Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds LS2 9JT, UK.
School of Chemical and Process Engineering, University of Leeds, Leeds LS2 9JT, UK.
Biomolecules. 2024 Oct 22;14(11):1344. doi: 10.3390/biom14111344.
Stroke is one of the leading causes of death and disability worldwide. The diagnosis of stroke remains largely clinical, yet widely used stroke scoring systems and brain imaging do not satisfactorily allow the distinction of ischaemic stroke (IS) patients from stroke mimics (SMs). Blood biomarkers are promising tools that could facilitate clinical triage.
This study recruited 66 patients with IS and 24 SMs. The levels of Glial fibrillary acidic protein (GFAP), Neuron-specific enolase (NSE), Neurofilament light chain (NfL) and blood-brain barrier (BBB) proteins [Occludin (OCLN), Zonula occludens 1 (ZO-1), Claudin-5] in blood serum were measured by enzyme-linked immunosorbent assay technique. Biomarker levels in IS patients and SMs were compared using the Mann-Whitney U test. Multivariable logistic regression analysis was used to evaluate the diagnostic performance of biomarkers in combination with the National Institutes of Health Stroke Scale (NIHSS) score.
More significant differences in circulating GFAP, NfL, OCLN, ZO-1, and Claudin-5 but not NSE were found in IS patients compared to SMs. A combination of circulating ZO-1, Claudin-5, and OCLN with NIHSS score gives the highest diagnostic accuracy, sensitivity, and specificity.
A prediction model with circulating BBB proteins in combination with NIHSS score differentiates between IS patients and SMs.
中风是全球范围内导致死亡和残疾的主要原因之一。中风的诊断在很大程度上仍然依赖于临床，但广泛使用的中风评分系统和脑部成像并不能令人满意地区分缺血性中风（IS）患者和中风模拟症（SM）患者。血液生物标志物是一种很有前途的工具，可以帮助进行临床分诊。
本研究招募了 66 名 IS 患者和 24 名 SM 患者。采用酶联免疫吸附试验技术检测血清中神经胶质纤维酸性蛋白（GFAP）、神经元特异性烯醇化酶（NSE）、神经丝轻链（NfL）和血脑屏障（BBB）蛋白[紧密连接蛋白（OCLN）、闭合蛋白 1（ZO-1）、Claudin-5]的水平。使用 Mann-Whitney U 检验比较 IS 患者和 SMs 之间的生物标志物水平。使用多变量逻辑回归分析评估生物标志物与国立卫生研究院中风量表（NIHSS）评分联合的诊断性能。
IS 患者的循环 GFAP、NfL、OCLN、ZO-1 和 Claudin-5 水平显著高于 SMs，而 NSE 水平则无显著差异。循环 ZO-1、Claudin-5 和 OCLN 与 NIHSS 评分相结合的组合具有最高的诊断准确性、敏感性和特异性。
一种结合 NIHSS 评分的循环 BBB 蛋白预测模型可区分 IS 患者和 SMs。
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