From the Stroke Research Centre, UCL Institute of Neurology, London, United Kingdom (A.C., D.W., D.J.W.); Hemorrhagic Stroke Research Group, Massachusetts General Hospital, Boston (A.C.); Departments of Neurology and Radiology, Hôpital Sainte-Anne, Université Paris Descartes, France (G.T., C.O., M.E.-G., J.-C.B.); Department of Neurology, the 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China (S.Y., M.L.); Department of Neurology and Center for Stroke Research, Charite Universitätsmedizin, Berlin, Germany (J.F.S., H.E., C.H.N.); Department of Diagnostic and Interventional Neuroradiology, and Neurology, Inselspital, University Hospital Bern, Switzerland (P.P.K.-G., M.E.-K., H.P.M., S.J.); Department of Neurology, Tokai University School of Medicine, Japan (W.T., Y.M., S.T.); Department of Neurology, University of Arizona, Tucson (C.S.K.); UCLA Comprehensive Stroke Center, Geffen School of Medicine, Los Angeles (J.L.S.); Univ. Lille, Inserm, CHU Lille, U1171, Degenerative and Vascular Cognitive Disorders, France (A.S., S.M., C.C.); Department of Neurology, Austin Health and Florey Institute, Heidelberg, Victoria, Australia (V.T.); Department of Statistical Science, University College London, United Kingdom (Z.F., G.A.); Department of Medicine (Neurology), McMaster University and Population Health Research Institute, Hamilton, Ontario, Canada (A.S.); Stanford Stroke Center, Palo Alto, CA (G.W.A.); Division of Neurology, Stroke and Cerebrovascular Health Program, University of British Columbia Hospital, Vancouver, Canada (O.R.B.); Lysholm Department of Neuroradiology, National Hospital, London, United Kingdom (H.R.J.); Department of Neurological Science, Nippon Medical School Graduate School of Medicine, Tokyo, Japan (J.A., K.K.); and Department of Rehabilitation Medicine, the Jikei University School of Medicine, Tokyo, Japan (W.K.).
Stroke. 2017 Aug;48(8):2084-2090. doi: 10.1161/STROKEAHA.116.012992.
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). Results- In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH ( P=0.014), PH ( P=0.013), and PHr ( P<0.00001). Five or more and >10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions- Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.
我们评估了急性缺血性脑卒中患者静脉溶栓前磁共振成像上脑微出血（CMB）的存在、数量和分布是否与颅内出血（ICH）风险增加或功能预后不良相关。方法：我们进行了一项个体患者数据荟萃分析，包括接受静脉组织型纤溶酶原激活剂治疗的急性缺血性脑卒中的前瞻性和回顾性研究。我们使用多水平混合效应逻辑回归，研究了治疗前 CMB 存在、负荷（1、2-4、≥5 和>10）和假定发病机制（严格的脑叶 CMB 定义为脑淀粉样血管病和非脑淀粉样血管病）与症状性 ICH、实质血肿（在[实质出血，PH]和远离缺血区[远隔实质出血，PHr]）以及 3 至 6 个月时不良功能结局（改良 Rankin 评分>2）之间的关系。结果：在 8 个中心的 1973 名患者中，CMB 的粗患病率为 1973 名患者中的 526 名（26.7%）。77 名患者发生症状性 ICH（77/1973，3.9%），210 名患者发生 PH（210/1806，11.6%），56 名患者发生 PHr（56/1720，3.3%）。在调整分析中，与无 CMB 患者相比，有 CMB 患者发生 PH（优势比：1.50；95%置信区间：1.09-2.07；P=0.013）和 PHr（优势比：3.04；95%置信区间：1.73-5.35；P<0.001）的风险增加，但与症状性 ICH 无关。CMB 的脑淀粉样血管病和非脑淀粉样血管病模式均与 PH 和 PHr 相关。CMB 负荷类别增加与症状性 ICH（P=0.014）、PH（P=0.013）和 PHr（P<0.00001）的风险增加相关。5 个或更多 CMB 和>10 CMB 独立预测 3 至 6 个月的不良结局（优势比：1.85；95%置信区间：1.10-3.12；P=0.020；优势比：3.99；95%置信区间：1.55-10.22；P=0.004）。结论：静脉溶栓治疗急性缺血性脑卒中后，CMB 负荷增加与 ICH（包括 PHr）风险增加和 3 至 6 个月功能预后不良相关。
