Causes and Effects Contributing to Sudden Death in Epilepsy and the Rationale for Prevention and Intervention.

Sudden unexpected death in epilepsy (SUDEP) claims the lives of one in every thousand epileptic patients each year. Autonomic, cardiac, and respiratory pieces to a mechanistic puzzle have not yet been completely assembled. We propose a single sequence of causes and effects that unifies disparate and competitive concepts into a single algorithm centered on ictal obstructive apnea. Based on detailed animal studies that are sometimes impossible in humans, and striking parallels with a growing body of clinical examples, this framework (1) accounts for the autonomic, cardiac, and respiratory data to date by showing the causal relationships between specific elements, and (2) highlights specific kinds of data that can be used to precisely classify various patient outcomes. The framework also justifies a "near miss" designation to be applied to any cases with evidence of obstructive apnea even, and perhaps especially, in individuals that do not require resuscitation. Lastly, the rationale for preventative oxygen therapy is demonstrated. With better mechanistic understanding of SUDEP, we suggest changes for detection and classification to increase survival rates and improve risk stratification.