Wilson, DR; (2018) Clinical relevance of neuroimaging biomarkers of small vessel disease in relation to intracranial haemorrhage. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Introduction: Small vessel disease is the underlying cause of most spontaneous (non-traumatic) ICH. Cerebral imaging markers of small vessel disease, particularly cerebral microbleeds (CMBs) and white matter hyperintensities of presumed vascular origin (WMH) offer clinicians and researchers an opportunity to further understand the pathogenesis and risk of ICH in patients with stroke. In this thesis I present a portfolio of studies aimed to show the clinical relevance of neuroimaging biomarkers of small vessel disease in relation to intracerebral haemorrhage (ICH). Methods: I ascertained patients primarily through the Clinical Relevance Of Cerebral Microbleeds In Stroke (CROMIS-2) study, a multicentre prospective observational study recruiting patients with both ICH and patients with ischaemic stroke associated with atrial fibrillation (AF) from 79 centres throughout the UK and one in the Netherlands. Data was also collected locally from ICH patients seen in the UCL Hospital’s comprehensive stroke service, international collaborations and through the meta-analysis of published studies. Main findings: 1) CMBs are associated with an increased relative risk of subsequent ICH in patients with ischaemic stroke (primarily treated with antiplatelet drugs) and the ICH risk increases more steeply with CMB burden than does the risk of ischaemic stroke; 2) In patients with AF anticoagulated after recent ischaemic stroke or TIA, CMB presence is independently associated with symptomatic intracranial haemorrhage risk, improves the predictive ability of clinical risk scores, and can inform anticoagulation decisions; 3) The presence of cerebral small vessel disease is associated with a lower risk of a macrovascular cause of ICH; 4) Lobar ICH location (compared to non-lobar location) is associated with higher recurrent ICH risk and lower new ischaemic stroke risk; 5) The CHA2DS2VASC score has similar modest predictive value in estimating the risk of ischaemic stroke in patients with ICH and concurrent AF, but risk prediction was not improved by adding SVD presence. Conclusion: These studies confirm the clinical relevance of neuroimaging markers of small vessel disease in the diagnosis and prediction of intracranial haemorrhage and provide a framework for future research

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