静脉注射重组组织型纤溶酶原激活剂（iv-rtPA）治疗缺血性脑卒中已有25年的历史。然而，关于这种疗法治疗脑小血管病（SVD）所致中风的有效性和安全性的前瞻性研究很少。我们使用所有关于静脉注射rtPA对SVD相关缺血性卒中（通过神经影像学、临床特征或两者结合来定义）的影响的可用数据，评估功能结果（改良Rankin评分，mRS）和症状性脑出血（sICH）。使用固定效应和随机效应模型，我们计算了关于优秀和良好结果（3个月时mRS分别为0-1和0-2）和sICH率的综合效应估计。23项研究符合资格标准，其中11项是比较性的，只有3项随机临床试验。在调整后的分析中，与安慰剂组相比，接受静脉注射rtPA的患者的优良结果（调整后的OR=1.53，95%CI:1.29-1.82，I2:0%）或良好结果（调整后的OR=1.68，95%CI:1.31-2.15，I2:0%）的几率增加。在报道sICH的6项研究中，治疗组的sICH发病率较高（M-H RR=8.83，95%CI:2.76-28.27）。静脉注射rtPA的SVD患者sICH合并率仅为0.72%（95%CI:0.12%-1.64%）。我们的结论是，当将SVD引起的缺血性中风单独考虑时，静脉注射rtPA治疗效果的可用数据不足以达到最高推荐水平，但似乎是安全的。尽管SVD相关缺血性中风的进一步治疗试验似乎是合理的，但我们的研究结果不应妨碍其在临床实践中继续用于这组患者。

关键词：脑缺血；腔隙性脑梗死；荟萃分析；小血管疾病；脑卒中；溶栓治疗。

Transl Stroke Res

•            DOI:                  10.1007/s12975-021-00890-9        

Abstract

Intravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) using all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we calculated the pooled effect estimates with regard to excellent and favorable outcomes (mRS=0-1 and 0-2 respectively, at 3 months), and the rate of sICH. Twenty-three studies fulfilled the eligibility criteria, 11 of which were comparative, and there were only 3 randomized clinical trials. In adjusted analyses, there was an increased odds of excellent outcome (adjusted OR=1.53, 95% CI: 1.29-1.82, I2: 0%) or favorable outcome (adjusted OR=1.68, 95% CI: 1.31-2.15,I2: 0%) in patients who received iv-rtPA compared with placebo. Across the six studies which reported it, the incidence of sICH was higher in the treatment group (M-H RR = 8.83, 95% CI: 2.76-28.27). The pooled rate of sICH in patients with SVD administered iv-rtPA was only 0.72% (95% CI: 0.12%-1.64%). We conclude that when ischemic stroke attributed to SVD is considered separately, available data on the effects of iv-rtPA therapy are insufficient for the highest level of recommendation, but it seems to be safe. Although further therapeutic trials in SVD-related ischemic stroke appear to be justified, our findings should not prevent its continued use for this group of patients in clinical practice.

         Keywords:                    Brain ischemia; Lacunar infarction; Meta-analysis; Small vessel disease; Stroke; Thrombolysis.