Genetics and genomics of stroke

Abstract

Stroke is defined as the acute onset of focal neurological disturbance arising due to a cerebrovascular cause, confirmed histopathologically or on imaging, where other causes have been excluded. Strokes may either be ischaemic (approximately 80% of cases) or haemorrhagic (20%). Although often thought of as a single disease, stroke represents the end stage of many different pathologies, each of which can result in cerebral ischaemia and/or haemorrhage. Therefore when investigating a stroke patient, investigations are performed to identify the underlying cause. Most cases of ischaemic stroke are caused by one of three pathologies: large vessel atherosclerotic disease (LVD), cerebral small vessel disease (SVD) or cardioembolism, although there are multiple rarer causes including cervical artery dissection. However, even with detailed investigation an underlying cause cannot be found in approximately a quarter of all ischaemic strokes. Haemorrhagic strokes are categorized according to the brain region they arise from; lobar or cortical haemorrhages are commonly caused by cerebral amyloid angiopathy, or an underlying structural lesion for example an arteriovenous malformation. Subcortical haemorrhages are usually associated with hypertension and believed to be often a manifestation of SVD. This chapter will briefly outline the genetic basis of strokes in general, and highlight key examples of familial forms of stroke.