Effects of low-dose alteplase and intensive blood pressure control on brain (micro-) circulation: imaging analyses from the ENCHANTED trial

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Copyright: Zhou, Zien
Abstract
Background and aims: Worldwide, the burden of acute ischaemic stroke (AIS) is high in terms of disability-adjusted life-years lost. Prior research shows that imaging features of brain frailty (atrophy and severe leucoaraiosis) and acute ischaemia (visible ischaemic lesions, hypoattenuation, large ischaemic lesion, swelling, and hyper-attenuated arteries) on non-contrast computerised tomography (CT) scans are associated with symptomatic intracerebral haemorrhage (sICH) and mortality in thrombolysis-treated AIS patients. This thesis aimed to elucidate other CT and magnetic resonance imaging (MRI) factors related to abnormalities in the brain (micro-) circulation (including fluid-attenuated inversion recovery hyperintense arteries [FLAIR-HAs], a single penetrating artery occlusion presented as a lacunar infarct, and vascular obstruction at different sites) that determine prognosis in thrombolysis-treated AIS patients, and that may modify the effects of treatment with either intravenous alteplase by dose or in the control of blood pressure (BP) according to intensity. Methods: Secondary analyses of datasets from the international randomised trial - Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) - were conducted after central classification of brain scan images. Results: FLAIR-HAs on MRI are frequently present in AIS due to presumed cardioembolism. They indicate a favourable prognosis in such thrombolysis-treated AIS patients, despite also being associated with an increased risk of intracerebral haemorrhage within the region of infarction. A meta-analysis of the ENCHANTED data with similar studies shows that FLAIR-HAs are not associated with the functional outcome overall but are associated with recovery, specifically in patients with endovascular therapy for AIS. FLAIR-HAs are also associated with early recanalisation or haemorrhagic complications, and early neurologic deterioration. My studies on lacunar AIS show no differences in the treatment effect of low- versus standard-dose alteplase, and early intensive versus guideline-recommended BP lowering, on functional recovery and sICH across lacunar and non-lacunar cases of AIS. Furthermore, functional recovery by alteplase dose or BP lowering intensity is not modified by the degree or site of vascular obstruction in cerebral vessels noted on CT or MRI angiography. Conclusions: My thesis has established that several CT/MRI brain imaging features of brain (micro-) circulation are important prognostic markers of functional recovery and sICH in thrombolysis-treated AIS patients. However, these imaging markers do not appear to modify the treatment effects of randomised alteplase dose and degree of BP-lowering among participants of the ENCHANTED trial.
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Publication Year
2022
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Thesis
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PhD Doctorate
UNSW Faculty
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