Dannenberg Steffen, Scheitz Jan F, Rozanski Michal, Erdur Hebun, Brunecker Peter, Werring David J, Fiebach Jochen B, Nolte Christian H
From the Klinik und Hochschulambulanz für Neurologie (S.D., J.F.S., M.R., H.E., C.H.N.), Center for Stroke Research (J.F.S., M.R., P.B., J.B.F., C.H.N.), and Excellence Cluster NeuroCure (J.F.S.), Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom (D.J.W.); and The National Hospital for Neurology and Neurosurgery, London, United Kingdom (D.J.W.).
Stroke. 2014 Oct;45(10):2900-5. doi: 10.1161/STROKEAHA.114.006448. Epub 2014 Aug 12.
Cerebral microbleeds (CMBs) are found in a substantial proportion of patients with ischemic stroke eligible for treatment with intravenous thrombolysis. Until now, there is limited data on the impact of multiple CMBs on occurrence of intracerebral hemorrhage (ICH) after intravenous thrombolysis.
Between 2008 and 2013, all patients receiving MRI-based intravenous thrombolysis were identified within our prospective thrombolysis register. Number of CMBs was rated on pretreatment T2*-weighted MRI by a rater blinded to clinical data and follow-up. Outcomes of interest were occurrence of symptomatic ICH (sICH) and parenchymal hemorrhage (PH).
Among 326 included patients, 52 patients had a single CMB (16.0%), 19 had 2 to 4 CMBs (5.8%), and 10 had ≥5 CMBs (3.1%). Frequency of sICH/PH was 1.2%/5.7% in patients without CMBs, 3.8%/3.8% in patients with a single CMB, 10.5%/21.1% in patients with 2 to 4 CMBs, and 30.0%/30.0% in patients with ≥5 CMBs, respectively (each P for trend<0.01). The unadjusted odds ratio per additional CMB for sICH was 1.19 (95% confidence interval, 1.07-1.33; P<0.01) and for PH was 1.13 (95% confidence interval, 1.03-1.24; P=0.01). Compared with patients without CMBs, both patients with 2 to 4 CMBs (P=0.02/P=0.02) and patients with ≥5 CMBs (P<0.01/P<0.01) had significantly increased odds ratios for sICH and PH, whereas in patients with a single CMB, odds ratios were not significantly increased (P=0.21/P=0.59). The association of CMB burden with sICH/PH remained significant after adjustment for possible confounders (age, age-related white matter changes score, atrial fibrillation, onset-to-treatment time, prior statin use, and systolic blood pressure on admission).
Our findings indicate a higher risk of sICH and PH after intravenous thrombolysis when multiple CMBs are present, with a graded relationship to increasing baseline CMB number.
在大量适合静脉溶栓治疗的缺血性卒中患者中发现了脑微出血（CMB）。到目前为止，关于多个CMB对静脉溶栓后脑内出血（ICH）发生的影响的数据有限。
在2008年至2013年期间，在我们的前瞻性溶栓登记册中确定了所有接受基于MRI的静脉溶栓治疗的患者。由对临床数据和随访不知情的评估者根据治疗前T2*加权MRI对CMB数量进行评级。感兴趣的结果是症状性ICH（sICH）和实质出血（PH）的发生情况。
在326例纳入患者中，52例有单个CMB（16.0%），19例有2至4个CMB（5.8%），10例有≥5个CMB（3.1%）。无CMB患者的sICH/PH发生率分别为1.2%/5.7%，单个CMB患者为3.8%/3.8%，2至4个CMB患者为10.5%/21.1%，≥5个CMB患者为30.0%/30.0%（各趋势P<0.01）。每增加一个CMB，sICH的未调整比值比为1.19（95%置信区间，1.07 - 1.33；P<0.01），PH的未调整比值比为1.13（95%置信区间，1.03 - 1.24；P = 0.01）。与无CMB患者相比，有2至4个CMB的患者（P = 0.02/P = 0.02）和有≥5个CMB的患者（P<0.01/P<0.01）的sICH和PH比值比均显著增加，而单个CMB患者的比值比未显著增加（P = 0.21/P = 0.59）。在对可能的混杂因素（年龄、年龄相关白质改变评分、心房颤动、发病至治疗时间、既往他汀类药物使用情况和入院时收缩压）进行调整后，CMB负担与sICH/PH的关联仍然显著。
我们的研究结果表明，存在多个CMB时静脉溶栓后发生sICH和PH的风险更高，且与基线CMB数量增加呈分级关系。
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