Sudden Unexpected Death in Epilepsy: Incidence, Risk Factors, and Proposed Mechanisms

Epilepsy is a common neurological disorder associated with increased morbidity and mortality, including premature death from different causes. Sudden unexpected death in epilepsy, or SUDEP, is one of the most common causes of death in people with epilepsy and originally brought to light by medical examiners. It accounts for 5% to 30% of all deaths in individuals with epilepsy and up to 50% in individuals with medically refractory epilepsy. It is commonly associated with a history of generalized tonic-clonic seizures and may be mitigated by other electroclinical risk factors, such as postictal electroencephalographic suppression, prone position, altered heart rate variability, conduction abnormalities, gender, or antiepileptic medications, to name a few. More recently, potential neuroimaging biomarkers have also been identified. Still, despite the increased mortality risk in people with epilepsy due to SUDEP, little is known about its underlying pathophysiology. The pathogenesis is likely to be multifactorial, resulting in neurogenic pulmonary edema or, in some cases, fatal cardiac arrhythmias. Medical examiners can provide an important role in our understanding of the magnitude of the problem and ongoing research into the underlying mechanisms. In this review, we discuss diagnostic criteria, incidence, risk factors, and current theories regarding the pathophysiology of SUDEP.