Division of Clinical Neurosciences, Bramwell Dott Building, Western General Hospital, Edinburgh, UK.
Cerebrovasc Dis. 2012;33(1):47-54. doi: 10.1159/000332810. Epub 2011 Dec 1.
A blood test that quantified the extent of brain damage following ischaemic stroke might be a useful surrogate outcome measure in trials of acute stroke treatments. Measures of neuronal and glial damage, such as neuron-specific enolase (NSE), glial fibrillary acidic protein, tau-protein, myelin-basic protein and S100-β are potential candidate biomarkers.
We systematically reviewed the relevant literature to find studies that correlated blood levels of neuronal and glial damage markers with imaging measures of infarct volume.
We identified studies with a comprehensive search of databases and the reference lists of relevant studies. We included studies that: (1) measured the highest level, or area under the curve (AUC) over time of markers of cerebral damage, (2) calculated infarct volume, and (3) correlated the two measures.
Seventeen studies met the criteria for the systematic review. There were sufficient data to provide summary estimates for S100-β and NSE. The peak level and AUC over time of both markers correlated with subacute infarct volume. Measurements of S100-β later than 24 h after stroke were better correlated with subacute infarct size than earlier measurements. However, scan times varied, and none was later than 8 days after stroke.
Peak and AUC levels of NSE and S100-β levels correlated with subacute infarct volume. Correlations of S100-β with infarct volume were stronger when measured after 24 h than closer to admission. Exploratory studies within clinical trials are necessary before blood markers of cerebral tissue damage can be recommended as surrogate endpoints.
一种能够量化缺血性中风后脑损伤程度的血液检测,可能成为急性中风治疗试验中有用的替代终点测量指标。神经元和神经胶质损伤的测量指标,如神经元特异性烯醇化酶(NSE)、神经胶质纤维酸性蛋白、tau 蛋白、髓鞘碱性蛋白和 S100-β,是潜在的候选生物标志物。
我们系统地回顾了相关文献,以发现与梗死体积的影像学测量相关的血液神经元和神经胶质损伤标志物的研究。
我们通过全面搜索数据库和相关研究的参考文献,确定了研究。我们纳入了以下研究:(1)测量脑损伤标志物的最高水平或时间曲线下面积(AUC);(2)计算梗死体积;(3)将这两个指标相关联。
17 项研究符合系统综述的标准。有足够的数据提供 S100-β 和 NSE 的汇总估计值。这两种标志物的峰值水平和 AUC 与亚急性梗死体积相关。中风后 24 小时以后测量的 S100-β 与亚急性梗死体积的相关性优于更早的测量。然而,扫描时间各不相同,没有一个时间晚于中风后 8 天。
NSE 和 S100-β 的峰值和 AUC 水平与亚急性梗死体积相关。当在 24 小时后测量时,S100-β 与梗死体积的相关性比更接近入院时更强。在将血液脑组织损伤标志物推荐为替代终点之前,需要在临床试验中进行探索性研究。