Investigating the effects of upright positions on cerebral hemodynamics and clinical outcomes in acute ischaemic stroke

The effects of upright positions (sitting and standing) on cerebral haemodynamics early post an ischaemic stroke are not well understood. Neither is their influence on longer term clinical outcomes. Concerns that early upright activity (sitting, standing and walking activities, often termed early mobilisation) may worsen cerebral perfusion within penumbral tissue early post stroke, particularly in people with occlusive disease, guided the development of the research in this thesis. This thesis is comprised of four studies that collectively aimed to shed light on the uncertainty around the effects of head positioning, particularly upright positions, on cerebral haemodynamics and clinical outcomes in acute ischaemic stroke. The first study, a comprehensive systematic review and meta-analysis, highlighted the dearth of studies assessing changes in cerebral haemodynamics in upright sitting and standing in acute ischaemic stroke. Yet getting out of bed, sitting up and walking, are early activity practices that, while part of routine stroke unit care, are not strongly guided by evidence. This review also showed the dearth of head positioning studies that examined occlusive disease as a patient-related factor that may contribute to further reductions in cerebral perfusion during upright activity. This review highlighted important research gaps to be addressed in the subsequent studies. The second study aimed to explore whether occlusive disease contributed to worse clinical outcomes in people with ischaemic stroke treated with very early mobilisation (more frequent out of bed upright activities, started <24h of stroke onset). This post hoc retrospective substudy of the A Very Early Rehabilitation (AVERT) trial showed a greater proportion of participants with occlusive disease having worse 3-month clinical outcomes (modified Rankin Scale, deaths) treated with very early mobilisation compared to usual care. However, no significant associations between occlusive disease, clin