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

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

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

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

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

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

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

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

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

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

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

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

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

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

Methods—We sought articles published between January 1990 and June 2008 by using MEDLINE, EMBASE, the COCHRANE databases, hand-searching, abstract books from conferences, and official websites. Two reviewers independently and in duplicate selected articles on the risks of CAS, irrespective of the type of treatment, study design, setting, or language. The 2 reviewers abstracted data and assessed the quality of the studies.

Results—Two hundred six independent studies (with 54 713 patients) were included. The overall 30-day risk of stroke or death was 4.7% (95% CI, 4.1 to 5.2) with substantial heterogeneity across studies. Symptomatic patients were about twice as likely as those with asymptomatic stenoses to have complications. The 30-day risk of stroke or death was 7.6% (3.6 to 9.1) in symptomatic and 3.3% (2.6 to 4.1) in asymptomatic patients. Risks increased with age, hypertension, and history of coronary artery disease; were unrelated to sex and the presence of contralateral carotid occlusion; and were lower in patients who had carotid restenosis after CEA and in those treated with the use of a cerebral protection device. Risks have also decreased over time.

Conclusions—Risks of CAS vary substantially across studies. Risks are overall higher than those of CEA in symptomatic patients. Some factors are likely to help select good candidates for CAS.

Methods—Electronic searches of MEDLINE, EMBASE, and the Cochrane central register of controlled trials were performed. A total of 20 randomized clinical trials with 108 286 patients reporting stroke were available for this clinical outcome analysis.

Results—Angiotensin receptor blockers were associated with a significant reduction in the risk of stroke than placebo with an OR of 0.91 (0.84 to 0.98). Angiotensin receptor blockers were associated with no significant reduction in the risk of stroke compared with angiotensin-converting enzyme inhibitors (OR, 0.93; 0.84 to 1.03) and calcium antagonists (OR, 1.16; 0.91 to 1.48).

Conclusions—Evidence of the benefit of angiotensin receptor blockers on the risk of stroke is provided when compared with placebo. There was no evidence of the benefit when comparing angiotensin receptor blockers with angiotensin-converting enzyme inhibitors and with calcium antagonists.

Methods—We prospectively followed a hospital-based cohort of 809 first-ever ischemic stroke patients for 1 to 4 years. We compared risks of death, recurrent stroke, and MI in patients with lacunar versus nonlacunar stroke, and performed an updated meta-analysis of recurrent stroke subtype patterns.

Results—During 1725 person-years of follow-up, 109 patients had a recurrent stroke and 31 had MI. All patients at baseline, and 93% with recurrent stroke, had brain imaging and more than half with recurrent stroke had diffusion-weighted MRI. Overall, there was no difference in recurrence risk after lacunar vs nonlacunar stroke, although there was a trend toward a lower recurrence risk in the early weeks after lacunar stroke. Lacunar recurrence was more likely after lacunar than nonlacunar stroke (OR, 6.5; 95% CI, 2.4–17.5; updated meta-analysis OR, 6.8; 95% CI, 4.2–11.2). MI risk was nonsignificantly lower after lacunar than nonlacunar stroke (rate ratio, 0.5; 95% CI, 0.2–1.1; rate ratio after excluding patients with previous ischemic heart disease: 0.3; 95% CI, 0.1–0.9).

Conclusions—Our finding of a trend toward a lower MI risk after lacunar vs nonlacunar stroke and confirmation of both a lower early recurrence risk after lacunar stroke and a tendency of recurrent stroke subtypes to "breed true" support the notion of a distinct nonatherothrombotic lacunar arteriopathy.

Methods—Case series.

Results—We describe 4 elderly patients presenting with a cluster of stereotyped somatosensory migraine auras, initially referred for "crescendo transient ischemic attacks". Neuroimaging in each patient revealed an unexpected finding of spontaneous focal subarachnoid hemorrhage conforming to a cortical sulcus in the contralateral hemisphere. We postulate that the episodic aura symptoms corresponded to recurrent cortical spreading depression triggered by the presence of subarachnoid blood, and speculate that such episodes could be a presenting feature of cerebral amyloid angiopathy in the absence of typical cerebral microbleeds or history of cognitive impairment.

Conclusions—Focal subarachnoid hemorrhage can present clinically with transient repetitive migraine auras. Awareness of this entity is important because misdiagnosis as cerebral ischemic events could lead to incorrect treatment. We recommend that elderly patients presenting with a cluster of new unexplained migraine auras should be investigated ideally with MRI to detect focal subarachnoid hemorrhage.

Methods—Severe vascular disruption and ischemic injury was produced in adult Sprague Dawley rats by transient occlusion of the middle cerebral artery for 1, 2, 4, or 8 hours, followed by 30 minutes of reperfusion. Fluorescein isothiocyanate-dextran (2 MDa) was injected intravenously before occlusion. After perfusion-fixation, brain sections were processed for ultrastructure or fluorescence imaging. We identified early evidence of tissue damage with Fluoro-Jade staining of dying cells.

Results—With increasing ischemia duration, greater quantities of high molecular weight dextran-fluorescein isothiocyanate invaded and marked ischemic regions in a characteristic pattern, appearing first in the medial striatum, spreading to the lateral striatum, and finally involving cortex; maximal injury was seen in the mid-parietal areas, consistent with the known ischemic zone in this model. The regional distribution of the severe vascular disruption correlated with the distribution of 24-hour 2,3,5-triphenyltetrazolium chloride pallor (r=0.75; P<0.05) and the cell death marker Fluoro-Jade (r=0.86; P<0.05). Ultrastructural examination showed significantly increased areas of swollen astrocytic foot process and swollen mitochondria in regions of high compared to low leakage, and compared to contralateral homologous regions (ANOVA P<0.01). Dextran extravasation into the basement membrane and surrounding tissue increased significantly from 2 to 8 hours of occlusion duration (Independent samples t test, P<0.05).

Conclusion—Severe vascular disruption, as labeled with high-molecular-weight dextran-fluorescein isothiocyanate leakage, is associated with severe tissue injury. This marker of severe vascular disruption may be useful in further studies of the pathoanatomic mechanisms of vascular disruption-mediated tissue injury.

Summary of Report—Clinically, the continuum of stroke research and care can be divided into primary prevention, acute interventions, secondary prevention, and poststroke recovery. From a technical/methodological standpoint, fundamental laboratory studies yield insights into basic disease mechanisms and applied laboratory studies further explore the biological basis of disease and evaluate possible therapeutic interventions. The results of these laboratory-based observations can inform clinical study design whereas questions raised by clinical observations can be explored in laboratory experiments (ie, "translational" research). Additional information is gained through observational, interventional, and synthetic (eg, meta-analytic) clinical studies. Outcomes/effectiveness research determines how well interventions perform in different "real-world" settings. The discussion provides examples of how several of these approaches can be used to address various research questions. The importance for stroke investigators to contribute to related public policy issues is also reviewed.

Conclusions—This is an exciting era for clinical investigators studying stroke and for those at the beginning stages of their careers. Whether taking a broad-based research approach or working on a specific, focused question, our combined efforts are leading to improved outcomes for patients with stroke, the very goal of Bill Feinberg's career.

Methods—Ninety-seven mice were assigned to sham, SAH+vehicle, SAH+Ac-YVAD-CMK (6 or 10 mg/kg), and SAH+Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK, 6 mg/kg) groups. Drugs were intraperitoneally injected 1 hour post-SAH. Pulmonary edema measurements, Western blot for interleukin-1β, interleukin-18, myeloperoxidase, matrix metalloproteinase (MMP)-2, MMP-9, cleaved caspase-3 and zona occludens-1, MMP zymography, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining, and immunostaining were performed on the lung at 24 hours post-SAH.

Results—Ten- but not 6-mg/kg of Ac-YVAD-CMK significantly inhibited a post-SAH increase in the activation of interleukin-1β and caspase-3 and the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive pulmonary endothelial cells, preventing neurogenic pulmonary edema. Another antiapoptotic drug, Z-VAD-FMK, also reduced neurogenic pulmonary edema. SAH did not change interleukin-18, myeloperoxidase, MMP-2, MMP-9, zona occludens-1 levels, or MMP activity.

Conclusions—We report for the first time that Ac-YVAD-CMK prevents lung cell apoptosis and neurogenic pulmonary edema after SAH in mice.

Methods—Five hundred subjects with acute ischemic stroke who could begin receiving study material within 6 hours of symptom onset were infused intravenously with either ancrod (0.167 IU/kg per hour) or placebo over 2 or 3 hours. The primary efficacy outcome was a dichotomized, modified Rankin score at 90 days with less stringent cut-points for higher prestroke modified Rankin score and pretreatment NIHSS total score ("responder analysis"). Safety variables included mortality, major bleeding, and intracranial hemorrhage.

Results—Although the desired changes in fibrinogen level were seen in >90% of ancrod subjects, interim analysis for futility led to the study being halted for lack of efficacy. Positive responder status in the interim dataset was seen in 39.6% of ancrod subjects and 37.2% of placebo subjects (P=0.47). Ninety-day mortality did not differ between the 2 groups (ancrod, 15.6%; placebo, 14.1%; P=0.32), and the incidence of symptomatic intracranial hemorrhage within the first 72 hours, although not significantly different in ancrod compared to placebo subjects (P=0.19), was approximately twice as high (3.9% vs 2.0%; P=0.19).

Conclusion—These results demonstrate that intravenous ancrod starting within 6 hours after symptom onset in a broad selection of subjects with ischemic stroke did not improve their outcome and revealed a trend to increased bleeding despite successful efforts to achieve rapid initial defibrinogenation and avoid prolonged hypofibrinogenemia.

Materials and Methods—Fifty patients with symptomatic carotid atherosclerosis underwent ¹⁸F-FDG PET/CT and MRI. Correlations and agreement between imaging findings were assessed by Spearman and Pearson rank correlation tests, t tests, and Bland-Altman plots.

Results—Spearman between plaque ¹⁸F-FDG standard uptake values and CT/MRI findings varied from -0.088 to 0.385. Maximum standard uptake value was significantly larger in plaques with intraplaque hemorrhage (1.56 vs 1.47; P=0.032). Standard uptake values did not significantly differ between plaques with an intact and thick fibrous cap and plaques with a thin or ruptured fibrous cap on MRI. (1.21 vs 1.23; P=0.323; and 1.45 vs 1.54; P=0.727). Pearson between CT and MRI measurements varied from 0.554 to 0.794 (P<0.001). For lipid-rich necrotic core volume, the CT–MRI correlation was stronger in mildly (≤10%) than in severely (>10%) calcified plaques (Pearson 0.730 vs 0.475). Mean difference in measurement ±95% limits of agreement between CT and MRI for minimum lumen area, volumes of vessel wall, lipid-rich necrotic core, calcifications, and fibrous tissue were 0.4±18.1 mm² (P=0.744), -41.9 ±761.7 mm³ (P=0.450), 78.4±305.0 mm³ (P<0.001), 180.5±625.7 mm³ (P=0.001), and -296.0±415.8 mm³ (P<0.001), respectively.

Conclusions—Overall, correlations between ¹⁸F-FDG PET and CT/MRI findings are weak. Correlations between CT and MRI measurements are moderate to strong, but there is considerable variation in absolute differences.

Methods—The trial cohorts were combined in a data set of 305 patients. Twenty-eight baseline variables were included in univariate and multivariate analyses to define the independent predictors of good outcomes (modified Rankin Scale score ≤2), mortality, and successful revascularization (Thrombolysis In Myocardial Ischemia 2 to 3 flow).

Results—In the univariate analysis, final revascularization, baseline National Institutes of Health Stroke Scale, age, and systolic blood pressure were associated with both good outcomes and mortality at 90 days (P<0.0018 for all). In the multivariate analysis, final revascularization (OR, 20.4; 95% CI, 7.7 to 53.9; P<0.0001), baseline National Institutes of Health Stroke Scale (OR, 0.86; 95% CI, 0.81 to 0.92; P<0.0001), and age (OR, 0.96; 95% CI, 0.95 to 0.98; P=0.0004) were independent predictors of good outcome. Final revascularization (OR, 0.28; 95% CI, 0.16 to 0.50; P<0.0001), baseline National Institutes of Health Stroke Scale score (odds ratio, 1.09; 95% CI, 1.04 to 1.14; P=0.0001), age (OR, 1.05; 95% CI, 1.03 to 1.07; P<0.0001), and internal carotid artery occlusion (OR, 2.17; 95% CI, 1.22 to 3.86; P=0.0084) were the strongest predictors of mortality. Systolic blood pressure (<150 versus ≥150 mm Hg; OR, 0.42; 95% CI, 0.26 to 0.70; P=0.0007) and M2 occlusion (OR, 3.86; 95% CI, 1.28 to 11.67; P=0.0168) were independent predictors of revascularization.

Conclusion—Final recanalization status represents the strongest predictor of clinical outcomes in patients undergoing thrombectomy. The ability to remove the clot is negatively influenced by systolic blood pressure on presentation perhaps because of the hydraulic forces imposed by higher blood pressures. Although internal carotid artery occlusions are associated with increased mortality, they do not appear to influence the chances of good outcomes. This finding supports the inclusion of internal carotid artery occlusions in future efficacy trials.

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

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

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

Methods—We compared consecutive patients with stroke arriving to our stroke center during the first 4 months of this new triage protocol (February 14 to June 14, 2005) versus the same 4-month period in 2004.

Results—The protocol resulted in an immediate doubling in the number of patients with acute stroke arriving to our regional stroke center within 2.5 hours of symptom onset. We observed a 4-fold increase in patients who were eligible for and treated with tissue plasminogen activator. The tissue plasminogen activator treatment rate for ischemic stroke patients increased from 9.5% to 23.4% (P=0.01), and one in 2 patients with ischemic stroke arriving within 2.5 hours received thrombolysis during this period (one in 5 of patients with ischemic stroke overall). The median onset-to-needle time for tissue plasminogen activator-treated patients was significantly reduced. Many implementation challenges were identified and addressed.

Conclusions—This prehospital triage was immediately successful in improving tissue plasminogen activator access for patients with ischemic stroke, enabling our center to achieve one of the highest tissue plasminogen activator treatment rates in North America and underscoring the need for coordinated systems of acute stroke care. Sustainability of such an initiative will be dependent on interdisciplinary teamwork, ongoing paramedic training, adequate hospital staffing, bed availability, and repatriation agreements with community hospitals.

Methods—A systematic review and meta-analysis was performed to determine the prognostic value of ES in different potential cerebral embolic sources. Studies were identified that used transcranial Doppler to detect ES and included prospective stroke/TIA follow-up. Numbers of ES-positive and ES-negative patients were extracted with stroke/TIA and stroke alone outcomes.

Results—ES are most frequent in large artery disease, less frequent in cardioembolic stroke, and infrequent in lacunar stroke. Data relating ES to future stroke risk were available for acute stroke, large artery disease, and the perioperative period of carotid endarterectomy. For symptomatic carotid stenosis, ES predicted stroke alone (OR, 9.57; 95%CI, 1.54 to 59.38; P=0.02) and stroke/TIA (OR, 6.36; 95% CI, 2.90–13.96; P<0.00001). For asymptomatic carotid stenosis, ES predicted stroke alone (OR, 7.46; 95% CI, 2.24–24.89; P=0.001) and stroke/TIA (OR, 12.00; 95% CI, 2.43–59.34; P=0.002) but with heterogeneity (P=0.004). In acute stroke ES predicted stroke alone (OR, 2.44; 95% CI, 1.17–5.08; P=0.02) and stroke/TIA (OR, 3.71; 95% CI, 1.64–8.38; P=0.002). A high frequency of ES immediately after carotid endarterectomy predicted stroke alone (OR, 24.54; 95% CI, 7.88–76.43; P<0.00001) and stroke/TIA (OR, 32.04; 95% CI, 11.36–90.39; P<0.00001).

Conclusion—ES predict stroke risk in acute stroke, symptomatic carotid stenosis, and postoperatively after carotid endarterectomy; in asymptomatic carotid stenosis, data are less robust. In these conditions ES may be useful in risk stratification and in assessing therapeutic efficacy. For other embolic sources, further prospective data are required.

Methods—All 79 hospitals in Sweden admitting acute stroke patients participate in Riks-Stroke. During 2001 to 2007, 104 876 patients (87% of survivors) responded to a follow-up questionnaire 3 months after acute stroke; this included questions on satisfaction with various aspects of stroke care.

Results—The majority (>90%) were satisfied with acute in-hospital stroke care. Dissatisfaction was closely associated with outcome at 3 months. Patient who were dependent regarding activities of daily living, felt depressed, or had poor self-perceived general health were more likely to be dissatisfied. Dissatisfaction with global acute stroke care was linked to dissatisfaction with other aspects of care, including rehabilitation and support by community services. Patients treated in stroke units were less often dissatisfied than patients in general wards, as were patients who had been treated in a small hospital (vs medium or large hospitals) and patient who had participated in discharge planning. In multivariate analyses, the strongest predictor of dissatisfaction with acute care was poor outcome (dependency regarding activities of daily living, depressed mood, poor self-perceived health).

Conclusions—Dissatisfaction with in-hospital acute stroke care is part of a more extensive complex comprising poor functional outcome, depressive mood, poor self-perceived general health, and dissatisfaction not only with acute care but also with health care and social services at large. Several aspects of stroke care organization are associated with a lower risk of dissatisfaction.

Methods—We performed a case-control study with 101 consecutive stroke patients and 100 consecutive acute coronary syndrome patients admitted to an emergency hospital. CD was investigated in all patients and was confirmed when both immunofluorescence and hemagglutination tests were positive. Clinical, laboratory, and ECG findings were analyzed.

Results—We found that age (P=0.006), female sex (P=0.01), systolic blood pressure (P=0.001), diastolic blood pressure (P=0.03), previous stroke/transient ischemic attack history (P<0.001), atrial fibrillation (P=0.005), other arrhythmias (P=0.05), and CD-positive serology (P=0.002) were more frequent among stroke patients than among patients with acute coronary syndromes. After a multivariable analysis with a backward elimination procedure, previous stroke/transient ischemic attack history (odds ratio=6.98; 95% CI, 2.99 to 16.29), atrial fibrillation (odds ratio=4.52; 95% CI, 1.45 to 14.04), and CD-positive serology (odds ratio=7.17; 95% CI, 1.50 to 34.19) remained independently associated with stroke.

Conclusions—CD seems to be an independent risk factor for ischemic stroke. For patients in or coming from endemic regions, CD should be considered an etiologic or contributing factor for stroke.

Methods—Patients were recruited with MR studies performed within 48 hours of ischemic stroke. Mismatch patterns based on diffusion-weighted/perfusion-weighted images were categorized as classical (majority of the diffusion-weighted image within the perfusion-weighted image lesion) or nonclassical (fragmented) patterns. The proportion of patterns was assessed with reference to time, vessel patency, mismatch volume, and infarct core location.

Results—Sixty-seven patients (33 classical [49.3%] and 34 nonclassical patterns [50.7%]) were studied within 48 hours (median age, 74.0 years). Compared to the nonclassical pattern, the classical pattern had a shorter time to MR (3.4 hours vs 10.4 hours; P=0.004) and a larger mismatch volume (62.0 mL vs 3.5 mL; P<0.0001). The positive predictors for the classical pattern were earlier time, vessel occlusion, superficial core location, and larger mismatch volume.

Conclusion—The classical mismatch pattern may fragment with time. Over 48 hours the classical pattern is seen earlier after stroke onset, with higher rates of vessel occlusion and larger mismatch volumes.

Summary of Case—We present a patient with cerebral microbleeds and likely amyloid angiopathy with evolving ischemic lesions visualized on diffusion-weighted imaging.

Conclusions—This case captures with serial MRI the evolving and dynamic nature of cerebral amyloid angiopathy and particularly illustrates the subclinical, yet progressive, ischemic aspects of this vasculopathic process.

Methods—MD and fractional anisotropy were measured in 6 regions of interest in normal-appearing white matter. Visible white matter lesions were quantified using the Fazekas scale. Both were correlated with systolic and diastolic BP.

Results—Systolic BP was positively and significantly correlated with MD in all 6 regions (r=0.31 to 0.45; P=0.037 to 0.002). MD was also correlated with diastolic BP in the genu of the corpus callosum (r=0.34, P=0.018). A summary factor derived from principal component analysis of the MD measurements accounted for 53.8% of the variance and correlated at r=0.51 (P<0.001) with systolic BP and r=0.33 (P=0.028) with diastolic BP. Fractional anisotropy did not correlate significantly with BP. Deep white matter Fazekas scores correlated with diastolic BP (=0.35, P=0.019).

Conclusions—The increase in MD without change in fractional anisotropy indicates that, in normal-appearing white matter, higher BP may be associated with increased extracellular fluid before any cytoarchitectural damage occurs.

Summary of Review—Possible mechanisms linking baroreflex impairment with unfavorable outcome in stroke may include increased cardiovascular morbidity and mortality, promotion of secondary brain injury due to local inflammation, hyperglycemia, or altered cerebral perfusion.

Conclusions—We suggest therefore that the modifying of autonomic functions may have important therapeutic implications in acute ischemic as well as in hemorrhagic stroke.

Methods—The volumes of subcortical and ependymal HWM regions were measured from high-resolution (1 mm³), 3-dimensional fluid-attenuated inversion recovery images acquired for 459 (283 females, 176 males) active participants in the San Antonio Family Heart Study. Subjects ranged in age from 19 to 85 years of age (47.9±13.5 years) and were part of 49 families (9.4±8.5 individuals per family).

Results—The volumes of whole-brain, subcortical, and ependymal HWM were highly heritable (h²=0.72, 0.66, and 0.73, respectively). The subcortical and ependymal HWM volumes shared 21% of genetic variability indicating significant pleiotropy. Genomewide linkage analysis showed only a suggestive bivariate linkage for subcortical and ependymal HWM volumes (log of odds=2.12) on chromosome 1 at 288 cM.

Conclusion—We replicated previous findings of high heritability for the whole-brain HWM volume. We also showed that subcortical and ependymal volume shared a significant portion of genetic variability and the bivarate linkage analysis produced a suggestive linkage near the locus previously identified in a study of whole-brain HWM volume and arterial pulse pressure.

Methods—This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40 000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for.

Results—Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (P=0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (n=42 of 256) in the EPO and 9.0% (n=24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38; P=0.01) without any particular mechanism of death unexpected after stroke.

Conclusions—Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis.

Summary of Review—The identification of gene mutations and genetic risk factors associated with cerebral cavernous malformation, hereditary hemorrhagic telangiectasia, and sporadic arteriovenous malformation has enabled the development of animal models for these diseases and provided new insights into their etiology. All of the genes associated with VMBs to date have known or plausible roles in angiogenesis and vascular remodeling. Recent work suggests that the angiogenic process most severely disrupted by VMB gene mutation is that of vascular stabilization, the process whereby vascular endothelial cells form capillary tubes, strengthen their intercellular junctions, and recruit smooth muscle cells to the vessel wall. In addition, there is now good evidence that in some cases, cerebral cavernous malformation lesion formation involves a genetic 2-hit mechanism in which a germline mutation in one copy of a cerebral cavernous malformation gene is followed by a somatic mutation in the other copy. There is also increasing evidence that environmental second hits can produce lesions when there is a mutation to a single allele of a VMB gene.

Conclusions—Recent findings begin to explain how mutations in VMB genes render vessels vulnerable to rupture when challenged with other inauspicious genetic or environmental factors and have suggested candidate therapeutics. Understanding of the cellular mechanisms of VMB formation and progression in humans has lagged behind that in animal models. New knowledge of lesion biology will spur new translational work. Several well-established clinical and genetic database efforts are already in place, and further progress will be facilitated by collaborative expansion and standardization of these.

Methods—The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality, was calculated using univariate and multivariate logistic regression.

Results—Over a 33-month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as transient ischemic attack. Among patients with stroke, 267 (46%) had LVO accounting for the stroke and 13 (13%) of patients with transient ischemic attack had LVO accounting for transient ischemic attack symptoms. LVO predicted 6-month mortality (OR, 4.5; 95% CI, 2.7 to 7.3; P<0.001). Six-month good outcome (modified Rankin Scale score ≤2) was negatively predicted by LVO (0.33; 0.24 to 0.45; P<0.001). Based on multivariate analysis, the presence of basilar and internal carotid terminus occlusions, in addition to National Institutes of Health Stroke Scale and age, independently predicted outcome.

Conclusion—Large vessel intracranial occlusion accounted for nearly half of acute ischemic strokes in unselected patients presenting to academic medical centers. In addition to age and baseline stroke severity, occlusion of either the basilar or internal carotid terminus segment is an independent predictor of outcome at 6 months.

Methods—We compared the prevalence of self-reported history of stroke or TIA in the REasons for Geographic And Racial Differences in Stroke (REGARDS) participants with HF (as defined by current digoxin use) and without HF. We excluded participants with atrial fibrillation or missing data. We examined the relationship between HF and history of stroke/TIA within tertiles of systolic blood pressure (SBP) adjusting for patient demographic and health characteristics.

Results—Prevalent stroke/TIA were reported by 66 (26.3%) of 251 participants with and 1805 (8.5%) of 21 202 participants without HF (P<0.0001). Within each tertile of SBP, the unadjusted OR (95% CI) for prior stroke/TIA among those with HF compared with those without HF (the reference group) was, 4.0 (2.8 to 5.8) for SBP <119.5 mm Hg, 2.7 (1.8 to 3.9) for SBP ≥119.5 but <131.5 mm Hg, and 2.3 (1.6 to 3.2) for SBP ≥131.5 mm Hg. After adjustment, the relationship between prior stroke/TIA and HF remained significant only within the lowest tertile of SBP (<119.5 mm Hg; 3.0; 1.5 to 6.1).

Conclusions—The odds of prevalent self-reported stroke/TIA are increased in participants with HF and most markedly increased in participants with low SBP. Longitudinal data are needed to determine whether this reflects stroke/TIA secondary to thromboembolism from poor cardiac function or secondary to cerebral hypoperfusion.

Methods—We conducted a prospective, randomized, multicenter, 3-arm trial (tight control [target 70 to 110 mg/dL], loose control [target 70 to 200 mg/dL], and control usual care [70 to 300 mg/dL]) to assess the feasibility and safety of 2 insulin infusion protocol targets in patients with acute ischemic stroke. The planned sample was 72 subjects.

Results—A total of 74 subjects were enrolled. Seventy-two (97%) had data available for the primary analyses and 73 (99%) had 3-month clinical outcome data. Median age was 67 years, median National Institutes of Health Stroke Scale score was 8, median glucose was 163 mg/dL, and median time to randomization was 10.7 hours. Fifty-nine percent of patients were diabetic, 35% received thrombolysis, and 14% of subjects died within 3 months. The loose control and usual care groups had median glucose concentrations of 151 mg/dL. The tight control group had a median glucose concentration of 111 mg/dL. The loose control group spent 90% of the first 24 hours in target and the tight group 44% of time in target. There was only one symptomatic patient with hypoglycemia in the loose control group (4%) and zero in the tight control group. The overall rates of hypoglycemia (<55 mg/dL) were 4% in control, 4% in loose, and 30% in tight. Exploratory efficacy analysis was conducted.

Conclusions—Insulin infusion for patients with acute ischemic stroke is feasible and safe using the insulin infusion protocol in the Glucose Regulation in Acute Stroke Patients (GRASP) trial. Exploratory efficacy analysis supports further comparative study.

Methods—Gait analysis was performed as subjects (N=13) with chronic poststroke hemiparesis walked at their self-selected walking speeds during walking with and without FES.

Results—Compared with delivering FES to only the ankle dorsiflexor muscles during the swing phase, delivering FES to both the paretic ankle plantarflexors during terminal stance and dorsiflexors during the swing phase provided the advantage of greater swing-phase knee flexion, greater ankle plantarflexion angle at toe-off, and greater forward propulsion. Although FES of both the dorsiflexor and plantarflexor muscles improved swing-phase ankle dorsiflexion compared with noFES, the improvement was less than that observed by stimulating the dorsiflexors alone, suggesting the need to further optimize stimulation parameters and timing for the dorsiflexor muscles during gait.

Conclusions—In contrast to the typical FES approach of stimulating ankle dorsiflexor muscles only during the swing phase, delivering FES to both the plantarflexor and dorsiflexor muscles can help to correct poststroke gait deficits at multiple joints (ankle and knee) during both the swing and stance phases of gait. Our study shows the feasibility and advantages of stimulating the ankle plantarflexors during FES for poststroke gait.

Methods—In a multicenter, double-blind, randomized, placebo-controlled Phase II trial, 40 patients with ischemic stroke were treated with either placebo or active drug between 3 and 12 hours after symptom onset in a dose-finding design. Ten patients received placebo, 6 patients received a total dose of 2 mg/kg, 12 patients received a total dose of 3 mg/kg, and 12 patients received a total dose of 4 mg/kg. We studied the pharmacodynamics of microplasmin and its effect on the clinical and hemodynamic parameters of the patients. MRI was used as a surrogate marker and matrix metalloproteinases serum concentrations were used as markers of neurovascular integrity. The study was underpowered to detect clinical efficacy.

Results—Microplasmin induced reversible effects on markers of systemic thrombolysis and neutralized ₂-antiplasmin by up to 80%. It was well tolerated with one of 30 treated patients developing a fatal symptomatic intracerebral hemorrhage. No significant effect on reperfusion rate or on clinical outcome was observed. Matrix metalloproteinase-2 levels were reduced in microplasmin-treated patients.

Conclusions—Microplasmin was well tolerated and achieved neutralization of ₂-antiplasmin. Further studies are warranted to determine whether microplasmin is an effective therapeutic agent for ischemic stroke.

Methods—An inception cohort of 204 patients with acute ischemic stroke or TIA was followed up for a mean of 2.3 years. At baseline, patients underwent ABI measurement and were assessed for risk factors, cardiovascular comorbidities, and cervical or intracranial artery stenosis. The association between low ABI (≤0.9) and the risk of the composite outcome of stroke, myocardial infarction, or death was examined by Kaplan–Meier and Cox regression analyses.

Results—A low ABI was found in 63 patients (31%) and was associated with older age, current smoking, hypertension, peripheral arterial disease, and cervical or intracranial stenosis. During a total of 453.0 person-years of follow-up, 37 patients experienced outcome events (8.2% per person-year), with a higher outcome rate per person-year in patients with low ABI (12.8% vs 6.3%, P=0.03). In survival analysis adjusted for age and stroke etiology, patients with a low ABI had a 2 times higher risk of stroke, myocardial infarction, or death than those with a normal ABI (hazard ratio=2.2; 95% CI, 1.1 to 4.5). Additional adjustment for risk factors and cardiovascular comorbidities did not attenuate the association.

Conclusions—A low ABI independently predicted subsequent cardiovascular risk and mortality in patients with acute stroke or TIA. ABI measurement may help to identify high-risk patients for targeted secondary stroke prevention.

Methods—We used ³¹P-MRS to study patients with a diagnosis of either migrainous infarction or migraine with persistent aura without infarction (aura duration >7 days) according to International Headache Society criteria. We compared clinical presentation and metabolite ratios between patient groups. We also studied healthy controls with no history of migraine.

Results—Patients with persistent aura without infarction had lower phosphocreatine-phosphate (PCr/Pi) ratios (mean±SD, 1.61±0.10) compared with controls (1.94±0.35, P=0.011) and with patients with migrainous stroke (1.96±0.16, P<0.0001). These differences were present in cortical tissue only. In migrainous stroke patients, the metabolite ratios did not differ significantly from those of controls without migraine.

Conclusions—The differences in cortical energy reserves between patients with migrainous stroke and in those with migraine with persistent aura suggest that the pathomechanisms of these conditions differ and that migrainous infarction does not simply represent a particularly severe form of migrainous aura. This finding supports the revised International Headache Society criteria, which now distinguish between migrainous infarction and migraine with persistent aura without infarction.

Methods—We used the Swiss IVT databank to compare outcome and complications of IVT-treated patients with CAD with IVT-treated patients with other etiologies (non-CAD patients). Main outcome and complication measures were favorable 3-month outcome, intracranial cerebral hemorrhage, and recurrent ischemic stroke. Modified Rankin Scale score ≤1 at 3 months was considered favorable.

Results—Fifty-five (5.2%) of 1062 IVT-treated patients had CAD. Patients with CAD were younger (median age 50 versus 70 years) but had similar median National Institutes of Health Stroke Scale scores (14 versus 13) and time to treatment (152.5 versus 156 minutes) as non-CAD patients. In the CAD group, 36% (20 of 55) had a favorable 3-month outcome compared with 44% (447 of 1007) non-CAD patients (OR, 0.72; 95% CI, 0.41 to 1.26), which was less favorable after adjustment for age, gender, and National Institutes of Health Stroke Scale score (OR, 0.50; 95% CI, 0.27 to 0.95; P=0.03). Intracranial cerebral hemorrhages (asymptomatic, symptomatic, fatal) were equally frequent in CAD (14% [7%, 7%, 2%]) and non-CAD patients (14% [9%, 5%, 2%]; P=0.99). Recurrent ischemic stroke occurred in 1.8% of patients with CAD and in 3.7% of non-CAD-patients (P=0.71).

Conclusion—IVT-treated patients with CAD do not recover as well as IVT-treated non-CAD patients. However, intracranial bleedings and recurrent ischemic strokes were equally frequent in both groups. They do not account for different outcomes and indicate that IVT should not be excluded in patients who may have CAD. Hemodynamic compromise or frequent tandem occlusions might explain the less favorable outcome of patients with CAD.

Methods—Seven patients with acute ischemic stroke (aged 31 to 88 years) who underwent intra-arterial therapy with the Alligator retrieval device at our center are presented.

Results—The Alligator retrieval device was able to retrieve the thrombus in 5 of 7 cases with good to excellent recanalization seen and was unsuccessful in 2 of 7 patients. Complete recanalization was obtained in one of 7 patients and near complete recanalization obtained in 4 of 7 patients. Three of the 7 patients had good outcome at 3 months and 3 of 7 patients died within 30 days of treatment.

Conclusion—The Alligator retrieval device was successfully able to remove thrombus in the majority of cases. It appears to have increased success in proximal occlusions in relatively straight segments. In properly selected cases, it may be a useful device in intra-arterial stroke management.

Methods—We conducted a cross-sectional study of patients with acute ischemic stroke recruited from 3 centers (Melbourne, Sydney, Singapore). The caliber of retinal arterioles and venules was measured from digital retinal photographs. Severe extracranial carotid disease was defined as stenosis ≥75% or occlusion determined by carotid Doppler using North American Symptomatic Carotid Endarterectomy Trial-based criteria.

Results—Among the 1029 patients with acute stroke studied, 7% of the population had severe extracranial carotid disease. Retinal venular caliber was associated with ipsilateral severe carotid disease (P<0.001 in multivariate models). Patients with wider retinal venular caliber were more likely to have severe ipsilateral carotid disease (multivariable-adjusted OR, 3.81; 95% CI, 1.80 to 8.07, comparing the largest and smallest venular caliber quartiles). The retinal venular caliber–carotid disease association remained significant in patients with large artery stroke.

Conclusions—In patients with acute stroke, retinal venular widening was strongly associated with ipsilateral severe extracranial carotid disease. Our findings suggest concomitant retinal and cerebral microvascular disease may be present in patients with carotid stenosis or occlusion disease. The pathogenesis of stroke due to carotid disease may thus be partially mediated by microvascular disease.

Methods—Initial CT scans with intraparenchymal hematoma from the first 1000 patients with stroke in the Oxford Vascular Study were independently categorized as intracerebral hemorrhage or hemorrhagic transformation of infarction by 5 neuroradiologists, both blinded and unblinded to clinical history. Thirty scans were reviewed twice. Agreement was quantified by the statistic.

Results—Seventy-eight scans showed intraparenchymal hematoma. Blinded pairwise interrater agreements for a diagnosis of intracerebral hemorrhage ranged from =0.15 to 0.48 with poor overall agreement (=0.35; 95% CI, 0.15 to 0.54) even after unblinding (=0.41; 0.21 to 0.60). Blinded intrarater agreements ranged from =0.21 to 0.92. Lack of consensus after unblinding was greatest in patients scanned ≥24 hours after stroke onset (67% versus 25%, P=0.001) and in minor stroke (National Institutes of Health Stroke Scale ≤5: 56% versus 29%, P=0.04) with disagreement in 75% of patients scanned ≥24 hours after minor stroke and in 48% of all 30-day stroke survivors in whom reliable diagnosis would be expected to influence long-term management.

Conclusion—Reliability of diagnosis of intraparenchymal hematoma on CT brain scan in minor stroke is poor, particularly if scanning is delayed. Immediate brain imaging is justified in patients with minor stroke.

Methods—One hundred seventy-three participants of a community-dwelling elderly cohort had neurological and neuropsychological examinations and brain MRI. Gait function was measured by Tinetti gait (0 to 12), balance (0 to 16) and total (0 to 28) scores. DTI assessed fractional anisotropy in the genu and splenium of the corpus callosum. Conventional MRI was used to evaluate for brain infarcts and white matter hyperintensity volume.

Results—Participants with abnormal gait had low fractional anisotropy in the genu of the corpus callosum but not the splenium. Multiple regressions analyses showed an independent association between these genu abnormalities and all 3 Tinetti scores (P<0.001). This association remained significant after adding MRI infarcts and white matter hyperintensity volume to the analysis.

Conclusions—The independent association between quantitative measures of gait function and DTI findings shows that white matter integrity in the genu of corpus callosum is an important marker of gait in the elderly. DTI analyses of white matter tracts in the brain and spinal cord may improve knowledge about the pathophysiology of gait impairment and help target clinical interventions.

Methods—Medical records were abstracted for consecutive ischemic stroke patients admitted from the Emergency Department within 48 hours of symptom onset at 35 academic medical centers participating in the University HealthSystem Consortium Ischemic Stroke Benchmarking Project between January 1, 2001 and March 31, 2001, and 32 centers between January 1, 2004 and June 30, 2004. Demographic and clinical characteristics of patients who presented within and after 2 hours of symptom onset were compared. Multivariate logistic regression was used to compare time to arrival by year and to identify patient characteristics associated with earlier hospital arrival.

Results—The study included 428 patients from 2001 and 481 from 2004. Although there was no difference in the percentage of patients who arrived within 2 hours between the 2 periods (37% in 2001 vs 38% in 2004, P=0.63), the percentage of these patients treated with IV t-PA increased (14.0% to 37.5%, P<0.0001). In risk-adjusted analysis, black patients had a lower odds of arriving within 2 hours (odds ratio=0.55; 95% CI, 0.39 to 0.78), whereas those with severe strokes were more likely to arrive promptly (odds ratio=2.17; 95% CI, 1.49 to 3.15).

Conclusions—There was no change in the proportion of stroke patients arriving at hospitals within 2 hours of symptom onset between 2001 and 2004; however, the rate of IV t-PA use increased, indicating system-level improvements of in-hospital care.

Methods—We used the person trade-off procedure developed by the World Health Organization Global Burden of Disease Project (WHO-GBDP) to generate disability weights (DWs) ranging from 0 (normal) to 1 (dead) for each of 7 mRS grades. The ratings of an international, 9-member panel of stroke experts were combined by a modified Delphi process.

Results—DWs (95% CI) were 0 for mRS 0, 0.046 (0.004 to 0.088) for mRS 1, 0.212 (0.175 to 0.250) for mRS 2, 0.331 (0.292 to 0.371) for mRS 3, 0.652 (0.625 to 0.678) for mRS 4, 0.944 (0.873 to 1.015) for mRS 5, and 1.0 for mRS 6. DWs of adjacent mRS levels were significantly different (P<0.001 for all). Coefficients of variation showed a high degree of consensus for DWs among panel members. DWs placed each of the 5 intermediate mRS states in different disability class levels of the WHO-GBDP anchor conditions and identified natural clusters to use when reducing the mRS to fewer categories.

Conclusions—Formal DW assignment confirms that the mRS is an ordered but unequally spaced scale. The availability of DWs for each mRS level now permits direct comparison of each poststroke outcome state with the outcomes of hundreds of other diseases in the WHO-GBDP and the expression of stroke burden in different populations by using the uniform metric of disability-adjusted life-years lost.

Methods—Over 8.5 years, we prospectively identified 82 consecutive patients with anterior inferior cerebellar artery territory infarction diagnosed by MRI. Each patient completed a standardized audiovestibular questionnaire and underwent a neuro-otologic evaluation, including bithermal caloric tests and pure tone audiogram.

Results—All but 2 (80 of 82 [98%]) patients had acute prolonged vertigo and vestibular dysfunction of peripheral, central, or combined origin. The most common pattern of audiovestibular dysfunction was the combined loss of auditory and vestibular function (n=49 [60%]). A selective loss of vestibular (n=4 [5%]) or cochlear (n=3 [4%]) function was rarely observed. We could classify anterior inferior cerebellar artery territory infarction into 7 subgroups according to the patterns of neuro-otological presentations: (1) acute prolonged vertigo with audiovestibular loss (n=35); (2) acute prolonged vertigo with audiovestibular loss preceded by an episode(s) of transient vertigo/auditory disturbance within 1 month before the infarction (n=13); (3) acute prolonged vertigo and isolated auditory loss without vestibular loss (n=3); (4) acute prolonged vertigo and isolated vestibular loss without auditory loss (n=4); (5) acute prolonged vertigo but without documented audiovestibular loss (n=24); (6) acute prolonged vertigo and isolated audiovestibular loss without any other neurological symptoms/signs (n=1); and (7) nonvestibular symptoms with normal audiovestibular function (n=2).

Conclusions—Infarction in the anterior inferior cerebellar artery territory can present with a broad spectrum of audiovestibular dysfunctions. Unlike a viral cause, labyrinthine dysfunction of a vascular cause usually leads to combined loss of both auditory and vestibular functions.

Methods—We measured the OEF by using positron emission tomography and ¹⁵O gas in 100 nondisabled patients with atherosclerotic MCA disease in the chronic stage. On MRI, the infarcts were categorized as territorial, border-zone (external or internal), deep perforator, and superior perforator infarcts. In 62 patients, BZRs were measured using ¹¹C-flumazenil. By using 3-dimensional stereotactic surface projections, the abnormally decreased BZR index ("BZR index") [(the extent of the pixels with Z score more than 2 compared with controls)x(average Z score in those pixels)] was calculated. In the hemisphere affected by MCA disease, the type of infarcts was correlated with the value of OEF or BZR index in the cerebral cortex of the MCA distribution.

Results—Compared with patients without internal border-zone infarcts, those with these infarcts (n=18) had significantly increased OEF and significantly high BZR index. Multivariate analysis revealed that internal border-zone infarction was independently associated with increased OEF and high BZR index.

Conclusions—In atherosclerotic MCA disease, internal border-zone infarction is associated with increased OEF and a decrease in BZRs in the overlying cerebral cortex, suggesting that hemodynamic compromise may induce internal border-zone infarction and cortical neuronal damage.

Methods—We prospectively enrolled 98 patients with intracerebral hemorrhage and recorded antiepileptic drug use as either prophylactic or therapeutic along with clinical characteristics. Antiepileptic drug administration and free phenytoin serum levels were retrieved from the electronic medical records. Patients with depressed mental status underwent continuous electroencephalographic monitoring. Outcomes were measured with the National Institutes of Health Stroke Scale and modified Rankin Scale at 14 days or discharge and the modified Rankin Scale at 28 days and 3 months. We constructed logistic regression models for poor outcome at 3 months with a forward conditional model.

Results—Seven (7%) patients had a clinical seizure, 5 on the day of intracerebral hemorrhage. Phenytoin was associated with more fever (P=0.03), worse National Institutes of Health Stroke Scale at 14 days (23 [9 to 42] versus 11 [4 to 23], P=0.003), and worse modified Rankin Scale at 14 days, 28 days, and 3 months. In a forward conditional logistic regression model, phenytoin prophylaxis was associated with an increased risk of poor outcome (OR, 9.8; 1.4 to 68.6; P=0.02), entering after admission National Institutes of Health Stroke Scale and age. Excluding patients with a seizure did not change the results. Levetiracetam was not associated with demographics, seizures, complications, or outcomes.

Conclusions—Phenytoin was associated with more fever and worse outcomes after intracerebral hemorrhage.

Methods—We used diffusion-weighted MRI in patients hospitalized for a pulmonary embolism to assess cerebral embolic events. Sixty consecutive patients were evaluated at diffusion-weighted MRI. All patients underwent neurological assessment before diffusion-weighted MRI and a contrast echocardiography to detect PFO the next day.

Results—Diffusion-weighted MRI showed bright lesions in 6 patients among the 60 consecutive patients with pulmonary embolism in a pattern consistent with embolic events. There was only one patient with a neurological deficit. After contrast echocardiography, a PFO was diagnosed in 15 patients (25%). The frequency of silent brain infarcts in patients with a PFO was significantly higher than in patients without PFO (5 [33.3%] of 15 versus one [2.2%] of 45 patients, P=0.003). By logistic regression analysis, PFO was identified as an independent predictor of silent brain infarcts (OR, 34.9 [3.1 to 394.3]; P=0.004).

Conclusions—In pulmonary embolism, cerebral embolic events are more frequent than the apparent neurological complication rate. The prevalence of silent brain infarcts is closely related to the presence of a PFO suggesting a high incidence of unsuspected paradoxical emboli in those patients.

Methods—This was a single blinded, randomized, pretest, posttest study using 2 age cohorts: younger (18 to 30 years) and older (50+ years). Stroke knowledge was measured by the 28-item Stroke Action Test taken before and after viewing either an Extended Parallel Process modified poster or a standard educational poster in widespread use and again 6 weeks later.

Results—Overall, there were 274 participants (222 younger and 52 older) with 139 randomly assigned to view the Extended Parallel Process poster and 135 assigned to view the standard poster. There was no significant difference (P>0.05) in the average Stroke Action Test score change between poster groups at all 3 testing intervals, although there was a nonsignificant greater drop in Stroke Action Test scores observed in the control group at the 6-week follow-up (-3.52 versus -2.60; P=0.46). The observed power for this difference was only 11% due to attrition of study participants (total 6-week follow-up, n=170). The younger group did significantly better on the Stroke Action Test from baseline to immediate posttest when viewing either poster (P<0.05).

Conclusions—A common stroke education poster modified according to the Extended Parallel Process model did not significantly increase stroke knowledge compared with a standard control. However, the Extended Parallel Process model may promote long-term stroke knowledge retention, although further studies are needed due to insufficient power from subject attrition.

Methods—Permanent middle cerebral artery occlusion was induced with an intraluminal filament. Diffusion- (DWI) and perfusion- (PWI) weighted magnetic resonance imaging was performed from 1 to 6 hours after stroke, with the PWI-DWI mismatch used to define the penumbra and thresholded apparent diffusion coefficient (ADC) maps used to define ischemic damage.

Results—There was significantly more ischemic damage in SHRSP than in WKY from 1 to 6 hours after stroke. The perfusion deficit remained unchanged in WKY (39.9±6 mm² at 1 hour, 39.6±5.3 mm² at 6 hours) but surprisingly increased in SHRSP (43.9±9.2 mm² at 1 hour, 48.5±7.4 mm² at 6 hours; P=0.01). One hour after stroke, SHRSP had a significantly smaller penumbra (3.4±5.8 mm²) than did WKY (9.7±3.8, P=0.03). In WKY, 56% of the 1-hour penumbra area was incorporated into the ADC lesion by 6 hours, whereas in SHRSP, the small penumbra remained static owing to the temporal increase in both ADC lesion size and perfusion deficit.

Conclusions—First, SHRSP have significantly more ischemic damage and a smaller penumbra than do WKY within 1 hour of stroke; second, the penumbra is recruited into the ADC abnormality over time in both strains; and third, the expanding perfusion deficit in SHRSP predicts more tissue at risk of infarction. These results have important implications for management of stroke patients with preexisting hypertension and suggest ischemic damage could progress at a faster rate and over a longer time frame in the presence of hypertension.

Methods—In a retrospective study of 14 patients, lesions on 90-day follow-up FLAIR and T2 fast spin echo MRI were outlined by 9 independent, blinded, experienced neuroradiologists. Voxel-wise interrater agreement was measured as (1) the volume of the intersection of individual rater's lesion outlines relative to the mean lesion volume (overlap ratio) and (2) the Hausdorff distance between the lesion markings.

Results—Mean patient age was 64.4 years (range, 45 to 79). Lesion volumes on FLAIR were, on average, 2.5 mL greater than were T2 volumes (median; P<0.001). We found considerable differences between raters' lesion markings, but interrater agreement was consistently better on FLAIR than on T2 images, as measured by a greater overlap ratio (P<0.0001) and a smaller Hausdorff distance (P<0.0001) on FLAIR than on T2.

Conclusions—FLAIR should be used to quantify follow-up infarct size to minimize interrater variability. Our study suggests that imaging analysis performed by 1 or a few trained readers may be preferred. Future studies should address objective and preferably automated criteria for final lesion delineation.

Methods—This is a retrospective study of consecutive patients with large middle cerebral artery infarction admitted to our neurocritical care unit from January 2007 to October 2008. Medical records, laboratory data, and imaging of cerebral edema and cranial venous sinuses were analyzed.

Results—Of the 14 patients identified to have large middle cerebral artery infarction and images of cranial venous drainages, 5 (35.7%) had fatal edema with clinical signs of transtentorial herniation. Four of the 5 patients developed fatal edema within 48 hours of ictus and were found to have abnormal ipsilateral cranial venous drainage, including atresia of the transverse sinus (one), occlusion of the internal jugular vein (one), and hypoplasia of the transverse sinus and internal jugular vein (2). The fifth patient had symmetrical bilateral cranial venous drainages and fatal edema at Day 5. Of the 9 patients with nonmalignant middle cerebral artery infarction, all had ipsilateral dominant or symmetrical bilateral venous drainages.

Conclusions—In this small case series, we demonstrated that only the patients with hypoplasia or occlusion of the ipsilateral cranial venous drainage developed early fatal edema after large middle cerebral artery infarction. Our results suggest a role of cranial venous outflow abnormalities in the development of brain edema after arterial ischemic stroke.

Methods—This study was a prospective, randomized, controlled trial with a blinded neurologic outcome evaluation comparison between prophylactic, catheter-based normothermia (CoolGard; ie, body core temperature 36.5°C) and conventional, stepwise fever management with anti-inflammatory drugs and surface cooling. Patients admitted to 1 of the 2 neurointensive care units were eligible for study inclusion when they had a (1) spontaneous subarachnoid hemorrhage with Hunt & Hess grade between 3 and 5, (2) spontaneous intracerebral hemorrhage with a Glasgow Coma Scale score ≤10, or (3) complicated cerebral infarction requiring intensive care unit treatment with a National Institutes of Health Stroke Scale score ≥15.

Results—A total of 102 patients (56 female) were enrolled during a 3.5-year period. Fifty percent had a spontaneous subarachnoid hemorrhage, 40% had a spontaneous intracerebral hemorrhage, and 10% had a complicated cerebral infarction. Overall median total fever burden during the course of treatment was 0.0°C hour and 4.3°C hours in the catheter and conventional groups, respectively (P<0.0001). Prophylactic normothermia did not lead to an increase in the number of patients who experienced a major adverse event. No significant difference was found in mortality and neurologic long-term follow-up.

Conclusions—Long-term, catheter-based, prophylactic normothermia significantly reduces fever burden in neurointensive care unit patients with severe cerebrovascular disease and is not associated with increased major adverse events.