Epilepsy-related and other causes of mortality in people with epilepsy: A systematic review of systematic reviews

Background: This systematic review of epilepsy mortality systematic reviews evaluates comparative risks, causes, and risk factors for all-cause mortality in people with epilepsy (PWE) to specifically establish the burden of epilepsy-related deaths. Methods: MEDLINE and Embase were searched from conception to 26/12/2018 for systematic reviews evaluating all-cause mortality in PWE of any age. Independent study selection, data extraction and quality assessment were performed. Deaths were separated into epilepsy-related and unrelated using a recently published classification system. Outcomes included standardized mortality ratio (SMR) and mortality rate (MR) in a primary analysis of comparative risks, causes, and risk factors for all-cause and epilepsy-related mortality. A narrative synthesis of review findings was used to present results, including from a secondary analysis of individual epilepsy-related death risk factors. Results: Six moderate or high-quality systematic reviews were included in the primary analysis, evaluating 103 observational studies. All-cause mortality remained similarly high between 1950 and present (median SMR range 2.2-3.4). Africa had the highest SMR (median 5.4, range 2.6-7.2). SMRs were also higher for children <18 years (median 7.5, range 3.1-22.4) than adults (median 2.6, range 1.3-8.7), and for epilepsy-related (median 3.8, range 0.0-82.4,) than unrelated causes (median 1.7, range 0.7-17.6). Structural brain disease conferred the greatest risk for all-cause mortality (SMR range 24.0-41.5). Common epilepsy-related causes included alcohol, drowning, pneumonia, and suicide. In secondary analysis of nine additional systematic reviews, epilepsy-related death risk factors were reported for sudden unexpected death in epilepsy (SUDEP), drowning and suicide. Conclusions: Premature all-cause mortality remains a major problem in PWE globally, particularly in children and young adults, with most being epilepsy-related and potentially preventable. SUDEP is only one of several other common and important epilepsy-related causes of death.