Methods—We conducted a prospective study on 93 175 older women (aged 50 to 79 years) in the Women’s Health Initiative Observational study cohort to examine the risk of ischemic stroke in relation to self-reported sleep duration. Cox models were used to investigate the putative associations, adjusting for multiple sociodemographic and lifestyle factors, depression, snoring, sleepiness symptoms, and other cardiovascular disease-related clinical characteristics.

Results—At baseline, 8.3% of subjects had reported their sleep duration as ≤5 hours per night and 4.6% reported long duration of sleep (≥9 hours/night). After an average of 7.5 years of follow-up, 1166 cases of ischemic stroke had occurred. Multivariable-adjusted relative risk (RR) and 95% CI for ischemic stroke (using a sleep time of 7 hours/night as the reference) were 1.14 (0.97, 1.33), 1.24 (1.04, 1.47), and 1.70 (1.32, 2.21) for women reporting ≤6, 8, and ≥9 hours of sleep. A modestly stronger association with sleep duration ≤6 hours per night (RR, 1.22; 1.03, 1.44) was noted among women without prevalent cardiovascular disease at baseline. Our analyses also reveal that the adverse effect of long sleep is likely independent of the increased risk for ischemic stroke associated with frequent snoring and sleepiness (RR, 1.31; 1.00, 1.72).

Conclusions—Habitual sleep patterns are important neurobehavioral determinants of risk for ischemic stroke in postmenopausal women. The underlying neurobiology and mechanistic mediators for the putative adverse effect of long sleep (≥9 hours/night) need further elucidation.

Method—Event-related desynchronization (ERD) during hand-grasping and self-paced finger-tapping tasks was examined in 38 right-hand-dominant patients with occlusive disease of the internal carotid or middle cerebral artery caused by diverse pathologies (atherosclerosis, 28; others, 10) and in 8 control subjects. All patients had no apparent motor impairments. The spatial distribution and the intensity (t value) of ERD in the beta band were analyzed with synthetic aperture magnetometry. According to the laterality index calculated from the ratios of peak t values on ipsilateral vs contralateral (with respect to the hand movement) hemispheres, the distribution of ERD was classified into 3 patterns: contralateral, bilateral, and ipsilateral.

Results—Abnormal ipsilateral dominant distribution of beta ERD was observed significantly more often during contralesional hand grasping in patients with atherosclerotic vascular lesion. It was accompanied by significantly higher t values on the ipsilateral hemisphere, without a decrease in those on the contralateral side. The age, the rating scores of periventricular hyperintensity, and ventricular size were all significantly higher in patients who showed the ipsilateral-dominant pattern.

Conclusion—Abnormal ipsilateral hyperactivity may indicate the presence of subclinical functional alterations related to atherosclerotic occlusive vascular disease.

Methods—Of 42 patients with spinal dural arteriovenous fistulae treated in our institution (surgery or endovascular treatment), 6 were paraplegic preoperatively (Grade IV on the McCormick scale and Grade V on the Aminoff scale, Grade 5 of modified Rankin Scale with motor ASIA between 0 and 10 for both lower limbs). Their clinical history revealed that paraplegia appeared progressively within a period of <3 months. All patients were clinically evaluated at 6 weeks, 6 months, and then annually during an average follow-up of 3 years. Patients received at least one spinal angiography and MRI test during the follow-up period.

Results—Total exclusion of the fistula was performed surgically in all cases and was confirmed by spinal angiography. No surgical complications were recorded. All patients improved postoperatively. Three patients showed almost normal walking (Grade I on the McCormick scale, I on the Aminoff scale, Grade 1 of modified Rankin Scale) and 3 were able to walk with a cane (Grade II on McCormick, Grade III on Aminoff scale, Grade 2 of modified Rankin Scale). MRI tests were normal in all patients.

Conclusions—Our results indicate that treatment of fistula is a necessary intervention, even in patients with complete paraplegia.

Methods—Three hundred consecutive cases (159 females, 141 males; mean age: 47 years; range, 0 to 87 years) were reviewed for patient demographics, clinical presentation, multiplicity, presence of cortical and spinal venous reflux, and outflow restrictions and classified into the 3 mentioned groups.

Results—The ventral epidural group (n=150) showed a female predominance, more benign clinical presentations, lower rate of cortical and spinal venous reflux, and no cortical and spinal venous reflux without restriction of the venous outflow. The dorsal epidural group (n=67) had a lower mean age and a higher rate of multiplicity. The lateral epidural group (n=63) presented later in life with a male predominance, more aggressive clinical presentations, and cortical and spinal venous reflux without evidence of venous outflow restriction. All differences were statistically significant (P<0.001).

Conclusion—Dural arteriovenous shunts predictably drain either in pial veins or craniofugally depending on the compartment involved by the dural arteriovenous shunt. Associated conditions (outflow restrictions, high-flow shunts) may change that draining pattern. The significant differences between the groups of the new classification support the hypothesis of biological and/or developmental differences in each epidural region and suggest that dural arteriovenous shunts are a heterogeneous group of diseases.

Methods—Twenty chronic hemiparetic poststroke patients with stiff knee gait and ability to walk on a treadmill were recruited. BoNT A was injected into several spastic muscles: the rectus femoris (200 U), semitendinosus (100 U) and triceps surae (200 U). Patients' neurological impairments (Ashworth scale, Duncan-Ely test, Stroke Impairment Assessment Set, and instrumented gait analysis), activity (ABILOCO and 10-m walking test), and participation (SATISPART-Stroke and 36-item Short-Form Health Survey) were assessed before and 2 months after the injection.

Results—BoNT A injection reduced the impairments. It improved Stroke Impairment Assessment Set (56.5 [48–63] to 56.5 [52.5 to 63]; P<0.001), reduced rectus femoris muscle tone (2 [1 to 2.5] to 0 [0 to 1]; P<0.001), and reduced semitendinosus muscle tone (1 [1 to 1.5] to 1 [0 to 1]; P<0.001). Gait analysis demonstrated increased knee flexion during the swing phase (22±19° to 27±16°; P=0.03), decreased external mechanical work (0.66±0.38 to 0.59±0.25 J kg^-1 m^-1; P=0.04), and demonstrated a lower energy cost (5.8±1.9 to 4.9±1.9 J kg^-1 m^-1; P=0.03). The patients' locomotion ability was improved (2.2±1.9 to 3.2±2.1 logits; P=0.03). The participation and quality of life remained unchanged.

Conclusions—BoNT A injections in several muscles improved the stiff knee gait and the locomotion ability in adult stroke patients.

Methods—We conducted a systematic review and stratified meta-analysis of published studies describing the efficacy of NXY-059 in experimental focal cerebral ischemia.

Results—Overall, NXY-059 improved infarct volume by 43.3% (95% CI, 34.7 to 52.8). Only 2 of 9 publications reported randomization, concealment of treatment allocation, and blinded outcome assessment. Studies not reporting these quality items gave substantially higher estimates of efficacy than did higher-quality studies.

Conclusions—The reported efficacy of NXY-059 in animal models of stroke is confounded by low study quality. The failure of SAINT II highlights the need for substantial improvements in the design, conduct, and reporting of animal studies; journals can play an important role in this by adopting standards for animal studies similar to those agreed over 10 years ago for clinical trials.

Methods—In cell culture, a human brain microvascular endothelial cell line was subjected to either hypoxia or H₂O₂-induced oxidative stress with or without lipoxygenase inhibitors. For in vivo studies, mice were subjected to 90 minutes middle cerebral artery occlusion, and the effects of either 12/15-LOX gene knockout or treatment with lipoxygenase inhibitors were compared. Expression of 12/15-LOX and claudin-5 as well as extravasation of immunoglobulin G were detected by immunohistochemistry. Edema was measured as water content of brain hemispheres according to the wet–dry weight method.

Results—Brain endothelial cells were protected against hypoxia and H₂O₂ by the lipoxygenase inhibitor baicalein. After focal ischemia, 12/15-LOX was increased in neurons and endothelial cells. The vascular tight junction protein claudin-5 underwent extensive degradation in the peri-infarct area, which was partially prevented by the lipoxygenase inhibitor baicalein. Leakage of immunoglobulin G into the brain parenchyma was significantly reduced in 12/15-LOX knockout mice as well as wild-type mice treated with baicalein. Likewise, brain edema was significantly ameliorated.

Conclusion—12/15-LOX may contribute to ischemic brain damage not just by causing neuronal cell death, but also by detrimental effects on the brain microvasculature. 12/15-LOX inhibitors may thus be effective as both neuroprotectants and vasculoprotectants.

Methods—The Writing Group members were appointed by the American Heart Association Stroke Council's Scientific Statement Oversight Committee. The panel included members with several different areas of expertise. Each of the panel's recommendations was weighted by applying the American Heart Association Stroke Council's Levels of Evidence grading algorithm. After being reviewed by panel members, the manuscript was reviewed by 4 expert peer reviewers and by members of the Stroke Council Leadership Committee and was approved by the American Heart Association Science Advisory and Coordinating Committee. We anticipate that this statement will need to be updated in 4 years.

Results—Evidence-based recommendations are provided for the prevention of ischemic stroke caused by sickle cell disease, moyamoya disease, cervicocephalic arterial dissection, and cardiogenic embolism. Recommendations on the evaluation and management of hemorrhagic stroke also are provided. Protocols for dosing of heparin and warfarin in children are suggested. Also included are recommendations on the evaluation and management of perinatal stroke and cerebral sinovenous thrombosis in children.

Methods—Patients were evaluated by the National Institutes of Health Stroke Scale, Mini-Mental State Examination, Barthel Index, Lawton Instrumental Activities of Daily Living Scale, modified Rankin Scale, Geriatric Depression Scale, and Hospital Anxiety and Depression Scale. Health-related quality of life was evaluated with the MOS–Short Form 36 and SIS 3.0.

Results—One hundred seventy-four stroke survivors were assessed (mean age, 56.9 years; 55.2% male). Hand function had a prominent floor effect (45.9%), whereas a ceiling effect was observed in the communication domain (17.3%). The internal consistency of SIS (Cronbach's =0.94) and SIS domains (item-dimension correlation, 0.17 to 0.89) were satisfactory; only the emotion domain had poor internal consistency (Cronbach's =0.49). Test-retest reliability was evaluated in 50 consecutive patients. Concerning the stability of the SIS, the weighted values ranged from 0.33 (item 3a) to 0.94 (item 7e). Intraclass correlation coefficient values for the SIS domains ranged from 0.48 (emotion) to 0.94 (hand function). Standard error of measurement values for SIS domains ranged from 6.85 (mobility) to 9.63 (social participation). Regarding convergent validity, a significant correlation (Spearman’s correlation coefficient, P<0.0001) was found between the SIS composite physical domain and the National Institutes of Health Stroke Scale (-0.69), modified Rankin Scale (-0.81), Barthel Index (0.87), Lawton Scale (0.76), and MOS–Short Form 36 physical component summary (0.61). SIS domain scores significantly decreased as modified Rankin Scale scores increased (discriminative validity; ANOVA, P<0.0001).

Conclusions—The Brazilian version of SIS 3.0 has satisfactory psychometric properties and can be used in stroke survivors to assess health-related quality of life.

Methods—The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study includes 3316 patients who were referred to coronary angiography at baseline between 1997 and 2000. 25-Hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured in 3299 and 3315 study participants, respectively. To account for the seasonal variation of vitamin D metabolites, we calculated z values for the 25(OH)D and 1,25(OH)2D concentrations within each month of blood draw.

Results—During a median follow-up time of 7.75 years, 769 patients died, including 42 fatal (ischemic and hemorrhagic) strokes. When compared with survivors in binary logistic-regression analyses, the odds ratios (with 95% CIs) for fatal stroke were 0.58 (0.43 to 0.78; P<0.001) per z value of 25(OH)D and 0.62 (0.47 to 0.81; P<0.001) per z value of 1,25(OH)2D. After adjustment for several possible confounders, these odds ratios remained significant for 25(OH)D at 0.67 (0.46 to 0.97; P=0.032) and for 1,25(OH)2D at 0.72 (0.52 to 0.99; P=0.047). Z values of 25(OH)D and 1,25(OH)2D were also reduced in the 274 patients who had a history of previous cerebrovascular disease events at baseline.

Conclusions—Low levels of 25(OH)D and 1,25(OH)2D are independently predictive for fatal strokes, suggesting that vitamin D supplementation is a promising approach in the prevention of strokes.

Methods—CAs were induced in Sprague-Dawley rats with or without cysteine cathepsin inhibitor, NC-2300. Expression of cathepsin B, K, S, and cystatin C, an endogenous inhibitor of cysteine cathepsins, in aneurysmal walls was examined in quantitative RT-PCR and immunohistochemistry. The activity of cysteine cathepsins and collagenase I and IV in aneurysmal walls was also assessed. Finally, expression of cysteine cathepsins and cystatin C in human CAs was examined.

Results—Quantitative RT-PCR and immunohistochemistry revealed upregulated expression of cathepsin B, K, and S in the late stage of aneurysm progression. In contrast, cystatin C expression was reduced with aneurysm progression. Treatment with NC-2300 resulted in the decreased incidence of advanced CAs. The activity of cysteine cathepsins and collagenase I and IV in aneurysmal walls was reduced and elastin content was increased in the NC-2300–treated group. Finally, immunohistochemistry for cysteine cathepsins and cystatin C expression in human CAs showed the same expression pattern as in the rat study.

Conclusions—Data obtained by using NC-2300 revealed an important role of cysteine cathepsins in the progression of CAs. Our findings strongly suggest that an imbalance between cysteine cathepsins and their inhibitor may cause the excessive breakdown of extracellular matrix in the arterial walls leading to the progression and rupture of CAs.

Methods—Six hundred sixty-eight people, aged 60 to 90 years, underwent repeated MRI scanning and neuropsychological testing within 3-year follow-up. We rated incident lacunar infarcts and change in periventricular and subcortical white matter lesion severity with a semiquantitative scale. We assessed the relationships between age, sex, baseline lesion load, risk factors, lesion progression, and change in cognitive function by multivariate regression analyses and additional stratified analyses.

Results—Baseline lesion load, higher age, high blood pressure, and current smoking were independently associated with progression of white matter lesions. Women had more marked progression of subcortical white matter lesions and incident lacunar infarcts compared with men. Carotid atherosclerosis was associated with incident lacunar infarcts. Higher blood pressure did not contribute to lesion progression in people with already severe lesions at baseline nor in the very old. Lesion progression was associated with a paralleled decline in general cognitive function and in particular with a decreased information processing speed.

Conclusions—Higher age, female sex, cigarette smoking, elevated blood pressure, and baseline lesion load were associated with small vessel disease progression. Age and baseline lesion load influenced the risk relations with blood pressure. Progression of small vessel disease was related to a paralleled decline in cognitive function.

Methods—After 60-minute middle cerebral artery occlusion and reperfusion, the adhesion of leukocytes and platelets in cerebral venules, infarct volume, and blood–brain barrier permeability were measured in wild-type mice (WT), RANTES-deficient mice (RANTES^-/-), WT mice transplanted with RANTES^-/- bone marrow (RANTES>WT), and control bone marrow chimeras (WT>WT). The concentration of RANTES and several cytokines was also measured by enzyme-linked immunosorbent assay and a cytometric bead array.

Results—The enhanced leukocyte and platelet adhesion, increased blood–brain barrier permeability, and tissue infarction elicited in WT and WT>WT mice after middle cerebral artery occlusion and reperfusion were significantly blunted in RANTES^-/- mice. Similar attenuation of the middle cerebral artery occlusion and reperfusion-induced responses were noted in RANTES>WT chimeras. Although RANTES deficiency did not alter the changes in tissue cytokine levels elicited by middle cerebral artery occlusion and reperfusion, plasma concentrations interleukin-6, interleukin-10, and interleukin-12 were all reduced.

Conclusions—These findings implicate blood cell-derived RANTES in the microvascular, inflammatory, and tissue injury responses of the brain to ischemia and reperfusion.

Methods—"Hip-Hop" Stroke uses culturally and age-appropriate music and dance to enhance an interactive didactic curriculum including the FAST mnemonic (Facial droop, Arm weakness, Speech disturbance, Time to call 911). The program occurred in central Harlem, New York City, a community with high stroke risk. During the 2006 to 2007 school year, 582 fourth, fifth, and sixth graders (9 to 11 years of age) participated in 1-hour sessions over 3 consecutive days. Stroke knowledge was tested before and after the program with a 94% group participant retention.

Results—Students learned and retained knowledge well for stroke localization (20% correct before intervention, 93% correct immediately afterward, and 86% correct after 3-month delay; P<0.001 both posttests versus baseline), the term "brain attack" (16% pretest, 95% immediate, 86% delayed; P<0.001), and to call 911 for stroke (78% pretest, 99.8% immediate, 98% delayed; P<0.001). FAST stroke symptoms (facial droop and slurred speech) were better retained than non-FAST symptoms (headache and blurred vision) at 3 months (P<0.001). For stroke prevention measures, dietary change and exercise were better learned than concepts of diabetes, hypertension, and cholesterol.

Conclusions—Elementary school children are educable about stroke, retain their knowledge well, and may be able to appropriately activate emergency services for acute stroke. Incorporating cultural elements such as hip-hop music may improve retention of stroke knowledge among the youth.

Methods—This study was based on a multicenter prospective registry of patients treated with IV-tPA divided into IHSs and OHSs. We recorded intrahospital delays and stroke outcomes.

Results—Among 367 patients treated with IV-tPA, 30 were IHSs. Baseline characteristics were similar except for a greater proportion of diabetes (36.7% vs 17.5%, P=0.01), cardiac failure (16.7% vs 5.3%, P=0.014), and atrial fibrillation (33.3% vs 17.5%, P=0.034) in IHSs than OHSs. In-hospital delays were significantly longer in IHSs for door-to-computed tomography time (39.5±18.7 vs 22.6±19.7 minutes, P<0.0001) and computed tomography-to-treatment time (92.0±26.1 vs 65.4±25.8 minutes, P<0.0001). No differences were observed in safety or efficacy.

Conclusions—In-hospital procedures for thrombolysis proceed more slowly in IHSs than in OHSs. Thrombolysis is safe and efficient in IHS.

Methods—The retrospective and prospective data of patients with radiologically confirmed cerebral venous thrombosis were collected from 4 centers located in Pakistan and United Arab Emirates. The demographic, clinical, radiological, and outcome data were recorded and analyzed. Primary outcome was death or dependency (modified Rankin score >2) at the time of hospital discharge.

Results—This study included 109 patients with cerebral venous thrombosis; the presenting features most commonly being observed were headache (81%), focal motor deficits (45%), seizures (39%), and mental status changes (37%). Important predisposing factors included systemic and central nervous system infection (18%), postpartum state (17%), hyperhomocystinemia (9%), genetic thrombophilia (5%), and oral contraceptive pill use (3%). Ninety-six (67%) patients received therapeutic anticoagulation. Seven patients died and 43 had poor outcome at discharge. Focal motor deficits (OR, 2.93; 95% CI, 1.2–7.5; P=0.018) and hemorrhagic infarctions (OR, 2.81; 95% CI, 1.04–7.85; P=0.041) were independent predictors of unfavorable outcome at discharge. Hemorrhagic infarction was the most significant factor of long-term unfavorable outcome (OR, 5.87; 95% CI, 1.49–23.02; P=0.011).

Conclusions—Infections and postpartum state were the most common predisposing factors for cerebral venous thrombosis in this cohort. Most patients (67%) were treated with anticoagulation therapy. Almost 50% of patients were dead or disabled at discharge.

Methods—We performed a retrospective study of 18 patients who had acute (<24 hours) DWI and follow-up fluid-attenuated inversion recovery imaging at 5, 30, and 90 days. Two expert readers segmented lesions and the mean volumes of both reads were used in all statistical analyses.

Results—Patient age was 65.8 (SD, 13.7) years and median NIHSS at baseline was 11.5. Inter-rater variability for lesion volume measurements was 3.7 (5.8) mL. Acute DWI volume was 19.3 (17.3) mL. Fluid-attenuated inversion recovery volumes for 5, 30, and 90 days were 34.3 (23.5), 18.6 (14.0), and 15.9 (13.8) mL, respectively. These volumes differed significantly (P<0.001). Linear regression revealed a strong correlation (r=0.96; P<0.001) between lesion volumes at 30 and 90 days with a slope that did not vary significantly from 1.0 (P=0.448).

Conclusions—Lesions continue to evolve between 5 and 90 days, but by 30 days lesion volume approaches final infarct volume. While clinical response is the most meaningful outcome measure, our findings suggest that lesion volumes measured at 30 days may provide a sufficient approximation for final infarct volume for use in early phase clinical trials.

Methods—To investigate the association between calcium intake and risk of CVD, a total of 41 526 Japanese men and women age 40 to 59 years without a history of CVD or cancer and who had completed a food consumption frequency questionnaire were enrolled in this study. The subjects were followed up from 1990 to 1992 to 2003, and after 533 692 person-years of follow-up, 1321 incident cases of stroke (664 ischemic, 425 intraparenchymal hemorrhage, and 217 subarachnoid hemorrhage) and 322 of coronary heart disease were documented.

Results—Total calcium intake showed an inverse association with the risk of total stroke; the multivariable hazard ratio and 95% CIs for the highest versus the lowest quintile were 0.70 (95% CI, 0.56 to 0.88; P for trend=0.02). Dairy calcium intake was inversely associated with risks of total and ischemic stroke with respective multivariable hazard ratios (95% CIs) of 0.69 (0.56 to 0.85; P for trend=0.007) and 0.69 (0.52 to 0.93; P for trend=0.05). Dietary calcium intake was not significantly associated with risk of coronary heart disease.

Conclusions—Dietary calcium intake, especially calcium from dairy products, was found to be associated with a reduced incidence of stroke among middle-aged Japanese.

Methods—We studied agreement of clinical diagnosis of vascular territory in consecutive patients with transient ischemic attack or minor stroke with diffusion-weighted MRI who had an acute ischemic lesion(s) in a single vascular territory (determined by a neuroradiologist). Three independent neurologists (one had seen the patients, the others had a clinical summary) diagnosed the most likely vascular territory (carotid or vertebrobasilar) for each patient blind to brain imaging.

Results—One hundred thirty-three (28.0%) of 476 patients had a high signal lesion on diffusion-weighted imaging of whom 115 (86.5%) had a minor stroke and 18 (13.5%) a transient ischemic attack. Interobserver agreement (kappa statistic) on the territory ranged from 0.46 to 0.60. The agreement with diffusion-weighted imaging was only moderate (observer 1: kappa=0.54, 95% CI=0.36 to 0.72; observer 2: 0.48, 0.31 to 0.64; observer 3: 0.48, 0.28 to 0.67). Only the presence of visual symptoms improved the accuracy of the vascular territory diagnosis (range of kappa: 0.63 to 0.77) but not the presence of motor, speech, or sensory symptoms. Sensitivity and specificity for the diagnosis of vertebrobasilar territory ranged between 54.2% and 70.8% and 84.4% to 91.7%, respectively.

Conclusions—The reliability of clinical diagnosis of the vascular territory is only moderate, highlighting the importance of sensitive brain imaging after transient ischemic attack or minor stroke. Further imaging-based research is required to determine the optimal clinical diagnostic criteria for classification of the vascular territory.

Methods—Retrovirus containing the EGFP gene was used to label dividing cells in striatal slices prepared from adult rat brains after middle cerebral artery occlusion. EGFP-targeted immunostaining and immunoelectron microscopy were performed to detect whether newborn neurons could anatomically form neuronal polarity and synapses with pre-existent neurons. Patch clamp recording on acute striatal slices of brains at 6 to 8 weeks after middle cerebral artery occlusion was used to determine whether the newborn neurons could display functional electrophysiological properties.

Results—EGFP-expressing (EGFP⁺) signals could be detected mainly in the cell body in the first 2 weeks. From the fourth to thirteenth weeks after their birth, EGFP⁺ neurons gradually formed neuronal polarity and showed a time-dependent increase in dendrite length and branch formation. EGFP⁺ cells were copositive for NeuN and glutamic acid decarboxylase (EGFP⁺-NeuN⁺-GAD₆₇⁺), MAP-2, and choline acetyltransferase (EGFP⁺-MAP-2⁺-ChAT⁺). They also expressed phosphorylated synapsin I (EGFP⁺-p-SYN⁺) and showed typical synaptic structures comprising dendrites and spines. Both GABAergic and cholinergic newborn neurons could fire action potentials and received excitatory and inhibitory synaptic inputs because they displayed spontaneous postsynaptic currents in picrotoxin- and CNQX-inhibited manners.

Conclusion—Ischemia-induced newly formed striatal GABAergic and cholinergic neurons could become functionally integrated into neural networks in the brain of adult rats after stroke.

Methods and Results—We report a series of 3 AD patients with MRI evidence of superficial siderosis. Two had neuropathological examination confirming superficial siderosis, AD, and CAA.

Conclusions—Superficial siderosis should be recognized within the spectrum of AD with CAA and considered as a possible antemortem diagnostic feature.

Methods—Wild-type and CD40-deficient mice were subjected to transient middle cerebral artery occlusion. Mice were either intravenously injected with Cy5.5-CD40MAb or control Cy5.5-IgGMAb. Noninvasive and ex vivo near-infrared fluorescence imaging was performed after injection of the compounds. Probe distribution and specificity was further assessed with single-plane illumination microscopy, immunohistochemistry, and confocal microscopy.

Results—Significantly higher fluorescence intensities over the stroke-affected hemisphere, compared to the contralateral side, were only detected noninvasively in wild-type mice that received Cy5.5-CD40MAb, but not in CD40-deficient mice injected with Cy5.5-CD40MAb or in wild-type mice that were injected with Cy5.5-IgGMAb. Ex vivo near-infrared fluorescence showed an intense fluorescence within the ischemic territory only in wild-type mice injected with Cy5.5-CD40MAb. In the brains of these mice, single-plane illumination microscopy demonstrated vascular and parenchymal distribution, and confocal microscopy revealed a partial colocalization of parenchymal fluorescence from the injected Cy5.5-CD40MAb with activated microglia and blood-derived cells in the ischemic region.

Conclusions—The study demonstrates that a CD40-targeted fluorescent antibody enables specific noninvasive detection of the inflammatory receptor CD40 after cerebral ischemia using optical techniques.

Methods—A multiethnic stroke-free cohort hospitalized with nonrheumatic AF was identified in a large health maintenance organization. Stroke risk factors (advanced age, diabetes, hypertension, and heart failure), warfarin use, and anticoagulation intensity were assessed. Crude ischemic stroke rates were calculated by Poisson regression for each group while using and not using warfarin. Cox proportional hazard models were constructed to assess the independent effect of race/ethnicity on ischemic stroke.

Results—Between 1995 and 2000, we identified 18 867 AF hospitalizations (78.5% white, 8% black, 9.5% Hispanic, and 3.9% Asian). Over the course of 63 204 person-years follow-up (median, 3.3 years), 1226 ischemic strokes were identified. The percent-time on warfarin did not differ by race/ethnicity. The median percent-time on warfarin that international normalized ratio was 2 to 3 was 54.5% overall, but it was lower in blacks at 47.8%, whereas the other groups had a rate of 54%. The rate ratios (95% CI) of ischemic stroke with warfarin compared to without warfarin for whites, blacks, Hispanics, and Asians were 0.79 (0.68 to 0.90), 0.92 (0.65 to 1.30), 0.71 (0.48 to 1.05), and 0.65 (0.34 to 1.23), respectively.

Conclusions—In this cohort, we did not observe a statistically significant lower rate of stroke with warfarin therapy among nonwhites (in particular blacks) with previous AF hospitalizations. The relatively small numbers of nonwhites renders our estimates less than precise and should be interpreted with caution.

Methods—Data from DEFUSE, a study of 74 patients with stroke who received intravenous tissue plasminogen activator in the 3- to 6-hour time window and underwent MRIs before and approximately 4 hours after treatment were analyzed. The MRA–DWI mismatch model was defined as (1) a DWI lesion volume less than 25 mL in patients with a proximal vessel occlusion; or (2) a DWI lesion volume less than 15 mL in patients with proximal vessel stenosis or an abnormal finding of a distal vessel. Favorable clinical response was defined as an improvement on the National Institutes of Health Stroke Scale score of at least 8 points between baseline and 30 days or a National Institutes of Health Stroke Scale score ≤1 at 30 days.

Results—Twenty-seven of 62 patients (44%) had an MRA-DWI mismatch. There was a differential response to early reperfusion based on MRA-DWI mismatch status. Reperfusion was associated with an increased rate of a favorable clinical response in patients with an MRA-DWI mismatch (OR, 12.5; 95% CI, 1.8 to 83.9) and a lower rate in patients without mismatch (OR, 0.2; 95% CI, 0.0 to 0.8).

Conclusions—The MRA-DWI mismatch model appears to identify patients with stroke who are likely to benefit from reperfusion therapy administered in the 3- to 6-hour time window after symptom onset. The criteria established for the MRA-DWI mismatch model in this study require validation in an independent cohort.

Methods—Primary ICH was induced in rats (n=6) by direct infusion of autologous blood into the striatum. The evolution of ICH damage was assessed by MRI estimates of T₂ and T_1sat relaxation times, cerebral blood flow, vascular permeability, and susceptibility-weighted imaging before surgery (baseline) and at 2 hours and 1, 7, and 14 days post-ICH. Behavioral testing was done before and at 1, 7, and 14 days post-ICH. Animals were euthanized for histology at 14 days.

Results—The MRI appearance of the hemorrhage and surrounding regions changed in a consistent manner over time. Two primary regions of interest were identified based on T₂ values. These included a core, corresponding to the bulk of the hemorrhage, and an adjacent rim; both varied with time. The core was associated with significantly lower cerebral blood flow values at all post-ICH time points, whereas cerebral blood flow varied in the rim. Increases in vascular permeability were noted at 1, 7, and 14 days. Changes in T_1sat were similar to those of T₂. MRI and histological estimates of tissue loss were well correlated and showed approximately 9% hemispheric tissue loss.

Conclusions—Although the cerebral blood flow changes observed with this ICH model may not exactly mimic the clinical situation, our results suggest that the evolution of ICH injury can be accurately characterized with MRI. These methods may be useful to evaluate therapeutic interventions after experimental ICH and eventually in humans.

Methods—The Northern Manhattan Study is a population-based study designed to determine stroke incidence, risk factors, and prognosis in a multiethnic urban population. First ischemic stroke patients age 40 or older were prospectively followed up for cardiac death defined as fatal MI, fatal congestive heart failure, or sudden death/arrhythmia and for nonfatal MI. Primary brain anatomic site was determined by consensus of research neurologists. Hazard ratios (HRs) and 95% CIs were calculated by Cox proportional-hazards models and adjusted for vascular risk factors (age, sex, history of coronary disease, hypertension, diabetes, cholesterol, and smoking), stroke severity, infarct size, and stroke etiology.

Results—The study population consisted of 655 patients whose mean age was 69.7±12.7 years; 44.6% were men and 51.3% were Hispanic. During a median follow-up of 4.0 years, 44 patients (6.7%) had fatal cardiac events. Of these, fatal MI occurred in 38.6%, fatal congestive heart failure in 18.2%, and sudden death in 43.2%. In multivariate models, clinical diagnosis of left parietal lobe infarction was associated with cardiac death (adjusted HR=4.45; 95% CI, 1.83 to 10.83) and cardiac death or MI (adjusted HR=3.30; 95% CI, 1.45 to 7.51). When analysis of anatomic location was restricted to neuroimaging (computed tomography, magnetic resonance imaging, or both [n=447]), left parietal lobe infarction was associated with cardiac death (adjusted HR=3.37; 95% CI, 1.26 to 8.97), and both left (adjusted HR=3.49; 95% CI, 1.38 to 8.80) and right (adjusted HR=3.13; 95% CI, 1.04 to 9.45) parietal lobe infarctions were associated with cardiac death or MI. We did not find an association between frontal, temporal, or insular stroke and fatal cardiac events, although the number of purely insular strokes was small.

Conclusions—Parietal lobe infarction is an independent predictor of long-term cardiac death or MI in this population. Further studies are needed to confirm whether parietal lobe infarction is an independent predictor of cardiac events and death. Surveillance for cardiac disease and implementation of cardioprotective therapies may reduce cardiac mortality in patients with parietal stroke.

Methods—Between 1988 and 1990, 34 776 men and 48 906 women aged 40 to 79 years completed a self-administered questionnaire including information about alcohol consumption. They were followed-up for a median duration of 14.2 years.

Results—Of the 83 682 respondents, 1628 died from stroke and 736 died from coronary heart disease. For men, heavy drinking (≥46.0 g ethanol/day) was associated with increased mortal