Methods— For the analysis, participants in the Jackson cohort of the Atherosclerosis Risk in Communities Study were followed from the date of the echocardiogram in cycle three to the date of the first ischemic stroke event (or death) or to December 31, 2004 if no ischemic stroke event (or death) was detected.

Results— There were 1886 participants in the study population (mean age 58.9 years, 65% women). Participants in the top quintile of LA diameter indexed to height (LA diameter/height; 2.57 to 3.55 cm/m) were more likely women, hypertensive, diabetic, and obese compared to those not in the top quintile. Over a median follow-up of 9.8 years for ischemic stroke and 9.9 years for all-cause mortality, there were 106 strokes and 242 deaths. In a multivariable model adjusting for traditional clinical risk factors, the top quintile of LA diameter/height was significantly related to ischemic stroke (HR 1.7; 95% CI: 1.1, 2.7) and all-cause mortality (HR 2.0; 95% CI: 1.5, 2.7). After further adjustment for left ventricular (LV) hypertrophy and low LV ejection fraction, the top quintile remained significantly related to all-cause mortality (HR 1.8; 95% CI: 1.3, 2.5).

Conclusions— In this population-based cohort of African Americans, LA size was a predictor of all-cause mortality after adjusting for traditional cardiovascular risk factors, LV hypertrophy, and low LV ejection fraction.

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— 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— In the ISAT cohort 278 SAH patients, 65 years or older, were enrolled. The patients were randomly allocated EVT (n=138) or NST (n=140). The primary outcome was the proportion of patients with a modified Rankin scale score of 0 to 2 (independent survival) at 1 year after the SAH. The rates of procedural complications and adverse events were also recorded.

Results— 83 of 138 (60.1%) patients allocated EVT were independent compared to 78 of 140 (56.1%) allocated NST (N.S.). 36 of 50 (72.0%) patients with internal carotid and posterior communicating artery aneurysms allocated EVT were independent compared to 26 of 50 (52.0%) allocated NST (P<0.05). 10 of 22 (45.5%) patients with middle cerebral artery aneurysms allocated EVT were independent compared to 13 of 15 (86.7%) allocated NST (P<0.05). The epilepsy frequency was 0.7% in the EVT group compared to 12.9% in the NST group (P<0.001).

Conclusions— In good grade elderly SAH patients with small anterior circulation aneurysms, EVT should probably be the favored treatment for ruptured internal carotid and posterior communicating artery aneurysms, whereas elderly patients with ruptured middle cerebral artery aneurysms appear to benefit from NST. EVT resulted in a lower epilepsy frequency than NST.

Methods— The Patient Treatment File was used to identify all patients discharged from any Veterans hospital between October 1990 and September 1997 with a diagnosis of ischemic stroke (ICD-9-CM codes 434, 436) listed as primary diagnosis. Demographic, morbidity, and mortality data were recorded. Chi-square tests were used to examine differences between diabetics and nondiabetics, and t tests were used for continuous variables. Cox proportional hazards regression was used to examine the effects of diabetes (DM) on the survival times controlling for multiple covariates.

Results— Of 48 733 ischemic stroke patients identified, 98% were male and 13 925 (25%) had DM. Mean age was similar between DM and non-DM (67.2 versus 67.5, P=NS). Prevalence of DM among stroke subjects increased from 25% to 31%. Charlson index >2 was much higher in DM (68.2% versus 47.9%, P<0.001). Mortality at 60 days and 1 year was similar in both groups (2.9 versus 2.7%, P=NS; 12.6 versus 13.1, P=NS). Kaplan-Meier survival plot showed that DM had shorter long term survival time (log-rank, P<0.001). Multivariate Cox proportional hazards regression showed a higher risk of death for diabetics (HR=1.15, 95% CI 1.11 to 1.19, P<0.001).

Conclusion— Despite greater comorbidity, postacute ischemic stroke mortality at 60 days and 1 year is not different between subjects with and without DM. Long term mortality after stroke is much lower among DM than that reported in older studies.

Methods— Sequential surveys of sites from an ongoing North American study investigating genetic risks for ischemic stroke (2003: 49 sites, response rate=100%; 2007: 53 sites; response rate=91%) assessed whether and how investigators enroll adults with impaired decision-making capacity and determined frequency of IRB approval for enrollment by surrogate authorization.

Results— Approximately 40% of sites report that their IRBs do not approve surrogate authorization to enroll stroke patients—43% (21/49) in 2003 and 35% (17/48) in 2007. Thirty-three percent of sites report evaluating eligible adults who lacked capacity to provide their own informed consent; 18% (9/49) in 2003 and 15% (7/48) in 2007 have enrolled these individuals. Surrogate enrollment is the most common method used. Most sites have not enrolled any individual lacking capacity to give his or her own consent.

Conclusions— Our study suggests that enrollment by surrogate authorization into stroke genetic research is often not approved by IRBs, and even when allowed is frequently not used. For disorders like stroke, this situation has significant implications for scientific validity.

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 18867 AF hospitalizations (78.5% white, 8% black, 9.5% Hispanic, and 3.9% Asian). Over the course of 63204 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— Our study design features a study cohort and a comparison cohort. The study cohort consists of all patients hospitalized with a principal diagnosis of sudden hearing loss (n=1,423), whereas the control cohort comprised all patients hospitalized for an appendectomy in 1998 (n=5692) as a surrogate for the general population. Each patient was tracked from hospitalization in 1998 until the end of 2003. Cox proportional hazard regressions were performed as a means of computing the 5-year stroke-free survival rates after adjustment for possible confounding factors.

Results— Of the total sample, 621 patients (8.7%) had strokes during the 5-year follow-up period: 180 (12.7% of the SSNHL patients) from the study cohort and 441 (7.8% of patients undergoing an appendectomy) from the control cohort. After adjusting for other factors, the hazard of stroke during the 5-year follow-up period was 1.64-times (95% CI, 1.31 to 2.07; P<0.001) greater for SSNHL patients than for appendectomy patients.

Conclusions— Our findings suggest that SSNHL can be an early warning sign of impending stroke. We suggest that SSNHL patients should undergo a comprehensive hematologic and neurological examination to help clinicians identify those potentially at risk for stroke developing in the near future.

Methods— We studied 748 patients with acute ischemic hemispheric stroke in the second European Cooperative Acute Stroke Study (ECASS-II). The patients had 2 serum glucose measurements, at baseline and at 24 hours. Four dynamic patterns were defined as baseline hyperglycemia present only at baseline, 24-hour hyperglycemia present only at 24 hours, persistent hyperglycemia, ie, hyperglycemia at baseline and at 24 hours, and persistent normoglycemia, ie, normoglycemia at baseline and at 24 hours. The end points were 7-day neurological improvement on National Institutes of Health Stroke Scale, 30-day favorable functional outcome (Barthel Index 95 or 100), 90-day negligible dependence (modified Rankin Scale 0 to 2), all-cause mortality within 90 days, and hemorrhagic transformation on CT within the first 7 days.

Results— In nondiabetic patients, persistent hyperglycemia was inversely associated with neurological improvement (OR=0.31; 95% CI=0.16 to 0.60), 30-day favorable functional outcome (OR=0.27; 95% CI=0.12 to 0.62), and 90-day negligible dependence (OR=0.36; 95% CI=0.17 to 0.73); it was associated with an increased risk of mortality within 90 days (OR=7.61; 95% CI=3.23 to 17.90) and for parenchymal hemorrhage (OR=6.64; 95% CI=2.63 to 16.78), whereas it was inversely associated with hemorrhagic infarction (OR=0.30; 95% CI=0.13 to 0.71). Delayed hyperglycemia at 24 hours was associated with the risks of death (OR=5.99; 95% CI=2.51 to 14.2) and parenchymal hemorrhage (OR=5.69; 95% CI-2.05 to 15.8) and inversely associated with no and negligible dependency (OR=0.40; 95% CI=0.20 to 0.78). Hyperglycemia at baseline only was not associated with any parameter of worse outcome. In patients with diabetes, the dynamic patterns of hyperglycemia did not suggest an association with stroke outcome.

Conclusions— Persistent hyperglycemia was associated with all bad outcome end points studied. In addition to a single glucose measurement, the pattern of change should be considered in the prediction of stroke outcome.

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— Healthy volunteers were recruited and screened for exclusions. Bilateral 2-MHz pulsed wave transcranial Doppler (TCD) probes were mounted by head frame, and baseline M1 MCA TCD measurements were obtained. ECP was then initiated using standard procedures for 30 minutes, and TCD readings were repeated at 5 and 20 minutes. Physiological correlates associated with ECP-TCD waveform morphology were identified, and measurable criteria for TCD assessment of ECP arterial mean flow velocity (MFV) augmentation were constructed.

Results— Five subjects were enrolled in the study. Preprocedural M1 MCA TCD measurements were within normal limits. Onset of ECP counterpulsation produced an immediate change in TCD waveform configuration with the appearance of a second upstroke at the dicrotic notch, labeled peak diastolic augmented velocity (PDAV). Although end-diastolic velocities did not increase, both R-MCA and L-MCA PDAVs were significantly higher than baseline end-diastolic values (P<0.05 Wilcoxon rank-sum test) at 5 and 20 minutes. Augmented MFVs (aMFVs) were also significantly higher than baseline MFV in the R-MCA and L-MCA at both 5 and 20 minutes (P<0.05).

Conclusions— ECP induces marked changes in cerebral arterial waveforms and augmented peak diastolic and mean MCA flow velocities on TCD in 5 healthy subjects.

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.

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— One hundred eighty-one AcoA aneurysms were treated with endovascular coil embolization between August 1991 and November 2005. Morphological characteristics that were analyzed included direction of the dome, location of the neck, association with hypoplasia or aplasia of AcoA complex vessels, sac, and neck size. Immediate clinical and anatomic results, long-term morbidity/mortality, recanalization rate, and delayed aneurysm thrombosis were analyzed. ORs were calculated for each anatomic and clinical result and logistic regression was used in formulating a predictive model.

Results— There were 115 females and 66 males. Age range was 9 to 86 years (mean 57). Factors significantly associated with complete embolization included small aneurysms (<10 mm), small neck (<4 mm), and anterior dome orientation. Factors significantly associated with aneurysm recanalization after long-term follow-up included aneurysm domes >10 mm, neck location on the AcoA, posterior dome orientation, and incomplete original embolization. Globally, the majority of patients remained neurologically intact or unchanged after the procedure (92.8%). Mortality was significantly influenced by the preoperative condition of the patient. The predictive model successfully represented the likely outcomes based on morphological features.

Conclusions— AcoA aneurysm coil embolization can be safely performed with acceptable rates of morbidity. Dome and neck orientation, sack and neck size, sac-to-neck ratio, and associated anomalies should be considered to accurately assess the probability of successful treatment for AcoA aneurysms.

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— This was a prospective cohort study of first disabling patients with stroke. Subjects were interviewed at 3, 6, and 12 months after stroke for modified Barthel Index, London Handicap Scale, Geriatric Depression Scale, and the World Health Organization Quality of Life questionnaire (abbreviated Hong Kong version). A latent curve model was developed to analyze how the dynamic changes in activities of daily living, handicap, and depressive mood related to the changes in HRQOL.

Results— Two hundred forty-seven of 303 patients (82%) followed up at 3 months after stroke could complete the quality-of-life questionnaire. Their mean age was 68.8 years. The latent curve model analysis revealed that initial physical health HRQOL was independently associated with activities of daily living, handicap, and depression. The other 3 HRQOL domain scores were primarily associated with depression only. The rates of change in all 4 domains of HRQOL were significantly and inversely associated with rate of change in the Geriatric Depression Scale only.

Conclusion— Change in mood in the postacute phase of stroke recovery is the most significant determinant of change in HRQOL. More attention should be paid to the detection and management of poststroke depression.

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— "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— Summary data on stroke, myocardial infarction, combined vascular events, and bleeding were obtained by treatment group from published vascular prevention trials. Data were analyzed using 10 statistical approaches which allow comparison of 2 ordinal or binary treatment groups. The results for each statistical test for each trial were then compared using Friedman 2-way analysis of variance with multiple comparison procedures.

Results— Across 85 trials (335 305 subjects) the test results differed substantially so that approaches which used the ordinal nature of stroke events (fatal/nonfatal/no stroke) were more efficient than those which combined the data to form 2 groups (P<0.0001). The most efficient tests were bootstrapping the difference in mean rank, Mann–Whitney U test, and ordinal logistic regression; 4- and 5-level data were more efficient still. Similar findings were obtained for myocardial infarction, combined vascular outcomes, and bleeding. The findings were consistent across different types, designs and sizes of trial, and for the different types of intervention.

Conclusions— When analyzing vascular events from prevention trials, statistical tests which use ordered categorical data are more efficient and are more likely to yield reliable results than binary tests. This approach gives additional information on treatment effects by severity of event and will allow trials to be smaller.

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— Rats (n=104) subjected to embolic middle cerebral artery (MCA) occlusion were randomly divided into 1 of 4 infusion groups with 26 rats per group: (1) the control group in which rats were administered saline, (2) the monotherapy rtPA group in which rtPA was intravenously administered at a dose of 10 mg/kg 4 hours after MCA occlusion, (3) the monotherapy S-0139 group in which S-0139 was intravenously given 2 hours after MCA occlusion, and (4) the combination of rtPA +S-0139 group in which S-0139 and rtPA were given 2 and 4 hours after MCA occlusion, respectively. Measurements of infarct volume and parenchymal hemorrhage, behavioral outcome, and immunostaining were performed on rats euthanized 1 and 7 days after stroke.

Results— The combination therapy of S-0139 and rtPA significantly (P<0.01) reduced infarct volume (24.8±0.9% versus 33.8±1.5% in control) and hemorrhagic area (7.1±6.1 µm² versus 36.5±19.2 µm² in control) and improved functional recovery compared with control saline-treated animals. Immunostaining analysis revealed that the combination therapy had the synergistically suppressed ischemia- and rtPA-induced ICAM-1, protease-activated receptor 1 (PAR-1), as well as accumulation of platelets in cerebral microvessels. Furthermore, the combination treatment synergistically reduced loss of laminin, ZO1, and occludin in cerebral vessels.

Conclusions— These data suggest that S-0139 provides the neuroprotection by suppressing ischemia- and rtPA-triggered molecules that evoke thrombosis and BBB disruption.

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— 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— hsp110/105 KO and wild-type mice were subjected to 30 minutes of transient middle cerebral artery occlusion followed by reperfusion for 24 hours. The infarct volume and neurological scores were measured and compared. The Hsp70 chaperone activity of thermally denatured firefly luciferase was measured in hsp110/105 KO embryonic fibroblasts.

Results— The infarct volume and neurological deficit scores were significantly (P<0.05) reduced in hsp110/105 KO mice compared with wild-type controls. In addition, hsp110/105 KO embryonic fibroblasts exhibited a dose-dependent suppression of Hsp70 chaperone activity by the presence of Hsp110/105.

Conclusions— These results demonstrate that hsp110/105 KO mice are resistant to ischemic injury and that the protective effects of hsp110/105 deficiency in cerebral ischemia may partly be mediated by an increase in the chaperone activity of Hsp70.

Methods— Emboli rerouting efficacy was assessed in vitro. Perfusion through the external femoral artery that was jailed by the device, cellular proliferation rate over the jailing mesh, and the resulting tissue coverage of the orifice were assessed in the swine iliofemoral bifurcation. Device-induced embolization was assessed in a swine kidney model.

Results— In vitro experiments demonstrated that particles as small as 60% of the pore dimension can be rerouted by the device, although at low efficacy, and rerouting efficacy approached 100% as the particle size approached the pore dimension. Repeat assessment of flow preimplantation and at various follow-up times by Doppler ultrasound showed no significant changes in the perfusion ratio of the jailed branch to the parent artery or the jailed branch to the naive contralateral artery either as a result of device implantation or at the follow-up times. Tissue coverage over the jailed ostium was limited to approximately 12% after stabilization. Cellular proliferation rate gradually decreased to diminishing level approximately 22 weeks postimplantation. The devices implanted across the renal arteries did not demonstrate any device-induced embolization after 1 month.

Conclusions— It is proposed that this device could be used to reroute emboli away from important intracranial vessels as a means of stroke prevention.

Methods— Lin^–-HSCs were injected intravenously at 24 hours after onset of a 45-minute transient cerebral ischemia. Effects of Lin^–-HSCs injection on infarct size, apoptotic cell death, postischemic inflammation and cytokine gene transcription were analyzed.

Results— Green fluorescent protein (GFP)-marked Lin^–-HSCs were detected at 24 hours after injection in the spleen and later in ischemic brain parenchyma, expressing microglial but no neural marker proteins. Tissue injury assessment showed significantly smaller infarct volumes and less apoptotic neuronal cell death in peri-infarct areas of Lin^–-HSC–treated animals. Analysis of immune cell infiltration in ischemic hemispheres revealed a reduction of invading T cells and macrophages in treated mice. Moreover, Lin^–-HSC therapy counter-regulated proinflammatory cytokine and chemokine receptor gene transcription within the spleen.

Conclusions— Our data demonstrate that systemically applied Lin^–-HSCs reduce cerebral postischemic inflammation, attenuate peripheral immune activation and mediate neuroprotection after ischemic stroke.

Methods— A prospective, multiracial cohort of 3298 stroke-free subjects with 6.5 years of mean follow-up time for vascular outcomes (stroke, myocardial infarction, vascular death) was used. Kidney function was estimated using serum creatinine and Cockcroft-Gault formula. Cox proportional hazards models were fitted to evaluate the relationship between kidney function and vascular outcomes.

Results— In multivariate analysis, Cockcroft-Gault formula between 15 and 59 mL/min was associated with a significant 43% increased stroke risk in the overall cohort. Blacks with Cockcroft-Gault formula between 15 and 59 mL/min had significantly increased risk of both stroke (hazard ratio, 2.65; 95% CI, 1.47 to 4.77) and combined vascular outcomes (hazard ratio, 1.59; 95% CI, 1.10–2.92).

Conclusion— Chronic kidney disease is a significant risk factor for stroke and combined vascular events, especially in blacks.

Methods— Data on purchased drugs for secondary stroke prevention during July 2005 to June 2006 by 17 902 patients >18 years discharged after stroke or TIA during the period 1997 to June 2005 were analyzed by age, gender, and year of discharge.

Results— Antiplatelets and warfarin were purchased by 87% of all stroke and 83% of all TIA patients, antihypertensives by 74% and 70%, and lipid lowering drugs by 41% and 39%, respectively.

Conclusion— Time after discharge had only a minor influence on the proportion of patients purchasing the medicines.

Methods— We calculated the adjusted hazard ratios of educational level for cardiovascular disease incidence within a 12-year study of 20 543 Japanese women aged 40 to 59 without history of stroke or heart disease.

Results— The respective age and area-adjusted hazard ratios for junior high school education and college or higher education compared to high school education were 1.63 (95% CI: 1.29, 2.06) and 1.41(95% CI: 0.96, 2.05) for total stroke, 2.20 (95% CI: 1.34, 3.60) and 2.20 (95% CI: 1.08, 4.48) for subarachnoid hemorrhage, and 1.90 (95% CI: 1.30, 2.76) and 1.60 (95% CI: 0.87, 2.93) for ischemic stroke. The U-shaped association with risk of total stroke was primarily observed for working women with single social roles at home. No association was found between educational level and risk of coronary heart disease or intraparenchymal hemorrhage.

Conclusions— A potential benefit of multiple social roles was suggested for stroke risk reduction among highly educated working women.

Methods— Thirty-nine statin-naïve Fisher grade 3 SAH subjects were double-blind randomized to receive simvastatin 80 mg/d (n=19) or placebo (n=20), stratified by Hunt and Hess grade. Primary end points were death and drug morbidity.

Results— Mortality was 3/20 in the placebo and 0/19 in the simvastatin group. Study drug was withdrawn in 1 subject in each treatment group for reversible liver enzyme or creatine phosphokinase elevation. Angiographically-confirmed vasospasm occurred in 8/20 placebo and 5/19 simvastatin-treated subjects. Vasospasm-related ischemic infarcts developed in 5/20 placebo and 2/19 simvastatin-treated subjects.

Conclusion— Simvastatin for the prevention of delayed cerebral ischemia is safe and feasible after SAH. A larger study is needed to test its efficacy.

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 and Results— We have systematically reviewed the diagnostic literature and found 21 studies testing 58 single biomarkers and 7 panels of several biomarkers. Although all show either a high sensitivity or specificity, there are limitations in the design and reporting of all the studies that mean no biomarker can be recommended for use in clinical practice.

Conclusions— We make recommendations for the design and reporting of studies of diagnostic blood biomarkers in stroke.

Methods— A systematic review of both topics is presented in terms of underlying pathophysiological mechanisms and application at the clinical level.

Results— Although the mechanisms of protection for both therapeutic strategies are multifold, both share features of downregulating metabolism. Both therapeutic strategies are robust neuroprotectants, but translating them to the clinical arena is challenging, though not impossible, and clinical studies have shown or suggest benefits of both treatments.

Conclusions— The strategy of metabolic downregulation should be further explored to identify effective neuroprotectants that can be easily applied clinically.