Sudden unexpected death in epilepsy: A critical view of the literature

Sudden unexpected death in epilepsy (SUDEP) is a sudden, unexpected, witnessed or unwitnessed, non-traumatic and non-drowning death, occurring in benign circumstances, in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus in which postmortem examination does not reveal other causes of death. Lower diagnostic levels are assigned when cases met most or all of these criteria, but data suggested more than one possible cause of death. The incidence of SUDEP ranged from 0.09 to 2.4 per 1000 person-years. Differences can be attributed to the age of the study populations (with peaks in the 20-40-year age group) and the severity of the disease. Young age, disease severity (in particular, a history of generalized TCS), having symptomatic epilepsy, and the response to antiseizure medications (ASMs) are possible independent predictors of SUDEP. The pathophysiological mechanisms are not fully known due to the limited data available and because SUDEP is not always witnessed and has been electrophysiologically monitored only in a few cases with simultaneous assessment of respiratory, cardiac, and brain activity. The pathophysiological basis of SUDEP may vary according to different circumstances that make that particular seizure, in that specific moment and in that patient, a fatal event. The main hypothesized mechanisms, which could contribute to a cascade of events, are cardiac dysfunction (included potential effects of ASMs, genetically determined channelopathies, acquired heart diseases), respiratory dysfunction (included postictal arousal deficit for the respiratory mechanism, acquired respiratory diseases), neuromodulator dysfunction, postictal EEG depression and genetic factors.