The bidirectional impact of sleep and circadian rhythm dysfunction in human ischaemic stroke: A systematic review

Summary Sleep and circadian rhythm disruption are potentially modifiable risk factors and consequences of ischaemic stroke. Pre-clinical evidence suggests a direct effect of sleep and endogenous circadian rhythm dysfunction on lesion volumes and post-stroke recovery. In humans, sleep and stroke literature has focused primarily on obstructive sleep apnoea. However, the bidirectional impact of non-apnoea related sleep disorders, sleep architecture, and endogenous circadian rhythm dysfunction in ischaemic stroke remains unclear. A systematic search of publications in three major databases from inception to August 7 2018 identified 67 studies meeting inclusion criteria. Long sleep duration or sleep disorders significantly increased the risk of ischaemic stroke. Inversely, ischaemic stroke was associated with sleep architectural and endogenous circadian rhythm disruption which were generally associated with post-stroke severity and functional outcome. Importantly, no studies examined direct measures of circadian rhythm dysfunction as a risk factor for ischaemic stroke. Most studies were moderate to high quality. However, methodology and stroke characteristics (e.g., stroke topography, stroke severity) were heterogenous thereby limiting generalisable conclusions. Furthermore, a priori neuroimaging outcomes in conjunction with sleep and circadian features were seldom assessed. The clinical pathogenic implications and methodological limitations of studies are discussed, and a research agenda for future studies is outlined.