Schmidt Tobias P, Albanna Walid, Weiss Miriam, Veldeman Michael, Conzen Catharina, Nikoubashman Omid, Blume Christian, Kluger Daniel S, Clusmann Hans, Loosen Sven H, Schubert Gerrit A
Department of Neurosurgery, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University Hospital, Aachen, Germany.
Clinic for Diagnostic and Interventional Neuroradiology, RWTH Aachen University Hospital, Aachen, Germany.
Front Neurol. 2022 Mar 10;13:841024. doi: 10.3389/fneur.2022.841024. eCollection 2022.
Outcome after aneurysmal subarachnoid hemorrhage (aSAH) is highly variable and largely determined by early brain injury and delayed cerebral ischemia (DCI). Soluble urokinase plasminogen activator receptor (suPAR) represents a promising inflammatory marker which has previously been associated with outcome in traumatic brain injury and stroke patients. However, its relevance in the context of inflammatory changes after aSAH is unclear. Here, we aimed to characterize the role of circulating suPAR in both serum and cerebrospinal fluid (CSF) as a novel biomarker for aSAH patients.
A total of 36 aSAH patients, 10 control patients with unruptured abdominal aneurysm and 32 healthy volunteers were included for analysis. suPAR was analyzed on the day of admission in all patients. In aSAH patients, suPAR was also determined on the day of DCI and the respective time frame in asymptomatic patients. One- and two-sample -tests were used for simple difference comparisons within and between groups. Regression analysis was used to assess the influence of suPAR levels on outcome in terms of modified Rankin score.
Significantly elevated suPAR serum levels (suPAR-SL) on admission were found for aSAH patients compared to healthy controls, but not compared to vascular control patients. Disease severity as documented according to Hunt and Hess grade and modified Fisher grade was associated with higher suPAR CSF levels (suPAR-CSFL). In aSAH patients, suPAR-SL increased daily by 4%, while suPAR-CSFL showed a significantly faster daily increase by an average of 22.5% per day. Each increase of the suPAR-SL by 1 ng/ml more than tripled the odds of developing DCI (OR = 3.06). While admission suPAR-CSFL was not predictive of DCI, we observed a significant correlation with modified Rankin's degree of disability at discharge.
Elevated suPAR serum level on admission as a biomarker for early inflammation after aSAH is associated with an increased risk of DCI. Elevated suPAR-CSFL levels correlate with a higher degree of disability at discharge. These distinct relations and the observation of a continuous increase over time affirm the role of inflammation in aSAH and require further study.
动脉瘤性蛛网膜下腔出血(aSAH)后的预后差异很大,主要由早期脑损伤和迟发性脑缺血(DCI)决定。可溶性尿激酶型纤溶酶原激活物受体(suPAR)是一种很有前景的炎症标志物,此前已与创伤性脑损伤和中风患者的预后相关。然而,其在aSAH后炎症变化背景下的相关性尚不清楚。在此,我们旨在明确血清和脑脊液(CSF)中循环suPAR作为aSAH患者新型生物标志物的作用。
共纳入36例aSAH患者、10例未破裂腹主动脉瘤对照患者和32例健康志愿者进行分析。所有患者均在入院当天检测suPAR。对于aSAH患者,还在发生DCI当天以及无症状患者的相应时间段检测suPAR。采用单样本和两样本检验进行组内和组间的简单差异比较。采用回归分析评估suPAR水平对改良Rankin评分预后的影响。
与健康对照相比,aSAH患者入院时血清suPAR水平(suPAR-SL)显著升高,但与血管对照患者相比无差异。根据Hunt和Hess分级以及改良Fisher分级记录的疾病严重程度与较高的脑脊液suPAR水平(suPAR-CSFL)相关。在aSAH患者中,suPAR-SL每天升高4%,而suPAR-CSFL每天显著更快升高,平均每天升高22.5%。suPAR-SL每升高1 ng/ml,发生DCI的几率增加两倍多(OR = 3.06)。虽然入院时的suPAR-CSFL不能预测DCI,但我们观察到其与出院时改良Rankin残疾程度显著相关。
入院时升高的suPAR血清水平作为aSAH后早期炎症的生物标志物与DCI风险增加相关。升高的suPAR-CSFL水平与出院时较高的残疾程度相关。这些不同的关系以及随时间持续升高的观察结果证实了炎症在aSAH中的作用,需要进一步研究。