The black box of perinatal ischemic stroke pathogenesis

An improved understanding of perinatal stroke epidemiology, classification, neuroimaging, and outcomes has emerged in recent years. Despite this, little is known regarding the pathophysiological mechanisms responsible for most cases. A multitude of possible associations and putative risk factors have been reported, but most lack definitive empirical evidence supporting primary causation. These include obstetrical and maternal factors, perinatal conditions, infectious diseases, prothrombotic abnormalities, cardiac disorders, medications, and many others. The bulk of evidence is weak, dominated by case reports and retrospective case series. Findings from the small number of case-control and cohort studies that exist are limited by heterogeneous populations and methodologies. The single largest barrier to ultimately understanding and potentially improving outcomes from this common and disabling condition is the lack of comprehensive, fully powered risk factor studies required to definitively describe perinatal stroke pathogenesis. This review summarizes current evidence and suggests future directions for research.