C-reactive protein and fatigue after subarachnoid haemorrhage

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.