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Objectives: We used a prospective clinical trial to examine the risks conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent strokes in the Secondary Prevention of Small Subcortical Strokes (SPS3) study cohort. Methods: The SPS3 trial enrolled 3,020 patients with lacunar strokes. Participants were stratified into groups of METS only, DM only, both, or neither using American Heart Association/National Heart, Lung, and Blood Institute and World Health Organization guidelines. Annualized event rates of strokes, myocardial infarction (MI), and all-cause mortality were calculated, and hazard ratios (HRs) referencing the “neither” group were computed, controlling for significantly associated baseline characteristics. Results: Among 2,999 participants, 25% had METS only, 6% had DM only, 32% had both conditions, and 37% had neither. Over a median of 3.8 years of follow-up, there were 274 recurrent strokes (240 ischemic, 34 hemorrhagic) and 74 MIs; among the 240 ischemic strokes, 134 (56%) were lacunar. The rates of any recurrent stroke (HR 1.7, 95% confidence interval [CI] 1.3–2.3) or lacunar stroke (HR 2.4, 95% CI 1.5–3.7) were significantly higher for those with concurrent METS and DM compared with those who had neither. Risk of incident MI was higher in participants with DM (HR 2.8, 95% CI 1.1–7.0) or concurrent DM and METS (HR 2.6, 95% CI 1.4–4.9). Conclusion: METS and DM were significant comorbid conditions in lacunar stroke patients and they were associated with stroke recurrence. In patients with lacunar infarcts, a vigilant approach to prevent development of DM in those with METS may be a potential strategy to reduce recurrent strokes.

To determine whether vascular and demographic factors predict worsening disability up to 8 years after lacunar stroke.SPS3 (Secondary Prevention of Small Subcortical Strokes) was a clinical trial in lacunar stroke patients with annual assessment of disability using the Older Americans Resources and Survey instrumental activities of daily living (IADL) scale (range 0-14). Generalized estimating equations modeled the likelihood of disability (IADL14) over time, adjusting for demographics, medical risk factors, cognition, mood, stroke location, and geographic region in univariate and multivariable models. IADL assessments after recurrent stroke were censored. We stratified by study region and age quartile.Among 2,820 participants, mean age was 63.4 years (SD 10.8), 63% were male, 36% had diabetes, 90% hypertension, and 10% prior stroke. Mean follow-up was 3.7 years. In multivariable models, female sex, education, diabetes, nonregular alcohol use, prior stroke, Cognitive Abilities Screening Instrument score, depression, mild cognitive impairment, and stroke location were associated with disability. The youngest age quartile had decreased odds of disability over time (odds ratio 0.90 per year, 95% confidence interval 0.85-0.95), whereas the oldest age quartile had increased odds (2.20, 95% confidence interval 1.75-2.75). Americans and Latin Americans had2-fold greater odds of disability per year compared with Spaniards (p0.0001).In lacunar stroke patients, older age was associated with worsening long-term disability, even without recurrence. Worse long-term function was associated with diabetes, cognitive status, and prior stroke, and regional differences may be attributable to variations in health care delivery or scale interpretation.

Objective: To assess whether adding clopidogrel to acetylsalicylic acid (ASA) has a long-term protective vascular effect in patients with lacunar stroke while taking ASA. Methods: Post hoc analysis of 838 patients with ASA failure and recent lacunar stroke from the Secondary Prevention of Small Subcortical Strokes Trial (SPS3) cohort randomly allocated to aspirin (325 mg/day) and clopidogrel (75 mg/day) or placebo. Primary efficacy outcome was stroke recurrence (ischemic and intracranial hemorrhage) and main safety outcome was major extracranial hemorrhage. Patients were followed for a mean period of 3.5 years. Results: The ASA failure group had a significantly higher risk of vascular events including ischemic stroke when compared with the non–ASA failure group (n = 2,151) in SPS3 ( p = 0.03). Mean age was 65.6 years and 65% were men. The risk of recurrent stroke was not reduced in the dual antiplatelet group, 3.1% per year, compared to the aspirin-only group, 3.3% per year (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.61–1.37). There was also no difference between groups for ischemic stroke (HR 0.90; 95% CI 0.59–1.38). The risk of gastrointestinal bleeding was higher in the dual antiplatelet group (HR 2.7; 95% CI 1.1–6.9); however, the risk of intracranial hemorrhage was not different. Conclusions: In patients with a recent lacunar stroke while taking ASA, the addition of clopidogrel did not result in reduction of vascular events vs continuing ASA only. Classification of evidence: This study provides Class I evidence that for patients with recent lacunar stroke while taking ASA, adding clopidogrel as compared to continuing ASA alone does not reduce the risk of recurrent stroke.

A 48-year-old right-hand-dominant woman presented to the emergency department with sudden onset of visual loss of her left visual field. She had a complicated medical history—end-stage renal disease requiring renal transplant 6 years prior to presentation secondary to biopsy-proven focal segmental glomerulosclerosis (FSGS), coronary artery disease, left atrial enlargement due to pulmonic stenosis, progressive sensorineural hearing loss 10 years prior and subsequent placement of a right cochlear implant, hypertension, and type 2 diabetes mellitus for the last year. At presentation, the patient's medications included cotrimoxazole prophylaxis, mycophenolate mofetil, tacrolimus, insulin, and folic acid. On examination, she was of short stature and had a low-grade fever and a left homonymous hemianopsia (L-HH). Within the next 3 weeks, she subsequently developed further visual disturbance to the point of being cortically blind in addition to new left upper extremity paresthesias. Initial CT head scan showed a subacute right occipital infarct and bilateral basal ganglia calcification. Subsequent CT imaging done 3 weeks later demonstrated interval development of new left temporoparietal and left occipital infarcts (figure, A). CT angiogram showed intracranial stenoses affecting basilar artery, both posterior cerebral arteries, and to a lesser degree bilateral anterior cerebral arteries and middle cerebral arteries, suggestive of possible atherosclerosis, but were not believed to be hemodynamically significant (figure, B). Due to her cochlear implant, significant streak artifact affected the interpretation of her CT scans and precluded her from obtaining an MRI.

We performed a systematic review and meta-analysis to assess whether the presence of cerebral microbleeds (CMBs) on pretreatment MRI scans of patients with acute ischemic stroke treated with thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (ICH).We searched PubMed for relevant studies and calculated pooled odds ratios (ORs) for symptomatic ICH, using the Mantel–Haenszel fixed-effects method, among individuals with vs without CMBs on pretreatment MRI scans. To minimize potential bias, sensitivity analysis was performed including studies providing data on patients treated only with IV thrombolysis.Ten eligible studies including 2,028 patients were pooled in meta-analysis. The overall prevalence of CMBs was 23.3%. Among patients with CMBs, 40 of 472 (8.5%; 95%confidence interval [CI]: 6.1%–11.4%) experienced a symptomatic ICH after thrombolysis compared with 61 of 1,556 patients (3.9%; 95% CI: 3%–5%) without CMBs. The pooled OR of ICH across all studies was 2.26 (95%CI: 1.46–3.49; p , 0.0001). Eight studies, including 1,704 patients (n 5 401 with CMBs), provided data on patients treated with IV thrombolysis only; OR for the presence of CMBs and the development of symptomatic ICH was 2.87 (95%CI: 1.76–4.69; p , 0.0001).Our meta-analysis of the available published data demonstrates an increased risk of symptomatic ICH after thrombolysis for acute ischemic stroke in patients with CMBs. However, we cannot fully exclude bias or confounding, so our results should be considered hypothesis generating. Detecting CMBs should not prevent thrombolytic treatment based on present evidence. Further analyses, taking into account CMB number and location, as well as measures of functional outcome, are needed.

Objective: To characterize the rates of recurrent intracranial hemorrhage (ICH), ischemic stroke, and death in survivors of primary ICH. Methods: Systematic review of studies reporting recurrent stroke in survivors of primary ICH, identified at index ICH and followed forward. Studies were identified by computerized search of the literature and review of reference lists. Results: Ten studies published between 1982 and 2000 reporting 1,880 survivors of ICH, followed for a total of 6,326 patient-years (mean follow-up, 3.4 patient-years), were included. The aggregate rate of all stroke from five studies was 4.3% per patient-year (95% CI, 3.5% to 5.4%). The rate in the three population-based studies was higher than in the two hospital-based studies, 6.2% versus 4.0% per patient-year ( p = 0.04). About three fourths of recurrent strokes were ICH. Considering all 10 studies, a total of 147 patients had a recurrent ICH, an aggregate rate of 2.3% per patient-year (95% CI, 1.9% to 2.7%). Based on data from four studies, patients with a primary lobar ICH had a higher rate of recurrent ICH than those with a deep, hemispheric ICH (4.4% versus 2.1% per patient-year; p = 0.002). The aggregate rates of subsequent ischemic stroke and mortality were 1.1% per patient-year (95% CI, 0.8% to 1.7%) and 8.8% per patient-year (95% CI, 5.2% to 11.0%). Conclusions: Recurrent stroke among survivors of primary ICH occurs at a rate of about 4% per patient-year, and most are recurrent ICH. Survivors of ICH have a higher risk of recurrent ICH than of ischemic stroke, and this has implications for the use of antithrombotic agents in these patients.

Objective: To quantitatively characterize domain-specific cognition in individuals with symptomatic lacunar stroke in a systematic review. Methods: Systematic searches of MEDLINE and EMBASE were conducted. Inclusion criteria were all articles published prior to December 2011 evaluating domain-specific cognitive status in individuals with a symptomatic lacunar infarct. Data extraction identified cognitive domains with reported impairment and effect size calculations and heterogeneity analyses were completed to assess the magnitude of this impairment for all studies with control group data. Results: Results of the search yielded 12 cross-sectional and 5 longitudinal studies that met inclusion criteria. Effect size calculations revealed small to medium effect sizes (ES) estimations for impairment after stroke in the domains of executive function (ES −0.44, 95% confidence interval [CI] −0.83, −0.50), memory (ES −0.55, 95% CI −0.96, −0.13), language (ES −0.63, 95% CI −0.92, −0.33), attention (ES −0.37, 95% CI −0.67, −0.07), and visuospatial abilities (ES −0.61, 95% CI −1.03, 0.19), and large effect sizes for global cognition (ES −0.90, 95% CI −1.48, −0.31) and information processing speed (ES −0.93, 95% CI −1.63, −0.23). Heterogeneity analyses revealed that a subset of these domains were heterogeneous and identified moderating factors accounting for this heterogeneity. Conclusions: Results of this systematic review are consistent with previous characterizations of cognitive impairment associated with lacunar strokes. However, impaired cognition in this stroke subtype appears less selective than previously thought, involving all major cognitive domains.

Objective: To assess the efficacy of carotid endarterectomy for stroke prevention in asymptomatic and symptomatic patients with internal carotid artery stenosis. Additional clinical scenarios, such as use of endarterectomy combined with cardiac surgery, are also reviewed. Methods: The authors selected nine important clinical questions. A systematic search was performed for articles from 1990 (the year of the last statement) until 2001. Additional articles from 2002 through 2004 were included using prespecified criteria. Two reviewers also screened for other relevant articles from 2002 to 2004. Case reports, review articles, technical studies, and single surgeon case series were excluded. Results: For several questions, high quality randomized clinical trials had been completed. Carotid endarterectomy reduces the stroke risk compared to medical therapy alone for patients with 70 to 99% symptomatic stenosis (16% absolute risk reduction at 5 years). There is a smaller benefit for patients with 50 to 69% symptomatic stenosis (absolute risk reduction 4.6% at 5 years). There is a small benefit for asymptomatic patients with 60 to 99% stenosis if the perioperative complication rate is low. Aspirin in a dose of 81 to 325 mg per day is preferred vs higher doses (650 to 1,300 mg per day) in patients undergoing endarterectomy. Conclusions: Evidence supports carotid endarterectomy for severe (70 to 99%) symptomatic stenosis (Level A). Endarterectomy is moderately useful for symptomatic patients with 50 to 69% stenosis (Level B) and not indicated for symptomatic patients with