Summary of Case— A 48-year-old woman presented with a recurrent symptomatic severe left middle cerebral artery stenosis. MRI depicted left hemispheric ischemic infarcts in the deep and subcortical white matter and in the cortical border zone. One-hour transcranial Doppler monitoring detected 64 microembolic signals distal to the arterial stenosis. Monitoring also revealed recurrent thrombus formation at the stenotic plaque with decline of poststenotic flow velocity followed by embolism with abrupt excessive flow velocity increase and subsequent normalization at the initial baseline level. Cerebrovascular reserve in the distribution territory of the stenosed artery as assessed by transcranial Doppler after carbon dioxide stimulation revealed a normal reserve capacity in periods with baseline poststenotic flow velocity and an exhausted reserve capacity when flow velocity was decreased due to stenotic thrombus formation.

Conclusion— In our patient, adherent thrombus formation resulted in an increasing severity of the stenosis with subsequent vasodilatation and diminution of flow resistance in the depending vascular distribution territory. MRI suggested that adherent thrombi were predominantly washed into terminal supply and border zone brain regions, ie, into regions with supposed maximum vasodilatation and least flow resistance immediately before thrombus avulsion. Preferred wash-in of emboli into regions with low blood flow resistance might be an additional mechanism besides impaired washout in patients with severe large artery disease.

Methods— Using a cross-sectional approach, a total of 100 SA stroke survivors were prospectively recruited from the ongoing West Birmingham Stroke Project. Indices of vessel wall characteristics (arterial stiffness and endothelial function [change in reflective index]) were measured noninvasively using the digital volume pulse analysis technique in a temperature-controlled environment, using a direct standardized approach. SA stroke subjects were compared to 60 EC stroke survivors, 60 SA with risk factors, and 73 healthy controls.

Results— Among stroke patients, both ethnic groups were comparable for cardiovascular risk profile, except for more diabetes mellitus in SA (P=0.007) subjects and a higher prevalence of atrial fibrillation in EC (P=0.04) subjects. According to the TOAST and Bamford classifications, SA subjects had more small vessel (P=0.04) and lacunar infarctions (P=0.01). SA subjects had higher measurements of arterial stiffness (P<0.001) and impaired endothelial-dependent vascular function (change in reflective index %; P<0.001). On univariate analysis, endothelial function was negatively correlated with fasting plasma glucose (r=–0.4; P<0.001) and total cholesterol level (r=–0.2; P<0.001). On multivariate analysis, glycemic status was independently associated with impaired endothelial function (P=0.008) and increased arterial stiffness (P<0.001) among SA subjects.

Conclusion— SA stroke survivors had more small vessel disease-related cerebrovascular events compared to EC subjects. Underlying glycemic status in SA subjects had an adverse impact on the vascular system, leading to abnormal vessel wall characteristics.

Methods— Probands were selected from Caribbean Hispanic subjects of the population-based Northern Manhattan Study. CIMT was measured by high-resolution B-mode ultrasound and expressed as the mean (IMTx) and mean of the maximum (IMTm). Variance components methodology was used to detect linkage using SOLAR and calculate locus-specific heritability. Ordered-subset Analysis was done based on history of hypertension and total cholesterol levels.

Results— Among 100 Dominican families, 1390 subjects had CIMT measured (848 females; mean age 46.2 years). CIMT had a heritability of 0.65 after adjusting for age, age², sex, cigarette pack-years, waist hip ratio, and BMI. Adjusted maximum multipoint LOD scores >2 were found on chromosomes 14q (D14S606) and 7p (D7S817). Linkage to chromosome 14q was significantly increased in a subset of families with the greatest history of hypertension (MLOD=4.12). The QTL on Ch14q accounted for 0.21 of the heritability of IMTm, and on Ch7p 0.27 of the heritability of BIFm.

Conclusions— Several QTLs for CIMT were found on chromosomes 7p and 14q. The QTL on 14q replicates a suggestive linkage peak delimited in the Framingham Heart Study. These QTLs accounted for a substantial amount of trait heritability and warrant further fine mapping.

Methods— Stroke-free subjects from the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study were evaluated. Aortic arch and proximal descending aortic plaques were assessed by transesophageal echocardiography (TEE). Vascular events (myocardial infarction, ischemic stroke, vascular death) were prospectively recorded, and their association with aortic plaques was assessed.

Results— 209 subjects were studied (age 67.0±8.6 years). Aortic arch plaques were present in 130 subjects (62.2%), large plaques (≥4 mm) in 50 (23.9%). Descending aortic plaques were present in 126 subjects (60.9%), large plaques in 41 (19.8%). During a follow-up of 74.4±26.3 months, 29 events occurred (12 myocardial infarctions, 11 ischemic strokes, 6 vascular deaths). After adjustment for risk factors, large aortic arch plaques were not associated with combined vascular events (hazard ratio [HR] 1.03, 95% confidence intervals [CI] 0.35 to 3.02) or ischemic stroke (HR 0.59, 95% CI 0.10 to 3.39). Large descending aortic plaques were also not independently associated with vascular events (HR 1.99, 95% CI 0.52 to 7.69) or ischemic stroke (HR 1.43, 95% CI 0.27 to 7.48).

Conclusions— In a population-based cohort, the incidental detection of plaques in the aortic arch or proximal descending aorta was not associated with future vascular events. Associated cofactors may affect the previously reported association between proximal aortic plaques and vascular events.

Methods— Follow-up data were collected in 43 cohorts in 18 populations in 8 European countries surveyed for cardiovascular risk factors. In 93 695 persons aged 19 to 77 years and free of major cardiovascular disease at baseline, total observation years were 1 234 252 and the number of stroke events analyzed was 3142. Hazard ratios were calculated by Cox regression analyses.

Results— Each year of age increased the risk of stroke (fatal and nonfatal together) by 9% (95% CI, 9% to 10%) in men and by 10% (9% to 10%) in women. A 10-mm Hg increase in systolic blood pressure involved a similar increase in risk in men (28%; 24% to 32%) and women (25%; 20% to 29%). Smoking conferred a similar excess risk in women (104%; 78% to 133%) and in men (82%; 66% to 100%). The effect of increasing body mass index was very modest. Higher high-density lipoprotein cholesterol levels decreased the risk of stroke more in women (hazard ratio per mmol/L 0.58; 0.49 to 0.68) than in men (0.80; 0.69 to 0.92). The impact of the individual risk factors differed somewhat between countries/regions with high blood pressure being particularly important in central Europe (Poland and Lithuania).

Conclusions— Age, sex, and region-specific estimates of relative risks for stroke conferred by classical risk factors in various regions of Europe are provided. From a public health perspective, an important lesson is that smoking confers a high risk for stroke across Europe.

Methods— The 3-City Study is a population-based prospective cohort of people aged ≥65 years followed up for, on average, 4.9 years. Among them, 1643 participants free of prevalent vascular events had quantitative measurements of WML volume at baseline using a fully automatic method. The risks of incident major vascular events according to WML volume were evaluated using Cox proportional hazards models.

Results— The risk of incident stroke significantly increased with increasing baseline WML volume and was multiplied by 5 for those in the highest quartile of WML volume. Nonstroke vascular events’ incidence was not associated with WML volumes, whatever their type.

Conclusions— WMLs are an independent predictor of stroke in the elderly. This association is specific because WMLs are not associated with the risk of other vascular events.

Methods— We conducted a prospective study of patients with acute TIA who presented to the ED. Clinical risk scoring using the ABCD² score was determined and Lp-PLA₂ mass (LpPLA₂-M) and activity (LpPLA₂-A) and high-sensitivity C-reactive protein (CRP) were measured. The primary outcome measure was a composite end point consisting of stroke or death within 90 days or identification of a high-risk stroke mechanism requiring specific early intervention (defined as ≥50% stenosis in a vessel referable to symptoms or a cardioembolic source warranting anticoagulation).

Results— The composite outcome end point occurred in 41/167 (25%) patients. LpPLA₂-M levels were higher in end point-positive compared to -negative patients (mean, 192±48 ng/mL versus 175±44 ng/mL, P=0.04). LpPLA₂-A levels showed similar results (geometric mean, 132 nmol/min/mL, 95% CI 119 to 146 versus 114 nmol/min/mL, 95% CI 108 to 121, P=0.01). There was no relationship between CRP and outcome (P=0.82). Subgroup analysis showed that both LpPLA₂-M (P=0.04) and LpPLA₂-A (P=0.06) but not CRP (P=0.36) were elevated in patients with >50% stenosis. In multivariate analysis using cut-off points defined by the top quartile of each marker, predictors of outcome included LpPLA₂-A (OR 3.75, 95% CI 1.58 to 8.86, P=0.003) and ABCD² score (OR 1.30 per point, 95% CI 0.97 to 1.75, P=0.08).

Conclusion— Many patients with TIA have a high-risk mechanism (large vessel stenosis or cardioembolism) or will experience stroke/death within 90 days. In contrast to CRP, both Lp-PLA₂ mass and activity were associated with this composite end point, and LpPLA₂-A appears to provide additional prognostic information beyond the ABCD² clinical risk score alone.

Methods— Combined data from 2 major substudies of the Warfarin Aspirin Recurrent Stroke Trial (WARSS) were evaluated. PICSS subjects were included if they were enrolled in the Antiphospholipid Antibodies and Stroke Study (APASS) and underwent a baseline aPL test (lupus anticoagulant, anticardiolipin antibodies, or both) within 1 month of the stroke. All patients in PICSS underwent transesophageal echocardiography for PFO as well as VaT, which was performed blinded to aPL status and treatment arm (325 mg/day aspirin or adjusted dose warfarin; target international normalized ratio, 1.4–2.8). The primary outcome event was the 2-year risk of recurrent stroke/TIA/death and was evaluated using Cox proportional hazards model. Because there was no treatment effect, warfarin and aspirin groups were combined to increase power. For the combined end point, power to detect HR of 2 was 47.8% for the PFO and aPL-positive group, and 75.3% for the valve thickening and aPL-positive group, assuming 2-sided type I error of 0.05.

Results— Five hundred twenty-five subjects were tested for the combined presence of PFO and aPL and were available for evaluation. The primary outcome event rate was 23.9% (HR, 1.39; 95% CI, 0.75–2.59) in the PFO-positive/aPL-positive group, compared to 13.9% (HR, 0.83; 95% CI, 0.44–1.56) in the PFO-positive/aPL-negative group, and 19.9% (HR, 1.16; 95% CI, 0.68–1.90) in the PFO-negative/aPL-positive group. Five hundred forty-five subjects tested for combined presence of aPL and left-side cardiac VaT were available for evaluation. The primary event rate was 22.6% (HR, 1.65; 95% CI, 0.88–3.09) in the VaT-positive/aPL-positive group, compared to 19.4% (HR, 1.50; 95% CI, 0.82–2.75) in the VaT-positive/aPL-negative group, and 20.2% (HR, 1.63; 95% CI, 0.81–3.25) in the VaT-negative/aPL-positive group.

Conclusions— The combined presence of aPL either with a PFO or with left-side cardiac VaT did not significantly increase risk of subsequent cerebrovascular events in this PICCS/APASS cohort of patients.

Methods— Using a list serve established by the American Academy of Neurology, a member posted a question regarding the safety of BS in patients with patent foramen ovale. A standardized questionnaire was used to gather data about patients with cerebral ischemic events, details of each case were reviewed, and the findings pooled.

Results— Five patients with ischemic complications of BS (all female, aged 42 to 90 years) were identified from 4 institutions, 3 ischemic strokes and 2 transient ischemic attacks. Events occurred either during or within 5 minutes of BS. Early brain MRIs confirmed acute infarction in 3, including one who had transient symptoms. MRI infarct volumes were small, and deficits were mild in those who developed stroke. Diagnostic evaluation revealed a patent foramen ovale alone in one case, a pulmonary arteriovenous malformation in one case, and a patent foramen ovale and/or pulmonary shunt in 3 cases.

Conclusions— Ischemic cerebrovascular complications can occur in patients who undergo BS and are associated with the presence of cardiac or pulmonary shunts. The true incidence and degree of disability remains unknown, and further study is indicated to assess the impact of technical differences in BS methodology. Novel methods to promote physician communication such as the use of electronic list serves may reduce barriers to reporting of drug, technique, or device complications and should be explored to identify rare complications that otherwise will likely go unappreciated.

Methods— A systematic search identified 23 case-control studies examining the prevalence of PFO in patients with CS versus control subjects with stroke of known cause. Using simple assumptions and Bayes’ theorem, we calculated the probability a PFO is incidental in patients with CS. Random effects meta-analyses estimated the odds ratio (OR) of a PFO in CS versus control subjects in different age populations, with or without atrial septal aneurysms, and were used to summarize across studies the probability that a PFO in CS is incidental.

Results— The summary OR (95% CIs) for PFO in CS versus control subjects was 2.9 (CI, 2.1 to 4.0). The corresponding ORs for young and old patients (< or ≥55 years) were 5.1 (3.3 to 7.8) and 2.0 (>1.0 to 3.7), respectively. The corresponding probabilities that a PFO in patients with CS is incidental were 33% (28% to 39%) in age-inclusive studies, 20% (16% to 25%) in younger patients, and 48% (34% to 66%) in older patients. These probabilities were much lower when an atrial septal aneurysm was present.

Conclusions— In patients with otherwise CS, approximately one third of discovered PFOs are likely to be incidental and hence not benefit from closure. This probability is sensitive to patient characteristics such as age and the presence of an atrial septal aneurysm, suggesting the importance of patient selection in therapeutic decision-making.

Methods— We used data of the International Study on Cerebral Vein and Dural sinus Thrombosis (ISCVT), a multicenter prospective observational study, to analyze gender-specific differences in clinical presentation, etiology, and outcome of cerebral venous thrombosis.

Results— Four hundred sixty-five of a total of 624 patients were women (75%). Women were significantly younger, had less often a chronic onset of symptoms, and had more often headache at presentation. There were no gender differences in ancillary investigations or treatment. A gender-specific risk factor (oral contraceptives, pregnancy, puerperium, and hormonal replacement therapy) was present in 65% of women. Women had a better prognosis than men (complete recovery 81% versus 71%l P=0.01), which was entirely due to a better outcome in female patients with gender-specific risk factors. Women without gender-specific risk factors are similar to men in clinical presentation, risk factor profile, and outcome. Logistic regression analysis confirmed that the absence of gender-specific risk factors is a strong and independent predictor of poor outcome in women with sinus thrombosis (OR, 3.7; CI, 1.9 to 7.4).

Conclusions— Our study identified important differences between women and men in presentation, course, and risk factors of cerebral venous and sinus thrombosis and showed that women with a gender-specific risk factor have a much better prognosis than other patients.

Methods— Sample size calculations were based on different definitions of vasospasm, enrichment strategies, sensitivity of short- and long-term outcome instruments for reflecting vasospasm-related morbidity, different event rates of vasospasm, calculation of effect size of vasospasm on outcome instruments, and different treatment effect sizes. Sensitivity analysis was performed for variable event rates of vasospasm for a given treatment effect size. Sample size tables were constructed for different rates of vasospasm and outcome instruments for a given treatment effect size.

Results— Vasospasm occurred in 12% to 30% of patients. Symptomatic deterioration and infarction from vasospasm exhibited the strongest relationship to mortality and morbidity after SAH. Enriching for vasospasm by selection of patients with thick SAH slightly decreased sample sizes. Assuming β=0.80, =0.05 (2-tailed) and treatment effect size of 50%, total sample size exceeds 5000 patients to demonstrate efficacy on 3-month patient-centered outcome (modified Rankin Scale).

Conclusions— Clinical trials targeting vasospasm and using traditional patient-centered outcome require very high sample sizes and will therefore be costly, time-consuming, and impractical. This will hinder development of new treatment strategies.

Methods— One hundred sixteen patients with subarachnoid hemorrhage who underwent surgical clipping within 24 hours of ictus were investigated. Validation of transpulmonary thermodilution-derived intermittent/continuous cardiac output and cardiac preload (global end diastolic volume) were compared with pulmonary artery catheter-derived reference cardiac output and pulmonary capillary wedge pressure or central venous pressure in 16 patients diagnosed with vasospasm. In a subsequent trial of 100 consecutive cases, clinical results between the new and standard management paradigms were compared.

Results— Transpulmonary thermodilution-derived intermittent cardiac output and transpulmonary thermodilution-derived continuous cardiac output showed close agreement to catheter-derived reference cardiac output with high correlation (r=0.85 and 0.77) and low percentage error (13.5% and 18.0%). Fluid responsiveness to defined volume loading was predicted better with global end diastolic volume than with pulmonary capillary wedge pressure and central venous pressure for larger receiver operating characteristic curve area. Patients receiving early goal-directed management by transpulmonary thermodilution experienced reduced frequencies of vasospasm and cardiopulmonary complications compared with those managed with standard therapy (P<0.05), whereas their functional outcomes at 3 months were not different (P=0.06).

Conclusions— Goal-directed hemodynamic management guided by transpulmonary thermodilution appears to have a therapeutic advantage for optimizing the prognosis of patients with subarachnoid hemorrhage with vasospasm over conventional methods.

Methods— Between 1996 and 2008, 787 consecutive patients with aneurysmal subarachnoid hemorrhage were enrolled in our prospective database. Demographics, serum creatinine levels, and discharge modified Rankin scores were recorded, and changes in creatinine clearance were calculated. A multiple logistic regression was performed using known predictors for poor outcome after aneurysmal subarachnoid hemorrhage in addition to burden of contrast-enhanced imaging and change in creatinine clearance.

Results— One hundred seventy-nine (23.1%) patients were at risk for renal failure during their hospitalization. In a multivariate model, those patients who developed risk for renal failure were twice as likely to have a poor 3-month outcome (OR, 2.01; P=0.021). Survival curves comparing those not at risk, those at risk (increasing severity classes Risk, Injury, and Failure, and the 2 outcome classes Loss and End-Stage Kidney Disease [RIFLE] R), and those with renal injury or failure (RIFLE I and F) demonstrated that risk of death increases significantly as one progresses through the RIFLE classes (log rank, P<0.0001).

Conclusions— In a large, consecutive series of prospectively enrolled patients with aneurysmal subarachnoid hemorrhage, we demonstrate, using the newly defined RIFLE classification for risk of renal failure, that even seemingly insignificant decreases in creatinine clearance are associated with significantly worse 3-month outcomes. This study highlights the importance of close surveillance of renal function and stresses the value of renal hygiene in the aneurysmal subarachnoid hemorrhage population.

Methods— We performed 2 complementary retrospective analyses. In a radiographic analysis, we measured and plotted the volumes of all hemorrhagic lesions detected by gradient-echo MRI among 46 consecutive patients with symptomatic primary lobar intracerebral hemorrhage diagnosed as probable or possible cerebral amyloid angiopathy. In a second neuropathologic analysis, we performed blinded qualitative and quantitative examinations of amyloid-positive vessel segments in 6 autopsied subjects whose MRI scans demonstrated particularly high microbleed counts (>50 microbleeds on MRI, n=3) or low microbleed counts (<3 microbleeds, n=3).

Results— Plotted on a logarithmic scale, the volumes of 163 hemorrhagic lesions identified on scans from the 46 subjects fell in a distinctly bimodal distribution with mean volumes for the 2 modes of 0.009 cm³ and 27.5 cm³. The optimal cut point for separating the 2 peaks (determined by receiver operating characteristics) corresponded to a lesion diameter of 0.57 cm. On neuropathologic analysis, the high microbleed-count autopsied subjects showed significantly thicker amyloid-positive vessel walls than the low microbleed-count subjects (proportional wall thickness 0.53±0.01 versus 0.37±0.01; P<0.0001; n=333 vessel segments analyzed).

Conclusions— These findings suggest that cerebral amyloid angiopathy-associated microbleeds and macrobleeds comprise distinct entities. Increased vessel wall thickness may predispose to formation of microbleeds relative to macrobleeds.

Methods— We performed a retrospective cohort study of patients with intracerebral hemorrhage (International Classification of Diseases, 9th Revision, Clinical Modification=431) extracted from the 2004 Nationwide Inpatient Sample. Multivariable logistic regression analyses and Cox proportional hazards regression were conducted to calculate the odds of death (within 7, 14, and 30 days) and the hazard ratio of death for patients with weekend intracerebral hemorrhage admissions compared with weekday intracerebral hemorrhage admissions. All analyses were adjusted for concurrent differences in length of stay, patient demographics, and comorbid disease.

Results— Weekend hospital admissions accounted for 26.8% of the 13 821 patients with a diagnosis of intracerebral hemorrhage in the National Inpatient Sample. Admission during the weekend was a statistically significant independent predictor of death within 7 days (OR, 1.14; 95% CI, 1.05 to 1.25), within 14 days (OR, 1.15; 95% CI, 1.05 to 1.25), and within 30 days (OR, 1.15; 95% CI, 1.05 to 1.25). The adjusted hazard of in-hospital death (hazard ratio, 1.12; CI, 1.05 to 1.20) indicates that the overall risk of in-hospital death with intracerebral hemorrhage is 12% higher with weekend admission.

Conclusion— Weekend admission for intracerebral hemorrhage was associated with increased risk-adjusted mortality when compared with admission during the remainder of the week.

Methods— We performed a retrospective analysis of a prospectively collected cohort of consecutive patients with ICH presenting to a single tertiary care hospital from 2002 to 2007. Demographic, clinical, and radiographic data were prospectively collected for all patients. Laboratory data and clinical course over the first 48 hours were retrospectively reviewed. Acute nephropathy was defined as any rise in creatinine of >25% or >0.5 mg/dL, such that the highest creatinine value was above 1.5 mg/dL.

Results— 539 patients presented during the study period and had at least 2 creatinine measurements. 348 (65%) received a CTA. Acute nephropathy developed in 6% of patients who received a CTA and in 10% of those who did not (P=0.1). Risk of nephropathy was 14% in those receiving no contrast (130 patients), 5% in those receiving 1 contrast study (124 patients), and 6% in those receiving >1 contrast study (244 patients). Neither CTA nor any use of contrast predicted nephropathy in univariate or multivariate analysis.

Conclusion— The risk of acute nephropathy after ICH was not increased by use of CTA. Studies of CIN that do not include a control group may overestimate the influence of contrast. Patients with ICH appear to have an 8% risk of developing "Hospital-Acquired Nephropathy."

Methods— We prospectively identified patients with spontaneous ICH, measured platelet activity (VerifyNow-ASA, Accumetrics) on admission, and recorded antiplatelet medication use. ICH volume was calculated using computerized volumetric analysis. Data were analyzed with nonparametric statistics and repeated measures ANOVA as appropriate. Patients were prospectively followed for functional outcomes. Data are presented as mean±SD or median [Q1 to Q3].

Results— Reduced platelet activity (≤550 aspirin reaction units [ARU]) was associated with increased ICH volume growth (P<0.05) for patients with the diagnostic CT within 12 hours. In the subset of patients not known to take aspirin, 24% had reduced platelet activity. Sixteen (24%) patients received a platelet transfusion 21.2±11.4 hours after symptom onset with an increase in platelet activity (448 [414–479] to 586 [530–639] ARU, P=0.001), but without impact on outcomes. Reduced platelet activity was associated with worse modified Rankin Scores at 3 months (P=0.02).

Conclusions— Reduced platelet activity was associated with early ICH volume growth and worse functional outcome. Because platelet activity can be increased with platelet transfusion, increasing platelet activity is a potential method to reduce ICH volume growth and improve functional outcomes.

Methods— Retrospective cohort study comparing clinical, seizure, and EEG features in term neonates with ischemic stroke or HIE and seizures within 7 days after birth, admitted at The Hospital for Sick Children. Putative clinical and EEG predictors of stroke were analyzed with univariate and multivariate methods.

Results— Sixty-two newborns with stroke (n=27) or HIE (n=35) were studied. With univariate analysis, predictors of stroke included delayed seizure onset (≥12-hours after birth) (P<0.0001; OR, 26.4; 95% CI, 6.8, 102.5), focal motor seizures (P=0.001; OR, 7.2; 95% CI, 2.0, 26.0) and pattern of neurological abnormalities (P<0.0001). With multivariate analysis, delayed seizure onset (P<0.0001; OR 39.7; 95% CI, 7.3, 217.0) and focal motor seizures (P=0.007; OR, 13.4; 95% CI, 2.1, 87.9) predicted stroke. Presence of both predictors had 100% positive predictive value and specificity, 61% negative predictive value and 37% sensitivity.

Conclusions— In neonates, onset of seizures beyond 12 hours of birth and clinically observed focal seizures are predictive of stroke. These preinvestigation indicators of stroke may facilitate earlier diagnosis and institution of specific management strategies.

Methods— We examined all adult patients (>16 years) with SCD followed in the hematology outpatient clinic at our university hospital with MRI, MR angiography, and transcranial Doppler.

Results— We evaluated 50 patients. The overall prevalence of MRI abnormalities was 60%. Abnormal MRI findings were more frequent when vessel tortuosity or stenoses were present on MR angiography (P<0.01). Patients with intracranial stenoses had significantly higher time-averaged maximum mean velocities (P=0.01). A time-averaged maximum mean velocity of 123.5 cm/s allowed the diagnosis of middle cerebral artery or internal carotid artery intracranial stenosis with sensitivity of 100% and specificity of 73% with an area under the receiver operator characteristic curve of 0.91 (CI, 0.79 to 1.00).

Conclusions— The frequency of brain imaging abnormalities detected by MRI/MR angiography in adults with SCD was higher than that described for children. Transcranial Doppler velocities in adult patients with intracranial stenoses were lower than those described for the pediatric population with SCD.

Material and Methods— Comparative CBF_MRI and CBF_PET were performed in patients with acute and subacute stroke. In a voxel-based seed-growing technique, predefined CBF_MRI thresholds (<40, <30, <20, <10 mL/100 g/min) were applied and the resulting volumes were compared with the hypoperfusion volume detected by the penumbral threshold (<20 mL/100 g/min) on CBF_PET. The volumetric comparison was expressed as the C-ratio (volume CBF_MRI/volume CBF_PET) to identify the best MRI threshold. The influence of vessel pathology, hypoperfusion size, and time point of imaging was described. The proportion of voxels correctly classified as hypoperfused and the proportion of voxel correctly classified as nonhypoperfused of the best CBF_MRI threshold was calculated and a Bland-Altman plot illustrated the method-specific differences.

Results— In 24 patients (median time MRI to PET: 68 minutes; 16 patients imaged within 24 hours after stroke), the median volume of hypoperfusion <20 mL/100 g/min (CBF_PET) was 78.5 cm³. Median hypoperfusion volume on CBF_MRI ranged from 245.9 cm³ (<40 mL/100 g/min) to 35.5 cm³ (<10 mL/10 g/min). On visual inspection, an excellent qualitative congruence was found. The quantitative congruence was best for the MRI-CBF threshold <20 mL/100 g/min (median C-ratio: 1.0), reaching a proportion of voxels correctly classified as hypoperfused of 76% and a proportion of voxel correctly classified as nonhypoperfused of 96%, but a wide interindividual range (C-ratio 0.3 to 3.5) was found. Ipsilateral vessel pathology, time point of imaging, and size of hypoperfusion did not significantly influence the C-ratio. The Bland-Altman analysis for the volumetric difference of CBF_MRI and CBF_PET found a good overall agreement but a large SD.

Conclusion— Hypoperfusion areas below the CBF_PET penumbral threshold can be well identified by the CBF_MRI threshold <20 mL/10 g/min at a group level, but a large individual variance (exceeding 20% of volume in nearly half of the patients) could not be explained. Our results support a prudent use of MRI-based quantitative CBF measurement in clinical routine.

Methods— The prospective Acute Stroke Accurate Prediction (ASAP) Study included a prespecified serial imaging subgroup who underwent DWI studies at baseline (<24 hours after symptom onset) and Day 5 (±2 days). DWI infarct volumes were calculated using the Analyze software (Rochester, Minn). Clinical outcomes were assessed at 3 months. Univariate and multivariable regression analysis was performed to assess the relationship between change in DWI lesion volume and excellent neurological outcome (modified Rankin Scale 0, 1, and Barthel Index ≥95).

Results— In total, 169 cases from the ASAP study had serial DWI scans with a measurable lesion at baseline, follow-up, or both. The median baseline National Institutes of Health Stroke Scale score was 6 (interquartile range, 3 to 13). For each 10 cm³ of growth in DWI infarct volume, the OR for achieving an excellent outcome by modified Rankin Scale was 0.52 (95% CI, 0.38 to 0.71) and for the Barthel Index was 0.64 (95% CI, 0.51 to 0.79). Adjusting for clinically important covariates, the OR for an excellent modified Rankin Scale outcome was 0.57 (95% CI, 0.37 to 0.88) and excellent Barthel Index outcome was 0.75 (95% CI, 0.56 to 1.01).

Conclusions— Based on these data, the likelihood of achieving an excellent neurological outcome diminishes substantially with growth in DWI infarct volume in the first 5 days after ischemic stroke of mild to moderate severity.

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 (72.8 versus 60.3%, P=0.09). Baseline National Institute of Health Stroke Scale scores (12.5 versus 11.3), NIHSS score at discharge (11.0 versus 9.5), 3-month-outcome modified Rankin Scale score, thrombolysis-related (17.1% versus 13.5%) or independent complications (32.4% versus 30.2%), and mortality after 3 months (13.5% versus 9.5%) were similar.

Conclusion— 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). Baseline characteristics, rates of rtPA-related and independent complications, as well as clinical outcomes were not different between women and men with AIS.

Methods— Joint outcome table specification was used to derive number needed to treat to benefit (NNTB) and number needed to treat to harm (NNTH) values summarizing treatment impact over the entire outcome range on the modified Rankin scale of global disability, including both expert-dependent and expert-independent (algorithmic and repeated random sampling) array generation.

Results— For the full 7-category modified Rankin scale, algorithmic analysis demonstrated that the NNTB for 1 additional patient to have a better outcome by ≥1 grades than with placebo must lie between 4.0 and 13.0. In bootstrap simulations, the mean NNTB was 7.1. Expert joint outcome table analyses indicated that the NNTB for improved final outcome was 6.1 (95% CI, 5.6–6.7) and the NNTH 37.5 (95% CI, 34.6–40.5). Benefit per 100 patients treated was 16.3 and harm per 100 was 2.7. The likelihood of help to harm ratio was 6.0.

Conclusions— Treatment with tissue plasminogen activator in the 3- to 4.5-hour window confers benefit on approximately half as many patients as treatment <3 hours, with no increase in the conferral of harm. Approximately 1 in 6 patients has a better and 1 in 35 has a worse outcome as a result of therapy.

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: 1.10 to 1.56; P=0.002) and no significant difference in mortality (odds ratio 1.04; 95% CI: 0.75 to 1.43; P=0.83) compared to placebo treated patients.

Conclusions— Treatment with tPA in the 3- to 4.5-hour time-window is beneficial. It results in an increased rate of favorable outcome without adversely affecting mortality.

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.

Methods— A computer-aided literature search was performed to identify randomized, controlled trials in which the experimental group received task-oriented circuit class training focusing on the lower limb. Studies published up to March 2008 were included. The methodological quality of each study was assessed and studies with the same outcome variable were pooled by calculating the summary effect sizes using fixed or random effects models.

Results— Six of the 445 studies screened, comprising 307 participants, were included. Physiotherapy Evidence Database scores ranged from 4 to 8 points with a median of 7.5 points. The meta-analysis demonstrated significant homogeneous summary effect sizes in favor of task-oriented circuit class training for walking distance (0.43; 95% CI, 0.17 to 0.68; P<0.001), gait speed (0.35; 95% CI, 0.08 to 0.62; P=0.012), and a timed up-and-go test (0.26; 95% CI, 0.00 to 0.51; P=0.047). Nonsignificant summary effect sizes in favor of task-oriented circuit class training were found for the step test and balance control.

Conclusions— This meta-analysis supports the use of task-oriented circuit class training to improve gait and gait-related activities in patients with chronic stroke. Further research is needed to investigate the cost-effectiveness and its effects in the subacute phase after stroke, taking comorbidity into account, and to investigate how to help people maintain and improve their physical abilities after their rehabilitation program ends.

Methods— We investigated functional reorganization after 4 weeks of treadmill training with partial body weight support in 18 chronic patients (mean age, 59.9±13.5 years) with mild to moderate paresis (Motricity Index affected leg: 77.7±10.5; range, 9 to 99) and gait impairment (Functional Ambulation Category: 4.4±0.6; range, 3 to 5) due to a single subcortical ischemic stroke using repeated 3.0-T functional MRI and an ankle-dorsiflexion paradigm.

Results— Walking endurance improved after training (2-minute timed walking distance: 121.5±39.0 versus pre: 105.1±38.1 m; P=0.0001). For active movement of the paretic foot versus rest, greater walking endurance correlated with increased brain activity in the bilateral primary sensorimotor cortices, the cingulate motor areas, and the caudate nuclei bilaterally and in the thalamus of the affected hemisphere.

Conclusions— Despite the strong subcortical contributions to gait control, rehabilitation-associated walking improvements are associated with cortical activation changes. This is similar to findings in upper limb rehabilitation with some differences in the involved cortical areas. We observed bihemispheric activation increases with greater recovery both in cortical and subcortical regions with movement of the paretic foot. However, although the dorsal premotor cortex appears to play an important role in recovery of hand movements, evidence for the involvement of this region in lower extremity recovery was not found.

Methods— Quantitative voxel-based analyses were used to determine whether infarct location could predict either initial motor ability or clinical improvement after CI therapy in chronic stroke patients.

Results— Although corona radiata infarcts were associated with worse in-laboratory motor ability at pretreatment, infarct location did not predict improvement in either the laboratory or the life situation after CI therapy.

Conclusions— The extent of improvement from CI therapy does not depend on the location of neurological damage, despite there being a pretreatment relationship between infarct location and in-laboratory motor ability. This dissociation could be explained by brain plasticity induced by CI therapy.

Methods— Patients with Mini-Mental State Examination scores ≥23 were prospectively and consecutively included 2 weeks after a first-ever ischemic brain infarct. Stroke features were based on MRI. Four domains were evaluated: instrumental and executive functions, episodic memory, and working memory (WM). Patients were scored using means and compared with education- and age-matched control subjects. Then we attributed Z-scores for each test and each domain. The most relevant cognitive tests characterizing CDF were determined using logistic regression.

Results— Among 177 patients (mean age, 50.6 years), 91.5% failed in at least one cognitive domain. WM was the most impaired domain (87.6%) with executive functions (64.4%), episodic memory (64.4%), and instrumental functions (24.9%) being relatively preserved. CDF was associated with age, education, depression, neurological deficit, and leukoaraiosis in bivariate analysis. Using logistic regression, WM tests and age predicted CDF (Modified Paced Auditorial Serial Addition Test: OR=0.96 CI=0.93 to 0.98; Owen-spatial-WM: OR=1.07 CI=1.02 to 1.12; age: OR=0.96 CI=0.93 to 0.98).

Conclusion— CDF appears to be almost constant, although underestimated, in subacute stroke. WM could reflect some hidden dysfunctioning, which may interfere with rehabilitation and return to work. Clinical routine may include WM tests in young patients with mild stroke.

Methods— A case-control study was conducted in southern China from 2007 to 2008. A total of 374 patients with incident ischemic stroke and 464 control subjects (mean age, 69 years) were recruited from 3 hospitals in Foshan. Information on frequency and duration of tea drinking, quantity of dried tea leaves, and types of tea consumed, together with habitual diet and lifestyle characteristics, was obtained from participants using a validated and reliable questionnaire. Logistic regression analyses were performed for tea consumption variables accounting for confounders that affect the ischemic stroke risk.

Results— A significant decrease in ischemic stroke risk was observed for drinking at least one cup of tea weekly (P=0.015) when compared with infrequent or nondrinkers, the risk reduction being largest by drinking one to 2 cups of green or oolong tea daily. Significant inverse dose-response relationships were also found for years of drinking and the amount of dried tea leaves brewed. The adjusted ORs for the highest level of consumption in terms of frequency of intake, duration of drinking, and average tea leaves brewed were 0.61 (95% CI, 0.40 to 0.94), 0.40 (95% CI, 0.25 to 0.64), and 0.27 (95% CI, 0.16 to 0.46), respectively.

Conclusion— Long-term tea consumption is associated with reduced risk of ischemic stroke.

Methods— We randomized 4731 patients with recent stroke or transient ischemic attack and no known coronary heart disease to atorvastatin 80 mg per day or placebo.

Results— After 4.9 years, at each level of LDL-C reduction, subjects with HDL-C value above the median or systolic BP below the median had greater reductions in stroke and major cardiovascular events and those with a reduction in triglycerides above the median or diastolic BP below the median showed similar trends. There were no statistical interactions between on-treatment LDL-C, HDL-C, triglycerides, and BP values. In a further exploratory analysis, optimal control was defined as LDL-C <70 mg per deciliter, HDL-C >50 mg per deciliter, triglycerides <150 mg per deciliter, and SBP/DBP <120/80 mm Hg. The risk of stroke decreased with as the level of control increased (hazard ratio [95% confidence interval] 0.98 [0.76 to 1.27], 0.78 [0.61 to 0.99], 0.62 [0.46 to 0.84], and 0.35 [0.13 to 0.96]) for those achieving optimal control of 1, 2, 3, or 4 factors as compared to none, respectively. Results were similar for major cardiovascular events.

Conclusions— We found a cumulative effect of achieving optimal levels of LDL-C, HDL-C, triglycerides, and BP on the risk of recurrent stroke and major cardiovascular events. The protective effect of having a higher HDL-C was maintained at low levels of LDL-C.

Methods— This was a population-based cohort of carotid endarterectomy performed in Medicare beneficiaries in New York. Clinical data were abstracted from medical charts to assess sociodemographics, clinical indication for carotid endarterectomy, disease severity, comorbidities, and deaths and strokes within 30 days of surgery. Appropriateness was based on validated criteria from a national expert panel. Differences in patients, providers, outcomes, and appropriateness were compared using ² tests. Differences in risk-adjusted rates of death or nonfatal stroke were compared using multiple logistic regression accounting for patient, physician, and hospital-level risk factors.

Results— Overall, 95.3% of patients undergoing carotid endarterectomy were white, 2.5% black, and 2.2% Hispanic (N=9093). Minorities had more severe neurological disease and more comorbidities and were more likely to be cared for by lower-volume surgeons and hospitals (P<0.0001). Rates of 30-day death/stroke were higher in Hispanics (9.5%) and blacks (6.9%) than whites (3.8%; P<0.0001). Multivariable analyses that adjusted for presurgical patient risk and provider characteristics found that blacks no longer had significantly worse outcomes (OR=1.37; CI, 0.78 to 2.40), although the higher risk of death/stroke in Hispanics persisted (OR=1.87; CI, 1.09 to 3.19). Minorities had higher rates of inappropriate surgery (Hispanics 17.6%, black 13.0%, white 7.9%; P<0.0001) largely due to higher comorbidity.

Conclusions— Minorities had worse outcomes and higher rates of inappropriate surgery. Differences in underlying presurgical risk factors and provider characteristics explained the higher risk of complications in blacks, but not Hispanics.

Methods— Survey respondents were drawn from our biracial population of 1.3 million using random-digit dialing in 1995, 2000, and 2005 to reflect the age, race, and gender distribution of stroke patients, based on an ongoing stroke incidence study in the same region. They were asked open-ended questions regarding stroke WS, RF, and, in 2005, specific questions regarding t-PA. Comparisons over time were made using ² analysis, and were corrected for multiple comparisons.

Results— Over the 10-year study period, 6209 surveys were completed. Knowledge of WS and RF improved between 1995 and 2000. Between 2000 and 2005, knowledge did not improve significantly; however, there was a significant improvement in knowledge of 3 warning signs (12% in 1995 vs 16% in 2005, P=0.0004). In 2005, only 3.6% of those surveyed were able to independently name t-PA or "clot buster" when asked: "Suppose you were having a stroke. Do you know of any medication your doctor could give you into the vein to increase your chance of recovering from a stroke?"–although 19% claimed to have heard of t-PA once it was mentioned to them.

Conclusion— Despite numerous national stroke public awareness campaigns, public knowledge of stroke WS and RF has not improved over the last 5 years. In addition, knowledge of t-PA as a treatment for IS is extremely poor. Public awareness messages in the future should focus on the possibility of urgent treatments, in addition to stroke WS and RF, so the public can translate their knowledge into action and present to medical attention more quickly. This may be the highest yield approach to increasing rates of treatment of IS with t-PA.

Methods— We sought to measure interrater reliability of the certification DVD among general users using methodology previously published for the DVD. All raters who used the DVD certification through the American Heart Association web site were included in this study. Each rater evaluated one of 3 certification groups.

Results— Responses were received from 8214 raters overall, 7419 raters using the Internet and 795 raters using other venues. Among raters from other venues, 33% of all responses came from registered nurses, 23% from emergency department MD/other emergency department/other physicians, and 44% from neurologists. Half (51%) of raters were previously National Institutes of Health Stroke Scale-certified and 93% were from the United States/Canada. Item responses were tabulated, scoring performed as previously published, and agreement measured with unweighted kappa coefficients for individual items and an intraclass correlation coefficient for the overall score. In addition, agreement in this study was compared with the agreement obtained in the original DVD validation study to determine if there were differences between novice and experienced users. Kappas ranged from 0.15 (ataxia) to 0.81 (Item 1c, Level of Consciousness-commands [LOCC] questions). Of 15 items, 2 showed poor, 11 moderate, and 2 excellent agreement based on kappa scores. Agreement was slightly lower to that obtained from expert users for LOCC, best gaze, visual fields, facial weakness, motor left arm, motor right arm, and sensory loss. The intraclass correlation coefficient for total score was 0.85 (95% CI, 0.72 to 0.90). Reliability scores were similar among specialists and there were no major differences between nurses and physicians, although scores tended to be lower for neurologists and trended higher among raters not previously certified. Scores were similar across various certification settings.

Conclusions— The data suggest that certification using the National Institute of Neurological Disorders and Stroke DVDs is robust and surprisingly reliable for National Institutes of Health Stroke Scale certification across multiple venues.

Methods— Using transgenic (Tg) rats overexpressing copper zinc superoxide dismutase (SOD1), we investigated the role of this intrinsic antioxidant in the restoration of cerebral blood flow (CBF) after CAR. Nine Tg and 11 wild-type (WT) rats were subjected to a nominal 15-minute cardiac arrest, and CBF was measured using the noninvasive arterial spin labeling MRI method before and during cardiac arrest, and 0 to 2 hours and 1 to 5 days after resuscitation.

Results— The SOD1-Tg rats showed rapid normalization of CBF 1 day after the insult, whereas CBF in WT animals remained abnormal for at least 5 days, showing a progressive increase in CBF from hypo- to hyperperfusion on postresuscitation days 1 to 5. The long-term outcome, as measured by survival time, change in body weight, and mapping of apparent diffusion coefficient (ADC) for ion/water homeostasis, was significantly better in the SOD1-Tg rats.

Conclusion— Our results support the notion that reactive oxygen species are at least partially responsible for microvascular reperfusion disorders.

Methods— The endovascular perforation model of SAH was produced and 112 mice were assigned to sham, SAH+ vehicle, and SAH+ N-Ac-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-CMK, 6 and 10 mg/kg) groups. Ac-YVAD-CMK, a selective inhibitor of IL-1β converting enzyme, or vehicle was administered intraperitoneally 1 hour post-SAH. EBI was assessed in terms of mortality within 24 hours, neurological scores, brain water content at 24 and 72 hours, Evans blue dye extravasation and Western blot for IL-1β, c-Jun N-Terminal kinase (JNK), matrix metalloproteinase (MMP)-9, and zonula occludens (ZO)-1 at 24 hours after SAH.

Results— High-dose (10 mg/kg) but not low-dose (6 mg/kg) treatment group significantly improved neurological scores, mortality, brain water content, and Evans blue dye extravasation compared with the vehicle group. Although both dosages of Ac-YVAD-CMK attenuated the mature IL-1β induction, only high-dose treatment group significantly inhibited the phosphorylation of JNK, MMP-9 induction, and ZO-1 degradation.

Conclusion— IL-1β activation may play an important role in the pathogenesis of EBI after SAH. The neurovascular protection of Ac-YVAD-CMK may be provided by the inhibition of JNK-mediated MMP-9 induction and the consequent preservation of tight junction protein ZO-1.

Methods— Male Sprague-Dawley rats were exposed to normobaric hyperoxia (95% O₂) or normoxia (21% O₂) during 5-hour filament occlusion of the middle cerebral artery followed by 19-hour reperfusion. Thirty minutes before reperfusion, saline or tPA was continuously infused to rats over 1 hour. Outcome parameters were neurological score, mortality rate, brain edema, hemorrhage volume, and MMP-9. Hemorrhage was quantified with a hemoglobin spectrophotometry method. Edema was evaluated as hemispheric enlargement. MMP-9 was measured by gelatin zymography.

Results— In normoxic rats, delayed tPA treatment at 4.5 hours after stroke onset resulted in high mortality, more severe neurological deficits, increased hemorrhage volumes, and augmented MMP-9 induction compared with saline. Rats treated with combined normobaric hyperoxia and tPA showed significantly reduced tPA-associated mortality, brain edema, hemorrhage, and MMP-9 augmentation as compared with tPA alone.

Conclusions— Our results suggest that early normobaric hyperoxia treatment may represent an important strategy to increase the safety of delayed tPA thrombolysis in ischemic stroke.

Methods— C57BL/6J mice were subjected to middle cerebral artery occlusion and were treated with or without TO901317 (30 mg/kg) starting 24 hours after middle cerebral artery occlusion and daily for 14 days.

Results— TO901317 significantly increased serum HDL-C level, promoted angiogenesis and vascular stabilization in the ischemic brain, and improved functional outcome after stroke. The increased HDL-C level significantly correlated with functional recovery after stroke. TO901317 also increased eNOS phosphorylation in the ischemic brain. Mechanisms underlying the TO901317-induced angiogenesis were investigated using eNOS knockout (eNOS–/–) mice. TO901317 treatment of eNOS–/– mice significantly increased HDL-C level but failed to increase angiogenesis and functional outcome after stroke. In vitro studies demonstrated that TO901317 and HDL-C significantly increased capillary tube formation and promoted eNOS phosphorylation activity in cultured mouse brain endothelial cells compared with nontreatment controls. However, TO901317 and high-density lipoprotein treatment-induced capillary tube formation were absent in eNOS-deficient mouse brain endothelial cell.

Conclusions— These data indicate that TO901317 treatment increases serum HDL-C level, which promotes angiogenesis through eNOS and leads to improvement of functional outcome after stroke.

Methods— Four daily doses of RTL were administered subcutaneously to C57BL/6 mice after middle cerebral artery occlusion, and lesion size and cellular composition were assessed in the brain and cell numbers were assessed in the spleen and thymus.

Results— Treatment with RTL551 (I-A^b molecule linked to MOG-35-55 peptide) reduced cortical and total stroke lesion size by approximately 50%, inhibited the accumulation of inflammatory cells, particularly macrophages/activated microglial cells and dendritic cells, and mitigated splenic atrophy. Treatment with RTL1000 (HLA-DR2 moiety linked to human MOG-35-55 peptide) similarly reduced the stroke lesion size in HLA-DR2 transgenic mice. In contrast, control RTL with a nonneuroantigen peptide or a mismatched major histocompatibility complex Class II moiety had no effect on stroke lesion size.

Conclusions— These data are the first to demonstrate successful treatment of experimental stroke using a neuroantigen-specific immunomodulatory agent administered after ischemia, suggesting therapeutic potential in human stroke.

Methods— Adult male CST-yellow fluorescent protein mice were subjected to permanent right middle cerebral artery occlusion (n=8/group). Foot-fault test was performed to monitor functional deficit and recovery. Pseudorabies virus tracer was injected into the left forelimb muscles at 1 or 4 weeks after middle cerebral artery occlusion (4 days before euthanasia), respectively. A third group of CST-yellow fluorescent protein mice without middle cerebral artery occlusion was used for normal control (n=6). The yellow fluorescent protein labeling of CST in the cervical cord and pseudorabies virus labeling of pyramidal neurons in the bilateral cortices were measured on vibratome sections using a confocal imaging system.

Results— Compared with normal animals, axonal density in the stroke-affected side of the cervical cord was significantly decreased at 11 days (P<0.001) and significantly increased at 32 days after stroke compared with the Day 11 values (P<0.05). Pseudorabies virus labeling was significantly decreased in the ischemic hemisphere 11 days after middle cerebral artery occlusion (P<0.001). In contrast, a significant increase was observed in pseudorabies virus labeling of bilateral cortices 32 days after stroke compared with 11 days (P<0.05). The CST axonal density in the denervated spinal cord and pyramidal neuron labeling in the bilateral cortices were significantly correlated with behavioral recovery (P<0.05).

Conclusions— Spontaneous functional recovery after stroke may, at least in part, be attributed to neuronal remodeling in the corticospinal system.

Methods— Twelve posterior cranial arteries obtained from human cadavers of 2 different age groups were compared morphologically and tested biomechanically before and after enzymatic degradation of elastin. Light, confocal, and scanning electron microscopy were used to analyze and determine structural differences, potentially attributed to aging.

Results— Aging affects structural morphology and the mechanical properties of intracranial arteries. In contrast to main systemic arteries, intima and media thicken while outer diameter remains relatively constant with age, leading to concentric hypertrophy. The structural morphology of elastin changed from a fiber network oriented primarily in the circumferential direction to a more heterogeneously oriented fiber mesh, especially at the intima. Biomechanically, cerebral arteries stiffen with age and lose compliance in the elastin dominated regime. Enzymatic degradation of elastin led to loss in compliance and stiffening in the young group but did not affect the structural and material properties in the older group, suggesting that elastin, though present in equal quantities in the old group, becomes dysfunctional with aging.

Conclusions— Elastin loses its functionality in cerebral arteries with aging, leading to stiffer less compliant arteries. The area fraction of elastin remained, however, fairly constant. The loss of functionality may thus be attributed to fragmentation and structural reorganization of elastin occurring with age.

Methods— Translation, text adaptation, video dubbing, and editing of the Italian NIHSS videotapes relied on a team of bilingual stroke neurologists. Three waves of training courses were organized for mixed classes of medical and nonmedical health professionals. The certification test was based on the usual set of 5 videotaped patients. Scoring rules were those provided by the National Institutes of Neurological Disorders and Stroke. Reliability of the Italian NIHSS was assessed using kappa statistics and compared with that of the original NIHSS.

Results— During 3 years, 850 nurses, 460 nonneurologist physicians, and 246 neurologists were trained. Pass rates were respectively 44%, 75%, and 87%, respectively. Overall, 80% of scale items showed moderate to excellent reliability. Independent significant predictors of test failure at multivariate logistic regression were nurse profession (OR, 5.41; 95% CI, 4.07 to 7.20), older age (OR, 1.03; 95% CI, 1.02 to 1.05), and first edition of the course (OR, 3.13; 95% CI, 2.43 to 4.05). The agreement across all items between NIHSS and the Italian NIHSS was 80% (kappa=0.70±0.18, z<0.001).

Conclusions— The Italian translation, supervised by experienced vascular neurologists, did not influence the clinimetric characteristics of the NIHSS. Our findings support the implementation of NIHSS video training in languages other than English.

Methods— Twenty-four hours after the induction of focal ischemia, cardiac function was measured in mice by endovascular catheterization of the heart. Immediately after hemodynamic measurements, mice were euthanized and brains were excised and sectioned to measure infarct volume and the severity of insular cortex injury. Myocardial damage was evaluated by hematoxylin-eosin staining. Serum and heart levels of norepinephrine (NE) were also determined.

Results— Cardiac dysfunction occurred in 9 out of 14 mice that underwent left pMCAO. In these 9 mice, the severity of left insular cortex lesion was greater than the mice with normal heart function. The serum and heart levels of NE were significantly higher in left pMCAO mice with heart dysfunction. Liner regression analysis indicates significant inverse correlation between the severity of left insular cortex damage and heart dysfunction. Mice that underwent right pMCAO did not exhibit cardiac dysfunction.

Conclusions— This study shows that left focal cerebral ischemia can produce cardiac dysfunction, which is associated with the extent of left insular cortex damage. Furthermore, mice exhibiting cardiac dysfunction had elevated levels of NE in the serum and heart.

Methods— The Michigan Behavioral Risk Factor Survey (BRFS) is a random-digit-dial telephone survey of adults conducted annually as part of the national BRFS. Questions regarding tPA treatment for acute stroke were included in the 2004 Michigan BRFS. We examined the prevalence of awareness using ² tests and generated multivariable logistic regression models.

Results— Among 4724 respondents, only 32.2% (95% CI=30.8 to 33.8%) were aware of the existence of tPA treatment for acute stroke, of whom 52.7% (50.0 to 55.4%) knew that it needed to be administered within 3 hours of symptom onset. Awareness of tPA was higher among middle aged adults, females, whites, and those with higher education and income. Awareness of the time window for tPA was higher among middle aged adults and whites.

Conclusions— In this population-based survey only a third of the public were aware of tPA as a treatment for stroke, and only 1 in 6 were aware that the treatment exists and needs to be given within 3 hours of symptom onset. Continuing efforts are necessary to increase public knowledge about tPA treatment for acute stroke.

Methods— 369 nonlacunar tPA-treated patients were studied. Patients were classified as SITS-MOST (SM) or non–SITS-MOST (NSM) according to SITS-MOST–criteria fulfilling. Clinical evaluation was assessed by NIHSS and functional outcome by mRS at 3 months (functional independency=mRS ≤2).

Results— Baseline NIHSS was 17. 169 (45.8%) patients were SM and 200 (54.1%) NSM. Recanalization (47.6%/50.3%, P=0.36), 24-hour-improvement (55.6%/49.5%, P=0.114), and SICH were similar (4.8%/5.1%, P=0.554). At discharge, clinical improvement in SM-group was higher (66.7%/55.7%, P=0.024). NSM tended to higher mortality (10.5%/16.1%, P=0.084) and lower functional independence (48.7%/39.6%, P=0.082).

Conclusion— Thrombolysis may be safe in patients not fulfilling SITS-MOST criteria. Testing thrombolysis in patients outside SITS-MOST could be considered in the future.

Methods— This is a substudy of EPITHET, a double-blind multi-center study of 100 patients randomized to tPA or placebo 3 to 6 hours after stroke onset. MRI was obtained before treatment, and at 3 to 5 days and 90 days after treatment. Presence of PDM (perfusion deficit/DWI_volume >1.2 and perfusion deficit at least 10 mL>DWI_volume) and CDM (NIHSS ≥8 and DWI_volume ≤25 mL) was determined for each patient. We assessed lesion growth and neurological improvement (decrease in NIHSS ≥8 points between baseline and 90 days, or a 90-day NIHSS ≤1).

Results— 86% of the patients had PDM, but only 41% had CDM. CDM detected PDM with a sensitivity of 46% and a specificity of 86%. We found statistically significant effects of reperfusion on the rate of neurological improvement (OR 9.92, 95% CI 1.91 to 51.64; P<0.01) and on absolute growth (difference: –59.60 mL, 95% CI –95.40 mL to –23.81 mL; P<0.01). Neither treatment with tPA nor reperfusion had a significantly different impact on lesion growth or clinical course in CDM patients compared to patients without CDM.

Conclusions— There was no increased benefit from tPA in patients with CDM. The beneficial effects of reperfusion were similar in patients with and without CDM.

Methods— We used Pulse Dye Densitometry to measure BV daily in 102 patients during the first 10 days after SAH. Fluid management was based on BV-measurements in the intervention group (n=54) and on fluid balance in the control group (n=48). Severe hypovolemia was defined as BV <50 mL/kg.

Results— In the intervention group 6.7% of BV measurements were in the severe hypovolemic range and in the control group 17.1% (mean weighted difference 7.7%; 95% CI: 1.4 to 13.9%). In the intervention group 21 patients (39%) had 1 or more measurements with severe hypovolemia versus 26 (54%) of the controls (RR 0.7; 95% CI: 0.5 to 1.1).

Conclusions— Guiding fluid management on daily measurements of blood volume reduces the incidence of severe hypovolemia after SAH. The effects on neurological outcome should be studied.

Methods— Coated-platelet levels were determined in 26 patients with a diagnosis of SICH and 52 controls.

Results— The patient population had significantly lower coated-platelet levels than the controls (mean±SD, 24.8±9.7% versus 32.9±12.6%, P=0.0035).

Conclusions— Decreased coated-platelet synthesis may be linked to the mechanisms involved in the events leading to SICH.

Methods— The National Acute Stroke Israeli Surveys (NASIS) included all patients admitted with acute stroke to any of the 28 hospitals nationwide during February through March 2003 and March through April 2007. We compared stroke severity and outcomes of ICH patients who received statins before the index event with those who did not, using multivariable logistic regression models adjusting for the propensity to use statins before the event.

Results— Among 3212 stroke patients, 312 had ICH and 89 of them were receiving statins at the time of the ICH. Patients on statins before ICH had lower baseline NIHSS scores, less systemic complications, higher proportions of good outcome (modified Rankin scale 0 to 3), lower death rates, and higher rates of discharge home or to a rehabilitation facility. On logistic regression analyses statin use before the event was associated with odds ratios of 0.46 for having a severe stroke defined as baseline NIHSS >15 (95% CI; 0.23 to 0.93), 2.97 for having good outcome (95% CI; 1.25 to 7.35) at discharge, and 0.25 for death or nursing facility disposition (95% CI; 0.09 to 0.63).

Conclusions— Use of statins before ICH is associated with reduced mortality and neurological disability and with a higher chance for good outcome, suggesting that statins may be protective in the setting of ICH.

Methods— BP was measured every 6 hours for the first 36 hours of emergent hospitalization in 565 consecutive patients (347 men, 70±11 years in age) presenting within 24 hours of an acute ischemic stroke. Neurological deterioration was defined as a ≥2-point increase in the National Institutes of Health stroke scale (NIHSS) score at 3 weeks compared to the admission score.

Results— At 3 weeks, 64 patients (11.3%) had deteriorated neurologically. For the group as a whole, high systolic BP (SBP) values measured at 12, 18, 24, and 36 hours postadmission were independently related to neurological deterioration after adjustment for age, sex, and known predictors, including admission NIHSS score, admission blood glucose level, and large infarct size. At 24 hours, the odds of neurological deterioration increased by 20% per 10-mm Hg increase in SBP. For cardioembolic stroke patients, high SBP values measured at 12 through 36 hours were independently related to neurological deterioration after multivariate adjustment. For patients having stroke other than cardioembolism, no SBP values at any time point were related to neurological deterioration.

Conclusions— Acute SBP values between 12 and 36 hours postadmission, but not those on admission or at 6 hours, were predictive of neurological deterioration within the initial 3 weeks of ischemic stroke, particularly for cardioembolic stroke patients.

Methods— BoNT-A (Dysport) was injected into several upper limb spastic muscles in a group of 20 patients. Neurological impairment (muscle tone and strength, dexterity, SIAS), activity (ABILHAND), participation (SATIS-Stroke), and quality of life (SF36) were assessed before and 2 months after the injections.

Results— BoNT-A injections improved muscle tone, but had no impact on dexterity, manual ability, social participation, and quality of life.

Conclusions— In this study, BoNT-A injections in spastic upper limbs significantly reduced neurological impairments, but had no functional impact.

Methods— One hundred smokers with first-ever ischemic stroke were prospectively enrolled to the study. Correlates of nicotine dependence as well as sociodemographic and clinical characteristics were assessed during hospitalization. Smoking status was determined at 3-month follow-up.

Results— Significant predictors of smoking abstinence at follow-up included: the Fagerström Test for Nicotine Dependence score, the Barthel Index, the number of smoking household members, and the Geriatric Depression Scale score.

Conclusions— Our results suggest that smoking cessation after ischemic stroke can be determined by the interplay of psychobiological and environmental factors.