Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy. It is defined as the sudden and unexpected, non-traumatic and non-drowning death of a person with epilepsy, without a toxicological or anatomical cause of death detected during the post-mortem examination. While the mechanisms underlying SUDEP are still poorly understood, it is possibly the most common cause of death as a result of complications from epilepsy, accounting for between 7.5 and 17% of all epilepsy-related deaths and 50% of all deaths in refractory epilepsy. The causes of SUDEP seem to be multifactorial and include respiratory, cardiac, and cerebral factors as well as the severity of epilepsy and seizures. Proposed pathophysiological mechanisms include seizure-induced cardiac and respiratory arrests. Among epileptics, SUDEP occurs in about 1 in 1,000 adults and 1 in 4,500 children annually. Rates of death as a result of prolonged seizures (status epilepticus) are not classified as SUDEP.

Categories

The overarching term SUDEP can be subdivided into four different categories: Definite, Probably, Possible, and Unlikely.

Risk factors

Consistent risk factors include: Genetic mutations have been identified that increase a person's risk for SUDEP (some are discussed below), but ultimately their genetic risk is determined by the function of multiple genes that is not yet well understood. Overlap is seen between these ion channel genes and the different sudden death disorders, including SUDEP, SIDS, sudden unexpected death (SUD), and sudden unexplained death in childhood (SUDC). Many of the genes are involved in long QT syndrome.

Mechanism

The mechanisms underlying SUDEP are not well understood but probably involve several pathophysiological mechanisms and circumstances. The most commonly involved are seizure-induced hypoventilation and cardiac arrhythmias, but different mechanisms may be involved in different individuals, and more than one mechanism may be involved in any one individual.

Management

Currently, the most effective strategy to protect against SUDEP in childhood epilepsy is seizure control, but this approach is not completely effective and is particularly challenging in cases of intractable epilepsy. The lack of generally recognized clinical recommendations available are a reflection of the dearth of data on the effectiveness of any particular clinical strategy, but based on present evidence, the following may be relevant:

Epidemiology