Fatigue, Toll-Like Receptor 4, and Pro-Inflammatory Cytokines in Adults With Subarachnoid Hemorrhage: A 6-Month Longitudinal Study.

Abstract

Fatigue is prevalent in subarachnoid hemorrhage (SAH) survivors. Biological mechanisms underlying fatigue post-SAH are not clear. Inflammation may contribute to the development of fatigue. This study aimed to examine the associations between inflammatory markers and fatigue during the first 6months post-SAH. Specific biomarkers examined included both early and concurrent expression of Toll-Like Receptor 4 (TLR4) messenger RNA (mRNA) and plasma concentrations of pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)1β, and IL6. We conducted a 6-month longitudinal study with a convenience sample of 43 SAH survivors. We collected blood samples on days 2, 3, and 7 and 2, 3, and 6months post-SAH to assess biomarkers. Fatigue was assessed by the PROMIS Fatigue Scale at 2, 3, and 6months. Linear mixed models were used to test the associations between early (days 2, 3, and 7) and concurrent (2, 3, and 6months) TLR4 mRNA expression (TagMan gene expression assays) and TNF-α, IL1β, and IL6 plasma concentrations (multiplex assays) and concurrent fatigue. 28% of SAH survivors experienced fatigue during the first 6months post-SAH. Fatigue levels in SAH survivors were higher than those of the U.S. population and consistent during the 6months. Experience of fatigue during the 6months post-SAH was associated with higher IL1β plasma concentrations on day 7 and IL1β, IL6, and TNF-α plasma concentrations during the 6months post-SAH. Inflammation appears to underlie the development of fatigue in SAH survivors.