Melbourne Medical School, University of Melbourne, Parkville, Victoria 3010, Australia.
Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia.
J Clin Neurosci. 2020 Jun;76:177-182. doi: 10.1016/j.jocn.2020.04.041. Epub 2020 Apr 19.
Delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a major contributor to morbidity and mortality. It is currently not possible to reliably predict patients at risk of DCI after aSAH. The aim of this study was to quantify cerebrospinal fluid (CSF) D-Dimer and plasminogen levels and to investigate any association with development of DCI. Cerebrospinal fluid (CSF) samples collected from 30 patients within 72 h post-aSAH (n = 13 DCI and n = 17 non-DCI patients) were analysed. DCI was diagnosed when angiographic vasospasm was detected in the presence of new onset neurological deficit. Enzyme-linked immunosorbent assays were used to quantify D-dimer concentrations while western blotting was used to quantify plasminogen levels. Significant differences in CSF proteins between DCI and non-DCI cohorts were verified using Mann-Whitney test. Sensitivity and specificity of these proteins for detecting DCI was examined using a ROC curve and verified with a Fischer's exact test. CSF levels of D-dimer within 72 h post aSAH were significantly elevated in DCI patients (54.29 ng/ml, 25.35-105.88 ng/ml) compared to non-DCI patients (26.75 ng/ml, 6.9-45.08 ng/ml) [p = 0.03]. In our sample population, D-dimer levels above 41.1 ng/ml had a sensitivity of 69.2% and specificity of 75% for predicting DCI. CSF levels of plasminogen (DCI: 0.50 signal-intensity/μl, 0.20-0.73 signal-intensity/μl, non-DCI: 0.28 signal-intensity/μl, 0.22-0.54 signal-intensity/μl) did not differ between the DCI and non-DCI cohort (p > 0.05). Our study suggests that elevated D-dimer in the first 72 h after aSAH may be a potential predictive biomarker for DCI.
迟发性脑缺血（DCI）是蛛网膜下腔出血（aSAH）后的主要致残和致死原因之一。目前还无法可靠地预测 aSAH 后发生 DCI 的患者。本研究旨在定量分析脑脊液（CSF）D-二聚体和纤溶酶原水平，并探讨其与 DCI 发展的相关性。收集 aSAH 后 72 小时内的 30 名患者的 CSF 样本（n=13 例 DCI 患者和 n=17 例非 DCI 患者）进行分析。当血管造影显示血管痉挛并伴有新出现的神经功能缺损时，诊断为 DCI。采用酶联免疫吸附试验（ELISA）检测 D-二聚体浓度，采用 Western blot 检测纤溶酶原水平。采用 Mann-Whitney 检验验证 DCI 组和非 DCI 组 CSF 蛋白之间的差异。采用 ROC 曲线分析这些蛋白检测 DCI 的敏感性和特异性，并采用 Fisher 精确检验进行验证。DCI 患者 aSAH 后 72 小时内的 CSF D-二聚体水平明显高于非 DCI 患者（54.29ng/ml，25.35-105.88ng/ml）[p=0.03]。在我们的样本人群中，D-二聚体水平高于 41.1ng/ml 时，预测 DCI 的敏感性为 69.2%，特异性为 75%。CSF 纤溶酶原水平（DCI：0.50 信号强度/μl，0.20-0.73 信号强度/μl，非 DCI：0.28 信号强度/μl，0.22-0.54 信号强度/μl）在 DCI 组和非 DCI 组之间无差异（p>0.05）。本研究表明，aSAH 后前 72 小时内 D-二聚体升高可能是 DCI 的潜在预测生物标志物。
