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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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