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

Abstract

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.

Impaired brain-heart axis in focal epilepsy: Alterations in information flow and implications for seizure dynamics

“…These studies propose a conceptualization of the CNS epileptic network and the ANS as an interconnected system. Furthermore, the compromised brain-heart functioning may be attributed to acquired or inherited dysfunctions in the ANS and the heart resulting from seizures or epilepsy ( Giussani et al, 2023 ; Li, O’Brien, Todaro, & Powell, 2019 ; Ravindran, Powell, Todaro, & O’Brien, 2016 ). Consequently, observed BHI differences could be indicative of these underlying alterations.…”

Energy Dynamics in Seizure Disorder: Reexamining the Sacred Disease

“…Even more compelling is the SUDEP phenomenon, the most common cause of death in the epileptic population, which usually follows generalized tonic-clonic seizures [267][268][269][270][271]. More common at night during sleep, it is said to result from autonomic dysfunction leading to respiratory or cardiac arrest.…”

Ictal Bradycardia and Asystole in Sleep-Related Hypermotor Epilepsy: A Study of 200 Patients

“…The mechanisms underlying sudden unexpected death in epilepsy patients (SUDEP), the most significant category of epilepsy-related deaths (up to 18%), are still poorly understood: they are likely to primarily involve post-ictal respiratory/cardiac events, although IB and IA have been considered as potential contributing factors [ 15 , 16 ]. Variants in several genes have been identified as possible high-risk factors in SUDEP, mainly those encoding sodium channels, but also others such as DEPDC5 [ 17 ].…”