Methods—One hundred eleven male rats were randomly assigned to sham-operated and MCAO treated with vehicle, 0.25 mg/kg and 1 mg/kg of FTY720, another selective sphingosine 1–phosphate receptor-1 agonist SEW2871 (5 mg/kg), or 0.25 mg/kg of FTY720 plus a sphingosine 1–phosphate antagonist, VPC23019 (0.5 mg/kg). Drugs were injected intraperitoneally immediately after reperfusion. Neurological score and infarct volume were assessed at 24 and 72 hours after MCAO. Western blotting, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling were conducted at 24 hours after MCAO.

Results—FTY720 significantly reduced infarct volume and improved neurological score at 24 and 72 hours after MCAO compared with the vehicle group. SEW2871 showed similar neuroprotective effects to FTY720, whereas VPC 20319 abolished the neuroprotective effects of FTY720. FTY720 significantly retained Akt and extracellular signal-regulated kinase phosphorylation and Bcl-2 expression and decreased cleaved caspase-3 expression and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling-positive neurons at 24 hours after MCAO. VPC23019 blocked the antiapoptotic effects of FTY720.

Conclusions—These data suggest that activation of sphingosine 1–phosphate-1 by FTY720 reduces neuronal death after transient MCAO.

Methods—We genotyped participants from the Copenhagen City Heart Study (n=10 352), the Copenhagen General Population Study (n=26 042), the Copenhagen Carotid Stroke Study (n=398 cases+796 control subjects), and the Copenhagen Ischemic Heart Disease Study (n=4901 cases+9798 control subjects) for the R103C, R287Q, and Arg^402-403ins variants in the EPHX2 gene and recorded hospital admissions due to ischemic stroke, myocardial infarction, and ischemic heart disease.

Results—The hazard/odds ratio for ischemic stroke did not differ from 1.0 for any of the EPHX2 genotypes or genotype combinations in the Copenhagen City Heart Study (P for trend=0.15 to 0.76), in the Copenhagen General Population Study (P for trend=0.75 to 0.95), and the Copenhagen Carotid Stroke Study (P for trend=0.08 to 1.00). Similar results were obtained for myocardial infarction and ischemic heart disease in the 3 studies.

Conclusions—Our results show with significant power that genetically reduced soluble epoxide hydrolase activity is not a major risk factor for ischemic stroke, myocardial infarction, or ischemic heart disease in the Danish population. This suggests that the relationship between the EPHX2 gene and risk of ischemic stroke and other cardiovascular disease does not exist or its effect size is likely to be quite small.

Methods—We performed a meta-analysis of randomized controlled trials. Electronic databases were searched from 1950 through April 2009. Strength training articles were assessed according to outcomes: strength, upper-limb function, and activities of daily living. The standardized mean difference (SMD) was calculated to estimate the pooled effect size with random-effect models.

Results—From the 650 trials identified, 13 were included in this review, totaling 517 individuals. A positive outcome for strength training was found for grip strength (SMD=0.95, P=0.04) and upper-limb function (SMD=0.21, P=0.03). No treatment effect was found for strength training on measures of activities of daily living. A significant effect for strength training on upper-limb function was found for studies including subjects with moderate (SMD=0.45, P=0.03) and mild (SMD=0.26, P=0.01) upper-limb motor impairment. No trials reported adverse effects.

Conclusions—There is evidence that strength training can improve upper-limb strength and function without increasing tone or pain in individuals with stroke.

Methods—A total of 2421 community-dwelling Japanese subjects aged 40 to 79 years who underwent the oral glucose tolerance test were followed up for 14 years.

Results—In multivariable analysis, the risks of ischemic stroke in both sexes and coronary heart disease (CHD) in women were significantly higher in subjects with diabetes determined by the World Health Organization criteria than in those with normal glucose tolerance even after adjustment for other confounding factors, but such association was not seen for CHD in men (ischemic stroke: adjusted hazard ratio [HR]=2.54, P=0.002 in men; adjusted HR=2.02, P=0.03 in women; CHD: adjusted HR=1.26, P=0.47 in men; adjusted HR=3.46, P=0.002 in women). Similar associations were observed for fasting plasma glucose levels of ≥7.0 mmol/L (ischemic stroke: adjusted HR=2.15, P=0.03 in men; adjusted HR=2.10, P=0.045 in women; CHD: adjusted HR=1.29, P=0.47 in men; adjusted HR=3.83, P=0.003 in women) and for 2-hour postload glucose levels of ≥11.1 mmol/L (ischemic stroke: adjusted HR=2.71, P=0.003 in men; adjusted HR=2.19, P=0.03 in women; CHD: adjusted HR=1.58, P=0.16 in men; adjusted HR=4.44, P<0.001 in women). The age-adjusted incidences of ischemic stroke and CHD did not significantly increase in subjects with impaired fasting glycemia or impaired glucose tolerance in either sex.

Conclusions—Our findings suggest that diabetes is an independent risk factor for ischemic stroke in both sexes and CHD in women in the Japanese population.

Methods—Four differentiation stages were identified on the basis of quantitative polymerase chain reaction expression of pluripotency, proliferation, and differentiation markers. Neural progenitors were transplanted at these 4 stages into rats with no, small, or large middle cerebral artery occlusion lesions. The fate of each transplant was compared with their pretransplantation status 1 to 4 months posttransplantation.

Results—The influence of the postischemic environment was limited to graft survival and occurrence of nonneuroectodermal structures after transplantation of very immature neural progenitors. Both effects were lost with differentiation. We identified a particular stage of differentiation characterized in vitro by a rebound of proliferative activity that produced highly proliferative grafts susceptible to threaten surrounding host tissues.

Conclusion—The effects of the ischemic environment on the formation of teratoma by transplanted human embryonic stem cell-derived neural progenitors are limited to early differentiation stages that will likely not be used for stem cell therapy. In contrast, hyperproliferation observed at later stages of differentiation corresponds to an intrinsic activity that should be monitored to avoid tumorigenesis.

Methods—Age-matched male and female Sprague-Dawley rats were stereotaxically infused with either ferrous citrate (FC) or saline (10 µL) into the right caudate nucleus. Beta-estradiol 3-benzoate (E₂) capsule was implanted subcutaneously at 24 hours before infusion of FC. The severity of brain injury and neurological deficits were measured by histological quantification and forelimb asymmetry test, respectively. The role of thioredoxin (Trx) in E₂-mediated neuroprotective effect was examined by intrastriatal administration of a Trx reductase inhibitor, 5,5-dithiobis-(2-nitrobenzoic acid), and small interfering RNA.

Results—FC induced greater brain injury in male rats than females. E₂ treatment reduced FC-induced brain injury in both sexes. E₂ significantly increased protein level and activity of Trx in the caudate nucleus of females but not males. Administration of female rats with 5,5-dithiobis-(2-nitrobenzoic acid) or Trx small interfering RNA to the caudate nucleus decreased the protective effect of E₂ against FC-induced injury. The protein and mRNA levels of estrogen receptor, but not estrogen receptorβ, were more abundant in the caudate nucleus of female rats.

Conclusions—Increase of brain Trx activity might play an important role in the E₂-mediated neuroprotective effect against FC-induced brain injury in female rats. Understanding of the sex differences in the Trx-mediated neuroprotective effect by E₂ might help in improving treatment of brain dysfunction after hemorrhagic stroke and/or head trauma.

Methods—Participants were 983 individuals (49% black) from the Atherosclerosis Risk in Communities (ARIC) Study who underwent cerebral magnetic resonance imaging in 1993–1995 and 2004–2006. Associations between BP (measured at each of 5 visits, in addition to a time-averaged cumulative BP) and progression of WMHs were analyzed and compared.

Results—Cumulative systolic BP (SBP) was the strongest BP predictor of WMH progression in adjusted models. Higher cumulative SBP (by 20 mm Hg) was associated with greater progression of WMHs and was similar in blacks (2.5 cm³, P<0.0001) and whites (2.6 cm³, P<0.0001). Higher cumulative SBP (per 20 mm Hg) was also associated with being in the top quintile of WMH progression (adjusted odds ratio=2.0; 95% CI, 1.6 to 2.6). Earlier SBP measurements were stronger predictors of WMH progression than were later SBP measurements, but in blacks only.

Conclusions—In this population-based cohort, cumulative SBP was a stronger predictor of WMH progression than SBP from individual visits, in both blacks and whites. Earlier BPs were stronger predictors than BPs measured at later time points in blacks only.

Methods—We collated outcome data for patients who were enrolled after 3 hours of stroke onset in thrombolysis trials and had mismatch on pretreatment imaging. We selected the trials on the basis of a systematic search of the Web of Knowledge. We compared favorable outcome, reperfusion and/or recanalization, mortality, and symptomatic intracerebral hemorrhage between the thrombolyzed and nonthrombolyzed groups of patients and the probability of a favorable outcome among patients with successful reperfusion and clinical findings for 3 to 6 versus 6 to 9 hours from poststroke onset. Results are expressed as adjusted odds ratios (a-ORs) with 95% CIs. Heterogeneity was explored by test statistics for clinical heterogeneity, I² (inconsistency), and L'Abbé plot.

Results—We identified articles describing the DIAS, DIAS II, DEDAS, DEFUSE, and EPITHET trials, giving a total of 502 mismatch patients thrombolyzed beyond 3 hours. The combined a-ORs for favorable outcomes were greater for patients who had successful reperfusion (a-OR=5.2; 95% CI, 3 to 9; I²=0%). Favorable clinical outcome was not significantly improved by thrombolysis (a-OR=1.3; 95% CI, 0.8 to 2.0; I²=20.9%). Odds for reperfusion/recanalization were increased among patients who received thrombolytic therapy (a-OR=3.0; 95% CI, 1.6 to 5.8; I²=25.7%). The combined data showed a significant increase in mortality after thrombolysis (a-OR=2.4; 95% CI, 1.2 to 4.9; I²=0%), but this was not confirmed when we excluded data from desmoteplase doses that were abandoned in clinical development (a-OR=1.6; 95% CI, 0.7 to 3.7; I²=0%). Symptomatic intracerebral hemorrhage was significantly increased after thrombolysis (a-OR=6.5; 95% CI, 1.2 to 35.4; I²=0%) but not significant after exclusion of abandoned doses of desmoteplase (a-OR=5.4; 95% CI, 0.9 to 31.8; I²=0%).

Conclusions—Delayed thrombolysis amongst patients selected according to mismatch imaging is associated with increased reperfusion/recanalization. Recanalization/reperfusion is associated with improved outcomes. However, delayed thrombolysis in mismatch patients was not confirmed to improve clinical outcome, although a useful clinical benefit remains possible. Thrombolysis carries a significant risk of symptomatic intracerebral hemorrhage and possibly increased mortality. Criteria to diagnose mismatch are still evolving. Validation of the mismatch selection paradigm is required with a phase III trial. Pending these results, delayed treatment, even according to mismatch selection, cannot be recommended as part of routine care.

Methods—We conducted a computerized MEDLINE search of the literature for reports on the treatment of intracranial aneurysms with a maximum dimension of ≤3 mm by using the search terms "small," "tiny," "intracranial aneurysm," "endovascular," and "coil." A total of 7 studies, including our institution's consecutive case series of 71 intracranial aneurysms, were included in this study. We extracted information regarding intraoperative complications, procedural mortality and morbidity, immediate- and long-term angiographic outcomes, and retreatment rate. The meta-analysis was performed with the statistical package Comprehensive Meta-Analysis.

Results—Approximately 61% of the aneurysms in this meta-analysis presented as ruptured, whereas 39% of the aneurysms were unruptured. Procedural rupture rates for very small aneurysms was 8.3% (95% CI, 6.0% to 11.4%). The mortality rate due to procedural rupture was 2.4% (95% CI, 1.2% to 4.7%). The morbidity rate due to thromboembolic complications was 1.9% (95% CI, 0.9% to 3.9%). Subarachnoid hemorrhage within 1 month of treatment occurred in 1.6% (95% CI, 0.6% to 3.7%) of cases. There was no statistically significant difference between unruptured and ruptured aneurysms for any of these outcomes.

Conclusion—Our meta-analysis suggests that treatment of very small aneurysms is feasible and effective in >90% of treated aneurysms. However, the risk of periprocedural rupture is higher than that reported for larger aneurysms. Similarly, the combined rate of periprocedural mortality and morbidity is not negligible (7.3%) and should be considered when considering the best therapeutic option for these aneurysms.

Methods—A group of 142 patients with a clinical diagnosis of TGA within 7 days of the clinical event and 40 controls were prospectively evaluated. Venous Doppler examination of both IJVs was performed at baseline and after a manometer-controlled Valsalva maneuver. Valvular insufficiency was diagnosed when there was reflux for >0.8 seconds during the Valsalva maneuver.

Results—Valve insufficiency was found in at least one jugular vein in 113 of 142 patients with TGA (79.5%) and in 10 of 40 controls (25.0%), P<0.01. The right side was affected more often than the left side, P<0.01, and 26.8% of the patients had bilateral incompetence.

Conclusions—Patients with TGA have a high prevalence of IJV valve insufficiency. This finding may have pathophysiologic implications. Doppler evaluation of the IJVs with dynamic maneuvers may help in the evaluation of this usually benign condition.

Methods—We reviewed medical records, radiology reports, and administrative databases to identify BAVMs, intracranial aneurysms (IAs: subarachnoid hemorrhage [SAH] and unruptured aneurysms), and other vascular malformations (OVMs: dural fistulas, cavernous malformations, Vein of Galen malformations, and venous malformations). Poisson regression (with robust standard errors) was used to test for trend. Random-effects meta-analysis generated a pooled measure of BAVM detection rate from 6 studies.

Results—We identified 401 BAVMs (197 ruptured, 204 unruptured), 570 OVMs, and 2892 IAs (2079 SAHs and 813 unruptured IAs). Detection rates per 100 000 person-years were 1.4 (95% CI, 1.3 to 1.6) for BAVMs, 2.0 (95% CI, 1.8 to 2.3) for OVMs, and 10.3 (95% CI, 9.9 to 10.7) for IAs. Neuroimaging utilization increased 12% per year during the time period (P<0.001). Overall, rates increased for IAs (P<0.001), remained stable for OVMs (P=0.858), and decreased for BAVMs (P=0.001). Detection rates increased 15% per year for unruptured IAs (P<0.001), with no change in SAHs (P=0.903). However, rates decreased 7% per year for unruptured BAVMs (P=0.016) and 3% per year for ruptured BAVMs (P=0.005). Meta-analysis yielded a pooled BAVM detection rate of 1.3 (95% CI, 1.2 to 1.4) per 100 000 person-years, without heterogeneity between studies (P=0.25).

Conclusions—Rates for BAVMs, OVMs, and IAs in this large, multiethnic population were similar to those in other series. During 1995 to 2004, a period of increasing neuroimaging utilization, we did not observe an increased rate of detection of unruptured BAVMs, despite increased detection of unruptured IAs.

Methods—We retrospectively reviewed prospectively collected clinical, laboratory, and radiologic data from 79 consecutive ICH patients who had brain magnetic resonance imaging performed within 72 hours of ICH symptom onset. We assessed the severity of WMHs on magnetic resonance imaging on the modified Scheltens scale and performed logistic-regression analysis to examine the association between WMHs and ICH volume. We also examined the association between WMH score and hematoma growth in a subset of 34 patients who had a baseline computed tomography scan within 12 hours of ICH onset and a follow-up scan within 72 hours.

Results—The ICH volume at 37.6±22.3 hours from ICH onset was 2-fold higher in patients with a high WMH score (≥14) than in those with a lower score. A high WMH score was independently associated with a larger ICH volume (odds ratio=1.152; 95% CI, 1.035 to 1.282; P=0.01). There was a trend for an association between WMH score and ICH volume growth (odds ratio=1.286; 95% CI, 0.978 to 1.692; P=0.062).

Conclusion—Severe WMHs are associated with larger ICH volumes and, to a lesser extent, with hematoma growth. Our findings suggest that WMHs may provide important prognostic information on patients with ICH and may have implications for treatment stratification. These findings require prospective validation, and the links between WMHs and ICH growth require further investigations.

Methods—HT was assessed 2 to 5 days after treatment in 97 patients. Hemorrhage was assessed by using susceptibility-weighted imaging sequences and was classified as petechial hemorrhagic infarction (HI) or parenchymal hematoma (PH).

Results—PH was more frequent in t-PA– (11/49) than in placebo- (4/48) treated patients (P=0.049). Patients with PH had larger DWI lesion volumes (63.1±56.1 mL) than did those without HT (27.6±39.0 mL, P=0.033). There were no differences in baseline systolic blood pressure (SBP) between patients with and without hemorrhage. Weighted average SBP 24 hours after treatment was higher in patients with PH (159.4±18.8 mL, P<0.011) relative to those without HT (143.1±20.0 mL). Multinomial logistic regression indicated that PH was predicted by DWI lesion volume (odds ratio=1.16 per 10 mL; 95% CI, 1.03 to 1.30), atrial fibrillation (odds ratio=9.33; 95% CI, 2.30 to 37.94), and 24-hour weighted average SBP (odds ratio=1.59 per 10 mm Hg; 95% CI, 1.14 to 2.23).

Conclusions—Pretreatment DWI lesion volume and postthrombolysis BP are both predictive of HT. Consideration should be given to excluding patients with very large baseline DWI volumes from t-PA therapy and to more stringent BP control after stroke thrombolysis.

Methods—We prospectively studied angiographically diagnosed patients with MMD. We compared demographic profiles, thyroid function test, and thyroid autoantibody status between MMD and control groups.

Results—A total of 63 patients with MMD, 71 patients with non-MMD stroke, and 200 healthy control subjects were included. The prevalence of elevated thyroid autoantibodies was higher in the MMD group than in other groups (P<0.01 for MMD versus non-MMD; P<0.001 for MMD versus control subjects). After adjusting for covariates, the elevated thyroid autoantibodies (OR, 4.871; 95% CI, 1.588 to 15.277) and smoking habits (OR, 0.206 for current smoker; 95% CI, 0.054 to 0.786) were independently associated with MMD versus non-MMD stroke.

Conclusions—Elevated thyroid autoantibodies were frequently observed in patients with MMD. The results of the present study suggest that immune aberrancies associated with or underlying thyroid autoimmunity are also playing a role in developing MMD.

Methods—In a population-based study of all patients with transient ischemic attack (TIA) or stroke in the Oxford Vascular Study, we studied the risk of TIA and stroke in patients with ≥50% contralateral asymptomatic carotid stenoses recruited consecutively from 2002 to 2009 and given intensive contemporary medical treatment.

Results—Of 1153 consecutively imaged patients presenting with stroke or TIA, 101 (8.8%) had ≥50% asymptomatic carotid stenoses (mean age, 75 years; 39% women; 40% age ≥80 years). During 301 patient-years of follow-up (mean, 3 years), there were 6 ischemic events in the territory of an asymptomatic stenosis, 1 minor stroke (initially 50% to 69% stenosis), and 5 TIAs (2 initially 50% to 69% stenosis; 3 to 70% to 99% stenosis), 3 of which led to subsequent endarterectomy. The average annual event rates on medical treatment were 0.34% (95% CI, 0.01 to 1.87) for any ipsilateral ischemic stroke, 0% (95% CI, 0.00 to 0.99) for disabling ipsilateral stroke, and 1.78% (95% CI, 0.58 to 4.16) for ipsilateral TIA.

Conclusions—In the first study of the prognosis of ≥50% asymptomatic carotid stenosis to be initiated in the last 10 years, the risk of stroke on intensive contemporary medical treatment was low. Larger studies are required to determine whether this apparent improvement in prognosis is generalizable.

Methods—During a 12-month period (2006–2007), we prospectively ascertained all strokes occurring in a population of 450 229. Multiple overlapping sources were used to identify people with stroke. A large number of volunteers assisted in finding stroke patients not admitted to hospital. Potential cases were reviewed by a group of stroke experts before inclusion.

Results—A total of 624 first-ever strokes occurred during the study period, 98.4% undergoing imaging. Despite a relatively low crude annual incidence rate of first-ever stroke FES (139; 95% CI, 128 to 149) per 100 000 residents, rates adjusted to the European population aged 45 to 84 years were higher than in most other countries: 616 (95% CI, 567 to 664) for ischemic stroke, 94 (95% CI, 75 to 113) for intracerebral hemorrhage, and 12 (95% CI, 5 to 19) for subarachnoid hemorrhage. Age-specific stroke incidence was higher in younger patients than is typically seen in Western countries. Comparison of age-specific incidence rates between regions revealed that stroke in Mashhad occurs approximately 1 decade earlier than in Western countries.

Conclusions—The results of this study provide evidence that the incidence of stroke in Iran is considerably greater than in most Western countries, with stroke occurring at younger ages. Ischemic stroke incidence was also considerably greater than reported in other regions.

Material and Methods—Twenty-two patients admitted within 6 hours of stroke onset were retrospectively included in this study. These patients underwent a first stroke CT protocol including CT-angiography (CTA) and perfusion-CT (PCT) on admission, and similar imaging after treatment, typically around 24 hours, to assess recanalization and reperfusion. Recanalization was assessed by comparing arterial patency on admission and posttreatment CTAs; reperfusion, by comparing the volumes of CBV, CBF, and MTT abnormality on admission and posttreatment PCTs. Collateral flow was graded on the admission CTA. Follow-up infarct volume was measured on the discharge noncontrast CT. The groups of patients with reperfusion, no reperfusion, recanalization, and no recanalization were compared in terms of imaging and clinical outcomes.

Results—Reperfusion (using an MTT reperfusion index >75%) was a more accurate predictor of follow-up infarct volume than recanalization. Collateral flow and recanalization were not accurate predictors of follow-up infarct volume. An interaction term was found between reperfusion and the volume of the admission penumbra >50 mL.

Conclusion—Our study provides evidence that reperfusion is a more accurate predictor of follow-up infarct volume in acute ischemic stroke patients than recanalization. We recommend an MTT reperfusion index >75% to assess therapy efficacy in future acute ischemic stroke trials that use perfusion-CT.

Methods—Twenty-five common variants were genotyped in a relatively large sample size including 1123 subjects with ischemic stroke cases (thrombosis stroke=716, lacunar infarction=407) and 557 normal control subjects. The association analyses were performed at both single nucleotide polymorphism and haplotype levels. False discovery rate q value method was applied for multiple testing corrections.

Results—rs11052413, a intergenic single nucleotide polymorphism, was most significantly associated with ischemic stroke independent of traditional cardiovascular risk factors in additive (OR=1.51, 95% CI=1.19 to 1.92, P=7.4x10^-4, q=0.018) and dominant models (OR=1.59, 95% CI=1.20 to 2.08, P=9.2x10^-4, q=0.023). In addition, both ZNF650 rs10204475 and intergenic single nucleotide polymorphism rs10486776 were associated with ischemic stroke as well as independent of traditional cardiovascular risk factors in dominant models (OR=1.47, 95% CI=1.12 to 1.96, P=0.005, q=0.040 and OR=1.53, 95% CI=1.15 to 2.02, P=0.003, q=0.036, respectively). No significant results were found in stroke subtype analysis after multiple corrections.

Conclusion—Our study confirmed previously reported associations between ischemic stroke and rs11052413, rs10486776, and ZNF 650 rs10204475 in a Chinese Han population. The mechanism whereby the genetic variants exert their effects on ischemic stroke remains to be further elucidated.

Methods—We conducted a cross-sectional study of a cohort of whites and blacks of both genders with a mean age of 45 years. Traditional cardiovascular risk factors were determined in cohort members. Carotid IMT was measured from high-resolution B-mode ultrasound images at 3 levels: the common carotid artery, the carotid artery bulb (bulb), and the internal carotid artery. Associations with risk factors were evaluated by multivariate linear regression analyses.

Results—Of 3258 who underwent carotid IMT measurements, common carotid artery, bulb, and internal carotid artery IMT were measured at all 3 separate levels in 3023 (92.7%). A large proportion of the variability of common carotid artery IMT was explained by cardiovascular risk factors (26.8%) but less so for the bulb (11.2%) and internal carotid artery (8.0%). Carotid IMT was consistently associated with age, low-density lipoprotein cholesterol, smoking, and hypertension in all segments. Associations with fasting glucose and diastolic blood pressure were stronger for common carotid artery than for the other segments. Hypertension, diabetes, and current smoking had qualitatively stronger associations with bulb IMT and low-density lipoprotein cholesterol with internal carotid artery IMT.

Conclusion—In our cohort of relatively young white and black men and women, a greater proportion of the variability in common carotid IMT can be explained by traditional cardiovascular risk factors than for the carotid artery bulb and internal carotid arteries.

Methods—Three neuroradiologists retrospectively reviewed CT angiograms (CTAs) performed in 573 consecutive patients who presented to our Emergency Department with primary ICH over a 9-year period to determine the presence and scoring of spot signs according to strict criteria. Baseline ICH and intraventricular hemorrhage volumes were independently determined by computer-assisted volumetric analysis. Medical records were independently reviewed for baseline clinical characteristics and modified Rankin Scale (mRS) at hospital discharge and 3-month follow-up. Poor outcome among survivors was defined as a mRS ≥4 at 3-month follow-up.

Results—We identified spot signs in 133 of 573 CTAs (23.2%), 11 of which were delayed spot signs (8.3%). The presence of any spot sign increased the risk of in-hospital mortality (55.6%, OR 4.0, 95% CI 2.6 to 5.9, P<0.0001) and poor outcome among survivors at 3-month follow-up (50.8%, OR 2.5, 95% CI 1.4 to 4.3, P<0.0014). The spot sign score successfully predicted an escalating risk of both outcome measures. In multivariate analysis, the spot sign score was an independent predictor of in-hospital mortality (OR 1.5, 95% CI 1.2 to 1.9, P<0.0002) and poor outcome among survivors at 3-month follow-up (OR 1.6, 95% CI 1.1 to 2.1, P<0.0065).

Conclusion—The spot sign score is an independent predictor of in-hospital mortality and poor outcome among survivors in primary ICH.

Methods—We determined the sex-specific incidence of symptomatic carotid stenosis and subsequent endarterectomy/stenting from 2002 to 2009 in consecutive patients with TIA or nondisabling ischemic stroke in the Oxford Vascular Study. We studied equivalent data from routine clinical practices in the wider Oxfordshire population.

Results—There was no sex difference in age-specific referral rates for carotid imaging in the Oxford Vascular Study (n=616; age-adjusted relative rate [RR] for males vs females=1.08; 95% CI, 0.79 to 1.46; P=0.64). However, rates of 50% to 99% symptomatic carotid stenosis were higher in men (RR=1.89; 95% CI, 1.31 to 2.71; P=0.0005). The same was seen in imaged patients (n=575) in the wider Oxfordshire population (RR=1.82; 95% CI, 1.31 to 2.53; P=0.003) and in pooled data (RR=1.87; 95% CI, 1.32 to 2.64; P=0.0003). Rates of symptomatic carotid occlusion were also higher in men in both populations (RR=3.19; 95% CI, 1.95 to 5.23; P<0.0001). Consequently, although men were more likely to undergo carotid intervention (RR=1.98; 95% CI, 1.43 to 2.75; P<0.0001), the proportion of patients with 50% to 99% symptomatic carotid stenosis who received intervention was similar for men and women (odds ratio=1.13; 95% CI, 0.57 to 2.25; P=0.72).

Conclusion—Lower rates of intervention for 50% to 99% symptomatic carotid stenosis in women can be explained by sex differences in population-based incidence. We found no evidence of any investigation or intervention bias.

Methods—Twenty subjects with chronic stroke completed a repeated baseline measures, randomized crossover trial in which walking performance was assessed during the last 4 weeks of clinical PT before discharge secondary to reaching a plateau, followed by 4 weeks of intensive LT and 4 weeks of no intervention. Outcome measures included clinical and physiological (metabolic) measures of walking overground and on a treadmill, and measures of daily stepping activity in the home and community, including during clinical PT and subsequent LT sessions.

Results—Stepping practice was more than 4-fold higher during LT versus clinical PT sessions, with significant improvements in daily stepping and gait efficiency only after LT. Changes in daily stepping after clinical PT and intensive LT were correlated (P<0.001) with the amount of stepping practice received during these interventions.

Conclusions—Intensive LT results in improved daily stepping in individuals poststroke who have been discharged from PT because of a perceived plateau in motor function. These improvements may be related to the amount and intensity of stepping practice.

Methods—Prospective cohort study among 21 860 men enrolled in the Physicians' Health Study who provided information on alcohol consumption at baseline and had no prior history of stroke or transient ischemic attack (TIA). Alcohol consumption was divided into 5 categories: <1 drink/wk, 1 drink/wk, 2 to 4 drinks/wk, 5 to 6 drinks/wk, and ≥1 drink/d. Possible functional outcomes included TIA, modified Rankin Scale (mRS)=0 to 1, mRS=2 to 3, and mRS=4 to 6. We used multinomial logistic regression to evaluate the relationship between levels of alcohol consumption and functional outcomes from stroke.

Results—During a mean of 21.6 years of follow-up, 766 TIAs and 1393 strokes (1157 ischemic, 222 hemorrhagic, and 14 unknown type) occurred. Men who consumed 1 drink/wk had lowest associated odds for any outcome. Compared with men who did not experience a TIA or stroke and who consumed <1 drink/wk, men who consumed 1 drink/wk had odds ratio (95% CI) for total stroke of 0.85 (0.60 to 1.21) for mRS=0 to 1, 0.84 (0.64 to 1.10) for mRS=2 to 3, and 0.60 (0.37 to 0.97) for mRS=4 to 6. The odds ratio for TIA was 0.95 (0.73 to 1.23). The pattern of association did not substantially differ for ischemic and hemorrhagic stroke. Higher alcohol consumption showed no association with functional outcome after stroke.

Conclusions—Our data do not show strong associations between alcohol consumption and functional outcome after stroke. Modest beneficial associations exist with low alcohol consumption.

Methods—H-I was induced in 7-day-old (P7) transgenic mice overexpressing the specific Apaf-1–inhibitory protein AIP. Apaf-1 inhibition was also achieved in P7 rats by protein transduction–enhanced delivery of recombinant AIP. Pups were euthanized 6 to 24 hours after H-I for assessing caspase activation and mitochondrial release of cytochrome c and AIF, and 7 days after H-I for analyzing brain tissue damage. Sensorimotor functions were assessed in rats up to 4 weeks after H-I.

Results—Transgenic overexpression of AIP protected against H-I brain injury, resulting in attenuated activation of caspase-9 and caspase-3, and attenuated brain tissue loss. In neonatal H-I rats, intraperitoneal injection of TAT-AIP, but not the control proteins TAT-GFP or AIP, decreased caspase activation and brain damage and improved neurological functions. Neuroprotection conferred by AIP was also associated with significantly reduced release of cytochrome c and AIF from mitochondria.

Conclusion—The Apaf-1 signaling pathway, which transmits cell death signals after mitochondrial damage to effector caspases, may be a legitimate therapeutic target for the treatment of neonatal H-I brain injury.

Methods—Continuous monitoring of arterial blood pressure, intracranial pressure, cerebral perfusion pressure, brain tissue oxygen, carbon dioxide, pH, and middle cerebral artery flow velocity was performed in 44 patients. Patients were given an infusion (2 mL/kg) of 23.5% HS. In 16 patients, xenon CT scanning was also performed. CBF in a region surrounding the tissue oxygen sensor was calculated. Data are mean±SD.

Results—Thirty minutes postinfusion, a significant increase in arterial blood pressure, cerebral perfusion pressure, flow velocity, brain tissue pH, and brain tissue oxygen was seen together with a decrease in intracranial pressure (P<0.05). Intracranial pressure remained reduced for >300 minutes and flow velocity elevated for >240 minutes. A significant increase in brain tissue oxygen persisted for 240 minutes. Average baseline regional CBF was 33.9±13.5 mL/100 g/min, rising by 20.3%±37.4% (P<0.05) after HS. Patients with favorable outcome responded better to HS in terms of increased CBF, brain tissue oxygen, and pH and reduced intracranial pressure compared with those with an unfavorable outcome. A sustained increase in brain tissue oxygen (beyond 210 minutes) was associated with favorable outcome (P<0.023).

Conclusion—HS augments CBF in patients with poor-grade subarachnoid hemorrhage and significantly improves cerebral oxygenation for 4 hours postinfusion. Favorable outcome is associated with an improvement in brain tissue oxygen beyond 210 minutes.

Methods—The contrast-enhanced carotid ultrasound examinations of 147 subjects (mean age 64±11 years, 61% male) were analyzed for the presence of intraluminal plaque, plaque neovascularization (Grade 1=absent; Grade 2=present), and degree of adventitial vasa vasorum (Grade 1=absent, Grade 2=present). These observations were correlated with preexisting cardiovascular risk factors, presence of CVD, and history of CVE (myocardial infarction and transient ischemic attack/stroke).

Results—The presence of intraluminal carotid plaque was directly correlated to cardiovascular risk factors, CVD, and CVE (P<0.05). Adventitial vasa vasorum Grade 2 was associated with significant more subjects with CVD than vasa vasorum Grade 1 (73 versus 54%, P=0.029). Subjects with intraplaque neovascularization Grade 2 had significantly more often a history of CVE than subjects with intraplaque neovascularization Grade 1 (38 versus 20%, P=0.031). Multivariate logistic regression analysis revealed that presence of plaque was significantly associated with CVD (odds ratio 4.7, 95% CI 1.6 to 13.8) and intraplaque neovascularization grade 2 with CVE (odds ratio 4.0, 95% CI 1.3 to 12.6).

Conclusion—The presence and degree of adventitial vasa vasorum and plaque neovascularization were directly associated with CVD and CVE in a retrospective study of 147 patients undergoing contrast-enhanced carotid ultrasound.

Methods—A retrospective review of our Get With the Guidelines Stroke (GWTG-Stroke) database from 01/2003 to 03/2008 identified 296 patients who received IV tPA within 3 hours of symptom onset without catheter-based reperfusion. GWTG-Stroke definitions for symptomatic intracranial (sICH), systemic hemorrhage, discharge functional status, and destination were applied. Follow-up modified Rankin Score was recorded when available.

Results—Of 296 patients, 181 (61.1%) had tPA infusion started at an outside spoke hospital (OSH) and 115 (38.9%) at the RSC hub. OSH patients were younger with fewer severe strokes than RSC patients. Patients treated based on telestroke were more frequently octogenarians than patients treated based on a telephone consult. Mortality, sICH, and functional outcomes were not different between OSH versus RSC and telephone versus telestroke patients. Among survivors, mean length of stay was shorter for OSH patients but discharge status was similar and 75% of patients walked independently at discharge.

Conclusions—Outcomes in OSH "drip and ship" patients treated in a hub-and-spoke network were comparable to those treated directly at an RSC. These data suggest that "drip and ship" is a safe and effective method to shorten time to treatment with IV tPA.

Methods—We conducted a systematic review of the excess risk of incident dementia conferred by stroke. Studies of the risk of incident dementia in the population with stroke compared with the population without stroke were identified and compared.

Results—Sixteen studies were identified with all but one conducted in a community setting. A history of stroke doubles the risk of incident dementia in the older population. This increase is not explained by demographic or cardiovascular risk factors or by prestroke cognitive decline. The excess risk of incident dementia diminishes with time after stroke and may be higher in those without an APOE 4 allele. There is no excess risk of incident dementia in those aged >85 years with a history of stroke compared to those aged >85 years without stroke.

Conclusions—The effect of stroke on dementia incidence in the population is not explained by common risk factors. At this time of population aging and increased stroke survival, more research is needed to determine to what extent efforts to reduce the incidence of stroke will affect the incidence of dementia.

Methods—Twenty-one surviving patients with ischemic stroke or transient ischemic attack were followed up after a mean interval of 5.5 years with repeat MRI and clinical assessment. Predictors of new microbleeds were tested in logistic regression.

Results—Of patients with microbleeds at baseline, 50% had new microbleeds at follow-up compared with 8% of those without baseline microbleeds (P=0.047). The presence of microbleeds at baseline predicted new microbleeds (OR, 12; 95% CI, 1.02 to 141.34; P=0.048), as did mean systolic blood pressure (OR, 1.28 per unit increase; 95% CI, 1.23 to 1.33; P<0.001). One patient had a stroke (intracerebral hemorrhage) during follow-up.

Conclusions—Patients with ischemic stroke or transient ischemic attack are at risk of developing new microbleeds over 5.5 years, despite most surviving patients remaining clinically stable. Systolic blood pressure is the strongest predictor of microbleed development; better control of hypertension may help prevent new microbleed formation.

Summary of Report—We report that 5-minute bilateral common carotid artery occlusion (BCCAO) in the mouse prompted reduction of infarct volumes triggered 24 hours later by 20-minute middle cerebral artery occlusion (MCAO). Pharmacological PARP-1 inhibition between BCCAO and MCAO did not impair preconditioning. The contents of the PARP-1 substrate NAD, those of its product poly(ADP-ribose), caspase-3 activation, and PARP-1 expression did not change after BCCAO within the preconditioned tissue. PARP-1 KO mice were similarly protected by the 5-minute BCCAO.

Conclusion—Data demonstrate that, at variance with the heart, PARP-1 is dispensable for brain ischemic preconditioning.

Methods—We collected data on consecutive patients with spontaneous ICH admitted to our institution between August 1, 2006 and December 31, 2008 and in whom DWI was performed within 28 days of admission. Patients with hemorrhage attributable to trauma, tumor, aneurysm, vascular malformation, and hemorrhagic conversion of arterial or venous infarction were excluded. Restricted diffusion within, contiguous with, or immediately neighboring the hematoma or chronic infarcts was not considered abnormal. Using multivariable logistic regression, we evaluated potential predictors of DWI abnormality including clinical and radiographic characteristics and treatments. A probability value <0.05 was considered significant in the final model.

Results—Among 118 spontaneous ICH patients (mean 59.6 years, 47.5% male, and 31.4% white) who also underwent MRI, DWI abnormality was observed in 22.9%. The majority of infarcts were small (median volume 0.25 mL), subcortical (70.4%), and subclinical (88.9%). Factors independently associated with DWI abnormality were prior ischemic stroke (P=0.002), MAP lowering by ≥40% (P=0.004), and craniotomy for ICH evacuation (P=0.001).

Conclusion—We found that acute brain infarction is relatively common after acute spontaneous ICH. Several factors, including aggressive blood pressure lowering, may be associated with acute ischemic infarcts after ICH. These preliminary findings require further prospective study.

Methods—A random sample of 23 216 adults (9480 men, 13 796 women) aged 20 to 54 years completed the pessimism scale in 1998, that is, at study baseline. Fatal and first nonfatal stroke events during a mean follow-up of 7.0 years were documented by linkage to the national hospital discharge and mortality registers leading to 105 events.

Results—Unadjusted hazard ratio was 0.44 (95% CI, 0.25 to 0.77) for participants in the lowest quartile (a low pessimism level) when compared with those in the highest quartile (a high pessimism level). After serial adjustments for sociodemographic characteristics, cardiovascular biobehavioral risk factors, depression, general feeling of stressfulness, and ischemic heart disease, the fully adjusted hazard ratio was 0.52 (95% CI, 0.29 to 0.93).

Conclusions—In this population of adult men and women, low level of pessimism had a robust association with reduced incidence of stroke.

Methods—Edema, BBB permeability, leukocyte-endothelial cell adhesion (LECA) and inflammatory cytokine levels were monitored in a murine model of CVST. The role of activated protein C (APC) was assessed in wild type mice (WT) receiving APC neutralizing antibody and in endothelial protein C receptor overexpressing mice (EPCR-tg). Neutrophil involvement was evaluated using an anti-CD18 antibody (Ab) and antineutrophil serum.

Results—Brain edema and increases in BBB permeability and LECA were noted 48 hours after CVST. APC immunoblockade exacerbated these responses, while EPCR-tg exhibited blunted responses, as did WT treated with either antineutrophil serum or the CD18 Ab.

Conclusions—The protein C pathway protects the brain against the deleterious microvascular responses to CVST, a response that appears to be linked to the recruitment of inflammatory cells.

Summary of Review—All randomized, placebo-controlled trials investigating the effect of statins on vasospasm, delayed cerebral ischemia, and functional outcome in patients with aneurysmal subarachnoid hemorrhage were included. Outcomes were the number of patients with transcranial Doppler vasospasm, delayed cerebral ischemia, poor outcome, and mortality during follow-up. Effect sizes were expressed in (pooled) risk ratio estimates. Data were pooled using random-effects models.

Results—In 4 studies, a total of 190 patients were included. No statistically significant effect was observed on transcranial Doppler vasospasm (pooled risk ratio, 0.99 [95% CI, 0.66 to 1.48]), delayed cerebral ischemia (pooled risk ratio, 0.57 [95% CI, 0.29 to 1.13]), poor outcome (pooled risk ratio, 0.92 [95% CI, 0.68 to 1.24]), or mortality (pooled risk ratio, 0.37 [95% CI, 0.13 to 1.10]).

Conclusion—The results of the present systematic review do not lend statistically significant support to the finding of a beneficial effect of statins in patients with aneurysmal subarachnoid hemorrhage as reported in a previous meta-analysis.