IMPORTANCE Cerebral microbleeds (CMBs) have been established as an independent predictor of cerebral bleeding. There are contradictory data regarding the potential association of CMB burden with the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). OBJECTIVE To investigate the association of high CMB burden (>10 CMBs on a pre-IVT magnetic image resonance [MRI] scan) with the risk of sICH following IVT for AIS. DATA SOURCES Eligible studies were identified by searching Medline and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 7, 2015. This meta-analysis has adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. STUDY SELECTION Eligible prospective study protocols that reported sICH rates in patients with AIS who underwent MRI for CMB screening prior to IVT. DATA EXTRACTION AND SYNTHESIS The reported rates of sICH complicating IVT in patients with AIS with pretreatment MRI were extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (low to moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysis was also performed in the included studies that provided complete patient data sets. MAIN OUTCOMES AND MEASURES Symptomatic intracerebral hemorrhage based on the European Cooperative Acute Stroke Study-II definition (any intracranial bleed with Ն4 points worsening on the National Institutes of Health Stroke Scale score). RESULTS We included 9 studies comprising 2479 patients with AIS. The risk of sICH after IVT was found to be higher in patients with evidence of CMB presence, compared with patients without CMBs (risk ratio [RR], 2.36; 95% CI, 1.21-4.61; P = .01). A higher risk for sICH after IVT was detected in patients with high CMB burden (>10 CMBs) when compared with patients with 0 to 10 CMBs (RR, 12.10; 95% CI, 4.36-33.57; P < .001) or 1 to 10 CMBs (RR, 7.01; 95% CI, 3.20-15.38; P < .001) on pretreatment MRI. In the individual-patient data meta-analysis, high CMB burden was associated with increased likelihood of sICH before (unadjusted odds ratio, 31.06; 95% CI, 7.12-135.44; P < .001) and after (adjusted odds ratio, 18.17; 95% CI, 2.39-138.22; P = .005) adjusting for potential confounders. CONCLUSIONS AND RELEVANCE Presence of CMB and high CMB burdens on pretreatment MRI were independently associated with sICH in patients with AIS treated with IVT. High CMB burden may be included in individual risk stratification scores predicting sICH risk following IVT for AIS.

Background and Purpose-We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods-We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3-to 6-month functional outcome (modified Rankin score >2). We performed a large-scale pooled individual patient data meta-analysis of quality observational studies to test the following hypotheses: (1) there is a relationship between increasing CMB burden and ICH risk 8,9 ; (2) strictly lobar CMBs (reflecting possible or probable cerebral amyloid angiopathy [CAA]) and mixed or strictly deep CMBs (likely associated with hypertensive arteriopathy) have different effects on ICH risk; (3) CMBs are associated more strongly with the risk of remote ICH than other ICH types 10 ; and (4) CMBs are associated with worse functional outcome. Results-In Methods Study Design and Inclusion CriteriaWe identified prospective or retrospective studies that assessed pretreatment MRI-defined CMBs, ICH, and 3-to 6-month functional outcome after acute ischemic stroke, treated solely with intravenous tPA from a systematic review prepared according to Preferred Reporting Items for Systematic Review and Meta-Analyses 7,11 (updated August 1, 2015). We searched PubMed for micro(-)bleed*, or micro(-)h(a) emorrhag*, or gradient-echo, or susceptibility-weighted in association with thromboly* or tPA, or tissue plasminogen activator 7 ; reference lists; and authors' own files. Figure I in the online-only Data Supplement shows a flow diagram.We collected anonymized individual patient detailed clinical data and CMB counts in lobar, deep, and infratentorial regions according to standardized definitions 6,12,13 using standardized report forms. A prespecified protocol was circulated to collaborators but not published. OutcomesWe defined ICH according to ECASS-2 (European Cooperative Acute Stroke Study II), 14,15 including hemorrhagic infarction, parenchymal hemorrhage (PH), and sICH 16 (acute intracerebral blood and associated increase in National Institutes of Health Stroke Scale ≥4 points, except 1 study 17 that used the definition in the PROACT-II trial [Prolyse in Acute Cerebral Thromboembolism]).18 Remote parenchymal hemorrhage (PHr) was defined as ICH remote from the symptomatic ischemic area. 10 We defined poor outcome at 3 to 6 months as modified...

Background and Purpose— Lesion volume on diffusion-weighted magnetic resonance imaging (DWI) before acute stroke therapy is a predictor of outcome. Therefore, patients with large volumes are often excluded from therapy. The aim of this study was to analyze the impact of endovascular treatment in patients with large DWI lesion volumes (>70 mL). Methods— Three hundred seventy-two patients with middle cerebral or internal carotid artery occlusions examined with magnetic resonance imaging before treatment since 2004 were included. Baseline data and 3 months outcome were recorded prospectively. DWI lesion volumes were measured semiautomatically. Results— One hundred five patients had lesions >70 mL. Overall, the volume of DWI lesions was an independent predictor of unfavorable outcome, survival, and symptomatic intracerebral hemorrhage ( P <0.001 each). In patients with DWI lesions >70 mL, 11 of 31 (35.5%) reached favorable outcome (modified Rankin scale score, 0–2) after thrombolysis in cerebral infarction 2b-3 reperfusion in contrast to 3 of 35 (8.6%) after thrombolysis in cerebral infarction 0-2a reperfusion ( P =0.014). Reperfusion success, patient age, and DWI lesion volume were independent predictors of outcome in patients with DWI lesions >70 mL. Thirteen of 66 (19.7%) patients with lesions >70 mL had symptomatic intracerebral hemorrhage with a trend for reduced risk with avoidance of thrombolytic agents. Conclusions— There was a growing risk for poor outcome and symptomatic intracerebral hemorrhage with increasing pretreatment DWI lesion volumes. Nevertheless, favorable outcome was achieved in every third patient with DWI lesions >70 mL after successful endovascular reperfusion, whereas after poor or failed reperfusion, outcome was favorable in only every 12th patient. Therefore, endovascular treatment might be considered in patients with large DWI lesions, especially in younger patients.