Abstract:

Objective  To systematically review the efficacy and safety of recombinant tissue-type plasminogen activator (rt-PA) intravenous thrombolysis in the treatment of acute ischemic stroke with hyperdense middle cerebral artery sign (HMCAS) on CT images. Methods  Search online databases such as PubMed, EMBASE/SCOPUS, Cochrane Central Register of Controlled Trials (CENTRAL) and China Biology Medicine (CBM) from January 1994 to December 2014 with key words: hyperdense middle cerebral artery sign/HMCAS/hyperdense artery sign/hyperdense cerebral artery sign, ischemic stroke/cerebral infarction/brain infarction/cerebral embolism, thrombolysis/thrombolytic therapy/rt-PA/recombinant tissue plasminogen activator both in Chinese and English, to collect randomized controlled trials (RCTs) or non-RCTs about rt-PA treating patients with acute ischemic stroke and HMCAS. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the risk of bias of included studies. Newcastle-Ottawa Scale (NOS) was used for quality assessment, and Meta-analysis was performed using RevMan 5.2 software. Results  A total of 8 studies were included after excluding duplicate ones and those which did not meet the inclusion criteria from 166 articles. There were 11 373 patients, including 2455 cases complicated with HMCAS (2316 treated by rt-PA and 139 treated by placebo) and 8918 cases without HMCAS. Meta-analysis showed the occurrence of unfavorable outcome in rt-PA treatment was significantly decreased compared to placebo in HMCAS-positive patients (OR = 0.360,95%CI: 0.150-0.850; P = 0.020), while there was no statistical difference in the occurrence of symptomatic intracerebral hemorrhage (sICH) between rt-PA and placebo treatment in HMCAS-positive patients (OR = 1.640, 95%CI: 0.380-7.040; P = 0.500). Meta-analysis also showed unfavorable outcome of rt-PA treatment was significantly higher in HMCAS-positive than in HMCAS-negative patients (OR = 2.830, 95% CI: 2.550-3.150; P = 0.000), while there was no statistical difference in the occurrence of sICH after rt-PA treatment (OR = 1.090, 95% CI: 0.500-2.410; P = 0.820). Conclusions  Although rt-PA intravenous thrombolysis is safe and effective in the treatment for HMCAS-positive patients with acute ischemic stroke, unfavorable outcome is easy to occur after 3 months of onset, however, the risk of symptomatic intracerebral hemorrhage is low.

Key words: Brain ischemia, Tissue plasminogen activator, Middle cerebral artery, Meta-analysis

摘要：

目的 系统评价合并大脑中动脉高密度征（HMCAS）的急性缺血性卒中患者重组组织型纤溶酶原激活物（rt-PA）静脉溶栓治疗的有效性和安全性。方法 以hyperdense middle cerebral artery sign/HMCAS/hyperdense artery sign/hyperdense cerebral artery sign、ischemic stroke/cerebral infarction/brain infraction/cerebral embolism、thrombolysis/thrombolytic therapy/rt-PA/recombinant tissue plasminogen activator，以及大脑中动脉高密度征/致密动脉征/大脑中动脉致密征/脑动脉高密度征、缺血性脑卒中/缺血性卒中/脑梗死/脑梗塞/脑栓塞、溶栓治疗/rt-PA/重组组织型纤溶酶原激活剂等中英文词组为检索词，计算机检索1994 年1 月-2014 年12 月美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、Cochrane 临床对照试验中心注册库，以及中国生物医学文献数据库等收录的关于rt-PA 静脉溶栓治疗合并HMCAS 的急性缺血性卒中随机或非随机对照临床试验；分别采用Newcastle-Ottawa 量表和RevMan 5.2 统计软件行文献质量评价和Meta 分析。结果 经剔除重复和不符合纳入标准者，166 篇英文文献中最终纳入8 项非随机对照临床试验共11 373 例患者［2455 例合并HMCAS（rt-PA 静脉溶栓治疗2316 例、安慰剂治疗139 例）、8918 例未合并HMCAS］。Meta 分析显示：rt-PA 静脉溶栓组患者不良预后风险低于安慰剂组（OR = 0.360，95%CI：0.150 ~ 0.850；P = 0.020），但症状性颅内出血发生率组间差异无统计学意义（OR = 1.640，95%CI：0.380 ~ 7.040；P = 0.500）；合并HMCAS 患者rt-PA 静脉溶栓治疗不良预后风险高于未合并者（OR = 2.830，95%CI：2.550 ~ 3.150；P = 0.000），但症状性颅内出血发生率组间差异无统计学意义（OR = 1.090，95%CI：0.500 ~ 2.410；P = 0.820）。结论 尽管rt-PA 静脉溶栓治疗合并HMCAS 的急性缺血性卒中患者安全、有效，但发病3 个月时易出现不良预后，而发生症状性颅内出血风险较低。

关键词: 脑缺血, 组织型纤溶酶原激活物, 大脑中动脉, Meta分析