Demystifying sudden unexplained death in epilepsy--are we close?

The cause of sudden unexplained death in epilepsy (SUDEP) is still elusive, despite multiple studies over the past few decades. This review assesses recent progress in the understanding of risk factors (situations that predispose patients to SUDEP) and terminal events (events immediately associated with death) that potentially contribute to SUDEP. Recent studies strongly support a close relationship between seizure episodes (especially generalized convulsions) and SUDEP. The lethal nature of some seizure-induced cardiorespiratory events has been documented fortuitously in rare patient cases, and these events have been consistently reproduced in SUDEP animal models. Nonetheless, SUDEP likely does not have a single cause, and risk factors identified thus far may vary in importance among persons with epilepsy. In the absence of a complete understanding of the pathophysiologic mechanisms underlying SUDEP, potential preventive measures for high-risk patients are offered for consideration. Seizure control is most important for reducing SUDEP risk. Circumstantial data suggest that heightened supervision of patients with frequent seizures may be beneficial. Relatively simple interventions may be sufficient to interrupt potentially lethal events such as periictal suffocation or apnea. However, application of these preventive measures to all epilepsy patients has not been proven to substantially reduce the rate of SUDEP. Additional clinical and laboratory investigations are needed to identify and confirm pathogenic factors and preventive measures.