Werring David J, Ozkan Hatice, Doubal Fergus, Dawson Jesse, Freemantle Nick, Hassan Ahamad, Le Suong Thi Ngoc, Mallon Dermot, Mendel Rom, Markus Hugh S, Minhas Jatinder S, Webb Alastair J S
Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK.
Centre for Clinical Brain Sciences, Row Fogo Centre for Research into Ageing and the Brain, University of Edinburgh, Edinburgh, UK.
Int J Stroke. 2025 Jan;20(1):7-20. doi: 10.1177/17474930241273685. Epub 2024 Sep 5.
Cerebral small vessel disease (CSVD) causes between 25% and 30% of all ischemic strokes. In acute lacunar ischemic stroke, despite often mild initial symptoms, early neurological deterioration (END) occurs in approximately 15-20% of patients and is associated with poor functional outcome, yet its mechanisms are not well understood.
In this review, we systematically evaluated data on: (1) definitions and incidence of END, (2) mechanisms of small vessel occlusion, (3) predictors and mechanisms of END, and (4) prospects for the prevention or treatment of patients with END.
We identified 67 reports (including 13,407 participants) describing the incidence of END in acute lacunar ischemic stroke. The specified timescale for END varied from <24 h to 3 weeks. The rate of END ranged between 2.3% and 47.5% with a pooled incidence of 23.54% (95% confidence interval (CI) = 21.02-26.05) but heterogeneity was high ( = 90.29%). The rates of END defined by National Institutes of Health Stroke Scale (NIHSS) decreases of ⩾1, ⩾2, ⩾3, and 4 points were as follows: 24.17 (21.19-27.16)%, 22.98 (20.48-25.30)%, 23.33 (16.23-30.42)%, and 10.79 (2.09-23.13)%, respectively, with lowest heterogeneity and greatest precision for a cutoff of ⩾2 points. Of the 20/67 studies (30%) reporting associations of END with clinical outcome, 19/20 (95%) reported worse outcomes (usually measured using the modified Rankin score at 90 days or at hospital discharge) in patients with END. In a meta-regression analysis, female sex, hypertension, diabetes, and smoking were associated with END.
END occurs in more than 20% of patients with acute lacunar ischemic stroke and might provide a novel target for clinical trials. A definition of an NIHSS ⩾2 decrease is most used and provides the best between-study homogeneity. END is consistently associated with poor functional outcome. Further research is needed to better identify patients at risk of END, to understand the underlying mechanisms, and to carry out new trials to test potential interventions.
脑小血管病(CSVD)导致的缺血性卒中占所有缺血性卒中的25%至30%。在急性腔隙性缺血性卒中中,尽管初始症状通常较轻,但约15%-20%的患者会出现早期神经功能恶化(END),且与功能预后不良相关,但其机制尚不清楚。
在本综述中,我们系统评估了以下数据:(1)END的定义和发生率;(2)小血管闭塞的机制;(3)END的预测因素和机制;(4)END患者预防或治疗的前景。
我们确定了67篇报告(包括13407名参与者),描述了急性腔隙性缺血性卒中中END的发生率。END的指定时间范围从<24小时到3周不等。END的发生率在2.3%至47.5%之间,合并发生率为23.54%(95%置信区间(CI)=21.02-26.05),但异质性较高(I²=90.29%)。美国国立卫生研究院卒中量表(NIHSS)评分下降≥1、≥2、≥3和≥4分所定义的END发生率分别为:24.17(21.19-27.16)%、22.98(20.48-25.30)%、23.33(16.23-30.42)%和10.79(2.09-23.13)%,其中以≥2分为截断值时异质性最低且精度最高。在报告END与临床结局相关性的20/67项研究(30%)中,19/20(95%)报告END患者的结局较差(通常使用90天或出院时的改良Rankin量表测量)。在一项荟萃回归分析中,女性、高血压、糖尿病和吸烟与END相关。
超过20%的急性腔隙性缺血性卒中患者会发生END,这可能为临床试验提供一个新的靶点。最常用的NIHSS评分下降≥2分的定义在不同研究间具有最佳的同质性。END始终与功能预后不良相关。需要进一步研究以更好地识别END风险患者,了解潜在机制,并开展新的试验以测试潜在的干预措施。