Abstract WMP109: Poststroke Fatigue as an Indicator of Cellular Energy Crisis

Abstract

Purpose: Post-stroke fatigue contributes to poor function, low quality of life and mortality. The etiology of post-stroke fatigue is unclear. We hypothesized that systemic inflammation impairs mitochondrial energy production, as reflected by decreased platelet respiration. The purpose of this study is to examine the association of systemic inflammation, platelet oxygen consumption rates (OCR) and fatigue in chronic ischemic stroke survivors. Methods: Data on fatigue (Fatigue Assessment Scale), depression (PHQ-9), pain (1-10 rating), sleep (Pittsburgh Sleep Quality Index), physical function (SIS 3.0), and whole blood were collected from 20 chronic ischemic stroke survivors. Cytokines were measured from plasma. Platelet OCR were measured using the Seahorse Extracellular Flux Analyzer. Results: Fatigue was negatively associated with C-reactive protein (CRP), but not IL-1β, TNF-α, IL-6. IL-9 or IL-1ra. Platelet OCR showed a U-shaped biphasic response with fatigue, initially decreasing then increasing as fatigue levels became more severe. Independent t-tests comparing data from extreme ends of the curve show that stroke survivors with high fatigue/high platelet OCR (right side of U; n=5) also have higher depression (p=0.03), poorer physical function (p=0.02) and higher pain levels (p=0.03) as compared to those with low fatigue/ high platelet OCR (left side of U; n=4) who have low depression, high physical function, and low pain. There were no differences in sleep quality or cytokines. Conclusions: These data suggest as platelets’ ability to make cellular energy becomes impaired, fatigue levels increase until a compensatory mechanism is initiated, which increases platelet cellular oxygen consumption, but does not resolve associated fatigue. Fatigue, depression, pain, poorer physical function and high OCR may indicate a systemic energy crisis in stroke survivors.