From the Department of Clinical Neurosciences, Western General Hospital, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
Stroke. 2014 Feb;45(2):563-70. doi: 10.1161/STROKEAHA.113.003128. Epub 2014 Jan 2.
A total of 25% of strokes are lacunar, and these are pathophysiologically different from large artery strokes. Despite emerging evidence of a substantial impact on physical disability and dementia, little attention has been paid to the development of specific treatments. The optimal use of the animal models of lacunar stroke used to test candidate interventions is not known.
We conducted a systematic review and meta-analysis of studies testing candidate interventions in animal models of lacunar stroke. We used random-effects meta-analysis to assess the impact of study characteristics and trim and fill to seek evidence of publication bias.
The efficacy of 43 distinct interventions was described in 57 publications. The median number of quality checklist items scored was 3 of 8 (interquartile range, 2-4). Many models reflected mechanisms of limited relevance to lacunar stroke. Meta-analysis of results from 27 studies showed that on average, infarct size and neurobehavioral outcome were improved by 34.2% (24.1-44.2) and 0.82 standardized mean difference (0.51-1.14), respectively. Four interventions improved both infarct size and neurobehavioral outcome but there were insufficient data for this finding to be considered robust. For infarct size, efficacy was lower in studies reporting blinding and higher in studies reporting randomization. For neurobehavior, efficacy was lower in randomized studies. For infarct size there was evidence of publication bias.
No intervention has yet been tested in sufficient range and depth to support translation to clinical trial. There is limited reporting of measures to reduce the risk of bias and evidence for a substantial publications bias.
总的来说，25%的中风是腔隙性的，这些与大动脉中风在病理生理学上是不同的。尽管有大量证据表明其对身体残疾和痴呆有实质性影响，但对特定治疗方法的关注甚少。用于测试候选干预措施的腔隙性中风动物模型的最佳应用尚不清楚。
我们对在腔隙性中风动物模型中测试候选干预措施的研究进行了系统回顾和荟萃分析。我们使用随机效应荟萃分析来评估研究特征的影响，并使用修剪和填充法来寻找发表偏倚的证据。
在 57 篇文献中描述了 43 种不同干预措施的疗效。评分的质量检查表项目中位数为 8 项中的 3 项（四分位距，2-4）。许多模型反映了与腔隙性中风相关性有限的机制。对 27 项研究结果的荟萃分析表明，平均而言，梗塞面积和神经行为学结果分别改善了 34.2%（24.1-44.2）和 0.82 标准化均数差（0.51-1.14）。有 4 种干预措施改善了梗塞面积和神经行为学结果，但由于数据不足，无法认为这一发现是可靠的。对于梗塞面积，报告盲法的研究中疗效较低，报告随机分组的研究中疗效较高。对于神经行为，随机研究中的疗效较低。对于梗塞面积，存在发表偏倚的证据。
没有一种干预措施在足够的范围和深度内进行过测试，无法支持临床试验。报告的减少偏倚风险的措施有限，并且有大量证据表明存在实质性的发表偏倚。
