Regional neurodegeneration correlates with sleep-wake dysfunction after stroke.

Abstract

Sleep-wake disruption is a key modifiable risk factor and sequela of stroke. The pathogenesis of post-stroke sleep dysfunction is unclear. It is not known whether post-stroke sleep pathology is due to focal infarction to sleep-wake hubs, or to accelerated post-stroke neurodegeneration in subcortical structures after stroke. We characterise the first prospective post-stroke regional brain volumetric and whole-brain, fibre-specific, white matter markers of objectively measured sleep-wake dysfunction. We hypothesised that excessively long sleep (≥8 hr) duration and poor sleep efficiency (<80%) measured using the Sensewear Armband 3-months post-stroke (n=112) would be associated with reduced regional brain volumes of a priori selected sleep-wake regions of interest when compared to healthy controls with optimal sleep characteristics (n=35). We utilised a novel technique known as whole brain fixel-based analysis to investigate the fibre-specific white-matter differences in participants with long sleep duration. Stroke participants with long sleep (n=24) duration exhibited reduced regional volumes of the ipsilesional thalamus and contralesional amygdala when compared to controls. Poor sleep efficiency after stroke (n=29) was associated with reduced ipsilesional thalamus, contralesional hippocampus, and contralesional amygdala volumes. Whole-brain fixel-based analyses revealed widespread macrostructural degeneration to the cortico-ponto-cerebellar tract in stroke participants with long sleep, with fibre reductions of up to 40%. Neurodegeneration to subcortical structures, which appear to be vulnerable to accelerated brain volume loss after stroke, may drive sleep-wake deficiencies post-stroke, independent of lesion characteristics and confounding comorbidities. We discuss these findings in the context of the clinicopathological implications of sleep-related neurodegeneration and attempt to corroborate previous mechanistic-neuroanatomical findings.