Medicine (RMH) - Theses
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ItemRadiological, clinical and genetic markers of ischaemic stroke outcome( 2018)Acute ischaemic stroke is caused by a blocked blood vessel in the cerebral circulation. It is the most common form of stroke worldwide and a major cause of disability and death. Over the past 20 years, major advances in acute stroke treatment and management have led to a reduction in stroke-related mortality, and thus an unavoidable side effect has been the concomitant rise in survivors living with life-changing disability, requiring ongoing clinical management and care. However, stroke outcome is not entirely represented as mortality rates and level of disability – there are a range of neurological sequelae that contribute an important additional burden to patients. Up to 13% of patients who have suffered an ischaemic stroke will develop seizures within 2 years. For clinicians the development of seizures represents a clinical challenge to manage, is difficult to predict and treat, and associated with poorer patient quality of life. However, at present no indications for antiepileptic drugs in preventing post stroke seizures and epilepsy exist and to date, no blood biomarkers and only few genetic biomarkers have been identified as being associated with an increased risk of post stroke seizure development. This multicentre (China, Brazil and Australia), multidisciplinary thesis examines novel imaging, genetic and clinical markers as methods for identifying patients at higher risk of developing seizures. Reperfusion therapies with thrombolysis and, more recently, endovascular thrombectomy have transformed outcomes for patients. This body of research targeted patient groups treated with modern cerebrovascular stent devices and revascularization techniques, in order to assess the implications of these novel stroke interventions, particularly in terms of the development of post stroke seizures. Multiple advanced neuroimaging techniques were used to determine capacity to identify patients at the highest risk of developing post stroke seizures. Results from these investigations showed that the Alberta Stroke Program Early CT Score on non-contrast CT, cortical involvement on CT perfusion parameters and extent of haemorrhagic transformation on non-contrast CT, can be used as radiological markers for stroke outcome, including the identification of higher risk patients for post stroke seizure development. Additionally, unlike previous work, international sites were included along with Australian sites, allowing the interrogation of whether ethnicity and environment influences the development of post stroke seizures. Results from this investigation revealed that, not only does occurrence of seizures differ across populations from different countries, but certain clinical markers, such as presence and treatment of atrial fibrillation, may influence seizure occurrence across populations. Our exploratory study assessing the genetic influence on the development of post stroke seizures has also laid important groundwork in developing genetic biomarkers for future studies and results from this thesis have identified potential genetic variants warranting further investigation. The results presented in this thesis have the potential to guide identification of individuals at higher risk of developing post stroke seizures and represent a step towards personalised medicine. In the future, if antiepileptogenic drugs become available, these results may inform the selection of an enriched population for trials and guide recruitment for biomarker studies of epileptogenesis.