Background and Purpose—We evaluated the association between 2 types of predictors of delayed cerebral ischemia after nontraumatic subarachnoid hemorrhage, including biomarkers of the innate immune response and neurophysiologic changes on continuous electroencephalography.Methods—We studied subarachnoid hemorrhage patients that had at least 72 hours of continuous electroencephalography and blood samples collected within the first 5 days of symptom onset. We measured inflammatory biomarkers previously associated with delayed cerebral ischemia and functional outcome, including soluble ST2 (sST2), IL-6 (interleukin-6), and CRP (C-reactive protein). Serial plasma samples and cerebrospinal fluid sST2 levels were available in a subgroup of patients. Neurophysiologic changes were categorized into new or worsening epileptiform abnormalities (EAs) or new background deterioration. The association of biomarkers with neurophysiologic changes were evaluated using the Wilcoxon rank-sum test. Plasma and cerebrospinal fluid sST2 were further examined longitudinally using repeated measures mixed-effects models.Results—Forty-six patients met inclusion criteria. Seventeen (37%) patients developed new or worsening EAs, 21 (46%) developed new background deterioration, and 8 (17%) developed neither. Early (day, 0–5) plasma sST2 levels were higher among patients with new or worsening EAs (median 115 ng/mL [interquartile range, 73.8–197]) versus those without (74.7 ng/mL [interquartile range, 44.8–102]; P=0.024). Plasma sST2 levels were similar between patients with or without new background deterioration. Repeated measures mixed-effects modeling that adjusted for admission risk factors showed that the association with new or worsening EAs remained independent for both plasma sST2 (β=0.41 [95% CI, 0.09–0.73]; P=0.01) and cerebrospinal fluid sST2 (β=0.97 [95% CI, 0.14–1.8]; P=0.021). IL-6 and CRP were not associated with new background deterioration or with new or worsening EAs.Conclusions—In patients admitted with subarachnoid hemorrhage, sST2 level was associated with new or worsening EAs but not new background deterioration. This association may identify a link between a specific innate immune response pathway and continuous electroencephalography abnormalities in the pathogenesis of secondary brain injury after subarachnoid hemorrhage.

中文翻译：

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可溶性 ST2 与非创伤性蛛网膜下腔出血后新的癫痫样异常有关。

背景和目的——我们评估了非创伤性蛛网膜下腔出血后迟发性脑缺血的 2 种预测因素之间的关联，包括先天免疫反应的生物标志物和连续脑电图的神经生理学变化。方法——我们研究了至少 72 小时的蛛网膜下腔出血患者在症状出现的前 5 天内收集连续的脑电图和血样。我们测量了先前与迟发性脑缺血和功能结果相关的炎症生物标志物，包括可溶性 ST2 (sST2)、IL-6 (白介素 6) 和 CRP (C 反应蛋白)。在一个亚组患者中可获得连续血浆样本和脑脊液 sST2 水平。神经生理学变化分为新的或恶化的癫痫样异常（EA）或新的背景恶化。使用 Wilcoxon 秩和检验评估生物标志物与神经生理学变化的关联。使用重复测量混合效应模型进一步纵向检查血浆和脑脊液 sST2。结果——46 名患者符合纳入标准。17 名 (37%) 患者出现新的或恶化的 EA，21 名 (46%) 出现新的背景恶化，8 名 (17%) 两者均未出现。早期（第 0-5 天）血浆 sST2 水平在新发或恶化的 EA 患者中较高（中位数 115 ng/mL [四分位距，73.8-197]）与没有（74.7 ng/mL [四分位距，44.8-102]）的患者相比]; 使用 Wilcoxon 秩和检验评估生物标志物与神经生理学变化的关联。使用重复测量混合效应模型进一步纵向检查血浆和脑脊液 sST2。结果——46 名患者符合纳入标准。17 名 (37%) 患者出现新的或恶化的 EA，21 名 (46%) 出现新的背景恶化，8 名 (17%) 两者均未出现。早期（第 0-5 天）血浆 sST2 水平在新发或恶化的 EA 患者中较高（中位数 115 ng/mL [四分位距，73.8-197]）与没有（74.7 ng/mL [四分位距，44.8-102]）的患者相比]; 使用 Wilcoxon 秩和检验评估生物标志物与神经生理学变化的关联。使用重复测量混合效应模型进一步纵向检查血浆和脑脊液 sST2。结果——46 名患者符合纳入标准。17 名 (37%) 患者出现新的或恶化的 EA，21 名 (46%) 出现新的背景恶化，8 名 (17%) 两者均未出现。早期（第 0-5 天）血浆 sST2 水平在新发或恶化的 EA 患者中较高（中位数 115 ng/mL [四分位距，73.8-197]）与没有（74.7 ng/mL [四分位距，44.8-102]）的患者相比]; 17 名 (37%) 患者出现新的或恶化的 EA，21 名 (46%) 出现新的背景恶化，8 名 (17%) 两者均未出现。早期（第 0-5 天）血浆 sST2 水平在新发或恶化的 EA 患者中较高（中位数 115 ng/mL [四分位距，73.8-197]）与没有（74.7 ng/mL [四分位距，44.8-102]）的患者相比]; 17 名 (37%) 患者出现新的或恶化的 EA，21 名 (46%) 出现新的背景恶化，8 名 (17%) 两者均未出现。早期（第 0-5 天）血浆 sST2 水平在新发或恶化的 EA 患者中较高（中位数 115 ng/mL [四分位距，73.8-197]）与没有（74.7 ng/mL [四分位距，44.8-102]）的患者相比];P = 0.024）。有或没有新背景恶化的患者的血浆 sST2 水平相似。调整入院风险因素的重复测量混合效应模型显示，血浆 sST2（β=0.41 [95% CI，0.09–0.73]；P = 0.01）和脑脊液 sST2与新的或恶化的 EA 的相关性仍然是独立的（ β=0.97 [95% CI，0.14–1.8]；P=0.021）。IL-6 和 CRP 与新的背景恶化或新的或恶化的 EA 无关。结论——在因蛛网膜下腔出血入院的患者中，sST2 水平与新的或恶化的 EA 相关，但与新的背景恶化无关。这种关联可以确定特定的先天免疫反应途径与蛛网膜下腔出血后继发性脑损伤发病机制中持续脑电图异常之间的联系。