The Impact of Cerebral Perfusion Strategies on Cerebral Haemodynamics in Acute Ischaemic Stroke

Background: Ischaemic stroke (IS) is a devastating neurological disease. It is a significant global public health problem, placing enormous burden on patients, relatives, the health care system, and society as a whole. It is generally accepted that cerebral haemodynamics, and associated parameters, are impaired following ischaemic stroke (IS). Recently, a wide range of cerebral perfusion strategies have been introduced. These aim to improve perfusion to the ischaemic penumbra and to restore cerebral blood flow, thereby enhancing neurological and functional recovery. Understanding how these strategies affect cerebral haemodynamics may give us the necessary understanding to optimise individualised stroke management, aiming to prevent secondary perfusion-related injury and to minimise its potential devastating impacts.

Objectives: This thesis aimed to determine how non-pharmacological (head positioning changes) and pharmacological (pressor therapy and intravenous thrombolysis) affect cerebral

haemodynamic and associated parameters, specifically cerebral autoregulation, in acute ischaemic stroke (AIS) patients, and whether such changes are associated with

neurological and functional improvements.

Methods: This dissertation presents a systematic review and four inter-related studies, as follows:

1) The systematic review synthesises findings from twenty studies which examined the feasibility, safety and clinical effectiveness of using pressor agents as induced hypertension therapy in AIS (Chapter 3);

2) A reproducibility study on how gradual changes in head positioning (GHP) affect cerebrovascular physiology in healthy older subjects (Chapter 5);

3) A prospective observational study on how GHP affect systemic and cerebral haemodynamic parameters in healthy controls and patients with AIS, up to 90 days post stroke symptom onset (Chapter 6);

4) A prospective observational study on using rapid head positioning (RHP) as a new dynamic cerebral autoregulation (dCA) paradigm, in both healthy controls and patients with AIS (Chapter 7);

5) A feasibility study evaluating changes in systemic and cerebral haemodynamic parameters during, and immediately after, intravenous thrombolysis (IVT) and up to 90 days post stroke symptom onset in AIS patients who received IVT (Chapter 8).

Conclusions: This PhD thesis carefully scrutinised various pharmacological and non-pharmacological perfusion strategies used in AIS, their impact on cerebral haemodynamics and associated parameters change. It also demonstrated beautifully how AIS patients act differently when compare to controls in different paradigm measurements. The heterogeneous nature of CA impairment and recovery, and the time course of CA changes in AIS, provide valuable information in facilitating personalised post-stroke recovery plan. Further largescale, prospective studies are needed in order to translate such important information into day-to-day clinical setting.