Methods— Adult Wistar rats weighing 200 to 250 g received occlusion of the right middle cerebral artery for 90 minutes. At 1 hour after reperfusion, electrodes were implanted to rats on the right frontal epidural space. Electric stimulation, at preset current (0 to 200 µA) and frequency (0 to 50 Hz), was performed for 1 week. Stroke animals were subjected to behavioral tests at 3 days and 1 week postmiddle cerebral artery and then immediately euthanized for protein and immunohistochemical assays. After demonstration of behavioral and histological benefits, subsequent experiments pursued the mechanistic hypothesis that electric stimulation exerted antiapoptotic effects through the phosphoinositide 3-kinase-dependent pathway; thus, cortical stimulation was performed in the presence or absence of specific inhibitors of phosphoinositide 3-kinase (LY294002) in stroke rats.

Results— Cortical stimulation abrogated the ischemia-associated increase in apoptotic cells in the injured cortex by activating antiapoptotic cascades, which was reversed by the phosphoinositide 3-kinase inhibitor LY294002 as reflected behaviorally and immunohistochemically. Furthermore, brain levels of neurotrophic factors (glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, vascular endothelial growth factor) were upregulated, which coincided with enhanced angiogenesis and suppressed proliferation of inflammatory cells in the ischemic cortex.

Conclusions— These results suggest that electric stimulation prevents apoptosis through the phosphoinositide 3-kinase pathway. Consequently, the ischemic brain might have been rendered as a nurturing microenvironment characterized by robust angiogenesis and diminished microglial/astrocytic proliferation, resulting in the reduction of infarct volumes and behavioral recovery. Electric stimulation is a novel and potent therapeutic tool for cerebral ischemia.

Methods— We examined the expression of endogenous markers of mitotic activity, proliferating cell nuclear antigen, and vimentin as a marker for neuronal progenitor cells, if any, in the adult rat cortex after spreading depression stimulation. Immunohistochemical analysis was also performed using antibodies for proliferating cell nuclear antigen, for vimentin, and for nestin. Nestin is a marker for activity dividing neural precursors.

Results— At the end of spreading depression (Day 0), glial fibrillary acidic protein-positive cells in the subpial zone and cortical Layer I demonstrated increased mitotic activity, expressing vimentin and nestin. On Day 1, nestin⁺ cells were found spreading in deeper cortical layers. On Day 3, vimentin^–/nestin⁺, neural precursor-like cells appeared in cortical Layers V to VI. On Day 6, new immature neurons appeared in cortical Layers V to VI. Induced spreading depression evokes cell division of astrocytes residing in the subpial zone, generating neural precursor-like cells.

Conclusions— Although neural precursor-like cells found in cortical Layers V to VI might have been transferred from the germinative zone rather than the cortical subpial zone, astrocytic cells in the subpial zone may be potent neural progenitors that can help to reconstruct impaired central nervous system tissue. Special caution is required when observing or treating spreading depression waves accompanying pathological conditions in the brain.

Methods— A comprehensive literature search was performed as per the Cochrane group guidelines. Only randomized controlled trials that compared overground physical therapy gait training to a placebo intervention or no treatment for chronic stroke patients with mobility deficits were included.

Results— Nine studies involving 499 participants matched the inclusion criteria and had moderate methodological quality. Results were mixed with no significant effect on the primary variable, gait function. Small effects for several performance variables were found: gait speed increased by 0.07 meters per second (95% confidence interval [CI]=0.05 to 0.10) based on 7 studies with 396 participants, timed up-and-go (TUG) test improved by 1.81 seconds (95% CI=–2.29 to –1.33) based on 3 studies and 118 participants, and 6-minute-walk test (6MWT) increased by 26.06 meters (95% CI=7.14 to 44.97) based on 4 studies with 181 participants. No significant differences in adverse events were found.

Conclusions— There is insufficient evidence to determine whether overground gait training directly benefits broad measures of gait function. Results from recent studies, however, suggest that specific training protocols may provide limited benefits for more uni-dimensional performance variables like gait speed, TUG test, and 6MWT.

Methods— Using the population of 2.3 million children (<20 years old) enrolled in a Northern Californian managed care plan (1993 to 2003), we performed electronic searches of (1) inpatient and outpatient diagnoses for International Classification of Diseases, 9th Revision codes suggestive of stroke and cerebral palsy; and (2) radiology reports for key words suggestive of infarction. Cases were confirmed through chart review. We calculated sensitivities and positive predictive values for the 2 search strategies.

Results— We identified 1307 potential cases from the International Classification of Diseases, 9th Revision code search and 510 from the radiology search. A total of 205 ischemic stroke cases were confirmed, yielding an ischemic stroke incidence of 2.4 per 100 000 person-years. The radiology search had a higher sensitivity (83%) than the International Classification of Diseases, 9th Revision code search (39%), although both had low positive predictive values. For perinatal stroke, the sensitivity of the stroke International Classification of Diseases, 9th Revision codes alone was 12% versus 57% for stroke and cerebral palsy codes combined; the radiology search was again the most sensitive (87%).

Conclusions— Our incidence estimate doubles that of prior US reports, a difference at least partially explained by our use of radiology searches for case identification. Studies relying purely on International Classification of Diseases, 9th Revision code searches may underestimate childhood ischemic stroke rates, particularly for neonates.

Methods— Serum bilirubin concentrations were measured in 78 724 health examinees (41 054 men, aged 30–89 years) from 1994 to 2001. The subjects with potential hepatobiliary diseases or Gilbert syndrome were excluded from analysis. Stroke incidence outcome was collected from hospital records of admission attributable to stroke from 1994 to 2007.

Results— Serum bilirubin measurements were divided into 4 levels: 0 to 10.2, 10.3 to 15.3, 15.4 to 22.1, and 22.2 to 34.2 µmol/L. The number of stroke cases was 1137 in men and 827 in women. In Cox proportional hazard models, participants with a higher level of bilirubin showed lower hazard ratios in men with ischemic stroke after adjustment for multiple confounding factors compared to the lowest level of bilirubin (hazard ratio [HR], 0.72; 95% CI, 0.58–0.90 in level 3; HR, 0.66; 95% CI, 0.49–0.89 in level 4; P for trend=0.016). The risk of all stroke types also decreased as bilirubin levels increased (HR, 0.81; 95% CI, 0.68–0.97 in level 3; HR, 0.74; 95% CI, 0.58–0.94 in level 4; P for trend=0.0071). However, these associations were not seen in hemorrhagic stroke or in women.

Conclusions— These findings suggest that serum bilirubin might have some protective function against stroke risk in men.

Methods— The data were derived from a cohort study of 3321 with 17.8 years of follow-up (1985 to 2002). Hazard ratios (HRs) and 95% CIs for strokes as related to body mass index were estimated by Cox proportional hazard models adjusted for age, hypertension, smoking, drinking, occupation, education, self-reported health, and age at menopause. A stratified analysis was conducted by age at menopause and smoking status.

Results— The obese group (body mass index ≥27.5 kg/m²) had higher risks of total stroke mortality (HR, 1.59; 95% CI, 1.05 to 2.42) and hemorrhagic stroke mortality (HR, 2.91; 95% CI, 1.37 to 6.19) than the normal weight group (18.5≤ body mass index <23.0). Among ever smokers, the obese group showed significantly increased risks of total stroke mortality (HR, 2.33; 95% CI, 1.00 to 5.43) and ischemic stroke mortality (HR, 7.21; 95% CI, 1.18 to 44.3). Obesity had more effect on stroke mortality among women who experienced menopause at age <50 than women with age ≥50. For the obese group of the former, the HR of total stroke was 2.04 (95% CI, 1.25 to 3.34) and that of hemorrhagic stroke 6.46 (95% CI, 2.42 to 17.25).

Conclusions— In this prospective study, obesity raised the risks of total stroke mortality and hemorrhagic stroke mortality among Korean menopausal women. It was more evident with women who experienced menopause at age <50. The obese group of ever smokers was at an increased risk of ischemic stroke mortality.

Methods— Two independent studies were performed. In the first, 342 SNPs from 52 candidate genes were genotyped in 307 IS cases and 324 control subjects. The SNPs significantly associated with IS were tested for replication in another cohort of 583 IS cases and 270 control subjects. In the second study, 212 SNPs from 62 candidate genes were analyzed in 710 IS cases with subtyping available and 3751 control subjects.

Results— None of the candidate genes (SNPs) were significantly associated with IS risk independent of known stroke risk factors after correction for multiple hypotheses testing.

Conclusion— These results are consistent with previous meta-analyses that demonstrate an absence of genetic association of variants in plausible candidate genes with IS risk. Our study suggests that the effect of the investigated SNPs may be weak or restricted to specific populations or IS subtypes.

Method— A total of 7760 patients who had received treatment for herpes zoster between 1997 and 2001 were included and matched with 23 280 randomly selected subjects. A 1-year stroke-free survival rate was then estimated using the Kaplan-Meier method. After adjusting for potential confounders, Cox proportional hazard regressions were carried out to compute the adjusted 1-year survival rate.

Results— Of the sampled patients, 439 patients (1.41%) developed strokes within the 1-year follow-up period, that is, 133 individuals (1.71% of the patients with herpes zoster) from the study cohort and 306 individuals (1.31% of patients in the comparison cohort) from the comparison cohort. The log rank test indicated that patients with herpes zoster had significantly lower 1-year stroke-free survival rates than the control (P<0.001). The adjusted hazard ratios of stroke after herpes zoster and herpes zoster ophthalmicus during the 1-year follow-up period were 1.31 and 4.28, respectively.

Conclusion— The risk for stroke increased after a zoster attack. Although varicella zoster virus vasculopathy is a well-documented complication that may induce a stroke postherpes zoster attack, it does not fully account for the unexpectedly high risk of stroke in these patients.

Methods— Consecutive patients with TIA were identified within a prospective population-based cohort study of stroke and TIA. The cohort was expanded by inclusion of patients with MIS and noncerebrovascular events referred to a daily TIA clinic serving the population. Diagnosis was assigned by a trained stroke physician independent of ABCD² score.

Results— Five hundred ninety-four patients were included (292 [49.2%] TIA, 45 [7.6%] MIS, and 257 [43.3%] noncerebrovascular). The mean ABCD² score showed a graded increase across diagnostic groups (MIS mean 4.8 [SD 1.4] versus TIA mean 3.9 [SD 1.5] versus noncerebrovascular mean 2.9 [SD 1.5]; P<0.00001). The ABCD² score discriminated well between noncerebrovascular and cerebrovascular events—TIA (c-statistic 0.68; 95% CI, 0.64 to 0.72), any vascular event (TIA+MIS; c-statistic 0.7; 95% CI, 0.66 to 0.74), and MIS (c-statistic 0.81; 95% CI, 0.75 to 0.87)—from noncerebrovascular events. Of ABCD² items, unilateral weakness (OR, 4.5; 95% CI, 3.1 to 6.6) and speech disturbance (OR, 2.5; 95% CI, 1.6, 4.1) were most likely overrepresented in TIA compared with noncerebrovascular groups.

Conclusion— The ABCD² score had significant diagnostic usefulness for discrimination of true TIA and MIS from noncerebrovascular events, which may contribute to its predictive usefulness.

Methods— Patients with Alzheimer disease with multiple (≥8) MBs on T2*-weighted MRI were matched for age, sex, and field strength with patients with Alzheimer disease without MBs on a 1:2 basis. We included 21 patients with multiple MBs (73±7 years, 33% female) and 42 patients without MBs (72±7 years, 38% female). Mini-Mental State Examination was used to assess dementia severity. Cognitive functions were assessed using neuropsychological tests. Medial temporal lobe atrophy (0 to 4), global cortical atrophy (0 to 3), and white matter hyperintensities (0 to 30) were assessed using visual rating scales. In a subset, apolipoprotein E genotype and cerebrospinal fluid amyloid β 1-42, total and phosphorylated at threonine 181 were determined.

Results— Patients with multiple MBs performed worse on Mini-Mental State Examination (multiple MB: 17±7; no MB: 22±4, P<0.05) despite similar disease duration. Atrophy was not related to presence of MBs, but patients with multiple MBs had more white matter hyperintensities (multiple MB: 8.8±4.8; no MB: 3.2±3.6, P<0.05). Adjusted for age, sex, white matter hyperintensities, and medial temporal lobe atrophy, the multiple MB group additionally performed worse on Visual Association Test object naming and animal fluency. Patients with multiple MBs had lower cerebrospinal fluid amyloid β 1-42 levels (307±61) than patients without MBs (505±201, P<0.05). Adjusted for the same covariates, total , and phosphorylated at threonine 181 were higher in the multiple MB group.

Conclusion— Microbleeds are associated with the clinical manifestation and biochemical hallmarks of Alzheimer disease, suggesting possible involvement of MBs in the pathogenesis of Alzheimer disease.

Methods— A case-control imaging study in a referral institutional tertiary care center was conducted. Systematic brain MRIs, including T2*-weighted sequences, were performed in 60 patients with IE within 7 days of hospital admission and in 120 age- and gender-matched control subjects without IE. Two neuroradiologists, who were blinded to patient characteristics, independently assessed the presence, location, and size of CMBs using a standardized form.

Results— The interobserver agreement level on the presence of CMBs was high with a coefficient range (95% CI) of 0.70 (0.42 to 0.98) for subcortical regions to 0.91 (0.82 to 0.99) for cortical areas. CMBs were more prevalent in patients with IE (57% [n=34]) than in control subjects (15% [n=18]; matched OR, 10.06; 95% CI, 3.88 to 26.07). Moreover, the OR of IE increased gradually with CMBs number with an OR of 6.12 (95% CI, 2.09 to 17.94) for one to 3 CMBs and of 20.12 (95% CI, 5.20 to 77.80) for >3 CMBs.

Conclusion— CMBs are highly frequent in patients with IE. The strong association found between IE and CMBs supports the need for further evaluation of CMBs as additional diagnostic criteria of IE.

Methods— The Northern Manhattan Study includes a stroke-free community-based sample of Hispanic, black, and white participants with quantitative measurement of WMH volume (WMHV) and inflammatory biomarkers. We measured the association between Lp-PLA2, MPO, and hsCRP levels, and log-transformed WMHV after adjusting for sociodemographic and vascular risk factors.

Results— The hsCRP (median, 2.42 mg/L; IQR, 1.04, 5.19), Lp-PLA2 (median, 220.97 ng/mL; IQR, 185.77, 268.05), and MPO (median, 15.14 ng/mL; IQR, 12.32, 19.69) levels were available in 527 The Northern Manhattan Study participants with WMHV data but no subclinical infarcts. Those with hsCRP in the upper quartile (Q4 >4.92 mg/L or >3 mg/L), Lp-PLA2 in Q4 (≥264.9 ng/mL), or MPO levels in Q3 (15.04–19.39 ng/mL) or Q4 (>19.39 ng/mL) each had greater WMHV, adjusting for sociodemographic and vascular risk factors. Adjusting for all biomarkers simultaneously, WMHV was 1.3-fold greater for Lp-PLA2 levels in Q4 compared to Q1 (β=0.28; P=0.008) and 1.25-fold greater for MPO levels above the median compared to below (β=0.22; P=0.02), but hsCRP was not associated with WMHV.

Conclusions— Relative elevations of the inflammatory markers Lp-PLA2 and MPO were associated with a greater burden of WMH independent of hsCRP.

Methods— In this prospective longitudinal hospital-based cohort study, asymptomatic PAD was detected by ankle brachial index measurement in consecutive patients with stroke and patients with TIA. They were assessed for stroke risk factors, ankle brachial index measurement, and laboratory parameters known to be associated with stroke risk. These patients were followed for composite vascular events, including stroke, TIA, myocardial infarction, and vascular death.

Results— In a 1-year period, 102 patients were evaluated, of whom 26% had asymptomatic PAD. All patients were followed for a median period of 2.1 years from the index stroke/TIA (range, 1.0 to 2.7 years) for vascular events. Kaplan–Meier curve showed fewer patients with asymptomatic PAD remained free of composite vascular events (48% compared with 84% in the no-PAD group; log rank, P=0.0001). Asymptomatic PAD was significantly associated with composite vascular events before (hazard ratio, 4.2; 95% CI, 1.9 to 9.3; P=0.0003) and after adjustment for confounders (hazard ratio, from Model 1, 2.8; 95% CI, 1.1 to 7.2; P=0.03 and Model 2, 3.4; 95% CI, 1.4 to 8.2, P=0.006). Asymptomatic PAD was also significantly associated with stroke before (hazard ratio, 6.5; 95% CI, 2.1 to 19.9; P=0.001) and after adjustment for confounders (hazard ratio from Model 1, 4.8; 95% CI, 1.5 to 15.3; P=0.009 and Model 2, 5.2; 95% CI, 1.5 to 17.6; P=0.008).

Conclusions— In patients with stroke or TIA, asymptomatic PAD is independently associated with recurrent vascular events and stroke.

Methods— Prospective longitudinal study was conducted of patients with aSAH with Fisher grade ≥2 and/or Hunt/Hess grade ≥3. Serum cTnI was collected on Days 1 to 5; cohort dichotomized into peak cTnI ≥0.3 ng/mL (elevated) or cTnI <0.3 ng/mL. Relationships among cTnI and aSAH severity, 12-lead electrocardiography early (≤4 days) and late (≥7 days), Holter monitoring on Days 1 to 5, and transthoracic echocardiogram (left ventricular ejection fraction and regional wall motion abnormalities) early (Days 0 to 5) and late (Days 5 to 12) were evaluated.

Results— Of 204 subjects, 31% had cTnI ≥0.3 ng/mL. cTnI ≥0.3 ng/mL was incrementally related to aSAH severity by admission symptoms (Hunt/Hess P=0.001) and blood load (Fisher P=0.028). More patients with cTnI ≥0.3 ng/mL had prolonged QTc on early (63% versus 30%, P<0.0001) and late electrocardiography (24% versus 7%, P=0.024). On Holter monitoring, more patients with cTnI ≥0.3 ng/mL had ventricular tachycardia/fibrillation (22% versus 9%, P=0.018) but not atrial fibrillation/flutter (P=0.241). Cardiac troponin I ≥0.3 ng/mL was associated with both early ejection fraction <50% (44% versus 5%, P<0.0001) and regional wall motion abnormalities (44% versus 4%, P<0.0001). Regional wall motion abnormalities predominated in basal and midventricular segments and persisted to some degree in 73% of patients affected, whereas ejection fraction <50% persisted in 59% of patients affected.

Conclusions— Cardiac injury is incrementally worse with increasing aSAH severity and associated with persistent QTc prolongation and ventricular arrhythmias. Regional wall motion abnormalities and depressed ejection fraction persist to some degree in the majority of those affected.

Methods— Patients with CT-confirmed stroke were randomized to 3 g/day encapsulated fish oil containing approximately 1.2 g total omega-3 (0.7 g docosahexaenoic acid; 0.3 g eicosapentaenoic acid) or placebo oil (combination palm and soy) taken daily over 12 weeks. Serum triglycerides, total cholesterol and associated lipoproteins, selected inflammatory and hemostatic markers, mood, and health-related quality of life were assessed at baseline and follow-up. The primary outcome was change in triglycerides. Compliance was assessed by capsule count and serum phospholipid omega-3 levels (Australian Clinical Trials Registration: ACTRN12605000207617).

Results— One hundred two patients were randomized to fish oil or placebo. Intention-to-treat and per-protocol (>85% compliance) analyses showed no significant effect of fish oil treatment on any lipid, inflammatory, hemostatic, or composite mood parameters measured. Adherence to treatment based on pill count was good (89%) reflected by increased serum docosahexanoic acid (P<0.001) and eicosapentaenoic acid (P=0.0006) in the fish oil group. Analysis of oil composition, however, showed some degradation and potentially adverse oxidation products at the end of the study.

Conclusions— There was no effect of 12 weeks of treatment with moderate-dose fish oil supplements on cardiovascular biomarkers or mood in patients with ischemic stroke. It is possible that insufficient dose, short duration of treatment, and/or oxidation of the fish oils may have influenced these outcomes.

Methods— We prospectively enrolled 42 patients with subarachnoid hemorrhage with clinical deterioration suspect for DCI (new focal deficit or Glasgow Coma Scale decrease ≥2 points) within 21 days after hemorrhage. All patients underwent NCT, CTP, and CTA scans on admission and directly after clinical deterioration. The gold standard was the clinical diagnosis DCI made retrospectively by 2 neurologists who interpreted all clinical data, except CTP and CTA, to rule out other causes for the deterioration. Radiologists interpreted NCT and CTP images for signs of ischemia (NCT) or hypoperfusion (CTP) not localized in the neurosurgical trajectory or around intracerebral hematomas, and CTA images for presence of vasospasm. Diagnostic values for DCI of NCT, CTP, and CTA were assessed by calculating sensitivities, specificities, positive predictive values, and negative predictive values with 95% CIs.

Results— In 3 patients with clinical deterioration, imaging failed due to motion artifacts. Of the remaining 39 patients, 25 had DCI and 14 did not. NCT had a sensitivity of 0.56 (95% CI, 0.37 to 0.73), specificity=0.71 (0.57 to 0.77), positive predictive value=0.78 (0.55 to 0.91), negative predictive value=0.48 (0.28 to 0.68); CTP: sensitivity=0.84 (0.65 to 0.94), specificity=0.79 (0.52 to 0.92), positive predictive value=0.88 (0.69 to 0.96), negative predictive value=0.73 (0.48 to 0.89); CTA: sensitivity=0.64 (0.45 to 0.80), specificity=0.50 (0.27 to 0.73), positive predictive value=0.70 (0.49 to 0.84), negative predictive value=0.44 (0.23 to 0.67).

Conclusion— As a diagnostic tool for DCI, qualitative assessment of CTP is overall superior to NCT and CTA and could be useful for fast decision-making and guiding treatment.

Methods— Forty-six patients were prospectively recruited in whom intra-arterial angiography was being performed. Contrast-enhanced MR angiography, CT angiography, and duplex ultrasound were also performed. Angiographic images were analyzed blinded to patient identity by 2 experienced neuroradiologists.

Results— Contrast-enhanced MR angiography had the highest sensitivity and specificity (Radiologist 1, 0.83 and 0.91, respectively; Radiologist 2, 0.89 and 0.87) for detecting ≥50% stenosis. CT angiography had good sensitivity (Radiologist 1, 0.68; Radiologist 2, 0.58) and excellent specificity (Radiologist 1, 0.92; Radiologist 2, 0.93), whereas duplex had low sensitivity (0.44) but excellent specificity (0.95). For vertebral origin stenosis ≥50%, sensitivities were similar for contrast-enhanced MR angiography (Radiologist 1, 0.91; Radiologist 2, 0.82) but relatively higher for CT angiography (Radiologist 1, 0.82; Radiologist 2, 0.82) and duplex (0.67).

Conclusions— Contrast-enhanced MR angiography is the most sensitive noninvasive technique to detect vertebral artery stenosis and also has high specificity. CT angiography has good sensitivity and high specificity. In contrast, ultrasound has low sensitivity and will miss many vertebral stenoses.

Methods— The authors conducted a prospective, cross-sectional study at an academic hospital. Consecutive patients with AVS (vertigo, nystagmus, nausea/vomiting, head-motion intolerance, unsteady gait) with ≥1 stroke risk factor underwent structured examination, including horizontal head impulse test of vestibulo-ocular reflex function, observation of nystagmus in different gaze positions, and prism cross-cover test of ocular alignment. All underwent neuroimaging and admission (generally <72 hours after symptom onset). Strokes were diagnosed by MRI or CT. Peripheral lesions were diagnosed by normal MRI and clinical follow-up.

Results— One hundred one high-risk patients with AVS included 25 peripheral and 76 central lesions (69 ischemic strokes, 4 hemorrhages, 3 other). The presence of normal horizontal head impulse test, direction-changing nystagmus in eccentric gaze, or skew deviation (vertical ocular misalignment) was 100% sensitive and 96% specific for stroke. Skew was present in 17% and associated with brainstem lesions (4% peripheral, 4% pure cerebellar, 30% brainstem involvement; ², P=0.003). Skew correctly predicted lateral pontine stroke in 2 of 3 cases in which an abnormal horizontal head impulse test erroneously suggested peripheral localization. Initial MRI diffusion-weighted imaging was falsely negative in 12% (all <48 hours after symptom onset).

Conclusions— Skew predicts brainstem involvement in AVS and can identify stroke when an abnormal horizontal head impulse test falsely suggests a peripheral lesion. A 3-step bedside oculomotor examination (HINTS: Head-Impulse—Nystagmus—Test-of-Skew) appears more sensitive for stroke than early MRI in AVS.

Methods— We modeled the effect of different carotid imaging strategies and timing on endarterectomy workload, stroke, and death at 1 and 5 years. We used all available data on stroke prevention after transient ischemic attack from systematic reviews (carotid imaging, medical and surgical interventions), population-based transient ischemic attack/stroke studies, government statistics, and stroke prevention clinics.

Results— Choice of imaging strategy affected speed of assessment, strokes prevented, and endarterectomy workload. The number of strokes prevented at 5 years varied by up to 22 per 1000 patients between imaging strategies for a given time to assessment. Delaying endarterectomy from 14 to approximately 30 days would fail to prevent up to 11 strokes per 1000 patients depending on the imaging strategy. Sensitive fast imaging (eg, ultrasound) was best for patients seen early; specific imaging (eg, CT angiography or contrast-enhanced MR angiography) was best for patients seen late after transient ischemic attack. Intra-arterial angiography conferred no advantage over noninvasive imaging.

Conclusions— Rapid access to sensitive noninvasive carotid imaging prevents most strokes. However, imaging strategies differ in their effect on stroke prevention by as much as 22 per 1000 patients and optimal imaging varies with time after transient ischemic attack TIA. Routine intra-arterial angiography should be avoided.

Methods— This was a double-blind, placebo-controlled, parallel-group, multicenter study of 681 patients stratified according to whether or not tissue plasminogen activator was administered and then randomly assigned to treatment with repinotan or placebo. A continuous 72-hour intravenous infusion of repinotan or placebo was to be started within 4.5 hours from the onset of ischemic symptoms. A Point-of-Care test was used to adjust the infusion rate if appropriate. The goal of Modified Randomized Exposure Controlled Trial (mRECT) was to show whether repinotan is statistically superior to placebo (≤0.10) as measured by the response rate on the primary efficacy variable, Barthel Index (≥85) at 3 months, using a Cochran-Mantel-Haenszel test.

Results— For the intention-to-treat population at 3 months, the response rate on the Barthel Index was 37.1% (127 of 342) for patients on repinotan and 42.4% (143 of 337) for patients taking the placebo (Cochran-Mantel-Haenszel probability value=0.149). No apparent safety concerns were identified.

Conclusions— mRECT demonstrated the feasibility of conducting a rigorous trial using a short therapeutic window demanding clinical and radiographic criteria to optimize patient selection and a Point-of-Care test to achieve a targeted exposure to repinotan. The study failed to demonstrate a clinical benefit of repinotan. The development of repinotan in acute ischemic stroke was discontinued.

Methods— Severity was assessed with the National Institutes of Health Stroke Scale, Barthel Index, and modified Rankin Scale score at enrollment (1 to 6 months after the index event) and 90 days poststroke in subjects having a stroke during the trial.

Results— Over 4.9 years, strokes occurred in 576 subjects. There were reductions in fatal, severe (modified Rankin Scale score 5 or 4), moderate (modified Rankin Scale score 3 or 2), and mild (modified Rankin Scale score 1 or 0) outcome ischemic strokes and transient ischemic attacks and an increase in the proportion of event-free subjects randomized to atorvastatin (P<0.001 unadjusted and adjusted). Results were similar for all outcome events (ischemic and hemorrhagic, P<0.001 unadjusted and adjusted) with no effect on outcome hemorrhagic stroke severity (P=0.174 unadjusted, P=0.218 adjusted). If the analysis is restricted to those having an outcome ischemic stroke (ie, excluding those having a transient ischemic attack or no event), there was only a trend toward lesser severity with treatment based on the modified Rankin Scale score (P=0.0647) with no difference based on the National Institutes of Health Stroke Scale or Barthel Index.

Conclusion— The present exploratory analysis suggests that the outcome of recurrent ischemic cerebrovascular events might be improved among statin users as compared with nonusers.

Methods— Acute ischemic stroke patients aged ≥18 years, who could not walk unassisted, were randomized to receive enoxaparin (40 mg once daily) or UFH (5000 U every 12 hours) for 10 days. Patients were stratified according to baseline stroke severity using the National Institutes of Health Stroke Scale score. End points for this analysis included stroke progression (≥4-point increase in National Institutes of Health Stroke Scale score), neurological outcomes up to 3 months postrandomization (assessed using National Institutes of Health Stroke Scale score and modified Rankin Scale score), and incidence of intracranial hemorrhage.

Results— Stroke progression occurred in 45 of 877 (5.1%) patients in the enoxaparin group and 42 of 872 (4.8%) of those receiving UFH. Similar improvements in National Institutes of Health Stroke Scale and modified Rankin Scale scores were observed in both groups over the 90-day follow-up period. Incidence of intracranial hemorrhage was comparable between groups (20 of 877 [2.3%] and 22 of 872 [2.5%] in enoxaparin and UFH groups, respectively). Baseline National Institutes of Health Stroke Scale score, hyperlipidemia, and Hispanic ethnicity were independent predictors of stroke progression.

Conclusions— The clinical benefits associated with use of enoxaparin for venous thromboembolism prophylaxis in patients with acute ischemic stroke are not associated with poorer long-term neurological outcomes or increased rates of symptomatic intracranial hemorrhage compared with UFH.

Methods— The factorial PRoFESS secondary stroke prevention trial assessed BP-lowering and antiplatelet strategies in 20 332 patients; 1360 were enrolled within 72 hours of ischemic stroke, with telmisartan (angiotensin receptor antagonist, 80 mg/d, n=647) vs placebo (n=713). For this nonprespecified subgroup analysis, the primary outcome was functional outcome at 30 days; secondary outcomes included death, recurrence, and hemodynamic measures at up to 90 days. Analyses were adjusted for baseline prognostic variables and antiplatelet assignment.

Results— Patients were representative of the whole trial (age 67 years, male 65%, baseline BP 147/84 mm Hg, small artery disease 60%, NIHSS 3) and baseline variables were similar between treatment groups. The mean time from stroke to recruitment was 58 hours. Combined death or dependency (modified Rankin scale: OR, 1.03; 95% CI, 0.84–1.26; P=0.81; death: OR, 1.05; 95% CI, 0.27–4.04; and stroke recurrence: OR, 1.40; 95% CI, 0.68–2.89; P=0.36) did not differ between the treatment groups. In comparison with placebo, telmisartan lowered BP (141/82 vs 135/78 mm Hg, difference 6 to 7 mm Hg and 2 to 4 mm Hg; P<0.001), pulse pressure (3 to 4 mm Hg; P<0.002), and rate-pressure product (466 mm Hg.bpm; P=0.0004).

Conclusion— Treatment with telmisartan in 1360 patients with acute mild ischemic stroke and mildly elevated BP appeared to be safe with no excess in adverse events, was not associated with a significant effect on functional dependency, death, or recurrence, and modestly lowered BP.

Methods— In phase 1, the reliability of emergency INR POC measurements in comparison to CL was determined. In phase 2, patients with ischemic stroke admitted within the time frame for systemic thrombolysis and who were either using OAC or for whom information on OAC status was not available were enrolled. Patients received thrombolysis if POC INR was ≤1.5. Precision and time gain was recorded for INR as measured by POC vs CL.

Results— In phase 1 (n=113), Bland-Altman analysis showed close agreement between POC and CL, and Pearson correlation was highly significant (r=0.98; P<0.01). In phase 2, 48 patients were included, of whom 70.8% were using OAC; 23 patients received thrombolysis. After subtracting the time needed for the diagnostic work-up, the net time gain was 28±12 minutes (mean±SD).

Conclusions— Measuring INR by POC in an emergency setting is sufficiently precise in OAC acute stroke patients and substantially reduces the time interval until INR values are available and therefore may hasten the initiation of thrombolysis.

Methods— Eligibility criteria included presentation ≤8 hours after stroke onset, age 18 years or older, National Institutes of Health Stroke Scale score ≥8, angiographic demonstration of focal intracerebral artery occlusion ≤14 mm, and either contraindication to intravenous tissue plasminogen activator or failure to improve 1 hour after intravenous tissue plasminogen activator administration. Exclusion criteria included known hemorrhagic diathesis or coagulopathy, platelet count <100 000, intracranial hemorrhage, blood glucose level of <51 mg/100 mL, or CT perfusion imaging demonstrating more than one-third at-risk territory with nonsalvageable brain (low cerebral blood volume). Data are presented as mean±SD.

Results— Twenty patients were enrolled (mean age, 63±18 years;14 women). Mean presenting National Institutes of Health Stroke Scale was 14±3.8 (median 13). Presenting thrombolysis in myocardial infarction score was 0 (85% of patients) or 1 (15%). Recanalization to thrombolysis in myocardial infarction score of 3 (60% of patients) or 2 (40% of patients; P<0.0001) was achieved. One (5%) symptomatic and 2 (10%) asymptomatic intracranial hemorrhages occurred. At 1-month follow-up, a modified Rankin scale score of ≤3 was achieved in 12 of 20(60%) patients and a modified Rankin scale score of ≤1 was achieved in 9 of 20 (45%) patients.

Conclusion— This Food and Drug Administration-approved prospective study suggests primary intracranial stenting for acute stroke may be a valuable addition to the stroke treatment armamentarium.

Methods— Only cases with first-onset depression <2 years after stroke were considered as PSD in the present series. Diagnosis of depression was established prospectively using DSM-IV criteria for major depression. Neuropathological evaluation included bilateral semiquantitative assessment of microvascular ischemic pathology and lacunes; statistical analysis included Fisher exact test, Mann-Whitney U test, and regression models.

Results— Macroinfarct site was not related to the occurrence of PSD for any of the locations studied. Thalamic and basal ganglia lacunes occurred significantly more often in PSD cases. Higher lacune scores in basal ganglia, thalamus, and deep white matter were associated with an increased PSD risk. In contrast, microinfarct and diffuse or periventricular demyelination scores were not increased in PSD. The combined lacune score (thalamic plus basal ganglia plus deep white matter) explained 25% of the variability of PSD occurrence.

Conclusions— The cumulative vascular burden resulting from chronic accumulation of lacunar infarcts within the thalamus, basal ganglia, and deep white matter may be more important than single infarcts in the prediction of PSD.

Methods— We studied 137 patients within 24 hours of stroke onset with MR diffusion- and perfusion-weighted imaging and a test of hemispatial neglect that distinguishes between viewer-centered and stimulus-centered neglect. Using multivariable linear regression, we identified the independent contributions of severity of ischemia in specific locations, volume of ischemia, and age in accounting for severity of each neglect type.

Results— Severity of hypoperfusion in angular gyrus was the only variable that significantly and independently contributed to severity of viewer-centered neglect. Volume of dysfunctional tissue and hypoperfusion in posterior frontal cortex also accounted for some variability in severity of viewer-centered neglect. Severity of hypoperfusion of superior temporal cortex was the only variable that independently and significantly contributed to severity of stimulus-centered neglect.

Conclusions— Location, severity, and volume of ischemia together determine the type and severity of neglect after right hemisphere stroke. Results also show that perfusion-weighted MRI can be used as a semiquantitative measure of tissue dysfunction in acute stroke and can account for a substantial proportion of the variability in functional deficits in the acute stage.

Methods— We analyzed consecutive cases of first-ever primary intracerebral hemorrhages from 1993 to 2000 in a prospective stroke register covering the Malmö region, Sweden (population approximately 250 000). Mortality rates during 28 days and 3 years of follow-up and recurrence rates were analyzed.

Results— A total of 474 cases were identified (46% women). In patients <75 years of age, 20% of the women and 23% of the men died within 28 days (P=0.38). The corresponding figures in patients ≥75 years were 26% and 41%, respectively (P=0.02). Male sex was an independent risk factor both for 28-day (OR, 1.5; 95% CI, 1.008 to 2.2) and 3-year mortality (OR, 1.7; 95% CI, 1.3 to 2.3). Other independent predictors of death were high age, central and brain stem hemorrhage location, intraventricular hemorrhage, increased volume, and decreased consciousness level. The recurrence rate was 5.1 per 100 person-years, 2.3 per 100 person-years for intracerebral hemorrhage and 2.8 per 100 person-years for cerebral infarction. Only age >65 years was significantly related to recurrent stroke.

Conclusion— Women had better survival than men after primary intracerebral hemorrhages. The difference is largely explained by a higher 28-day mortality in male patients >75 years. However, the underlying reasons are yet to be explored.

Methods— The study sample included Medicare fee-for-service beneficiaries ≥65 years of age discharged with ischemic stroke in 2002 from 5070 hospitals, 317 of which were JC-certified by June 2007. Hierarchical logistic regression and Cox proportional hazards models were used to compare in-hospital mortality, 30-day mortality, and 30-day readmission for patients treated at future JC-certified versus noncertified hospitals.

Results— Among 366 551 patients, 18% (66 300) were treated at hospitals with centers that were JC-certified within the first few years of the program. These patients were younger, more likely to be white and male, and had fewer comorbidities and hospitalizations within the prior year. Unadjusted in-hospital mortality (4.7% versus 5.5%), 30-day mortality (9.8% versus 11.3%), and readmissions (13.8% versus 14.6%) were lower in the future JC-certified hospitals (all P<0.001). These differences remained after risk adjustment (in-hospital mortality: OR, 0.93; 95% CI, 0.90 to 0.96; 30-day mortality: OR, 0.92; 95% CI, 0.87 to 0.96; 30-day readmission: hazard ratio, 0.97; 95% CI, 0.95 to 0.99).

Conclusions— JC Primary Stroke Center-certified hospitals had better outcomes than noncertified hospitals even before the program began. Cross-sectional studies assessing the effects of stroke center certification need to account for these pre-existing differences.

Method— This analysis used the MEDPAR database, which is a claims-based dataset that contains every fee-for-service Medicare-eligible hospital discharge in the US. Cases potentially eligible for rt-PA treatment based on diagnosis were defined as those with a hospital DRG code of 14, 15, or 559, and that also had an ICD-9 code of 433, 434, or 436. Thrombolysis use was defined as an ICD-9 code of 99.1. Study interval was July 1, 2005 to June 30, 2007. Hospital locations were mapped using ArcView software; population densities and regions of the US are based on US Census 2000.

Results— There were 4750 hospitals in the MEDPAR database, which included 495 186 ischemic stroke admissions during the study period. Of these hospitals, 64% had no reported treatments with rt-PA for ischemic stroke, and 0.9% reported >10% treatment rates within the MEDPAR dataset. Bed size, rural or underserved designation, and population density were significantly associated with reported rt-PA treatment rates, and remained significant in the multivariable regression. Approximately 162 million US citizens reside in counties containing a hospital reporting a ≥2.4% treatment rate within the MEDPAR dataset.

Conclusion— We report the first description of US hospital rt-PA treatment rates by hospital. Unfortunately, we found that 64% of US hospitals did not report giving rt-PA at all within the MEDPAR database within a 2-year period. These tended to be hospitals that were smaller (average bed size of 95), located in less densely populated areas, or located in the South or Midwest. In addition, 40% of the US population resides in counties without a hospital that administered rt-PA to at least 2.4% of ischemic stroke patients, although distinguishing transferred patients is problematic within administrative datasets. Such national-based resource-utilization data is important for planning at the local and national level, especially for such initiatives as telemedicine, to reach underserved areas.

Methods— Three hundred ninety stroke survivors constituted the study population. Information on survival data during 5 years of follow-up, all hospital admissions since 1971, all outpatient and primary care consultations, and all municipal social service support during the year before and after the index stroke admission and patient interviews 1 week after discharge were obtained.

Results— The risk of death or a new stroke was high in the early phase after admission but then decreased rapidly during the next few months. Mortality during the first 5 years was influenced by age and functional ability, whereas the risk of stroke recurrence was influenced by number of previous strokes, hypertension diagnosis, and sex. On a day-by-day basis, 35% were dependent on municipal support before and 65% after the stroke. The corresponding proportions in outpatient care were 6% and 10%, and for hospital inpatient care 1% to 2% and 2% to 3%. Of the health care provided, nursing care dominated.

Conclusions— The risk of dying or having a new stroke event decreased sharply during the early postmorbid phase. Healthcare utilization increased after discharge but was still moderate on a day-by-day basis, except for municipal social service support, which was substantial.

Methods— Consecutive patients with stroke treated with recombinant tissue plasminogen activator in 10 Japanese stroke centers were included.

Results— A total of 600 patients (377 men, 72±12 years old) were studied. Median National Institutes of Health Stroke Scale scores decreased from 13 before recombinant tissue plasminogen activator to 8 at 24 hours later. Symptomatic intracerebral hemorrhage within 36 hours with a ≥1-point increase from the baseline National Institutes of Health Stroke Scale score developed in 23 patients (3.8%; 95% CI, 2.6% to 5.7%). At 3 months, 43 patients had died (7.2%; 5.4% to 9.5%), and 199 patients (33.2%; 29.5% to 37.0%) had a modified Rankin Scale score ≤1. Analysis of 399 patients with a premorbid modified Rankin Scale score ≤1 who met the criteria of the European license (≤80 years old, an initial National Institutes of Health Stroke Scale score ≤24, etc) showed that 40.6% (35.9% to 45.5%) had a 3-month modified Rankin Scale score ≤1. After multivariate adjustment, younger age, lower initial National Institutes of Health Stroke Scale score, absence of internal carotid artery occlusion, higher Alberta Stroke Program Early CT Score on CT, and absence of intravenous antihypertensives just before recombinant tissue plasminogen activator were independently related to a 3-month modified Rankin Scale score ≤1. Congestive heart failure and hyperglycemia were independently related to mortality.

Conclusions— Three-month outcomes of patients receiving low-dose intravenous recombinant tissue plasminogen activator therapy in the present study were similar to those from postmarketing surveys using 0.9 mg/kg alteplase.

Methods— Adeno-associated viral vector (AAV)-VEGF, an adeno-associated viral vector expressing VEGF, was injected into the brain of 3-, 12-, and 24-month-old mice. AAV-LacZ-injected mice were used as controls (n=6). Before euthanasia at 6 weeks after vector injection, the mice were intraperitoneally injected with 5-bromodeoxyuridine for 3 consecutive days. The vascular density and the number of neuroprogenitors were analyzed.

Results— Injection of AAV-VEGF increased the vascular density in the brain of 3-, 12-, and 24-month-old mice by 22%±7% (AAV-VEGF: 320±15 per 10x field versus AAV-LacZ: 263±8, P<0.05), 20%±8 (AAV-VEGF: 300±9 versus AAV-LacZ: 250±11, P<0.05), and 7%±16% (AAV-VEGF: 257±27 versus AAV-LacZ: 236±13, P=0.283), respectively. There were more VEGF receptor-positive neuroprogenitors in the subventricular zone of AAV-VEGF-injected 3- (22±2) and 12-month-old mice (21±5) than that of 24-month-old mice (7±1). More 5-bromodeoxyuridine-positive endothelial cells and neuroprogenitors were detected around the injection site and subventricular zone of 3- (13±4) and 12-month-old mice (14±5) than that of 24-month-old mice (1±1). VEGF receptor 2 was upregulated in AAV-VEGF-injected brains of 3- and 12-month-old mice, but not in 24-month-old mice.

Conclusion— The angiogenic and neurogenic response to VEGF stimulation is attenuated in the aged mouse brain, which may be due to reduced VEGF receptor activity.

Methods— In Experiment 1, mice were exposed to 3 weeks of daily restraint (3 hours) and then subjected to either 8 minutes of cardiac arrest/cardiopulmonary resuscitation (CA/CPR) or sham surgery. Anxiety-like behavior, microglial activation, and neuronal damage were assessed on postischemic Day 4. In Experiment 2, mice were infused intracerebroventricularly with minocycline (10 µg/day) to determine the effect of inhibiting post-CA/CPR microglial activation on the development of anxiety-like behavior and neuronal death.

Results— CA/CPR precipitated anxiety-like behavior and increased microglial activation and neuronal damage within the hippocampus relative to sham surgery. Prior exposure to stress exacerbated these measures among CA/CPR mice, but had no significant effect on sham-operated mice. Treatment with minocycline reduced both neuronal damage and anxiety-like behavior among CA/CPR animals. Anxiety-like behavior was significantly correlated with measures of microglial activation but not neuronal damage.

Conclusions— A history of stress exposure increases the pathophysiological response to ischemia and anxiety-like behavior, whereas inhibiting microglial activation reduces neuronal damage and mitigates the development of anxiety-like behavior after CA/CPR. Thus, modulating inflammatory signaling after cerebral ischemia may be beneficial in protecting the brain and preventing the development of affective disorders.

Methods— By means of Western blotting, patch-clamp electrophysiology, single-cell Fura-2 acetoxymethyl-ester microfluorometry, immunohistochemistry, and confocal microscopy, we investigated the regional and temporal changes of NCX1 protein in microglial cells of the peri-infarct and core regions after permanent middle cerebral artery occlusion. The exchanger expression and activity were measured in primary microglia isolated ex vivo from the core region of adult rat brains 7 days after permanent middle cerebral artery occlusion and in cultured microglia under in vitro hypoxia.

Results— One day after permanent middle cerebral artery occlusion, NCX1 protein expression was detected in some microglial cells adjacent to the soma of neurons in the infarct core. More interestingly, 3 and 7 days after permanent middle cerebral artery occlusion, NCX1 signal strongly increased in the round-shaped microglia invading the infarct core. Cultured microglial cells obtained from the core also displayed increased NCX1 expression as compared with contralateral cells and showed enhanced NCX activity in the reverse mode of operation. Similarly, NCX activity and NCX1 protein expression were significantly enhanced in BV2 microglia exposed to oxygen and glucose deprivation, whereas NCX2 and NCX3 were downregulated. Interestingly, in NCX1-silenced cells, [Ca²⁺]_i increase induced by hypoxia was completely prevented.

Conclusion– The upregulation of NCX1 expression and activity observed in microglia after permanent middle cerebral artery occlusion suggests a relevant role of NCX1 in modulating microglia functions in the postischemic brain.

Methods— Male SV129 mice were exposed to a 20-minute middle cerebral artery occlusion; hippocampi were then analyzed for Shh mRNA and protein expression by real-time polymerase chain reaction, immunoblot, and immunohistochemistry. Primary cell cultures of neurons, astrocytes, and NPCs were exposed to 16 hours of hypoxia (1% O₂) and analyzed by real-time polymerase chain reaction and immunoblot for Shh expression. Proliferation of NPCs, in vivo and in vitro, was measured by bromodeoxyuridine incorporation.

Results— Among the cell types examined in vitro, only NPC and neurons increased Shh mRNA under hypoxic conditions. Furthermore, hypoxia increased proliferation of NPCs and this proliferation was enhanced by the addition of recombinant Shh or blocked by the pathway-specific inhibitor, cyclopamine. Middle cerebral artery occlusion was associated with a transient 2-fold increase in the mRNA encoding both Shh and its transcription factor, Gli1, 0.5 days after ischemia. Within the hippocampus, Shh protein was increased approximately 3-fold 3 and 7 days after ischemia and was observed predominantly within cells in the CA3 and hilar regions. Shh was expressed only in mature neurons. In vivo, cyclopamine suppressed ischemia-induced proliferation of subgranular NPCs.

Conclusion— The Shh pathway plays a role in the proliferation of NPCs induced by ischemia/hypoxia and might participate in injury remodeling.

Methods— Clinical and radiological data from consecutive tpa-ineligible stroke patients with large anterior circulation infarcts involving either the entire internal carotid artery or the proximal middle cerebral artery territory were analyzed. Stroke subtypes were categorized according to TOAST criteria. Neurological deficits were assessed with the NIH stroke scale (NIHSS), and vessel recanalization was determined using the thrombolysis in myocardial infarction (TIMI) scale at the end of MRRT. Good outcome was defined as a modified Rankin score (mRS) ≤2.

Results— Fifty patients were included with a median age of 68. Thirteen patients died and 17 patients achieved an mRS ≤2 at 90 days. Variables associated with survival on multivariate analysis were admission NIHSS <20 (OR 15 95% CI 1 to 230) and postprocedure TIMI score 2 to 3 (OR 35.5 95% CI 2.3 to 603.9). Variables associated with good outcome included admission NIHSS <20 (OR 9.4 95% CI 1.3 to 71.3), day 1 NIHSS <15 (OR 6.4 95% CI 1.1 to 38.4), and postprocedure TIMI 3 (OR 7.4 95% CI 1.1 to 50.3).

Conclusions— MMRT resulted in high survival and good outcome rates in these critically ill patients. Lower baseline impairment and vessel recanalization increase the chances for good outcome. Our results suggest that the benefits of MMRT may merit further study and could be generalized to centers outside the United States and Europe.

Methods— We reviewed medical records of consecutive ischemic stroke admissions treated with intravenous thrombolysis over a 10-year period at our tertiary care hospital. The National Institutes of Health Stroke Scale score on admission was used to determine baseline stroke severity. The closest documented blood pressure values to the time of tissue plasminogen activator bolus (range, 0 to 10 minutes) were considered as pretreatment blood pressure. Pretreatment blood pressure protocol violations were identified as systolic blood pressure >185 or diastolic blood pressure >110 mm Hg prebolus. sICH was defined as brain imaging evidence of intracranial hemorrhage with clinical worsening by the National Institutes of Health Stroke Scale score increase of ≥4 points.

Results— Among 510 patients with ischemic stroke treated with intravenous tissue plasminogen activator (282 men; mean age, 65±15 years), sICH occurred in 31 patients (6.1%). Blood pressure protocol violations were present in 63 patients (12.4%) and they were more frequent in patients with sICH (26% versus 12%; P=0.019). After adjusting for demographic characteristics, onset-to-treatment time, baseline National Institutes of Health Stroke Scale, stroke risk factors and medications, pretreatment blood pressure protocol violations were independently associated with a higher likelihood of sICH (OR, 2.59; 95% CI, 1.07 to 6.25; P=0.034).

Conclusions— These data support current guidelines advising not to use intravenous tissue plasminogen activator when pretreatment blood pressure exceeds the prespecified thresholds by showing that blood pressure protocol violations are independently associated with a higher likelihood of sICH.

Methods— We conducted a retrospective review of patients with CIS who presented to our stroke center. Thrombolytic treatment was compared between cocaine-positive (n=29) and cocaine-negative (n=75) patients. We also compared patients with CIS treated with tissue plasminogen activator versus those who did not receive tissue plasminogen activator (n=58). Safety outcomes were determined by the incidence of symptomatic intracerebral hemorrhage, in-hospital mortality, and modified Rankin Scale at hospital discharge.

Results— There were no complications in tissue plasminogen activator-treated patients with CIS. Cocaine-positive and cocaine-negative treated patients had similar stroke severity and safety outcomes. Patients with CIS treated with tissue plasminogen activator had more severe strokes on baseline National Institutes of Health Stroke Scale but similar safety outcomes compared with nontreated patients with CIS.

Conclusion— Thrombolytic therapy for CIS appears to be safe in this small study. Further research is needed to more definitively assess safety and efficacy of tissue plasminogen activator for CIS.

Methods— A total of 141 ischemic stroke patients on warfarin therapy were enrolled in this study. One hundred five patients with similar demographic features who do not use warfarin were chosen as controls. We compared vascular risk factors and radiological findings including CMBs and leukoaraiosis between the groups.

Results— CMBs on gradient-echo MRI (GE-MRI) were found in 31 patients (22%) and 17 controls (16%) and there was not a significant difference between 2 groups (P=0.25). Study patients with CMBs were older than patients without CMBs (P=0.04) and frequency of leukoaraiosis was significantly higher (P=0.008). Mean duration of warfarin treatment was not different between the patients with and without CMBs (P=0.83).

Conclusion— Although patients with CMBs were older and had more leukoaraiosis the impact of warfarin treatment on CMBs is still controversial.

Methods— Using data from the Stroke Prevention in Young Women study, a population-based case-control study including 297 women aged 15 to 49 years with ischemic stroke and 422 women without stroke, we evaluated whether polymorphisms in genes regulating endothelial function, including endothelin-1 (EDN), endothelin receptor type B (EDNRB), and nitric oxide synthase-3 (NOS3), confer susceptibility to migraine and stroke.

Results— EDN SNP rs1800542 and rs10478723 were associated with increased stroke susceptibility in whites (OR, 2.1; 95% CI, 1.1–4.2 and OR, 2.2; 95% CI, 1.1–4.4; P=0.02 and 0.02, respectively), as were EDNRB SNP rs4885493 and rs10507875, (OR, 1.7; 95% CI, 1.1–2.7 and OR, 2.4; 95% CI, 1.4–4.3; P=0.01 and 0.002, respectively). Only 1 of the tested SNP (NOS3 rs3918166) was associated with both migraine and stroke.

Conclusions— In our study population, variants in EDN and EDNRB were associated with stroke susceptibility in white but not in black women. We found no evidence that these genes mediate the association between migraine and stroke.

Summary of Review— This "neuroprotection strategy" has focused primarily on targets in the neurotoxic environment that occurs under ischemic conditions. In many cases, these agents were designed to tackle events that are known to start almost immediately after onset of ischemia, which is far before a realistic therapeutic time window opens for most, if not all, patients with stroke. In other instances, they were evaluated beyond a realistic timeframe in which one could expect significant salvageable tissue or penumbra to exist. Surprisingly, most of these agents were not evaluated in conjunction with strategies for improving perfusion to the affected tissue, indicating an overoptimistic assumption that neuroprotection alone could be sufficient to halt injury caused by an abrupt interruption of brain blood flow.

Conclusions— We provide a constructive translational medicine perspective about how one could improve the drug development process with the hope that the probability for success can increase in our quest to establish a novel therapy for stroke.

Methods— We performed a systematic review of all studies published from 1980 to 2008 inclusive that reported the risk of stroke and death due to CEA in relation to the time between presenting symptom and surgery. Pooled estimates of risk by the time since the last event were obtained by Mantel–Haenszel meta-analysis.

Results— Of 494 published operative series, only 47 stratified risk by timing of surgery. The pooled absolute risks of stroke and death after urgent CEA were high in patients with stroke-in-evolution (20.2%, 95% CI 12.0 to 28.4) and in patients with crescendo TIA (11.4%, 6.1 to 16.7), with no trends toward reduced risks in more recent studies. However, there was no significant difference between early and later CEA in neurologically stable patients with recent TIA or nondisabling stroke (<1 week versus ≥1 week, OR=1.2, 0.9 to 1.7, P=0.17; <2 weeks versus ≥2 weeks, OR=1.2, 0.9 to 1.6, P=0.13).

Conclusions— Emergency endarterectomy for stroke-in-evolution has a high operative risk, but the risk may be somewhat lower in patients with crescendo TIA. Surgery in the first week in neurologically stable patients with TIA or minor stroke is not associated with a substantially higher operative risk than delayed surgery. More data are required on the risk and benefit of more urgent surgery for TIA and minor stroke and for early versus delayed surgery in patients with major nondisabling stroke.

Methods— This cross-sectional study examined associations of hopelessness and depressive symptoms with carotid artery intimal-medial thickening (IMT) in 559 women (62% white, 38% black; mean±SD age, 50.2±2.8 years) without evidence of clinical CVD from the Study of Women’s Health Across the Nation (SWAN) Heart Study. Hopelessness was measured by 2 questionnaire items; depressive symptoms were measured with the 20-item Center for Epidemiological Studies Depression Scale. Mean and maximum IMT were assessed by B-mode ultrasonography of the carotid arteries.

Results— Increasing hopelessness was significantly related to higher mean (P=0.0139) and maximum (P=0.0297) IMT in regression models adjusted for age, race, site, income, and CVD risk factors. A weaker pattern of associations was noted for depressive symptoms and mean (P=0.1056) and maximum (P=0.0691) IMT. Modeled simultaneously in a risk factor-adjusted model, hopelessness was related to greater mean IMT (P=0.0217) and maximum IMT (P=0.0409), but depressive symptoms were unrelated to either outcome (P>0.4). No interactions with race or synergistic effects of depressive symptoms and hopelessness were observed.

Conclusions— Among middle-aged women, higher levels of hopelessness are associated with greater subclinical atherosclerosis independent of age, race, income, CVD risk factors, and depressive symptoms.

Methods— IMT was measured by B-mode ultrasound and DNA was collected from a population-based sample of South Asian (n=328), Chinese (n=302), and European Caucasian (n=268) participants. Genetic association was measured using multivariate linear regression including adjustment for covariates.

Results— The most robust association across all models tested was observed for a SNP (rs3791398) in histone deacetylase 4 (HDAC4; P=1.8e-5 to P=3.6e-5), while another strong association signal was observed with natriuretic peptide receptor a/guanylate cyclase A (NPR1) (rs10082235, P=5.4e-5). Seven of 13 previously reported functional candidate genes contained a SNP that was marginally associated (0.01<P≤0.05).

Conclusion— This initial multi-ethnic high-density association study of carotid IMT suggests some novel loci requiring further evaluation in follow-up studies.

Methods— We examined relations of carotid IMT to prospective trajectories of cognitive function among 538 (aged 20 to 93, 39% male, 66% white) participants in the Baltimore Longitudinal Study of Aging (BLSA) free of known cardiovascular, cerebrovascular, and neurological disease. Participants underwent initial carotid ultrasonography and repeat neuropsychological testing on up to 8 occasions over up to 11 years of follow-up. Mixed-effects regression analyses were adjusted for age, gender, race, education, mean arterial pressure, body mass index, total cholesterol, smoking, depressive symptoms, and cardiovascular medication use.

Results— Individuals with greater carotid IMT displayed accelerated decline in performance over time on multiple tests of verbal and nonverbal memory, as well as a test of semantic association fluency and executive function.

Conclusions— Carotid IMT predicts accelerated cognitive decline, particularly in the domain of memory, among community-dwelling individuals free of vascular and neurological disease.

Methods— The sample consisted of 3C-Dijon study participants who had 2 cerebral MRIs, at entry and at 4-year follow-up. WML volumes were estimated using a fully automatic procedure. We performed analysis of covariance to evaluate the relationship between apolipoprotein E genotype and WML load and progression.

Results— Multivariable analyses showed that 44 individuals had both significantly higher WML volume at baseline and higher WML increase over 4-year follow-up than noncarriers and heterozygous of the 4 allele for apolipoprotein E genotype.

Conclusion— These findings suggest it might be important to take into account WML severity when assessing the relationship between apolipoprotein E and dementia.

Methods— In 172 individuals, circulating EPC were defined by the surface markers CD31 and von Willebrand factor. ARWMC were rated on CT scan using the ARWMC scale and divided into 3 groups based on ARWMC scale score (ARWMC score 0 [none], score 1–10 [mild-to-moderate], score >10 [severe]). Severity of ARWMC was correlated with levels of EPC and vascular risk factors.

Results— On univariate analysis, EPC were found to be significantly lower in patients with severe ARWMC (P=0.01). ARWMC were also associated with hypertension (P<0.001), age (P<0.001), creatinine clearance (P=0.031), C-reactive protein (P<0.001), and use of angiotensin-converting enzyme or angiotensin receptor blocker (P=0.004). Multiple logistic regression analysis identified EPC level, age, hypertension, and hypertriglyceridemia as significant independent predictors of severe ARWMC.

Conclusions— Levels of circulating EPC were significantly lower in patients with severe ARWMC. Other variables significantly associated with severe ARWMC were age, hypertension, and hypertriglyceridemia. Further study is required to delineate the pathophysiological relationship between EPC, vascular risk factors, and ARWMC.

Methods— We studied 149 patients with acute ischemic stroke of SVD etiology according to Trial Of Org 10172 In Acute Stroke Treatment criteria and 25 age-matched control subjects. Patients were classified into focal-SVD: 39 patients with isolated lacunar infarct without leukoaraiosis and diffuse-SVD: 110 patients with an isolated lacunar infarct with leukoaraiosis or with multiple lacunar infarcts with or without leukoaraiosis. Baseline data included vascular risk factors and extensive laboratory tests, including plasma Aβ levels.

Results— Median [quartiles] Aβ_1-40 levels (40.4 [35.1, 50.5] versus 55.1 [42.3, 69.6] pg/mL), but not Aβ_1-42 levels, were significantly higher in the diffuse-SVD group than in focal-SVD group (P<0.001) and control subjects (P<0.001). No differences in Aβ_1-40 levels were found between focal-SVD and control subjects. Logistic regression analysis showed that age (OR, 1.06; 95% CI, 1.01 to 1.12), history of hypertension (OR, 3.5; 95% CI, 1.3 to 9.2), and plasma β-amyloid_1-40 levels over the median value (OR, 17.3; 95% CI, 3.0 to 99 for the third quartile and OR, 6.0; 95% CI, 1.6 to 23 for the fourth quartile) were independently associated with the diffuse-SVD subtype.

Conclusions— Plasma β-amyloid_1-40 levels are independently associated with the diffuse-SVD subtype. These results are consistent with the pathophysiological role of fraction Aβ_1-40 in disrupting endothelial vascular function.

Methods— We performed a retrospective cohort study for patients admitted from our emergency department with a new diagnosis of transient ischemic attack confirmed by a neurologist. ABCD² scores were calculated and patients with a score of ≥4 were placed in the high-risk cohort. Tests evaluated included electrocardiogram, CT, MRI, MR angiography, carotid ultrasonography, and echocardiography. Specific test findings considered to signify positive diagnostic tests were created a priori.

Results— We identified 256 patients with transient ischemic attack for inclusion; 167 (61%) were female, the median age was 60 years (interquartile range, 50 to 72), and 162 (63%) patients had an ABCD² score of ≥4. Rates of completion of diagnostic testing were electrocardiogram, 270 (100%); CT, 224 (88%); MRI, 89 (35%); MR angiography, 68 (27%); carotid ultrasonography, 125 (49%); and echocardiography, 135 (53%). Univariate analysis found a significant association only with elevated ABCD² score and carotid duplex testing (P<0.05).

Conclusion— An elevated ABCD² score may help predict patients with severe carotid occlusive disease but does not predict positive outcome in other commonly ordered tests for patients being evaluated for transient ischemic attack. An elevated ABCD² score cannot be recommended as a tool to guide diagnostic testing in patients presenting acutely with transient ischemic attack.

Methods— We assessed symptoms of chronic bronchitis, frequency of flu-like illnesses, and behavior during acute febrile infection in 370 consecutive patients with ischemic or hemorrhagic stroke or TIA and 370 age- and sex-matched control subjects randomly selected from the population.

Results— Cough with phlegm during ≥3 months per year (grade 2 symptoms of chronic bronchitis) was associated with stroke or TIA independent from smoking history, other risk factors, and school education (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.17 to 5.94; P=0.021). There was also an independent association between frequent flu-like infections (>2 per yr) and stroke/TIA (OR 3.54; 95% CI 1.52 to 8.27; P=0.003). Simultaneous assessment of chronic bronchitis and frequent flu-like infections did not attenuate the effect of either factor. Patients reported more often than control subjects to continue to work despite febrile infection (OR 3.68, 95% CI 1.80 to 7.52, multivariate analysis).

Conclusions— Our results suggest that chronic bronchitis is among those chronic infections that increase the risk of stroke. Independent from chronic bronchitis, a high frequency of flu-like illnesses may also be a stroke risk factor. Infection-related behavior may differ between stroke patients and control subjects.

Methods— We conducted a cross-sectional cohort study in a university hospital from January 2002 to December 2003. Consecutive Chinese patients with acute ischemic stroke underwent CT brain, MRI brain (with MR angiography and diffusion-weighted imaging sequences), and carotid duplex.

Results— In total, 251 patients were included in the analysis. Of these, 109 (43%) had concurrent stenoses. Patients who had concurrent stenoses, as compared with those without concurrent stenoses, had more symptomatic stenoses (84% versus 58%; OR, 4.0; 95% CI, 2.1 to 7.3; P<0.001), more concomitant perforating artery infarct, pial infarct, and borderzone infarct (14% versus 4%; OR, 3.6; 95% CI, 1.4 to 9.7; P=0.007), more multiple diffusion-weighted imaging lesions (55% versus 37%; OR, 2.1; 95% CI, 1.3 to 3.4; P=0.005), and more infarcts in the territory of the leptomeningeal branches of middle cerebral artery (26% versus 13%; OR, 2.2; 95% CI, 1.2 to 4.3; P=0.01). In multivariate regression analysis, smoking; prior stroke; the presence of concomitant pial infarct, pial infarct, and borderzone infarcts; multiple diffusion-weighted imaging lesions; and symptomatic stenoses were significantly associated with concurrent stenoses. Among patients with concurrent stenoses, those who had tandem lesions, as compared with those who had nontandem lesions, had more perforating artery infarct and borderzone infarcts (27% versus 8%; OR, 4.3; 95% CI, 0.9 to 19.8; P=0.04); more concomitant pial infarct, pial infarct, and borderzone infarcts (18% versus 0%; P=0.02), and more multiple diffusion-weighted imaging lesions (65% versus 23%; OR, 6.2; 95% CI, 2.2 to 17.2; P<0.001). Infarcts in the territory of middle cerebral artery leptomeningeal branches and symptomatic stenoses were more common in patients with tandem lesions.

Conclusions— Concomitant perforating artery infarct, pial infarct, and borderzone infarcts; multiple diffusion-weighted imaging lesions, and infarcts in the leptomeningeal branches of the middle cerebral artery were more common in patients with concurrent stenoses, especially those with tandem lesions. This study suggested that the combination of hemodynamic compromise attributable to concurrent stenoses and artery-to-artery embolization is a common stroke mechanism in these patients.

Methods— Consecutive patients with ischemic stroke referred to a neurovascular ultrasound laboratory were evaluated from March 2007 to February 2008. PI was defined as (peak systolic velocity–end-diastolic velocity)/mean flow velocity as recommended. Transcranial Doppler was examined in both middle cerebral arteries and vertebral arteries, and basilar arteries. All patients with ischemic stroke were subdivided according to the presence of proximal internal carotid arterial steno-occlusion (ICS).

Results— The numbers of patients enrolled for the present analysis as ischemic stroke without and with ICS were 272 and 92, respectively. PIs measured in the cerebral arteries did not show a significant difference in the two groups, in spite of the fact that mean flow velocities of both basilar arteries and vertebral arteries were significantly elevated in the patients with ICS. Plasma tHcy was found to be independently associated with graded increases of PIs in all cerebral arteries in the patients without ICS, even adjusted for the potential confounders. However, there was no association between tHcy and PI in the patients with ICS.

Conclusion— Plasma tHcy was directly associated with increased cerebral arterial resistance. But in clinical situations when the cerebral arterial hemodynamics were altered as in the patients with ICS, the effect of tHcy on arterial remodeling could be obscured.

Methods— We studied clinical, MRI, and angiographic data of 86 consecutive MMI patients. The lesions were correlated with clinical findings, and long-term outcomes, divided into mild and severe (modified Rankin scale >3), were assessed by telephone interview. Central poststroke pain (CPSP) was defined as persistent pain with visual numeric scale ≥4.

Results— The lesions were located mostly in the rostral medulla (rostral 76%, rostral+middle 16%), while ventro-dorsal lesion patterns include ventral (V, 20%), ventral+middle (VM, 33%), and ventral+middle+dorsal (VMD, 41%). Clinical manifestations included motor dysfunction in 78 patients (91%), sensory dysfunction in 59 (73%), and vertigo/dizziness in 51 (59%), each closely related to involvement of ventral, middle, and dorsal portions, respectively (P<0.001, each). Vertebral artery (VA) atherosclerotic disease relevant to the infarction occurred in 53 (62%) patients, mostly producing atheromatous branch occlusion (ABO). Small vessel disease (SVD) occurred in 24 (28%) patients. ABO was more closely related to VMD (versus V+VM) than was SVD (P=0.035). During follow-up (mean 71 months), 11 patients died, and recurrent strokes occurred in 11. Old age (P=0.001) and severe motor dysfunction at admission (P=0.001) were factors predicting poor prognosis. CPSP, occurring in 21 patients, was closely (P=0.013) related to poor clinical outcome.

Conclusion— MMI usually presents with a rostral medullary lesion, with a good clinical ventro-dorsal imaging correlation, caused most frequently by ABO followed by SVD. A significant proportion of patients remain dependent or have CPSP.

Methods— Leukocyte/lymphocyte subsets were assessed serially by white blood cell count and fluorescence-activated cell sorter analysis in ischemic stroke patients (n=50) at baseline, day 1, and day 4 after stroke onset and compared to an age-matched control group (n=40). Concomitantly, monocytic human leukocyte antigen-DR expression and the in vitro function of blood monocytes measured by the production of tumor necrosis factor- upon stimulation with lipopolysaccharide were assessed. Associations of these immunologic parameters with stroke specific factors (National Institutes of Health Stroke Scale, infarct size) were explored. Multivariable logistic regression analysis was applied to identify early predictors for poststroke respiratory and urinary tract infections.

Results— Infarct volume was the main factor associated with lymphocytopenia on day 1 and day 4 poststroke. Particularly, blood natural killer cell counts were reduced after stroke. Monocyte counts increased after ischemia paralleled by a profound deactivation predominantly after extensive infarcts. Reduced T helper cell counts, monocytic human leukocyte antigen-DR expression, and monocytic in vitro production of tumor necrosis factor- were associated with infections in univariate analyses. However, only stroke volume prevailed as independent early predictor for respiratory infections (OR 1.03; CI 1.01 to 1.04).

Conclusions— Infarct volume determines the extent of lymphocytopenia, monocyte dysfunction, and is a main predictor for subsequent infections.

Methods— Serum samples were collected at 4 annual intervals in 52 stroke-free participants from the Northern Manhattan Study (NOMAS) and assayed for hsCRP and Lp-PLA₂ mass and activity levels using standard techniques. Log transformation of levels was performed as needed to stabilize the variance. Stability of marker levels over time was assessed using random effects models unadjusted and adjusted for demographics and other risk factors. In addition, samples from 37 initially stroke-free participants with stroke (n=17) or MI (n=20) were available for measurement before and after the vascular event (median 5 days, range 2 to 40 days). Levels before and after events were compared using nonparametric tests.

Results— HsCRP and Lp-PLA₂ activity levels were stable over time, whereas Lp-PLA₂ mass levels decreased on average 5% per year (P=0.0015). Using accepted thresholds to define risk categories of Lp-PLA₂ mass, there was no significant change over time. HsCRP increased after stroke (from median 2.2 mg/L prestroke to 6.5 mg/L poststroke; P=0.0067) and MI (from median 2.5 mg/L pre-MI to 13.5 mg/L post-MI; P<0.0001). Lp-PLA₂ mass and activity levels both decreased significantly after stroke and MI (for Lp-PLA₂ mass, from median 210.0 ng/mL to 169.4 ng/mL poststroke, P=0.0348, and from median 233.0 ng/mL to 153.9 post-MI, P<0.0001).

Conclusion— Lp-PLA₂ mass levels decrease modestly, whereas hsCRP and Lp-PLA₂ activity appear stable over time. Acutely after stroke and MI, hsCRP increases whereas Lp-PLA₂ mass and activity levels decrease. These changes imply that measurements made soon after stroke and MI are not reflective of prestroke levels and may be less reliable for long-term risk stratification.

Methods— Thirty-five experts participated in the consensus process. The presented recommendations were approved during a meeting of the consensus group in October 2008 in Giessen, Germany. The project was an initiative of the German Competence Network Stroke and performed under the auspices of the Neurosonology Research Group of the World Federation of Neurology.

Results— Recommendations are given on how examinations should be performed in the time-limited situation of acute stroke, including criteria to assess the quality of the acoustic bone window, the use of echo contrast agents, and the evaluation of intracranial vessel status. The important issues of the examiners’ training and experience, the documentation, and analysis of study results are addressed. One central aspect was the development of standardized criteria for diagnosis of arterial occlusion. A transcranial color-coded duplex sonography recanalization score based on objective hemodynamic criteria is introduced (consensus on grading intracranial flow obstruction [COGIF] score).

Conclusions— This work presents consensus statements in an attempt to standardize the application of transcranial color-coded duplex sonography in the setting of acute stroke research, aiming to improve the reliability and reproducibility of the results of future stroke studies.

Methods— Baseline and follow-up DWI and PWI lesions and 30-day fluid-attenuated inversion recovery scans of 32 patients were coregistered. Lesion geography was defined by the proportion of the DWI lesion superimposed by a T_max (time when the residue function reaches its maximum) >4 seconds PWI lesion; Type 1: >50% overlap and Type 2: ≤50% overlap. Three-dimensional structure was dichotomized into a single lesion (one DWI and one PWI lesion) versus multiple lesions. Lesion reversal was defined by the percentage of the baseline DWI or PWI lesion not superimposed by the early follow-up DWI or PWI lesion. Final infarct prediction was estimated by the proportion of the final infarct superimposed on the union of the DWI and PWI lesions.

Results— Single lesion structure with Type 1 geography was present in only 9 patients (28%) at baseline and 4 (12%) on early follow-up. In these patients, PWI and DWI lesions were more likely to correspond with the final infarcts. DWI reversal was greater among patients with Type 2 geography at baseline. Patients with multiple lesions and Type 2 geography at early follow-up were more likely to have early reperfusion.

Conclusion— Before thrombolytic therapy in the 3- to 6-hour time window, Type 2 geography is predominant and is associated with DWI reversal. After thrombolysis, both Type 2 geography and multiple lesion structure are associated with reperfusion.

Methods— At 15 North Carolina hospitals, we enrolled a prospective nonconsecutive sample of admitted TIA patients. We excluded patients not undergoing a DWMRI within 24 hours of admission and patients for whom a dichotomized (≤ or >3) ABCD² score could not be calculated. We conducted a medical record review to determine disabling ischemic stroke outcomes within 90 days.

Results— Over 35 months, 944 TIA patients met inclusion criteria, of whom 4% (n=41) had a disabling ischemic stroke within 90 days. In analyses stratified by low versus moderate/high ABCD² score, the combination of a low risk ABCD² score and a negative early DWMRI had excellent sensitivity (100%, 95% CI 34 to 100) for identifying low-risk patients. In patients classified as moderate to high risk, a negative early DWMRI predicted a low risk of disabling ischemic stroke within 90 days (sensitivity 92%, 95% CI 80 to 97; NLR 0.11, 95% CI 0.04 to 0.32).

Conclusions— After risk stratification by the ABCD² score, early DWMRI enhances the prediction of a low risk for disabling ischemic stroke within 90 days. Further study is warranted in a large, consecutive TIA population of early DWMRI as a sensitive negative predictor for disabling stroke within 90 days.

Methods— In vivo MRI data of carotid plaques from 12 patients scheduled for endarterectomy were acquired for model reconstruction. Histology confirmed that 5 of the 12 plaques had rupture. Plaque wall stress (PWS) and flow maximum shear stress were extracted from all nodal points on the lumen surface of each plaque for analysis. A critical PWS (maximum of PWS values from all possible vulnerable sites) was determined for each plaque.

Results— Mean PWS from all ulcer nodes in ruptured plaques was 86% higher than that from all nonulcer nodes (123.0 versus 66.3 kPa, P<0.0001). Mean flow maximum shear stress from all ulcer nodes in ruptured plaques was 170% higher than that from all nonulcer nodes (38.9 versus 14.4 dyn/cm2, P<0.0001). Mean critical PWS from the 5 ruptured plaques was 126% higher than that from the 7 nonruptured ones (247.3 versus 108 kPa, P=0.0016 using log transformation).

Conclusion— The results of this study show that plaques with prior ruptures are associated with higher critical stress conditions, both at ulcer sites and when compared with nonruptured plaques. With further validations, plaque stress analysis may provide additional stress indicators helpful for image-based plaque vulnerability assessment.

Methods— In 123 first-ever lacunar stroke patients we performed 24-hour ambulatory BP monitoring after the acute stroke-phase. We counted BMBs on T2*-weighted gradient-echo MR images. Because a different etiology for BMBs according to location has been suggested, we distinguished between BMBs in deep and lobar location.

Results— BMBs were seen in 36 (29.3%) patients. After adjusting for age, sex, number of antihypertensive drugs, asymptomatic lacunar infarcts, and white matter lesions, we found 24-hour, day, and night systolic and diastolic BP levels to be significantly associated with the presence and number of BMBs (odds ratios 1.6 to 2.3 per standard deviation increase in BP). Distinguishing between different locations, various BP characteristics were significantly associated with the presence of deep (or combined deep and lobar) BMBs, but not with purely lobar BMBs.

Conclusions— Our results underline the role of a high 24-hour BP load as an important risk factor for BMBs. The association of BP levels with deep but not purely lobar BMBs is in line with the idea that different vasculopathies might be involved. Deep BMBs may be a particular marker of BP-related small vessel disease, but longitudinal and larger studies are now warranted to substantiate these findings.

Methods— Thirty patients with a premorbid modified Rankin score ≤1 and NIHSS between 5 and 22 were included. All had admission CT, CTA, and CT perfusion scans to evaluate for salvageable brain tissue. Recanalization effectiveness was assessed by angiograms obtained within 30 hours after intervention. Patient, treatment characteristics, and immediate and 3-month outcomes were analyzed.

Results— Mean NIHSS at presentation was 13 (median=12). Mean interval between time last-seen well and angiogram was 12.75 hours (median=10). Twenty-six patients (86.7%) presented with complete-to-near-complete vessel occlusion (thrombolysis in myocardial infarction [TIMI] 0/1); 4 had partial vessel occlusion (TIMI 2). Interventions included intra-arterial pharmacological thrombolysis (n=10), mechanical thrombectomy(n=21; Merci, 16; intracranial stent, 9; extracranial stent, 3), angioplasty (n=14; intracranial, 11; extracranial, 3). Nine patients received GPIIb/IIIa inhibitors (eptifibatide); all received heparin. Partial-to-complete recanalization (TIMI 2/3) was achieved in 20 patients (66.7%). Procedure-related complications included vascular perforations (n=3) and femoral access site complication (n=1). One patient had an embolic anterior cerebral artery infarct during intervention; another had progression of brain stem infarct. Symptomatic intracerebral hemorrhage occurred in 3 patients (10%), with 2 being primarily subarachnoid in location. Total in-hospital mortality including procedural mortality, disease progression, or other comorbidities was 23.3% (n=7). Mean discharge NIHSS was 9.5, representing an overall NIHSS 3.5-point improvement. Overall, mean modified Rankin score at death or last follow-up (mean=10.6 months) was 4.2. At 3 months, total mortality was 33.3% (n=10), 20% had modified Rankin score ≤2, and 33% had modified Rankin score ≤3. Among survivors, mean modified Rankin score at 3-month follow-up was 3.

Conclusion— Our data show that delayed endovascular revascularization of carefully selected patients is safe, effective, and improves clinical outcome.

Methods— This prospective study included patients with spontaneous ganglionic intracerebral hemorrhage and severe intraventricular hemorrhage with acute obstructive posthemorrhagic hydrocephalus who received an EVD (n=32). The treatment algorithm started with IVF (4 mg recombinant tissue plasminogen activator every 12 hours) until clearance of the third and fourth ventricles from blood. Thereupon, EVD was clamped and if clamping was unsuccessful, communicating posthemorrhagic hydrocephalus was assumed and LD placed. EVD was removed if there was neither an increase of intracranial pressure nor ventricle enlargement on CT. A ventriculoperitoneal shunt was indicated if "LD weaning" was unsuccessful for >10 days. Outcome was assessed at 90 and 180 days using the modified Rankin Scale.

Results— IVF resulted in fast clearance of the third and fourth ventricles (73±50 hours). However, early EVD removal was only possible in 4 patients. The remaining 28 patients developed communicating posthemorrhagic hydrocephalus. In all of these patients, early LD was capable to replace EVD. EVD exchange was not necessary and EVD duration was 105±59 hours. Only one patient required a ventriculoperitoneal shunt. At 180 days, 20 (62.5%) patients had a good (modified Rankin Scale 0 to 3) outcome and 5 (15.6%) patients had died. One patient had asymptomatic ventricular rebleeding.

Conclusions— In patients with secondary intraventricular hemorrhage and posthemorrhagic hydrocephalus, the combined treatment approach of IVF and early LD is safe and feasible, avoids EVD exchange, and may markedly reduce the need for shunt surgery.

Methods— We conducted a case-control study using the Dutch PHARMO Record Linkage System database. Cases (n=6763) were patients with a first hip/femur fracture; controls were matched by age, sex, and region. Odds ratio (OR) for the risk of hip/femur fracture was derived using conditional logistic regression analysis, adjusted for disease and drug history.

Results— An increased risk of hip/femur fracture was observed in patients who experienced a stroke at any time before the index date (adjusted OR, 1.96; 95% CI, 1.65–2.33). The fracture risk was highest among patients who sustained a stroke within 3 months before the index date (adjusted OR, 3.35; 95% CI, 1.87–5.97) and among female patients (adjusted OR, 2.12; 95% CI, 1.73–2.59). The risk further increased among patients younger than 71 years (adjusted OR, 5.12; 95% CI, 3.00–8.75). Patients who had experienced a hemorrhagic stroke tended to be at a higher hip/femur fracture risk compared with those who had experienced an ischemic stroke.

Conclusions— Stroke is associated with a 2.0-fold increase in the risk of hip/femur fracture. The risk was highest among patients younger than 71 years, females, and those whose stroke was more recent. Fall prevention programs, bone mineral density measurements, and use of bisphosphonates may be necessary to reduce the occurrence of hip/femur fractures during and after stroke rehabilitation.

Methods— We used 5 biennial waves (1998–2006) from the Health and Retirement Study to assess risk factors associated with falling accidents and fall-related injuries among stroke survivors. We abstracted demographic data, living status, self-evaluated general health, and comorbid conditions. We analyzed the rate ratio (RR) of falling and the OR of injury within 2 follow-up years using a multivariate random effects model.

Results— We identified 1174 stroke survivors (mean age±SD, 74.4±7.2 years; 53% female). The 2-year risks of falling, subsequent injury, and broken hip attributable to fall were 46%, 15%, and 2.1% among the subjects, respectively. Factors associated with an increased frequency of falling were living with spouse as compared to living alone (RR, 1.4), poor general health (RR, 1.1), time from first stroke (RR, 1.2), psychiatric problems (RR, 1.7), urinary incontinence (RR, 1.4), pain (RR, 1.4), motor impairment (RR, 1.2), and past frequency of ≥3 falls (RR, 1.3). Risk factors associated with fall-related injury were female gender (OR, 1.5), poor general health (OR, 1.2), past injury from fall (OR, 3.2), past frequency of ≥3 falls (OR, 3.1), psychiatric problems (OR, 1.4), urinary incontinence (OR, 1.4), impaired hearing (OR, 1.6), pain (OR, 1.8), motor impairment (OR, 1.3), and presence of multiple strokes (OR, 3.2).

Conclusions— This study demonstrates the high prevalence of falls and fall-related injuries in stroke survivors, and identifies factors that increase the risk. Modifying these factors may prevent falls, which could lead to improved quality of life and less caregiver burden and cost in this population.

Methods— Participants in this prospective, single-blinded, randomized, clinical trial were 78 incident stroke survivors admitted over 18 months and identified via neuropsychological assessment as having attention deficit. Participants were randomly allocated to standard care plus up to 30 hours of APT or standard care alone. Both groups were impaired (z≤–2.0) across measures of attention at baseline, with the exception of Paced Auditory Serial Addition Test, which was below average (z≤–1.0). Outcome assessment occurred at 5 weeks and 6 months after randomization. The primary outcome was Integrated Visual Auditory Continuous Performance Test Full-Scale Attention Quotient.

Results— APT resulted in a significantly greater (P<0.01) improvement on the primary outcome than standard care. Difference in change on the Cognitive Failures Questionnaire approached significance (P=0.07). Differences on other measures of attention and broader outcomes were not significant.

Conclusion— APT is a viable and effective means of improving attention deficits after incident stroke.

Methods— The Apathy Assessed cohort was formed from stroke survivors participating in a longitudinal study of health-related quality of life after stroke. A family caregiver completed an apathy questionnaire by telephone at 1, 3, 6, and 12 months after stroke (n=408). Group-based trajectory modeling and ordinal regression were used to identify distinctive groups of individuals with similar trajectories of apathy over the first year after stroke and predictors of apathy trajectory.

Results— Both 3- and 5-group trajectory models fit the data. We used the 5-group model because of the potential to further explore the apathy construct. The largest group (50%) had low apathy and 33% had minor apathy that remained stable throughout the first year after stroke. A small proportion (3%) of the study sample had high apathy that remained high. Two other groups of almost equal size (7%) showed worsening and improving apathy. Poor cognitive status, low functional status, and high comorbidity predicted higher apathy. High apathy had a significant negative effect on physical function, participation, health perception, and physical health over the first 12 months after stroke.

Conclusion— Some degree of apathy was prevalent and persistent after stroke and was predicted by older age, poor cognitive status, and low functional status after stroke. Even a minor level of apathy had an important and statistically significant impact on stroke outcomes.

Methods— Stroke patients were prospectively assessed by means of the NIH Stroke Scale, Barthel index, and modified Rankin scale. Proxies and patients answered the Hospital Anxiety and Depression Scale and the SIS 3.0. Comparisons of patient-proxy mean scores (paired t test), effect size, and intraclass correlation coefficients (ICC) were calculated for each of the SIS domains, and weighted kappa for individual items.

Results— 180 proxy-patient pairs were assessed. Proxies were younger (mean age: 43.1 versus 57.9 years) and had a higher education level (P<0.0001). The bias between patient-proxy mean differences was low (from 5.3, Strength, to 0.1, Communication). Proxies significantly scored patients as more severally affected in Strength (41.7 versus 36.6; P<0.0001) and ADL (46.2 versus 43.1; P=0.01) domains, and Composite Physical Domain (CPD; 39.7 versus 34.9; P<0.0001). The magnitude of difference was small (size effect: 0.21). ICC values for the SIS domains ranged from 0.17 (Emotion) to 0.79 (Hand function). The ICC value for the CPD was 0.83. Memory, Communication, Emotion, and Social Participation domains had ICC lower values. The weighted kappa values for the SIS items ranged from 0.09 (item 4e) to 0.80 (item 7d). Highest values (moderate/high agreement) were observed for the SIS-16 and CPD (kappa values: 0.31 to 0.80).

Conclusions— Agreement between stroke patients and proxies was acceptable for most SIS domains and SIS-16. Proxy’s assessment of SIS subjective domains should be taken with caution.

Methods— We reviewed all Merci thrombectomy cases of either terminal ICA or M1 occlusions and classified them according to diffusion MRI patterns of (1) completed basal ganglia infarct (pure M1a), (2) near-completed basal ganglia infarct (incomplete M1a), and (3) relative sparing of deep MCA field (M1b). We compared the M1a and M1b patients with respect to neurological deficit on presentation, recanalization rates, hospital length of stay, and disability on discharge. We also determined whether deep MCA compromise predicted hematomal hemorrhagic transformation (HT) and whether this correlated with worse clinical outcome at discharge.

Results— The M1a group had worse pre-Merci NIHSS (21 versus 14, P=0.004), worse discharge NIHSS (12 versus 4, P<0.001), longer hospital length of stay (11.5 versus 6.4 days, P=0.003), and higher rates of discharge mRS ≥3 (OR 8.4, 95% CI 2.1 to 44.7) despite equivalent recanalization rates when compared to the M1b group. The M1a group had a higher rate of parenchymal hematomal HT (OR 6.7, 95% CI 1.02 to 183.3). Patients with such hematomal HT had higher rates of death or dependency discharge (100% versus 60%, OR=infinite).

Conclusions— Among patients with ICA and M1 occlusions, preintervention diffusion MRI evidence of advanced injury in the basal ganglia bodes worse dysfunction and disability at discharge, longer hospital stays, and higher rates of hemorrhage after intervention when compared to other diffusion patterns.

Methods— This was a case–cohort study of patients with acute ischemic stroke seen between July 2003 and March 2005 and captured in the Registry of the Canadian Stroke Network. After stratifying by age category, we assessed for evidence of effect modification by age on the reduction in stroke fatality associated with stroke unit/organized care.

Results— Among 3631 patients with ischemic stroke, stroke case-fatality at 30 days was lower for patients admitted to a stroke unit compared with those admitted to general medical wards (10.2% versus 14.8%; P<0.0001 with an absolute risk reduction=4.6%, number needed to treat=22). All age groups achieved a similar benefit of stroke unit care versus general medical ward care (absolute risk reduction for 30-day stroke fatality was 4.5% for <60 years; 3.4% for 60 to 69 years; 5.3% for 70 to 79 years; and 5.5% for those >80 years). Increasing levels of organized care were associated with lower stroke fatality or institutionalization. The beneficial effect of stroke units/organized care on survival was seen even after adjustment for multiple prognostic factors and after excluding patients on palliative approach. There was no evidence of effect modification by age in any analyses.

Conclusions— Stroke units and organized inpatient care reduce death or institutionalization with the same magnitude of effect across all age groups.

Methods— This was a prospective cohort study of patients with acute ischemic stroke in the province of Ontario, Canada, admitted to stroke centers participating in the Registry of the Canadian Stroke Network between July 1, 2003 and March 31, 2005. Primary outcomes were the following selected indicators of quality stroke care: (1) use of thrombolysis; (2) dysphagia screening; (3) admission to a stroke unit; (4) carotid imaging; (5) antithrombotic therapy; and (6) warfarin for atrial fibrillation at discharge. Secondary outcomes were risk-adjusted stroke fatality, discharge disposition, pneumonia, and length of hospital stay.

Results— Among 3631 patients with ischemic stroke, 1219 (33.6%) were older than 80 years. There were no significant differences in stroke care delivery by age group. Stroke fatality increased with age, with a 30-day risk adjusted fatality of 7.1%, 6.5%, 8.8%, and 14.8% for those aged 59 or younger, 60 to 69, 70 to 79, and 80 years or older, respectively. Those aged older than 80 years had a longer length of hospitalization, increased risk of pneumonia, and higher disability at discharge compared to those younger than 80. This group was also less likely to be discharged home.

Conclusions— In the context of a province-wide coordinated stroke care system, stroke care delivery was similar across all age groups with the exception of slightly lower rates of investigations in the very elderly. Increasing age was associated with stroke severity and stroke case-fatality.

Methods— Self-reported data from the 2005 and 2007 Behavioral Risk Factor Surveillance System were used (n=765 368). The potential contributors for self-reported stroke prevalence (n=27 962) were demographics (age, sex, geography, and race/ethnicity), socioeconomic status (education and income), common risk factors (smoking and obesity), and chronic diseases (hypertension, diabetes, and coronary heart disease). Multivariate logistic regression was used in the analysis.

Results— The age- and sex-adjusted OR comparing self-reported stroke prevalence in the 11-state Stroke Belt versus non-Stroke Belt region was 1.25 (95% CI, 1.19 to 1.31). Unequal black/white distribution by region accounted for 20% of the excess prevalence in the Stroke Belt (OR reduced to 1.20; 1.15 to 1.26). Approximately one third (32%) of the excess prevalence was accounted either by socioeconomic status alone or by risk factors and chronic disease alone (OR, 1.12). The OR was further reduced to 1.07 (1.02 to 1.13) in the fully adjusted logistic model, a 72% reduction.

Conclusions– Differences in socioeconomic status, risk factors, and prevalence of common chronic diseases account for most of the regional differences in stroke prevalence.

Methods— Temporal changes in microvascular SphK activity and expression were measured after HPC. The SphK inhibitor dimethylsphingosine or sphingosine analog FTY720 was administered to adult male Swiss-Webster ND4 mice before HPC. Two days later, mice underwent a 60-minute transient middle cerebral artery occlusion and at 24 hours of reperfusion, infarct volume, neurological deficit, and hemispheric edema were measured.

Results— HPC rapidly increased microvascular SphK2 protein expression (1.7±0.2-fold) and activity (2.5±0.6-fold), peaking at 2 hours, whereas SphK1 was unchanged. SphK inhibition during HPC abrogated reductions in infarct volume, neurological deficit, and ipsilateral edema in HPC-treated mice. FTY720 given 48 hours before stroke also promoted ischemic tolerance; when combined with HPC, even greater (and dimethylsphingosine-reversible) protection was noted.

Conclusions— These findings indicate hypoxia-sensitive increases in SphK2 activity may serve as a proximal trigger that ultimately leads to sphingosine-1-phosphate-mediated alterations in gene expression that promote the ischemia-tolerant phenotype. Thus, components of this bioactive lipid signaling pathway may be suitable therapeutic targets for protecting the neurovascular unit in stroke.

Methods— Adult mice subjected to transient middle cerebral artery occlusion underwent chronic intermittent hypoxia starting either 1 or 5 days after ischemia and brain damage was assessed by T2-weighted MRI at 43 days. In addition, we investigated the potential neuroprotective effect of hypoxia applied after oxygen glucose deprivation in primary neuronal cultures.

Results— The present study shows for the first time that a late application of hypoxia (5 days) after ischemia reduced delayed thalamic atrophy. Furthermore, hypoxia performed 14 hours after oxygen glucose deprivation induced neuroprotection in primary neuronal cultures. We found that hypoxia-inducible factor-1 expression as well as those of its target genes erythropoietin and adrenomedullin is increased by hypoxic postconditioning. Further studies with pharmacological inhibitors or recombinant proteins for erythropoietin and adrenomedullin revealed that these molecules participate in this hypoxia postconditioning-induced neuroprotection.

Conclusions— Altogether, this study demonstrates for the first time the existence of a delayed hypoxic postconditioning in cerebral ischemia and in vitro studies highlight hypoxia-inducible factor-1 and its target genes, erythropoietin and adrenomedullin, as potential effectors of postconditioning.

Methods— A unilateral infarction was induced in mouse brain by photoinduction after injection of Rose Bengal. The volume of the infarction was analyzed using the public domain National Institutes of Health image program. The level of protein-conjugated acrolein at the locus of infarction and in plasma was measured by Western blotting and enzyme-linked immunosorbent assay, respectively. The levels of polyamines at the locus of infarction and in plasma were measured by high-performance liquid chromatography.

Results— The level of protein-conjugated acrolein was greatly increased, and levels of spermine and spermidine were decreased at the locus of infarction at 24 hours after the induction of stroke. The size of infarction was significantly decreased by N-acetylcysteine, a scavenger of acrolein. It was also found that the increases in the protein-conjugated acrolein, polyamines, and polyamine oxidases in plasma were observed after the induction of stroke.

Conclusions— The results indicate that the induction of infarction is well correlated with the increase in protein-conjugated acrolein at the locus of infarction and in plasma.

Methods— Postnatal Day 7 rats were subjected to unilateral carotid artery occlusion and hypoxia. Rats were treated immediately after HI with TAT-NBD, the JNK inhibitor TAT-JBD, and/or the TNF- inhibitor etanercept. We determined brain damage, NF-B and AP-1 activity, Gadd45β, XIAP, (P-)TAK1, TNF-, and TNF receptor expression.

Results— Our data confirm that TAT-NBD treatment reduces brain damage without inhibiting TNF- production. We now show that TAT-NBD treatment increased HI-induced AP-1 activation concomitantly with reduced Gadd45β, XIAP, and increased (P)-TAK1 expression. Combined inhibition of NF-B and JNK/AP-1 abrogated HI-induced TNF- production. However, this treatment reduced the neuroprotective effect of NF-B inhibition alone. We show that etanercept was detectable in the HI brain after intraperitoneal administration and that etanercept treatment also reduced the neuroprotective effect of NF-B inhibition. Finally, NF-B inhibition decreased HI-induced upregulation of TNF-R1 and increased TNF-R2 expression.

Conclusions— When NF-B was inhibited after neonatal cerebral HI, JNK/AP-1 activity was increased and required for increased TNF- expression. Our data indicate that the switch to JNK/AP-1 activation preserves HI-induced TNF- expression and thereby might contribute to the neuroprotective effect of TAT-NBD possibly through a TNF-R2 dependent mechanism.

Methods— The premature rabbit pups, delivered by cesarean section, were treated with intraperitoneal glycerol at 2 hours postnatal age to induce IVH. The development of IVH was diagnosed by head ultrasound at 24 hours of age. Neurobehavioral, histological, and ultrastructural evaluation and diffusion tensor imaging studies were performed at 2 weeks of age.

Results— Although 25% of pups with IVH (IVH pups) developed motor impairment with hypertonia and 42% developed posthemorrhagic ventriculomegaly, pups without IVH (non-IVH) were unremarkable. Immunolabeling revealed reduced myelination in the white matter of IVH pups compared with saline- and glycerol-treated non-IVH controls. Reduced myelination was confirmed by Western blot analysis. There was evidence of gliosis in IVH pups. Ultrastructural studies in IVH pups showed that myelinated and unmyelinated fibers were relatively preserved except for focal axonal injury. Diffusion tensor imaging showed reduction in fractional anisotropy and white matter volume confirming white matter injury in IVH pups.

Conclusion— The rabbit pups with IVH displayed posthemorrhagic ventriculomegaly, gliosis, reduced myelination, and motor deficits, like humans. The study highlights an instructive animal model of the neurological consequences of IVH, which can be used to evaluate strategies in the prevention and treatment of posthemorrhagic complications.

Methods— Blood flow in AAAs was examined using fluorescein isothiocyanate–labeled red blood cells (RBCs) as a flow indicator in 16 anesthetized C57BL/6J mice before and after MCA occlusion up to 7 experimental days.

Results— We observed paradoxical flow in AAAs; labeled RBCs entered from both the MCA and anterior cerebral artery sides and the opposing flows met at a branching T-junction, where the flows combined and passed into a penetrating arteriole. The dually fed T-junction was not fixed in position, but functionally jumped to adjacent T-junctions in response to changing hemodynamic conditions. On MCA occlusion, RBC flow from the MCA side immediately stopped. After a period of "hesitation," blood started to move retrogradely in one of the MCA branches toward the MCA stem. The retrograde blood flow was statistically significantly (P<0.05), serving to feed blood to other MCA branches after a lag period. In capillaries, MCA occlusion induced immediate RBC disappearance in the ischemic core and to a lesser extent in the marginal zone near AAAs. At day 3 after ischemia, we recognized the beginning of remodeling with angiogenesis centering on AAAs.

Conclusions— AAAs appear to play a key role in local hemodynamic homeostasis, both in the normal state and in the development of collateral channels and revascularization during ischemia.

Methods— Primary ICH was induced in rats. Simvastatin (2 mg/kg), atorvastatin (2 mg/kg), or phosphate-buffered saline (n=6 per group) was given daily for 1 week. MRI studies were performed 2 to 3 days before ICH, and at 1 to 2 hours and 1, 2, 7, 14, and 28 days after ICH. The ICH evolution was assessed via hematoma volume measurements using susceptibility-weighted imaging (SWI) and tissue loss using T₂ maps and hematoxylin and eosin (H&E) histology. Neurobehavioral tests were done before ICH and at various time points post-ICH. Additional histological measures were performed with doublecortin neuronal nuclei and bromodeoxyuridine stainings.

Results— Initial ICH volumes determined by SWI were similar across all groups. Simvastatin significantly reduced hematoma volume at 4 weeks (P=0.002 versus control with acute volumes as baseline), whereas that for atorvastatin was marginal (P=0.09). MRI estimates of tissue loss (% of contralateral hemisphere) for treated rats were significantly lower (P=0.0003 and 0.001, respectively) than for control at 4 weeks. Similar results were obtained for H&E histology (P=0.0003 and 0.02, respectively). Tissue loss estimates between MRI and histology were well correlated (R²=0.764, P<0.0001). Significant improvement in neurological function was seen 2 to 4 weeks post-ICH with increased neurogenesis observed.

Conclusions— Simvastatin and atorvastatin significantly improved neurological recovery, decreased tissue loss, and increased neurogenesis when administered for 1 week after ICH.

Methods— A cohort study was done in 12 centers admitting 5515 consecutive patients with acute stroke in The Netherlands. A multilevel logistic regression model was used to relate the likelihood of treatment with thrombolysis to characteristics of the organizational culture of the centers. Organizational culture was defined by 10 characteristics and scored by a panel. A sum score was created by adding all scores and dividing by 10.

Results— Thrombolysis rates varied from 5.7% to 21.7%. We observed an association between thrombolysis and the availability of informal and formal feedback (OR, 1.18; 95% CI, 1.09 to 1.28); a learning culture (OR, 1.12; 95% CI, 1.02 to 1.23); uncompromising, individual clinical leadership (OR, 1.12; 95% CI, 1.03 to 1.23); explicit goals (OR, 1.08; 95% CI, 1.01 to 1.17); and with the sum score (OR, 1.12; 95% CI, 1.02 to 1.23).

Conclusions— Several cultural characteristics of the hospital organization are related to thrombolysis rate. Organizational culture may be an important target for interventions aimed at increasing rates of thrombolysis for acute ischemic stroke in hospitals.

Methods— Two researchers independently reviewed the literature. Crossdisciplinary electronic databases were interrogated using the following key words: Stroke*; Cerebrovasc*; Modified Rankin*; Rankin Scale*; Oxford Handicap*; Observer variation*. Data were extracted according to prespecified criteria with decisions on inclusion by consensus.

Results— From 3461 titles, 10 studies (587 patients) were included. Reliability of modified Rankin Scale varied from weighted =0.95 to =0.25. Overall reliability of mRS was =0.46; weighted =0.90 (traditional modified Rankin Scale) and =0.62; weighted =0.87 (structured interview).

Conclusion— There remains uncertainty regarding modified Rankin Scale reliability. Interobserver studies closest in design to large-scale clinical trials demonstrate potentially significant interobserver variability.

Methods— Stroke severity and dependency have been categorized as mild, moderate, or severe. We studied 2 acute stroke unit cohorts, measuring Scandinavian Stroke Scale (SSS), modified Rankin Scale (mRS), Barthel Index (BI), and modified National Institutes of Health Stroke Scale (mNIHSS). Receiver operating characteristic (ROC) curves were examined to determine the ability of full and categorized scales to predict death and dependency. A weighted kappa analysis assessed agreement between the categorized scales.

Results— When scales are categorized, the area under the ROC curve is significantly reduced; however, the differences are small and may not be practically important. BI, mRS, and SSS all have excellent agreement with each other when categorized, whereas mNIHSS has substantial agreement with mRS and BI.

Conclusions— Little predictive information is lost when stroke scales are categorized. There is substantial to almost perfect agreement among categorized scales. Therefore the use and categorization of a variety of stroke severity or dependency scales is acceptable in analyses.

Methods— From June 2007 to December 2008, patients with anterior circulation ischemic stroke were evaluated for a "total mismatch" profile. MRI was performed at admission and at day 1. The score was assessed at baseline and the modified Rankin scale score was assessed at day 30.

Results— Among 52 patients, 3 showed a total mismatch with arterial occlusion confirmed on magnetic resonance angiography. All had fluctuating symptoms (National Institutes of Health Stroke Scale scores, 0 to 10) and received intravenous tissue plasminogen activator. Day 1 DWI disclosed minimal changes in all patients. Outcome was favorable in all patients (day 30 modified Rankin scale, 0–1).

Conclusion— PWI may be helpful for treatment decisions in patients without DWI damage and fluctuating clinical course.

Methods— We performed a systematic review and meta-analysis of randomized controlled trials assessing the use of endothelin-receptor antagonists (ETRAs) in patients with SAH.

Results— Three studies met eligibility criteria, enrolling 867 patients. ETRAs significantly reduced the occurrence of DINDs (OR 0.68 [0.49 to 0.95]) and radiographic vasospasm (OR 0.31 [0.19 to 0.49]), but did not have any impact on mortality (OR 1.09 [0.69 to 1.72]) or poor neurological outcomes (OR 0.87 [0.63 to 1.20]). Any benefit of ETRAs may have been partially offset by adverse effects, including hypotension(OR 2.39 [1.37 to 4.17]) and pulmonary complications (OR 2.12 [1.51 to 2.98]).

Conclusions— Although ETRAs reduce radiographic vasospasm and DINDs, there is currently no evidence that they improve outcomes.

Methods— Following a guideline-based algorithm, we screened consecutive patients with ischemic stroke and patients with transient ischemic attack for asymptomatic coronary artery disease using the Framingham Heart Study Coronary Risk Score (FCRS) cutoff of high risk (≥20%) for experiencing a hard coronary artery disease event over a 10-year period. Patients with high FCRS received dobutamine stress echocardiogram outpatient screening, additional treatment (β-blocker), or further management (cardiologist referral).

Results— From July 2004 to September 2007, among 693 patients, 501 (72%) met study criteria, of which 80 (16%) had FCRS ≥20%. Elevated serum glucose, nonhigh-density lipoprotein, triglycerides, homocysteine, glycosylated hemoglobin as well as large vessel atherosclerotic stroke mechanism were more frequent in high versus low FCRS patients (P<0.05). Among high FCRS patients, 35 (44%) had dobutamine stress echocardiogram performed. Leading reasons for dobutamine stress echocardiogram nonperformance were patient noncompliance (42%) and primary care physician refusal (33%).

Conclusions— Screening for coronary artery disease risk using FCRS is feasible in hospitalized patients with stroke, but outpatient adherence to stress testing is challenging largely due to patient and primary care physician-related factors.

Methods— This study followed a cohort of 6291 residents in Kangwha County, aged ≥55 years in March 1985, for their cause-specific mortality for 20.8 years up to December 31, 2005. We calculated hazard ratio of mortality by experience or frequency of binge drinking using the Cox proportional hazard model. Binge drinking was defined as having ≥6 drinks on one occasion.

Results— In men, binge drinkers who drink daily had an increased risk of mortality from all causes (hazard ratio, 1.33; 95% CI, 1.11 to 1.60) as compared with nondrinkers. They showed much increased risks of mortality from total stroke (hazard ratio, 1.86; 95% CI, 1.16 to 2.99) and hemorrhagic stroke (hazard ratio, 3.39; 95% CI, 1.38 to 8.35). Female binge drinkers also showed an increased risk of mortality from cardiovascular disease as compared with female nondrinkers, but the outcome was not statistically significant.

Conclusions— The results of this study suggest that frequent binge drinking has a harmful effect on hemorrhagic stroke in Korean men. These findings need to be confirmed in further studies.

Methods— In 2013 stroke-free Framingham offspring (mean±SD age, 58±9.5 years; 53% women), we related baseline plasma ADMA levels (1995–1998) to subsequent brain magnetic resonance imaging measures (1999–2004) of subclinical vascular injury: presence of silent brain infarcts (SBIs) and large white-matter hyperintensity volumes (LWMHs; defined as >1 SD above the age-specific mean).

Results— Prevalences of SBIs and LWMHs were 10.7% and 12.6%, respectively. In multivariable analyses adjusting for age, sex and traditional stroke risk factors, higher ADMA levels were associated with an increased risk of prevalent SBIs (odds ratio [OR] per 1-SD increase in ADMA=1.16; 95% CI, 1.01 to 1.33; P=0.04). We observed that participants in the upper 3 age-specific quartiles (Qs) of plasma ADMA values had an increased prevalence of SBIs (OR for Q2–Q4 vs Q1=1.43; 95% CI, 1.00 to 2.04; P<0.05). The prevalence of SBIs in Q1and Q2–Q4 was 8.3% and 11.6%, respectively. The prevalence of LWMHs did not differ according to ADMA concentrations.

Conclusions— Higher plasma ADMA values were associated with an increased prevalence of SBIs, after adjustment for traditional stroke risk factors. Thus, ADMA may be a potentially useful new biomarker of subclinical vascular brain injury, which is an important correlate of vascular cognitive impairment and risk of stroke.

Methods— From a group of DNA samples collected at baseline in a prospective cohort of 14 916 initially healthy American men, we assessed 16 TRPM7 tag–single-nucleotide polymorphisms (SNPs) (dbSNP: rs11854949, rs4775899, rs11635825, rs12905120, rs16973487, rs7173321, rs7163283, rs17520378, rs17520350, rs4775892, rs7174839, rs17645523, rs3109894, rs616256, rs11070795, and rs313158) from 245 white men who subsequently had an incident ischemic stroke and from 245 age- and smoking habit–matched white men who remained free of reported vascular disease during follow-up (controls).

Results— All SNPs examined were in Hardy-Weinberg equilibrium. Overall allele, genotype, and haplotype distributions were similar between cases and controls. Marker-by-marker conditional logistic-regression analysis, adjusted for potential risk factors, showed no evidence for an association between any of the SNPs tested and ischemic stroke. Further investigation with an Entropy Blocker–defined, haplotype-based approach showed similar null findings. Prespecified analysis limited to participants without baseline diabetes and hypertension (ie, low-risk group) again showed similar null findings.

Conclusions— The present prospective investigation provides no evidence of a role for the TRPM7 gene in the risk of incident ischemic stroke.

Methods— One hundred twenty older adults with diagnosed cardiovascular disease were recruited from outpatient cardiology clinics. Each participant underwent a comprehensive neuropsychological test battery and a blood draw.

Results— Participants with the SELP 1087A allele performed more poorly on tests of attention (Trail Making Test A: t[116]=3.20, P=0.002), executive function (Trail Making Test B: t[116]=2.89, P=0.005), psychomotor speed (Digit–Symbol Coding: t[117]=2.54, P=0.012), and memory (California Verbal Learning Test Discrimination: t[116]=2.05, P=0.04). There were no significant differences between the SELP genotype groups on demographic/medical variables or C-reactive protein levels.

Conclusions— Contrary to expectations, the present analyses showed that older patients with cardiovascular disease with the SELP 1087A allele performed more poorly on neuropsychological testing. Findings from the present study were counter to previous research with coronary artery bypass graft candidates. Further work using neuroimaging and alternative measures of cardiovascular function is needed to clarify the mechanisms of this association.

Methods— A total of 1209 patients with stroke and 1174 controls were examined using a case–control methodology. The 1425G/A SNP in PRKCH was genotyped by allele-specific real-time PCR assay.

Results— The 1425G/A SNP in PRKCH was significantly associated with both ischemic stroke (odds ratio [OR]=1.31; 95% confidence interval [CI], 1.08 to 1.60; P=0.0058) and cerebral hemorrhage (OR=1.94; 95% CI, 1.21 to 3.10; P=0.0054) under a dominant model. Even after age- and sex-adjustment, the significant associations remained (in ischemic stroke, for AA+AG versus GG, OR=1.37, 95% CI, 1.12 to 1.67, P=0.0019; in cerebral hemorrhage, for AA+AG versus GG, OR=1.96, 95% CI, 1.21 to 3.19, P=0.0064).

Conclusions— The 1425G/A SNP in PRKCH increases the risk of both ischemic stroke and cerebral hemorrhage in the Chinese population.

Methods— Women (18 to 50 years) with and without migraine and free from cardiovascular disease were evaluated with tests of coagulation (von Willebrand factor activity, prothrombin fragment), fibrinolysis (tissue-type plasminogen activator antigen), inflammation (high-sensitivity C-reactive protein), and oxidative stress (homocysteine, total nitrate/nitrite concentrations, thiobarbituric acid–reactive substances).

Results— Sixty-one participants had migraine with aura (MA), 64 had migraine without aura (MO), and 50 were controls. Compared with controls, women with migraine had higher adjusted odds ratios for elevated von Willebrand factor activity of 6.51 (95% CI, 1.94 to 21.83) in those with MA and of 4.59 (95% CI, 1.37 to 15.38) in those with MO, elevated high-sensitivity C-reactive protein of 7.99 (95% CI, 2.32 to 27.61) in those with MA and of 2.63 (95% CI, 0.73 to 9.45) in those with MO, and for lower nitrate/nitrite levels of 6.60 (95% CI, 2.06 to 21.16) in those with MA and of 3.03 (95% CI, 0.90 to 10.15) in those with MO. Within the migraine group, von Willebrand factor activity was correlated with tissue-type plasminogen activator antigen (P=0.035) and nitrate/nitrite (P=0.024). There was a trend with high-sensitivity C-reactive protein (P=0.09).

Conclusions— In premenopausal women with migraine, particularly in those with MA, there is evidence of increased endothelial activation, a component of endothelial dysfunction.

Methods— Charts of all patients with symptomatic intracranial atherosclerotic disease from July 2004 to September 2007 were reviewed and assessed for history of transient ischemic attack or stroke. Patients were either treated with "best medical therapy" (Medical Therapy Group) or PTAS plus antiplatelet agents (PTAS Group) and followed prospectively. A favorable outcome was defined as the absence of transient ischemic attacks, strokes, or vascular death; modified Rankin Scale of ≤3; and no endovascular reintervention of symptomatic in-stent restenosis.

Results— One hundred eleven patients fulfilled entry criteria, with 58 (52.3%) and 53 patients (47.7%) enrolled in the Medical Therapy and PTAS Groups, respectively. Thirty-eight patients of the Medical Therapy Group (65.5%) had a favorable outcome compared with 37 patients of the PTAS Group (69.8%). Combined ischemic end point data for the occurrence of transient ischemic attack, stroke, and vascular death was similar with 14 (24%) events in the Medical Therapy Group versus 15 (28.3%) events in the PTAS Group.

Conclusion— Overall, the combined ischemic end point was the same in the Medical Therapy and PTAS Groups.

Methods— Six hundred ninety-nine patients enrolled in a prospective cohort study involving CT angiographic imaging in acute stroke were dichotomized according to the presence of a PO, including a subgroup of 177 subjects with middle cerebral artery M1 occlusion.

Results— The median NIHSS score of patients found to have a PO was higher than the overall median (9 versus 5, P<0.0001). The median NIHSS score of patients with middle cerebral artery M1 occlusion was 14. NIHSS score ≥10 had 81% positive predictive value for PO but only 48% sensitivity with the majority of subjects with PO presenting with lower NIHSS scores. All patients with NIHSS score ≥2 would need to undergo angiographic imaging to detect 90% of PO.

Conclusions— High NIHSS score correlates with the presence of a proximal arterial occlusion in patients presenting with acute cerebral ischemia. No NIHSS score threshold can be applied to select a subgroup of patients for angiographic imaging without failing to capture the majority of cases with clinically important occlusive lesions. The finding of minimal clinical deficits should not deter urgent angiographic imaging in otherwise appropriate patients suspected of acute stroke.

Methods— We retrospectively reviewed CT angiograms performed in all patients who presented to our emergency department over a 9-year period with primary intracerebral hemorrhage and had a follow-up noncontrast head CT within 48 hours of the baseline CT angiogram. Three neuroradiologists reviewed the CT angiograms and determined the presence and characteristics of spot signs according to strict radiological criteria. Baseline and follow-up intracerebral hemorrhage volumes were determined by computer-assisted volumetric analysis.

Results— We identified spot signs in 71 of 367 CT angiograms (19%), 6 of which were delayed spot signs (8%). The presence of any spot sign increased the risk of significant hematoma expansion (69%, OR=92, P<0.0001). Among the spot sign characteristics examined, the presence of ≥3 spot signs, a maximum axial dimension ≥5 mm, and maximum attenuation ≥180 Hounsfield units were independent predictors of significant hematoma expansion, and these were subsequently used to construct the spot sign score. In multivariate analysis, the spot sign score was the strongest predictor of significant hematoma expansion, independent of time from ictus to CT angiogram evaluation.

Conclusion— The spot sign score predicts significant hematoma expansion in primary intracerebral hemorrhage. If validated in other data sets, it could be used to select patients for early hemostatic therapy.

Methods— Among 741 patients enrolled in a prospective cohort study involving CT angiographic imaging in acute stroke, 134 cases with proximal middle cerebral artery occlusion and 235 control subjects with no occlusions were identified. CT angiography was used to identify occlusions and grade the extent of collateral vessels in the sylvian fissure and leptomeningeal convexity. History of symptom fluctuation or progressive worsening was obtained on admission.

Results— Prehospital symptoms were unrelated to occlusion or collateral status. In cases, 37.5% imaged within 1 hour were found to have diminished collaterals versus 12.1% imaged at 12 to 24 hours (P=0.047). No difference in worsening was seen between cases and control subjects with adequate collaterals, but cases with diminished sylvian and leptomeningeal collaterals experienced greater risk of worsening compared with control subjects measured either by admission to discharge National Institutes of Health Stroke Scale increase ≥1 (55.6% versus 16.6%, P=0.001) or ≥4 (44.4% versus 6.4%, P<0.001).

Conclusion— Most patients with proximal middle cerebral artery occlusion rapidly recruit sufficient collaterals and follow a clinical course similar to patients with no occlusions, but a subset with diminished collaterals is at high risk for worsening.

Methods— We optimized predictive performance based on the area under the receiver operating curve for logistic regression and used simulated data to illustrate the effect of an unbalanced (unequal number of infarcting and surviving voxels) training set on predicted infarct risk. We then tested the performance and optimality of models based on perfusion-weighted, diffusion-weighted, and structural MRI modalities by changing the proportion of mismatch voxels in balanced training material.

Results— Predictive performance (area under the receiver operating curve) based on all brain voxels is excessively optimistic and lacks sensitivity in performance in mismatch tissue. The ratio of infarcting and noninfarcting voxels used for training predictive algorithms significantly biases tissue infarct risk estimates. Optimal training strategy is obtained using a balanced training set. We show that 60% of noninfarcted voxels consists of mismatch voxels in an optimal balanced training set for the patient data presented.

Conclusions— An equal number of infarcting and noninfarcting voxels should be used when training predictive models. The choice of test and training sets critically affects predictive model performance and should be closely evaluated before comparisons across patient cohorts.

Methods— Brain temperature, cerebral blood flow, and metabolism were measured using proton MR spectroscopy and ¹⁵O-positron emission tomography, respectively, in 21 normal subjects and 37 patients. Positron emission tomography images were coregistered with MR images and resliced automatically using image analysis software. Regions of interest placed in both cerebral hemispheres on MR images were automatically superimposed in these resliced positron emission tomography images.

Results— A significant correlation was observed between brain temperature difference (affected hemisphere–contralateral hemisphere) and both cerebral blood volume and oxygen extraction fraction ratio (affected hemisphere/contralateral hemisphere; r=0.607; P=0.0004 and r=0.631; P=0.0002). With abnormally elevated cerebral blood volume or oxygen extraction fraction ratio defined as higher than the mean +2 SDs obtained from normal subjects, brain temperature difference provided 86% or 92% sensitivity and 87% or 84% specificity with 80% or 73% positive and 91% or 95% negative predictive values for detecting abnormally elevated cerebral blood volume or oxygen extraction fraction ratios, respectively.

Conclusions— Brain temperature measured using proton MR spectroscopy can detect cerebral hemodynamic impairment in patients with unilateral chronic major cerebral artery steno-occlusive disease.

Methods— Forty-five symptomatic patients with 30% to 69% carotid artery stenosis underwent a multisequence MRI protocol, which included contrast-enhanced images. FC status (ie, discrimination between fibrotic and/or calcified plaques, plaques with a lipid-rich necrotic core and an intact and thick FC, and plaques with a lipid-rich necrotic core and a thin and/or ruptured FC) was independently assessed by 3 observers of which one also scored all images on a different occasion. Linear weighted kappa coefficients () were calculated as indicators of inter- and intraobserver agreement.

Results— On a per-slice basis, interobserver agreement was good (=0.60, 0.64, and 0.71), whereas intraobserver agreement was very good (=0.86). On a per-plaque basis, interobserver agreement was good (=0.64, 0.69, and 0.78), whereas intraobserver agreement was very good (=0.96).

Conclusion— This study found good interobserver and very good intraobserver agreement in assessing FC status of carotid artery plaques. Future studies are warranted to determine the predictive value of FC status assessment by multisequence MRI, including contrast-enhanced images, on the occurrence of (recurrent) cerebral ischemic events.

Methods— We performed T2*-weighted MRI in 27 patients with hereditary cerebral hemorrhage with amyloidosis–Dutch type to assess the presence and location of microbleeds, intracranial hemorrhages, and superficial siderosis. Using the Boston criteria, subjects were categorized as having: no hemorrhages, possible CAA, probable CAA, and hemorrhagic lesions not qualifying for CAA. The sensitivity of the Boston criteria was calculated separately using intracranial hemorrhages only and using intracranial hemorrhages and microbleeds.

Results— The sensitivity of the Boston criteria for probable CAA increased from 48% to 63% when microbleeds were included. For symptomatic subjects only, the sensitivity was 100%. No hemorrhages were identified in the deep white matter, basal ganglia, thalamus, or brainstem. Superficial siderosis, observed in 6 patients, did not increase the sensitivity of the Boston criteria in our study group.

Conclusions— Our data show that using T2*-weighted MRI and including microbleeds increase the sensitivity of the Boston criteria. The exclusion of hemorrhages in the deep white matter, basal ganglia, thalamus, and brainstem does not lower the sensitivity of the Boston criteria.

Methods— Fibrinolytic and amidolytic activities of t-PA were investigated in vitro over a range of clinically relevant minocycline concentrations. A suture occlusion model of 3-hour temporary cerebral ischemia in rats treated with t-PA and 2 different minocycline regimens was used. Blood–brain barrier basal lamina components, matrix metalloproteinases (MMPs), hemorrhage formation, infarct size, edema, and behavior outcome were assessed.

Results— Minocycline did not affect t-PA fibrinolysis. However, minocycline treatment at 3 mg/kg IV decreased total protein expression of both MMP-2 (P=0.0034) and MMP-9 (P=0.001 for 92 kDa and P=0.0084 for 87 kDa). It also decreased the incidence of hemorrhage (P=0.019), improved neurologic outcome (P=0.0001 for Bederson score and P=0.0391 for paw grasp test), and appeared to decrease mortality. MMP inhibition was associated with decreased degradation in collagen IV and laminin-1 (P=0.0001).

Conclusions— Combination treatment with minocycline is beneficial in t-PA–treated animals and does not compromise clot lysis. These results also suggest that neurovascular protection by minocycline after stroke may involve direct protection of the blood–brain barrier during thrombolysis with t-PA.

Methods— Patients with moderate motor deficits due to stroke 1 to 12 months prior were randomized (double blinded) to 9 weeks of immediate-release ropinirole or placebo, each with PT, and followed up for 3 additional weeks. Drug dose (0.25 to 4 mg once daily) was titrated weekly, as tolerated. The primary end point was gait velocity during the 12 weeks of study participation.

Results— Patients in the ropinirole+PT group averaged 2.4 mg/d by end of week 9, although the target dose was at least 3 mg/d. Ropinirole+PT was generally safe and well tolerated, including no drug-related serious adverse events. Across all 33 enrollees, significant gains were found over time for gait velocity and for most secondary end points. However, gains did not differ by treatment assignment. PT and occupational therapy were commonly prescribed outside of the trial, although the extent of these was not correlated with study outcomes.

Conclusions— At doses achieved in this trial, increased dopaminergic tone via ropinirole+PT was generally well tolerated but did not show any improvement over and above the effects of PT alone.

Methods— Eight patients with aneurysmal subarachnoid hemorrhage and hemoglobin <10 g/dL were studied with ¹⁵O-positron emission tomography before and after transfusion of 1 U red blood cells. Paired t tests were used to analyze the change in global and regional CBF, oxygen extraction fraction, and oxygen metabolism after transfusion. DO₂ was calculated from CBF and arterial oxygen content. CBF, oxygen metabolism, and DO₂ are reported in mL/100 g/min.

Results— Transfusion resulted in a 15% rise in hemoglobin (8.7±0.8 to 10.0±1.0 g/dL) and arterial oxygen content (11.8±1.0 to 13.6±1.1 mL/dL; both P<0.001). Global CBF remained stable (40.5±8.1 to 41.6±9.9), resulting in an 18% rise in DO₂ from 4.8±1.1 to 5.7±1.4 (P=0.017). This was associated with a fall in oxygen extraction fraction from 0.49±0.11 to 0.41±0.11 (P=0.11) and stable oxygen metabolism. Rise in DO₂ was greater (28%) in regions with oligemia (low DO₂ and oxygen extraction fraction ≥0.5) at baseline but was attenuated (10%) within territories exhibiting angiographic vasospasm, where CBF fell 7%.

Conclusions— Transfusion of red blood cells to anemic patients with subarachnoid hemorrhage resulted in a significant rise in cerebral DO₂ without lowering global CBF. This was associated with reduced oxygen extraction fraction, which may improve tolerance of vulnerable brain regions to further impairments of CBF. Further studies are needed to confirm the benefit of transfusion on delayed cerebral ischemia and balance this against potential systemic and cerebral risks.

Methods— In this monocentric retrospective study we analyzed mortality, long-term functional outcome, and quality of life of all consecutive patients that were treated by SDC for malignant cerebellar infarction in our institution between 1995 and 2006.

Results— A total of 57 patients were identified. All of them were treated by bilateral SDC. An external ventricular drainage was inserted in 82%, necrotic tissue was evacuated in 56% of patients. There were no fatal procedural complications. Five patients were lost for follow-up. In the remaining 52 patients, the mean follow-up interval was 4.7 years (1 to 11 years). Within the first 6 months after surgery 16 of 57 patients (28%) had died. At follow-up, 21 of 52 patients (40%) had died and 4 patients (8%) lived with major disability (mRS 4 or 5). Twenty-one patients (40%) lived functionally independent (mRS 0 to 2). The presence of additional brain stem infarction was associated with poor outcome (mRS ≥4; hazard ratio: 9.1; P=0.001). Quality of life in survivors was moderately lower than in healthy controls.

Conclusions— SDC is a safe procedure in patients with malignant cerebellar infarction. Infarct- but not procedure-related early mortality is substantial. Long-term outcome in survivors is acceptable, particularly in the absence of brain stem infarction.

Methods— Data of 5305 patients in acute stroke trials from the Virtual International Stroke Trials Archive (VISTA) data set were analyzed. Data for temperatures at baseline, eighth, 24th, 48th, and 72nd hours, and seventh day were assessed in relation to outcome (poor versus good) based on the modified Rankin Scale at 3 months. Hyperthermia was defined as temperature >37.2°C and poor outcome as 90-day modified Rankin Scale >2. Hazard ratios with 95% CIs were reported for hyperthermia in relation to the outcome. Logistic regression models, in relation to hyperthermia, were fitted for a set of preselected covariates at different time points to identify predictors/determinants of hyperthermia.

Results— The average age of patients was 68.0±11.9 years, 2380 (44.9%) were females, and 42.3% (2233) received thrombolysis using recombinant tissue plasminogen activator. After adjustment, hyperthermia was a statistically significant predictor of poor outcome. The hazard ratios (95% CI) for poor outcome in relation to hyperthermia at different time points were: baseline 1.2 (1.0 to 1.4), eighth hour 1.7 (1.2 to 2.2), 24th hour 1.5 (1.2 to 1.9), 48th hour 2.0 (1.5 to 2.6), 72nd hour 2.2 (1.7 to 2.9), and seventh day 2.7 (2.0 to 3.8). Gender, stroke severity (National Institutes of Health Stroke Scale score >16), white blood cell count, and antibiotic use were significantly associated with hyperthermia (P≤0.01).

Conclusions— Hyperthermia, in acute ischemic stroke, is associated with a poor clinical outcome. The later the hyperthermia occurs within the first week, the worse the prognosis. Severity of stroke and inflammation are important determinants of hyperthermia after ischemic stroke. In patients with acute ischemic stroke, aggressive measures to prevent and treat hyperthermia could improve the clinical outcomes.

Methods— In this retrospective single-center study 56 consecutive patients with acute space-occupying cerebellar infarction treated surgically between 1996 and 2005 were included. Baseline data included clinical findings, Glasgow Coma Scale on admission and before surgery, NIHSS on admission, mass effects on neuroimaging, and surgical treatment strategies. Modified Rankin Scale, NIHSS, and Scale for the Assessment and Rating of Ataxia were used to assess outcome.

Results— 39.3% of patients had died, 51.8% had a mRS ≤3, 35.7% had a mRS ≤2, 28.6% had a mRS ≤1. There were no significant differences in survival between treatment groups. In multivariate analysis age and mRS score at discharge were the most evident independent predictors for outcome.

Conclusions— So far this is the largest study on long-term outcome after space-occupying cerebellar infarction. The value of different treatment strategies and prognostic factors for patient selection remain unclear and should be evaluated in larger prospective case-series or registries. To investigate the issue of preventive SDC randomized trials are needed.

Methods— We examined patients with acute ischemic stroke treated with intravenous tissue plasminogen activator within 3 hours of symptom onset who were enrolled in the placebo arms of 2 trials (Stroke-Acute Ischemic NXY Treatment [SAINT] I and II Trials) of a putative neuroprotectant. Early CT changes were graded using the Alberta Stroke Program Early CT Score (ASPECTS). Post–tissue plasminogen activator symptomatic intracerebral hemorrhage was defined as a worsening in National Institutes of Health Stroke Scale of ≥4 points within 36 hours with evidence of hemorrhage on follow-up neuroimaging. Good clinical outcome was defined as a modified Rankin scale of 0 to 2 at 90 days.

Results— Symptomatic intracerebral hemorrhage occurred in 5.6% of 965 patients treated with tissue plasminogen activator. In multivariable analysis, symptomatic intracerebral hemorrhage was increased with baseline antiplatelet use (single antiplatelet: OR, 2.04, 95% CI, 1.07 to 3.87, P=0.03; double antiplatelet: OR, 9.29, 3.28 to 26.32, P<0.001), higher National Institutes of Health Stroke Scale score (OR, 1.09 per point, 1.03 to 1.15, P=0.002), and CT changes defined by ASPECTS (ASPECTS 8 to 9: OR, 2.26, 0.63 to 8.10, P=0.21; ASPECTS ≤7: OR, 5.63, 1.66 to 19.10, P=0.006). Higher National Institutes of Health Stroke Scale was associated with decreased odds of good clinical outcome (OR, 0.82 per point, 0.79 to 0.85, P<0.001). There was no relationship between baseline antiplatelet use or CT changes and clinical outcome.

Conclusions— Along with higher National Institutes of Health Stroke Scale and extensive early CT changes, baseline antiplatelet use (particularly double antiplatelet therapy) was associated with an increased risk of post–tissue plasminogen activator symptomatic intracerebral hemorrhage. Of these factors, only National Institutes of Health Stroke Scale was associated with clinical outcome.

Methods— One hundred one clinically depressed patients with ischemic stroke within 4 months of index stroke were randomly assigned to an 8-week brief psychosocial–behavioral intervention plus antidepressant or usual care, including antidepressant. The primary end point was reduction in depressive symptom severity at 12 months after entry.

Results— Hamilton Rating Scale for Depression raw score in the intervention group was significantly lower immediately posttreatment (P<0.001) and at 12 months (P=0.05) compared with control subjects. Remission (Hamilton Rating Scale for Depression <10) was significantly greater immediately posttreatment and at 12 months in the intervention group compared with the usual care control. The mean percent decrease (47%±26% intervention versus 32%±36% control, P=0.02) and the mean absolute decrease (–9.2±5.7 intervention versus –6.2±6.4 control, P=0.023) in Hamilton Rating Scale for Depression at 12 months were clinically important and statistically significant in the intervention group compared with control.

Conclusion— A brief psychosocial–behavioral intervention is highly effective in reducing depression in both the short and long term.

Methods— This was a single-blind, randomized, controlled trial with a 6-month follow-up. Ninety-seven subjects were recruited within 6 weeks of stroke onset and were randomly assigned to conventional rehabilitative treatment plus gait training with body weight support on a treadmill (experimental group; n=52) and conventional treatment with overground gait training only (control group; n=45). All subjects were treated in 60-minute sessions every weekday for 4 weeks. Outcome measures were Motricity Index, Trunk Control test, Barthel Index, Functional Ambulation Categories, 10-meter and 6-minute Walk Tests, and Walking Handicap Scale. Assessments were made at baseline, after 20 sessions of treatment, 2 weeks after treatment, and 6 months after stroke.

Results— After treatment, all patients were able to walk. Both groups showed improvement in all outcome measures (P<0.0063) at the end of the treatment and at follow-up. No differences were seen between the 2 groups before, during, and after treatment and at follow-up.

Conclusions— In subacute patients with stroke, gait training on a treadmill with body weight support is feasible and as effective as conventional gait training. However, the need for more personnel for treadmill training makes the use of robotically assisted systems more compelling.

Methods— Twelve individuals (60.6±14.5 years of age; 5 male) with chronic stroke (69.1±82.2 months; 5 with right-sided hemiparesis) participated in the study. The intervention consisted of a SLE knee extension/flexion protocol 3 times per week for 4 weeks. Using Doppler ultrasound, bilateral femoral artery blood flow, diameter, and peak flow velocity were assessed at baseline, after 2 weeks, and after 4 weeks of SLE.

Results— Using repeated-measures analysis of variance, femoral artery blood flow, arterial diameter, and blood flow velocity in the hemiparetic limb were significantly improved (P<0.0001) after the SLE. No significant changes occurred in the nontrained limb for any outcome measures.

Conclusions— These data suggest that a 4-week SLE training program that increases muscular activity in the hemiparetic limb improves femoral artery blood flow, diameter, and peak velocity. SLE may be an important training strategy in stroke rehabilitation to minimize the vascular changes that occur poststroke due to decreased activity of the hemiparetic limb.

Methods— Using data from 1176 patients with a definite or possible transient ischemic attack or minor stroke included in the SOS-TIA registry (January 2003 to June 2007), we studied the usefulness of the conventional ABCD² score cutoff as well as the NICE criteria for urgent admission to a stroke unit defined as presence of symptomatic internal carotid artery stenosis ≥50%, symptomatic intracranial artery stenosis ≥50%, or major cardiac source of embolism.

Results— Among 697 patients with an ABCD² score <4, 20% required immediate consideration for emergency treatment (eg, symptomatic internal carotid stenosis ≥50% in 9.1% of patients, symptomatic intracranial stenosis in 5.0%, atrial fibrillation in 5.9%, other major cardiac source of embolism in 2.1%) in comparison to 31.6% of 497 patients with an ABCD² score ≥4. The sensitivity and specificity of ABCD² score ≥4 or NICE criteria for discriminating between patients requiring admission or not were <62% with low positive predictive values (<30%) and high negative predictive values (≥80%).

Conclusions— One in 5 patients with an ABCD² score <4 had high-risk disease requiring urgent treatment decision-making. When triaging on an ABCD² score, we recommend adding systematic carotid ultrasound (or a default angiographic CT scan) and electrocardiography within 24 hours before postponing complete transient ischemic attack evaluation.

Methods— From the state hospital discharge database, admissions with a primary diagnosis of stroke discharged from 2002 to 2006 were identified. Age group–specific stroke admission rates, hospital charges, length of stay, intensive care unit utilization, medical complications, and discharge disposition (in-hospital death, discharged home, discharge to rehabilitation facility) were compared between AAs and CAs by multiple-linear or logistic-regression analysis.

Results— There were 58 272 stroke admissions during the 5-year period. Stroke admission rates were persistently higher for AAs in all age groups except those ≥85 years old. Hospital charges totaled $1.51 billion; 24.0% ($362.5 million) of this total was attributable to racial disparities, 70.8% ($256.5 million) of which stemmed from the 36.6% of patients <65 years old. Most of the acute outcomes were poorer for AAs compared with CAs across age groups.

Conclusions— Racial disparities in stroke admissions are more pronounced in younger age groups and result in significant economic consequences. Although AA stroke patients experienced generally worse acute outcomes than did CAs, these differences appear to be relatively consistent across age groups.

Methods— We assessed the effect of G-CSF on ischemic lesion evolution in a rat permanent-suture occlusion model with diffusion- and perfusion-weighted magnetic resonance imaging and the neuroprotective effect of G-CSF in a rat embolic stroke model.

Results— With a constant perfusion deficit, vehicle-treated animals showed an expanding apparent diffusion coefficient lesion volume that matched the perfusion deficit volume at 3 hours, with the 24-hour infarct volume equivalent to the perfusion deficit. In G-CSF–treated rats, the apparent diffusion coefficient lesion volume did not increase after treatment initiation, and the infarct volume at 24 hours reflected the initial apparent diffusion coefficient lesion volume. In the embolic model, we observed a significant decrease in infarct volume in G-CSF–treated animals compared with the vehicle-treated group.

Conclusions— These results confirm the potent neuroprotective activity of G-CSF in different focal ischemia models. The magnetic resonance imaging data demonstrate that G-CSF preserved the perfusion/diffusion mismatch.

Methods— HI was induced by right CCA ligation and 75 minutes 8% oxygen. Histochemistry and immunocytochemistry described the time course of early cellular changes in the CNS. For neuroprotection by MC stabilization, pups were treated with Cromolyn (CR) during the initial 24 hours post-HI; brains were examined through 4 weeks.

Results— Brain MC number and activation were elevated in ipsilateral hemisphere immediately after HI (P<0.05), before detection of cleaved caspase-3 in neurons (NeuN+; 2 hours post-HI), astroglial activation (GFAP+ with swollen cell body, 4 hours post-HI), or microglial activation (OX42+, 4 hours post-HI). TNF--positive MCs were present in a subpopulation of MCs in control animals and the percent of TNF- MCs increased dramatically ipsilaterally immediately after HI (P<0.01). Microglial TNF- was evident at 4 hours; endothelial cells had no detectable TNF- until 48 hours post-HI. Cromolyn prevented MC migration, reduced brain damage/neuronal loss, glial activation, and brain atrophy through 4 weeks of recovery (P<0.05).

Conclusions— MCs are early responders to HI in neonatal brain. MC stabilization provides lasting protection and suggests a new target for therapeutic interventions.

Methods— By electronic and manual searches of the literature, we identified studies describing the efficacy of EPO in experimental focal cerebral ischemia. Data on study quality, EPO dose, time of administration, and outcome measured as infarct volume or functional deficit were extracted. Data from all studies were pooled by means of a meta-analysis.

Results— Sixteen studies were included in the meta-analysis. When administered after the onset of ischemia, EPO and its analogues reduced infarct size by 32% and improved neurobehavioral deficits significantly. A meta-regression suggests higher doses of EPO to be associated with smaller infarct volumes. When administered earlier than 6 hours EPO was more effective compared to a later treatment initiation. Both hematopoietic and nonhematopoietic EPO analogues showed efficacy in experimental stroke.

Conclusion— In conclusion, this analysis further strengthens confidence in the efficacy of EPO and its analogues in stroke therapy. Nonhematopoietic EPO analogues which are known to have less systemic adverse effects compared to EPO are also promising candidate stroke drugs. Further experimental studies are required that evaluate the safety of a combination of EPO with thrombolysis and whether EPO is also effective in animals with comorbidity.

Methods— Sprague-Dawley rats were anesthetized with isoflurane and subjected to 2 hour of MCAo. Animals were treated with either DHA (low doses=3.5 or 7 mg/kg; medium doses=16 or 35 mg/kg; and high dose=70 mg/kg) or an equivalent volume of saline intravenously 3 hours after MCAo onset. Neurologic status was evaluated during occlusion (60 minutes) and on days 1, 2, 3, and 7 after MCAo. Seven days after MCAo, brains were perfusion-fixed, and infarct areas and volumes were determined.

Results— Only the low and medium doses of DHA significantly improved the neurologic score compared with vehicle-treated rats at 24 hours, 48 hours, 72 hours, and 7 days. DHA markedly reduced total corrected infarct volume in all treated groups compared with vehicle-treated rats (3.5 mg/kg, 26±9 mm³; 7 mg/kg, 46±12 mm³; 16 mg/kg, 37±5 mm³; and 35 mg/kg, 34±15 mm³ vs vehicle, 94±12 mm³). Cortical and striatal infarct volumes were also significantly reduced by treatment with DHA. No neuroprotective effects were observed with 70 mg/kg DHA.

Conclusions— We conclude that DHA experimental therapy at low and medium doses improves neurologic and histologic outcomes after focal cerebral ischemia and might provide benefits in patients after ischemic stroke.

Methods— One hundred thirty-eight patients with suspected or known aneurysms and other cerebral vascular diseases detected by MR angiography underwent digital subtraction angiography examinations. Postprocessing techniques, including VR and the single artery highlighting method, were performed by a 3-dimensional specialist. The VR-digital subtraction angiography was obtained as the gold standard.

Results— The rotational digital subtraction angiography and VR-digital subtraction angiography revealed 146 aneurysms in 122 patients and no aneurysms in 16 patients. Of the 276 vessels examined, 136 vessels had 146 aneurysms and 140 vessels had none. Per vessel and per aneurysm sensitivities were 100%, whereas the per vessel accuracy ranged from 97.5% to 98.6% and the per aneurysm accuracy ranged from 95.1% to 97.0%.

Conclusions— VR 3-dimensional time-of-flight MR angiography at 3 T has excellent sensitivity, accuracy, and correlation with VR-digital subtraction angiography and is comparable to catheter cerebral angiography for the evaluation of patients with intracranial aneurysms who tolerate MR angiography well.

Methods— Patients with internal carotid artery and M1 occlusion were prospectively studied. MRI studies, including DWI, T2*, and MRA, were performed before and within 30 minutes and 24 hours after t-PA infusion. The NIHSS score was obtained before and 7 days after t-PA administration. The relationship between the presence of the M1 SVS and no early recanalization and patient outcome was examined.

Results— A total of 48 patients (29 men; mean age, 74.6±11.2 years) were enrolled. M1 SVS was present in 13 (27.1%) patients and absent in 35 (72.9%) patients. There were no significant differences in clinical characteristics between the 2 groups. Follow-up MRA within 30 minutes after t-PA infusion revealed that 20 (57.1%) of the 35 patients without the M1 SVS had early recanalization, but that none of the 13 patients with the M1 SVS had early recanalization (P=0.0002). Seven days after t-PA infusion, dramatic improvement was more frequently observed in patients without the M1 SVS (51.4%) than in those with the M1 SVS (0%, P=0.0007).

Conclusion— The M1 SVS on T2* appears to be a strong predictor for no early recanalization after t-PA therapy.

Methods— In the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort (624 patients with cerebral vein and dural sinus thrombosis), we analyzed the predictors and the impact on outcome of diagnostic delay. Primary outcome was a modified Rankin Scale score >2 at the end of follow-up. Secondary outcomes were modified Rankin Scale score 0 to 1 at the end of follow-up, death, and visual deficits (visual acuity or visual field).

Results— Median delay was 7 days (interquartile range, 3 to 16). Patients with disturbance of consciousness (P<0.001) and of mental status (P=0.042), seizure (<0.001), and with parenchymal lesions on admission CT/MR (P<0.001) were diagnosed earlier, whereas men (P=0.01) and those with isolated intracranial hypertension syndrome (P=0.04) were diagnosed later. Between patients diagnosed earlier and later than the median delay, no statistically significant differences were found in the primary (P=0.33) and in secondary outcomes: modified Rankin Scale score 0 to 1 (P=0.86) or deaths (P=0.53). Persistent visual deficits were more frequent in patients diagnosed later (P=0.05). In patients with isolated intracranial hypertension syndrome, modified Rankin Scale score >2 at the end of follow-up was more frequent in patients diagnosed later (P=0.02).

Conclusions— Diagnostic delay was considerable in this cohort and was associated with an increased risk of visual deficit. In patients with isolated intracranial hypertension syndrome, diagnostic delay was also associated with death or dependency.

Methods— C57BL mice were administered 100% oxygen for 1 hour at 2.5 atmosphere absolute for 5 consecutive days and subjected to SBI. Neurological status and brain edema were evaluated at 24 hours and 72 hours after the brain insult. Fluorescent immunostaining and Western blotting were performed to study hypoxia-inducible factor-1 and COX-2, respectively. Two doses of COX-2 inhibitor, NS398 (3 mg/kg and 10 mg/kg) were used to verify the role of COX-2 signaling pathway in the mechanism of HBO-PC.

Results— HBO-PC improved neurological status and decreased brain edema at 24 hours and 72 hours after SBI. HBO-PC by itself and SBI independently increased COX-2 levels by 2-fold and 4-fold, respectively. HBO-PC, however, reduced increase in hypoxia-inducible factor-1 and COX-2 expression after SBI. The HBO-PC-induced improvement in neurological status and brain edema was reversed by a suboptimal dose of the COX-2 inhibitor, NS398 (10 mg/kg intraperitoneally; 1/4th of dose shown to provide neuroprotection), which itself had no effect on investigated end points.

Conclusions— HBO-PC attenuates postoperative brain edema and improves neurological outcomes after SBI. The HBO-PC-induced neuroprotection is mediated through COX-2 signaling pathways.

Summary of Review— This review discusses reasons for the lack of translational success based on the therapeutic targets tested and the pathophysiology of stroke. New recanalization therapies and alternative therapeutic strategies are discussed concerning mitochondria-mediated cell death. Mitochondrial death-regulation pathways are divided into 3 categories: Upstream signaling pathways, agents that target mitochondria directly, and downstream death-execution effectors. The apoptosis signal-related kinase/c-Jun-terminal kinase pathway is used as an example to provide rationale as to why inhibiting signaling pathway upstream of mitochondrial dysfunction is a promising therapeutic approach. Finally, the mechanisms of autophagy and mitochondrial biogenesis are discussed in relation to stroke.

Conclusions— Increasing evidence suggests that reperfusion is necessary for improved neurological outcomes after stroke. Development of improved recanalization methods with increased therapeutic windows will aid in improving clinical outcome. Adjunct neuroprotective interventions must also be developed to ensure maximal brain tissue salvage. Targeting prodeath signaling pathways upstream of mitochondrial damage is promising for potential clinically effective treatment. Further understanding of the roles of equilibrium of autophagy and mitochondrial biogenesis in the pathogenesis of stroke could also lead to novel therapeutics.

Summary of Case— In 2 patients with severe acute brain injury (traumatic and spontaneous intracranial hemorrhage), spreading depolarizations were inhibited by the noncompetitive N-methyl-d-aspartate receptor antagonist ketamine. This restored electrocorticographic activity.

Conclusions— These anecdotal electrocorticographic findings suggest that ketamine has an inhibitory effect on spreading depolarizations in humans. This is of potential interest for future neuroprotective trials.

Methods— We searched PubMed and EMBASE (January 1999 to September 2008) for studies of >50 coiled aneurysms. Two reviewers independently extracted data. We grouped studies reporting on only ruptured aneurysms, posterior circulation aneurysms, and studies with large proportions of aneurysms >10 mm to assess possible determinants for incomplete occlusion, reopening, and retreatment.

Results— Forty-six studies totalling 8161 coiled aneurysms met inclusion criteria. Immediately after coiling, 91.2% (95% CI, 90.6% to 91.9%) of the aneurysms were adequately occluded. Aneurysm reopening occurred in 20.8% (95% CI, 19.8% to 21.9%) and retreatment was performed in 10.3% (95% CI, 9.5% to 11.0%). Reopening rate was lower in studies reporting on ruptured aneurysms only compared with all studies (11.4% versus 20.8%; relative risk, 0.55; 95% CI, 0.47 to 0.64) and higher in studies focusing on posterior circulation aneurysms compared with studies with >85% anterior circulation aneurysms (22.5% versus 15.5%; relative risk, 1.5; 95% CI,1.2 to 1.7). Regression analysis showed higher retreatment rates with increasing proportion of aneurysms >10 mm (β=0.252; 95% CI, 0.073 to 0.432). We could not find a relation between reopening and type of coils used.

Conclusion— At follow-up, one fifth of all coiled intracranial aneurysms shows reopening of which half is retreated. Possible risk factors for aneurysm reopening are location in the posterior circulation and size >10 mm. To confirm our findings, a meta-analysis on individual well-reported patient data is desirable.

Methods— Nine hundred seventy-two patients with transient ischemic attack or ischemic stroke were prospectively and consecutively enrolled in the Netherlands Stroke Survey. We applied 7 large antiplatelet trials’ enrollment criteria.

Results— In total, 886 patients were discharged alive and available for secondary prevention. Mean follow-up was 2.5 years. The annual rate of transient ischemic attack, stroke, or nonfatal myocardial infarction was 6.7%. The proportions of patients fulfilling the trial enrollment criteria ranged from 25% to 67%. Mortality was significantly higher in ineligible patients (27% to 41%) than in patients fulfilling enrollment criteria (16% to 20%). Rates of vascular events were not higher in trial-eligible patients than in ineligible patients.

Conclusions— Our data confirm that patients with ischemic attack and stroke enrolled in randomized clinical trials are only partially representative of patients in clinical practice. Use of less strict enrollment criteria could enhance "generalizability" and result in more efficient selection of patients for randomized clinical trials.

Methods— Using the data from the Rochester Stroke and Transient Ischemic Attack Registry and resources of the Rochester Epidemiology Project, medical records of all residents of Rochester, Minn, with a diagnosis of incident transient ischemic attack from 1985 through 1994 were examined (N=284). Patients were scored on the ABCD and ABCD2 scales and new scores were created by adding hyperglycemia and a history of hypertension. The end points of stroke and death were collected previously and were verified through the Rochester Epidemiology Project data.

Results— Although our study did find that scores >4 had a statistically significant predictive value for future stroke, a substantial proportion of strokes within 7 days (9 of 36 cases [25%]) occurred in patients with low or intermediate risk scores (≤4) on the ABCD2 scale. Including history of hypertension and hyperglycemia on presentation increased the sensitivity of the score to identify patients who had a stroke within 7 days.

Conclusions— Reliance on the ABCD and ABCD2 scores misses some patients who will have a stroke within 7 days of a transient ischemic attack. Adding hyperglycemia and a history of hypertension to the predictive model could be useful, but the value of these additions need to be evaluated further.

Methods— We studied 5494 Japanese individuals (ages 30 to 79, without stroke or MI at baseline) who completed a baseline survey and received follow-up through December 2005. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease study equation modified by the Japanese coefficient. CKD was defined as an estimated GFR <60 mL/min/1.73m². BP categories were defined by the European Society of Hypertension and European Society of Cardiology 2007 criteria.

Results— In 64 395 person-years of follow-up, we documented 346 incidences of cardiovascular diseases (CVD; 213 strokes and 133 MI events). Compared with the GFR (≥90 mL/min/1.73m²) group, the hazard ratios (95% confidential intervals) for stroke were 1.9 (1.3 to 3.0) in the GFR 50 to 59 mL/min/1.73m² group and 2.2 (1.2 to 4.1) in the GFR <50 mL/min/1.73m² group. Results for cerebral infarction were similar. Compared with the optimal BP subjects without CKD, the normal BP, high-normal BP, and hypertensive subjects without CKD showed increased risks of CVD and stroke; however the impact of each BP category on CVD (P for interaction: 0.04 in men, 0.49 in women) and stroke (0.03 in men, 0.90 in women) was more evident in men with CKD.

Conclusions— CKD may increase the association of BP and CVD in a Japanese urban population.

Methods— We evaluated associations of gravidity and parity with incidence of stroke in the Shanghai Women’s Health Study (SWHS), a population-based cohort study of 74 942 Chinese women aged 40 to 70 years at enrollment (1996 to 2000). We also examined the association between number of children and stroke prevalence in both SWHS participants and their husbands. Stroke cases were ascertained through in-person interviews and linkage with vital statistics registries.

Results— During a mean follow-up of 7.3 years, 2343 incident cases of stroke were identified. Women with more pregnancies or live births had a significantly increased risk for incident stroke. After adjustment for socioeconomic status and other potential confounders, women with ≥5 pregnancies had a hazard ratio for incident stroke of 1.45 (95% CI, 1.18 to 1.77) compared with those with only one pregnancy. At baseline recruitment, 859 and 1274 prevalent cases of stroke were reported among SWHS participants and their husbands, respectively. Stroke prevalence increased with increasing number of children in both women and men. Adjusted ORs of prevalent stroke for having ≥5 children versus having one child were 1.61 (95% CI, 1.16 to 2.23) in women and 1.45 (1.11 to 1.89) in men.

Conclusions— High gravidity or parity may be related to increased risk of stroke in women. Chronic stress and adverse lifestyle factors related to childrearing may contribute importantly to the increased risk.

Methods— Data were retrospectively collected from the Taiwan National Health Insurance Research Database, which is comprised of 1 073 891 random subjects from among Taiwan’s 23 million residents. The study cohort comprised all patients with a diagnosis of OAG (International Classification of Diseases, 9th Revision, Clinical Modification code 365.1 to 365.11) in 2001 (n=4032). The comparison cohort was comprised of randomly selected patients (5 for every patient with OAG, n=20 160) matched with the study group in terms of age, gender, geographic location, and comorbid medical disorders. Patients were tracked from their index visits for 5 years. Cox proportional hazard regression was used to compute the 5-year stroke-free survival rate after adjusting for possible confounding factors.

Results— Stroke developed in 14.9% of patients with OAG and 9.5% of patients in the comparison cohort during the 5-year follow-up period. Patients with OAG had significantly lower 5-year stroke-free survival rates than patients in the comparison cohort. After adjusting for patients’ demographic characteristics and selected comorbidities, patients with OAG were found to have a 1.52-fold (95% CI, 1.40 to 1.72) higher risk of having a stroke than the matched comparison cohort.

Conclusions— Patients with OAG demonstrated a significantly increased risk of stroke development during the 5-year follow-up period.

Methods— Through the National Hospital Discharge Register linked with the Cause of Death Register, 12 904 males and 15 250 females with first strokes were detected for the period 1987 to 2006. Cardiovascular risk factor data were available for random population samples of men and women aged 50 years from 1963 to 2003.

Results— Incidence and mortality rates for all-stroke were unchanged. Rates for subarachnoid hemorrhage declined for the age group 45 to 54 in men, but not significantly in any other age group of men or women. Mortality rates of intracerebral hemorrhage declined for women aged 65 to 74, with no significant changes in any other age group. Ischemic stroke incidence did not change, but mortality increased for men and women aged 75 and older, whereas mortality declined for the age group 20 to 44 for men. In the general population there were significant reductions in smoking, total cholesterol, and blood pressure levels in both men and women, whereas diabetes prevalence, body weight, and BMI increased among both sexes, and triglycerides increased in men.

Conclusion— Contrary to myocardial infarction, stroke incidence and mortality did not change. Monitoring of cardiovascular risk factors in the community is important.

Methods— We analyzed 5-year mortality data of all consecutive patients aged 15 to 49 with first-ever ischemic stroke treated at the Department of Neurology, Helsinki University Central Hospital, from January 1994 to September 2003. We followed up the patients using data from the mortality registry of Statistics Finland. We used life table analyses for calculating mortality risks. Kaplan-Meier method allowed comparisons of survival between clinical subgroups. We used the Cox proportional hazard model for identifying predictors of mortality. Stroke severity was measured using the National Institutes of Health Stroke Scale and the Glasgow Coma Scale.

Results— Among the 731 patients (mean age, 41.5±7.4 years; 62.8% males) followed, 78 died. Cumulative mortality risks were 2.7% (95% CI, 1.5% to 3.9%) at 1 month, 4.7% (3.1% to 6.3%) at 1 year, and 10.7% (9.9% to 11.5%) at 5 years with no gender difference. Those ≥45 years of age had lower probabilities of survival. Among the 30-day survivors (n=711), stroke caused 21%, cardioaortic and other vascular causes 36%, malignancies 12%, and infections 9% of the deaths. Malignancy, heart failure, heavy drinking, preceding infection, type 1 diabetes, increasing age, and large artery atherosclerosis causing the index stroke independently predicted 5-year mortality adjusted for age, gender, relevant risk factors, stroke severity, and etiologic subtype.

Conclusions— Despite the overall low mortality after an ischemic stroke in young adults, several recognizable subgroups had substantially increased risk of death in the long term.

Methods— Cross-sectional and prospective data from a nationally representative survey of noninstitutionalized civilian U.S. population aged 25 or older (n=20 050) with a baseline history of stroke (n=644) followed up from survey participation (1988–1994) through mortality assessment in 2000. Relationships between BMI and mortality attributable to all causes or cardiovascular causes were examined after adjusting for established prognosticators after stroke.

Results— Stroke survivors were more likely to be overweight (BMI 25 to 29 kg/m²) or obese (BMI ≥30 kg/m²) than those without stroke (64.3% versus 53.2%, P=0.003). In multivariable analysis, overall risk for all-cause mortality increased per kg/m² of higher BMI (P=0.030), but an interaction between age and BMI (P=0.009) revealed that the association of higher BMI with mortality risk was strongest in younger individuals and declined linearly with increasing age, such that in the elderly, overweightness and obesity had a protective effect. The results were similar for the cardiovascular mortality outcome.

Conclusions— Higher BMI after stroke is associated with a greater risk of all-cause and cardiovascular death among younger individuals. Younger stroke survivors may especially benefit from more vigorous efforts to monitor and treat obesity.

Methods— A 2-step postal survey was sent to all of the 2475 institutions providing medical or care services for individuals with dementia in Japan’s Ibaraki prefecture (population, 2 966 000) requesting information on EOD cases. Data were then reviewed and collated.

Results— We identified 617 subjects with EOD. The estimated prevalence of EOD in the target population was 42.3 per 100 000 (95% CI, 39.4 to 45.4). Of the illnesses that cause EOD, vascular dementia was the most frequent (42.5%) followed by Alzheimer disease (25.6%), head trauma (7.1%), dementia with Lewy bodies/Parkinson disease with dementia (6.2%), frontotemporal lobar degeneration (2.6%), and other causes (16.0%).

Conclusions— The prevalence of EOD in Japan appeared to be similar to that in Western countries with the notable exception that vascular dementia was the most frequent cause of EOD in Japan.

Methods— We investigated the cross-sectional relations of plasma ADMA with CCA-IMT and ICA/bulb IMT in 2958 Framingham Heart Study participants (mean age, 58 years; 55% women).

Results— In unadjusted analyses, ADMA was positively related to both CCA-IMT (β per SD increment, 0.012; P<0.001) and ICA/bulb IMT (β per SD increment, 0.059; P<0.001). In multivariable analyses (adjusting for age, sex, systolic blood pressure, antihypertensive treatment, smoking status, diabetes, BMI, total-to-HDL cholesterol ratio, log C-reactive protein, and serum creatinine), plasma ADMA was not associated with CCA-IMT (P=0.991), but remained significantly and positively related to ICA/bulb IMT (β per SD increment, 0.0246; P=0.002).

Conclusions— In our large community-based sample, we observed that higher plasma ADMA concentrations were associated with greater ICA/bulb IMT, but not with CCA-IMT. These data are consistent with the notion that ADMA promotes subclinical atherosclerosis in a site-specific manner, with a greater proatherogenic influence at known vulnerable sites in the arterial tree.

Methods— We tested the hypothesis that variants in 2 genes encoding vascular endothelial growth factor and vascular endothelial growth factor receptor-2 are associated with susceptibility to stroke and its recurrence in a Chinese case–control study comprising 1849 patients with stroke and 1798 control subjects and replicated the investigation in an independent study comprising 327 cases and 327 control subjects. The correlation of variants with carotid artery intima media thickness was examined in 1123 healthy individuals.

Results— Compared with their corresponding wild-type genotypes, one coding variant, rs2305948 (Val297Ile), in the vascular endothelial growth factor receptor-2 gene was associated with increased susceptibility to intracerebral hemorrhage (additive model: OR, 2.06; 95% CI, 1.64 to 2.59; P=7.6x10^–10; dominant model: OR, 2.20; 95% CI, 1.70 to 2.84; P=1.5x10^–9), a promoter variant rs2071559 (–604T>C) in the gene was associated with reduced susceptibility to atherothrombotic stroke (additive model: OR, 0.82; 95% CI, 0.71 to 0.93; P=0.003; dominant model: OR, 0.78; 95% CI, 0.65 to 0.92; P=0.004) and was reversely correlated with carotid artery intima media thickness (P=2.8x10^–5). Replication in the second study yielded similar results. During a median 4.5 years of follow-up for the first stroke population, 355 recurrent strokes were documented. Subjects carrying 297Ile had a higher risk for stroke recurrence (relative risk, 1.40; 95% CI, 1.12 to 1.75; P=0.003), and those with –604C had a lower risk for recurrence (relative risk, 0.71; 95% CI, 0.58 to 0.89; P=0.002) than their wild-type carriers.

Conclusions— The vascular endothelial growth factor receptor-2 gene variants may serve as novel genetic markers for the risk of stroke and its recurrence.

Methods— One hundred sixty-three patients with symptomatic carotid stenosis and initial mild stroke (121) or TIA (42) were evaluated within 6 hours from onset of symptoms in a single tertiary hospital. Neurological recurrence (NR) was defined as a clearly defined new neurological event (TIA or stroke) or an increase of 4 points in the initial NIHSS. The NR rate was determined at 72 hours, 7 days, and 14 days. Disability was defined as a score of 3 to 6 on the modified Rankin scale at 14 days.

Results— Forty-five patients (27.6%) had NR, including 6 patients with 2 episodes in different time periods: 34 (20.9%) within the first 72 hours; 11 (6.7%) between 72 hours and 7 days; and 6 (3.7%) at 14 days. Only carotid stenosis ≥70% was associated with NR; diabetes was marginally associated. At 2 weeks, 19 patients (11.7%) had disability; 14 of them experienced NR in the first 72 hours.

Conclusions— Patients with first-ever mild stroke or TIA and symptomatic carotid stenosis are at high risk for NR, especially within the first 72 hours. Our results suggest the necessity of testing pharmacological or interventional strategies for use during the hyperacute stroke phase in these patients.

Methods— 216 consecutive patients presenting with posterior circulation TIA or stroke were recruited and prospectively followed for 90 days. 8 patients with vertebral dissection were excluded. CE-MRA or CTA at presentation and 90-day follow-up was available in 182. Any posterior circulation TIA/stroke in the month before the presenting episode was recorded.

Results— Taking the first event (including TIA/stroke in the previous month) as the index case recurrent stroke risk in patients with stenosis was 30.5% versus 8.9% in those without; RR 3.4 (95% CI 1.7 to 7.0), P<0.001). Taking the presenting episode as the index case the risk was 13.8% versus 4.1%; RR 3.4 (95% CI 1.1 to 10.5) P=0.0274. The probability of recurrence was highest soon after the initial event.

Conclusions— The presence of vertebro-basilar stenosis identifies a group of patients with posterior circulation stroke who have a high early recurrent stroke risk. Early intervention might reduce recurrent stroke risk. Vertebral stenosis can now be treated by stenting, but determining whether this reduces the early stoke risk requires randomized controlled trials.

Methods— Consecutive patients with acute cerebral ischemia underwent serial National Institutes of Health Stroke Scale and bilateral transcranial Doppler monitoring with breathholding. Steal magnitude (%) was calculated from transient mean flow velocity reduction in the affected arteries at the time of velocity increase in normal vessels. Excessive sleepiness and likelihood of sleep apnea were evaluated by the Epworth Sleepiness Scale and Berlin Questionnaire.

Results— Among 153 patients (age, 61±14 years; 48% women; 21% transient ischemic attack) admitted within 48 hours from symptom onset, 21 (14%) had steal phenomenon (median steal magnitude, 20%; interquartile range, 11%; range, 6% to 45%), and 11 (7%) had RRHS. RRHS was most frequent in patients with proximal arterial occlusions (17% versus 1%; P<0.001). The following factors were independently (P<0.05) associated with RRHS (multivariate logistic regression model): male gender, younger age, persisting arterial occlusions, and excessive sleepiness (P<0.001). A 1-point increase in the Epworth Sleepiness Scale was independently related to an increased likelihood of RRHS of 36% (95% CI, 7% to 73%).

Conclusions— RRHS and hemodynamic steal can be found in 7% and 14%, respectively, of consecutive patients with stroke without other known causes for deterioration. Patients with persisting arterial occlusions and excessive sleepiness can be particularly vulnerable to the steal.

Methods— In this retrospective multicenter study, prospectively collected data of 217 patients with anterior circulation stroke treated with intravenous or intraarterial thrombolysis within 6 hours after symptom onset were analyzed. Pretreatment DWI-ASPECTS scores were assessed by 2 independent investigators. For bleeding risk analysis, DWI-ASPECTS scores were either categorized into 0 to 7 (n=105) or 8 to 10 (n=112) or in 3 groups of similar sample size (DWI-ASPECTS 0 to 5 [n=69], 6 to 7 [n=70], and 8 to 10 [n=78]).

Results— DWI-ASPECTS scores correlated well with the DWI lesion volume (r=0.77, P<0.001, Spearman Rank test). Interobserver reliability for the assessment of DWI-ASPECTS was moderate (weighted kappa 0.441 [95% CI 0.373 to 0.509]). Twenty-three (10.6%) patients developed sICH. The sICH rate was significantly higher in patients with DWI-ASPECTS scores 0 to 7 (n=21, 15.1%) as compared to patients with DWI-ASPECTS scores 8 to 10 (n=2, 2.6%, P=0.004). sICH risk was 20.3%, 10%, and 2.6% in the 0 to 5, 6 to 7, and 8 to 10 DWI-ASPECTS groups, respectively. DWI-ASPECTS remained an independent prognostic factor for sICH after adjustment for clinical baseline variables (age, NIHSS, time to thrombolysis).

Conclusions— DWI-ASPECTS predicts sICH risk after thrombolysis and may be helpful to contributing to quick sICH risk assessment before thrombolytic therapy.

Methods— Thirteen consecutive AVM patients were assessed by 4D radial acquisition contrast-enhanced MRA and DSA. The 4D rCE-MRA images were independently assessed regarding the location, nidal size, Spetzler–Martin grade, and identification of arterial feeders, drainage pattern, and any other vascular anomalies.

Results— 4D rCE-MRA correctly depicted the size, venous drainage pattern, and prominent arterial feeders in all cases. Spetzler–Martin grade was correctly determined between reviewers and between the different imaging modalities in all cases except 1. The nidus size was in good correlation between the reviewers, where r=0.99, P<0.000001. There was very good agreement between reviewers regarding the individual scans (=0.63 to 1), whereas the agreement between the DSA and 4D rCE-MRA images was also good (=0.61 to 0.85).

Conclusions— We have developed a 4D radial acquisition contrast-enhanced MRA sequence capable of imaging intracranial AVMs approximating that of DSA. Image analysis demonstrates equivalency in terms of grading AVMs using the Spetzler–Martin grading scale. This 4D rCE-MRA sequence has the potential to avoid some applications of DSA, thus saving patients from potential procedural risks.

Methods— Ten neonates with a unilateral thalamic hemorrhage and cerebral sinovenous thrombosis were studied. Diagnosis was suspected using cranial ultrasound and confirmed with MRI/MR venography. Eight infants had a repeat MRI at 3 to 7 months. Neurodevelopmental outcome was assessed from 3 months until 5 years.

Results— One infant died. Seven infants were treated with low-molecular-weight heparin. No side affects were noted. MRI showed involvement of multiple sinuses, additional intraventricular hemorrhage, and white matter lesions in all infants. Recanalization was present on the repeat MRI at 3 months in all infants. Treatment was delayed in one infant and anticoagulation was started only after extension of the thalamic hemorrhage. He required a ventriculoperitoneal drain for posthemorrhagic ventricular dilatation and developed cerebral visual impairment and global delay. Two other infants showed global delay and one of them also developed postneonatal epilepsy. Mild asymmetry in tone was present in 4 children.

Conclusions— Cerebral sinovenous thrombosis was found in 10 neonates with unilateral thalamic hemorrhage. Diagnosis was suspected on cranial ultrasound and confirmed with MRI/MR venography. Treatment with low-molecular-weight heparin in newborn infants with a thalamic hemorrhage due to cerebral sinovenous thrombosis appears to be safe and should be considered. Long-term follow-up will be needed to assess cognitive outcome.

Methods— In this prospective, multicenter, single-arm study, 125 patients with neurological deficits as defined by a National Institutes of Health Stroke Scale score ≥8, presented within 8 hours of symptom onset, and an angiographic occlusion (Thrombolysis In Myocardial Infarction [TIMI] Grade 0 or 1) of a treatable large intracranial vessel were enrolled. Patients who presented within 3 hours from symptom onset had to be ineligible or refractory to recombinant tissue plasminogen activator therapy. All patients were followed clinically for 90 days postprocedure.

Results— A total of 125 target vessels in 125 patients were treated by the Penumbra System. Postprocedure, 81.6% of the treated vessels were successfully revascularized to TIMI 2 to 3. There were 18 procedural events reported in 16 patients (12.8%), 3 patients (2.4%) had events that were considered serious. A total of 35 patients (28%) were found to have intracranial hemorrhage on 24-hour CT of which 14 (11.2%) were symptomatic. All cause mortality was 32.8% at 90 days with 25% of the patients achieving a modified Rankin Scale score of ≤2.

Conclusions— These results suggest the Penumbra System allows safe and effective revascularization in patients experiencing ischemic stroke secondary to large vessel occlusive disease who present within 8 hours from symptom onset.

Methods— We randomly assigned 32 elective first-time coronary artery bypass graft patients to receive placebo or 375 U/kg, 750 U/kg, or 1500 U/kg of recombinant human erythropoietin divided in 3 daily doses, starting the day before surgery. Primary outcomes were feasibility and safety, and secondary outcomes were neurocognitive dysfunction at discharge and 2 months.

Results— All subjects were male, mean age 60 years (range 46 to 73). No significant differences were found in pump time, cross-clamp time, or hospital length of stay. Mortality and pure red cell aplasia were not observed. One patient in the 375 U/kg group had ST changes compatible with myocardial injury immediately postoperative, but no other thrombotic complications were observed. Neurocognitive dysfunction occurred in 21/32 (66%) of patients at discharge and 5/32 (16%) at 2 months. Neurocognitive dysfunction at discharge by group was: placebo 6/8 (75%), 375 U/kg 4/8 (50%), 750 U/kg 6/8 (75%), and 1500 U/kg 5/8 (63%). Neurocognitive dysfunction at 2 months by group was: placebo 3/8 (38%), 375 U/kg 1/8 (13%), 750 U/kg 1/8 (13%), and 1500 U/kg 0/8 (0%). Neurocognitive dysfunction at 2 months for erythropoietin at any dose was 2/24 (8.3%) versus 3/8 (38%) for placebo (P=0.085).

Conclusions— This study demonstrates feasibility and safety for the use of human recombinant erythropoietin as a neuroprotectant in coronary artery bypass graft surgery. A trend in the reduction of neurocognitive dysfunction at 2 months was associated with erythropoietin use. A multicenter randomized controlled trial is warranted.

Methods— From the Registry of the Canadian Stroke Network, we identified all consecutive patients presenting with acute ischemic stroke or transient ischemic attack at 12 provincial stroke centers (Ontario, Canada, 2003 to 2006) and selected those with unilateral symptomatic carotid stenosis of moderate (50% to 69%) or severe (70% to 99%) degree. Using linkages to administrative databases, we identified patients who underwent carotid endarterectomy within 6 months after the symptomatic event and calculated the time intervals between the index event and surgery. We compared the timing of surgery according to age, sex, degree of stenosis, index event, geographic region, and year. Logistic regression assessed variables associated with early surgery.

Results— One hundred five patients underwent endarterectomy for unilateral symptomatic carotid stenosis (50% to 99%) within 6 months of the index event. The median time from index event to surgery was 30 days (interquartile range, 10 to 81). Only one third (38 of 105) received endarterectomy within the recommended 2-week target timeframe, and in one fourth (26 of 105), surgery was delayed >3 months. Surgery within 2 weeks was more likely if the index event was a transient ischemic attack rather than a stroke. Access to early endarterectomy varied markedly between hospitals across the province and improved over time from 2003 to 2006.

Conclusions— In this hospital-based cohort, the majority of patients undergoing carotid endarterectomy after a transient ischemic attack or stroke had surgery delayed well beyond the period of maximum effectiveness. To enhance secondary stroke prevention, greater efforts are needed to minimize delays to diagnosis and surgical treatment for patients with symptomatic carotid stenosis.

Methods— From 1997 to 2006, 202 of 275 patients with arteriovenous malformation received embolization before microsurgery (n=176) or radiosurgery (n=26). Patients were examined before and after endovascular embolization and at clinical follow-up (mean, 43.4±34.6 months). Outcome was classified according to the modified Rankin Scale. New neurological deficits after embolization were defined as minimal (no change in overall modified Rankin Scale), moderate (modified Rankin Scale ≤2), or significant (modified Rankin Scale >2).

Results— Two hundred two patients were treated in 377 embolization procedures. There were a total of 29 new clinical deficits after embolization (8% of procedures; 14% of patients), of which 19 were moderate or significant. Postembolization deficits resolved in a significant number of patients over time (P<0.0001). Five patients had persistent neurological deficits due to embolization (1.3% of procedures; 2.5% of patients). In multivariate analysis, the following variables significantly predicted new neurological deficit after embolization: complex arteriovenous malformation with treatment plan specifying more than one embolization procedure (OR, 2.7; 95% CI, 1.4 to 8.6), diameter <3 cm (OR, 3.2; 95% CI, 1.2 to 9.1), diameter >6 cm (OR, 6.2; 95% CI, 1.0 to 57.0), deep venous drainage (OR, 2.7; 95% CI, 1.1 to 6.9), or eloquent location (OR, 2.4; 95% CI, 1.0 to 5.7). These variables were weighted and used to compute an arteriovenous malformation Embolization Prognostic Risk Score for each patient. A score of 0 predicted no new deficits, a score of 1 predicted a new deficit rate of 6%, a score of 2 predicted a new deficit rate of 15%, a score of 3 predicted a new deficit rate of 21%, and a score of 4 predicted a new deficit rate of 50% (P<0.0001).

Conclusions— Small and large size, eloquent location, deep venous drainage