Daniel Sean, Hou Ruihua, Galea Ian, Bulters Diederik
Department of Neurosurgery, Wessex Neurological Centre, Southampton General Hospital, Southampton, UK.
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Brain Behav Immun Health. 2025 Jun 30;48:101046. doi: 10.1016/j.bbih.2025.101046. eCollection 2025 Oct.
Subarachnoid haemorrhage (SAH) is a severe type of intracranial bleed that causes significant morbidity. One of the most overlooked yet commonly reported symptom is persistent fatigue. Fatigue in the general population has been associated with inflammation and elevated C-reactive protein (CRP). Since inflammation and raised CRP are observed post-SAH, we hypothesized that CRP is associated with fatigue severity after SAH.
Data from 95 patients (26 males, 69 females; mean age 56 years) previously recruited to the SAS trial, a prospective randomised controlled trial (2016-2019) investigating the efficacy of sulforaphane after SAH, were analyzed. In this study CRP was measured on days 1, 7, and 28 post-SAH, and fatigue severity assessed using the Short-Form Health Survey (SF-36) on days 28, 90, and 180. Multivariable regression was conducted controlling for confounders, including age, gender, initial volume of blood on CT and World Federation of Neurological Surgeons (WFNS) grade.
There was a robust association between the severity of fatigue at day 28 and CRP levels at baseline (OR = -2.67 (-1.23 to -0.18), p = 0.001) and CRP on day 28 (OR = -2.56 (-1.01 to -0.12), p = 0.013), even after controlling for confounders including blood volume and WFNS. There was no suggestion of an association between day 7 CRP and fatigue on day 28 (OR = -1.07 (-0.82 to 0.25), p = 0.287). There were no associations with any other fatigue timepoints.
CRP and fatigue in SAH patients are associated. The timings of the associations of baseline and day 28 CRP (but not day 7) with day 28 fatigue, and their independence from bleed severity suggest that fatigue is related partly to the magnitude of the initial response to the SAH and partly due to the degree of ongoing response at day 28 but not due to other events occurring in between. The lack of association of early CRP with fatigue beyond day 28 suggests that later fatigue is not driven by the initial CRP-related response to SAH. Further studies are needed to examine later CRP and the determinants of persistent fatigue.
蛛网膜下腔出血（SAH）是一种严重的颅内出血类型，会导致显著的发病率。最常被忽视但又经常被报告的症状之一是持续疲劳。一般人群中的疲劳与炎症和C反应蛋白（CRP）升高有关。由于SAH后会观察到炎症和CRP升高，我们推测CRP与SAH后的疲劳严重程度有关。
分析了95名患者（26名男性，69名女性；平均年龄56岁）的数据，这些患者先前被纳入SAS试验，这是一项前瞻性随机对照试验（2016 - 2019年），旨在研究SAH后萝卜硫素的疗效。在本研究中，在SAH后的第1天、第7天和第28天测量CRP，并在第28天、第90天和第180天使用简短健康调查问卷（SF - 36）评估疲劳严重程度。进行多变量回归以控制混杂因素，包括年龄、性别、CT上的初始出血量和世界神经外科医师联盟（WFNS）分级。
第28天的疲劳严重程度与基线时的CRP水平（OR = -2.67（-1.23至-0.18），p = 0.001）以及第28天的CRP（OR = -2.56（-1.01至-0.12），p = 0.013）之间存在显著关联，即使在控制了包括出血量和WFNS在内的混杂因素之后也是如此。第7天的CRP与第28天的疲劳之间没有关联迹象（OR = -1.07（-0.82至0.25），p = 0.287）。与其他任何疲劳时间点均无关联。
SAH患者的CRP与疲劳有关。基线和第28天的CRP（而非第7天）与第28天疲劳的关联时间以及它们与出血严重程度的独立性表明，疲劳部分与对SAH的初始反应程度有关，部分与第28天的持续反应程度有关，而不是由于其间发生的其他事件。早期CRP与第28天之后的疲劳缺乏关联表明，后期疲劳并非由对SAH的初始CRP相关反应驱动。需要进一步研究来检查后期的CRP以及持续疲劳的决定因素。
