europe. Analysis was performed on intention-to-treat basis. A fixed-effects model was used as more appropriate than a random-effects model when combining a small number of studies. Results—: Among 47 potentially eligible articles, 3 were included in the meta-analysis. In 14 527 patients, non-VKAs were associated with a significant reduction of stroke/systemic embolism (odds ratios, 0.85 [95% CI, 074–0.99]; relative risk reduction, 14%; absolute risk reduction, 0.7%; number needed to treat, 134 over 1.8–2.0 years) compared with warfarin. Non-VKAs were also associated with a significant reduction of major bleeding compared with warfarin (odds ratios, 0.86 [95% CI, 075–0.99]; relative risk reduction, 13%; absolute risk reduction, 0.8%; number needed to treat, 125), mainly driven by the significant reduction of hemorrhagic stroke (odds ratios, 0.44 [95% CI, 032–0.62]; relative risk reduction, 57.9%; absolute risk reduction, 0.7%; number needed to treat, 139). Conclusions—: In the context of the significant limitations of combining the results of disparate trials of different agents, non-VKAs seem to be associated with a significant reduction in rates of stroke or systemic embolism, hemorrhagic stroke, and major bleeding when compared with warfarin in patients with previous stroke or transient ischemic attack.

Background and objectives: Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins. Low BDNF concentrations have been noted in patients with traditional cardiovascular disease risk factors and have been associated with the increased risk of stroke/transient ischemic attack (TIA). We aimed to study the correlation of BDNF serum levels with acute stroke severity and its potential role as a biomarker in predicting functional outcome. Materials and methods: We systematically searched PubMed, Web of Science, and the Cochrane database using specific keywords. The endpoints examined were the correlation of BDNF with functional outcome, the National Institute of Health stroke scale (NIHSS) measured at the acute phase, and stroke infarct volume. We also compared serum BDNF levels between stroke patients and healthy controls. Results: Twenty-six records were included from the initial 3088 identified. Twenty-five studies reported NIHSS and BDNF levels on the first day after acute stroke. Nine studies were further meta-analyzed. A statistically significant negative correlation between NIHSS and BDNF levels during the acute phase of stroke was noted (COR: −0.3013, 95%CI: (−0.4725; −0.1082), z = −3.01, p = 0.0026). We also noted that BDNF levels were significantly lower in patients with stroke compared to healthy individuals. Due to the heterogeneity of studies, we only conducted a qualitative analysis regarding serum BDNF and functional outcome, while no correlation between BDNF levels and stroke infarct volume was noted. Conclusions: We conclude that in the acute stroke phase, stroke severity is negatively correlated with BDNF levels. Concurrently, patients with acute stroke have significantly lower BDNF levels in serum compared to healthy controls. No correlations between BDNF and stroke infarct volume or functional outcome at follow-up were noted.

Seizures appear at stroke presentation, during the acute phase or as a late complication of stroke. Thrombolysis has not been investigated as a risk factor despite its potential neurotoxic effect. We try to identify risk factors for seizures during the acute phase of ischemic stroke in a cohort including thrombolysed patients. We undertook a case–control study at a single stroke center using data from Acute Stroke Registry and Analyse of Lausanne (ASTRAL). Patients with seizure occurring during the first 7 days following stroke were retrospectively identified. Bi-variable and multivariable statistical analyses were applied to compare cases and randomly selected controls. We identified 28 patients experiencing from seizures in 2,327 acute ischemic strokes (1.2 %). All seizures occurred during the first 72 h. Cortical involvement, thrombolysis with rt-PA, arterial recanalization, and higher initial NIHSS were statistically associated with seizures in univariated analysis. Backward linear regression identified cortical involvement (OR 7.53, 95 % CI 1.6–35.2, p < 0.01) and thrombolysis (OR 4.6, 95 % CI 1.6–13.4, p = 0.01) as being independently associated with seizure occurrence. Overall, 3-month outcome measured by the modified Rankin scale (mRS) was comparable in both groups. In the subgroup of thrombolysed patients, outcome was significantly worse at 3 months in the seizure group with 9/12 (75 %) patients with mRS ≥3, compared to 6/18 (33.3 %) in the seizure-free group (p = 0.03). Acute seizures in acute ischemic stroke were relatively infrequent. Cortical involvement and thrombolysis with rt-PA are the principal risk factors. Seizures have a potential negative influence on clinical outcome in thrombolysed patients.

Background and Purpose—: The ASTRAL score was externally validated showing remarkable consistency on 3-month outcome prognosis in patients with acute ischemic stroke. The present study aimed to evaluate ASTRAL score’s prognostic accuracy to predict 5-year outcome. Methods—: All consecutive patients with acute ischemic stroke registered in the Athens Stroke Registry between January 1, 1998, and December 31, 2010, were included. Patients were excluded if admitted >24 hours after symptom onset or if any ASTRAL score component was missing. End points were 5-year unfavorable functional outcome, defined as modified Rankin Scale 3 to 6, and 5-year mortality. For each outcome, the area under the receiver operating characteristics curve was calculated; also, a multivariate Cox proportional hazards analysis was performed to investigate whether the ASTRAL score was an independent predictor of outcome. The Kaplan–Meier product limit method was used to estimate the probability of 5-year survival for each ASTRAL score quartile. Results—: The area under the receiver operating characteristics curve of the score to predict 5-year unfavorable functional outcome was 0.89, 95% confidence interval 0.88 to 0.91. In multivariate Cox proportional hazards analysis, the ASTRAL score was independently associated with 5-year unfavorable functional outcome (hazard ratio, 1.09; 95% confidence interval, 1.08–1.10). The area under the receiver operating characteristics curve for the ASTRAL score’s discriminatory power to predict 5-year mortality was 0.81 (95% confidence interval, 0.78–0.83). In multivariate analysis, the ASTRAL score was independently associated with 5-year mortality (hazard ratio, 1.09, 95% confidence interval, 1.08–1.10). During the 5-year follow-up, the probability of survival was significantly lower with increasing ASTRAL score quartiles (log-rank test <0.001). Conclusions—: The ASTRAL score reliably predicts 5-year functional outcome and mortality in patients with acute ischemic stroke.