Unifying the definitions of sudden unexpected death in epilepsy

Abstract

SUMMARYSudden unexpected death in epilepsy (SUDEP) is a category of death in people with epilepsy occurring in the absence of a known structural cause of death and is most likely heterogeneous with regard to mechanisms and circumstances. SUDEP is particularly difficult to investigate in research studies for several reasons, including its relatively low incidence, its unpredictable occurrence often in unwitnessed settings, and its low rate of complete autopsy examinations. Over the past two decades, two complementary definitions have been used in most SUDEP studies, but often with variations. We propose here a unified SUDEP definition and classification to resolve current ambiguities and to retrieve cases that would not have been further studied if the previous definitions were used. The proposed Unified SUDEP Definition and Classification contains, in addition to concepts inherent in the previous definitions, nine main recommendations. (1) The word ''unexpected,'' and not the word ''unexplained,'' should be uniformly used in the term SUDEP. (2) The SUDEP category should be applied when appropriate, whether or not a terminal seizure is known to have occurred. (3) The ''Possible SUDEP'' category should be used only for cases with competing causes of death, with cases left unclassified when data are insufficient to reasonably permit their classification. (4) Cases that would otherwise fulfill the definition of SUDEP should be designated as ''SUDEP Plus'' when evidence indicates that a preexisting condition, known before or after autopsy, could have contributed to the death, which otherwise is classified as SUDEP (e.g., coronary insufficiency with no evidence of myocardial infarction or long-QT syndrome with no documented primary ventricular arrhythmia leading to death). (5) To be considered SUDEP, the death should have occurred within 1 h from the onset of a known terminal event. (6) For status epilepticus as an exclusion criterion for SUDEP, the duration of seizure activity should be 30 min or more. (7) A specific category of SU-DEP due to asphyxia should not be designated, the distinction being largely impractical on circumstantial or autopsy evidence, with more than one mechanism likely to be contributory in many cases. (8) Death occurring in water but without circumstantial or autopsy evidence of submersion should be classified as ''Possible SUDEP.'' If any evidence of submersion is present, the death should not be classified as SUDEP. (9) A category of ''Near-SUDEP'' should be agreed to include cases in which cardiorespiratory arrest was reversed by resuscitation efforts with subsequent survival for more than 1 h. Scenarios that demonstrate the basis for each SUDEP category are described. If disagreement exists about which category fits a particular case, we suggest the use of consensus decision by a panel of informed reviewers to adjudicate the classification of the case.

Mortality and SUDEP in epilepsy patients treated with vagus nerve stimulation

“…Deaths were designated as epilepsy or not epilepsy-related and SUDEP cases were classified using the unified definition. 6 When death occurred shortly after an event, but not within one hour, the death was classified as a fatal near SUDEP. 6,7 Deaths were expressed as rate per person-years of follow-up with exact 95% confidence intervals (CIs) and SMRs calculated using, as a reference population, published mortality statistics from the Office of National Statistics (ONS) for England and Wales from 1995 until 2010.…”

Severe Respiratory Acidosis in Status Epilepticus as a Possible Etiology of Sudden Death in Lesch–Nyhan Disease: A Case Report and Review of the Literature

“…SUDEP is a rare but known complication of epilepsy defined as a sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death that occurs in benign circumstances in an individual with epilepsy, with or without evidence for a seizure, and excludes documented status epilepticus, in which post-mortem examination does not reveal a cause of death (Nashef et al 2012). SUDEP typically presents in patients with poorly controlled generalized convulsions, though seizures are hypothesized to contribute to sudden death in other situations such as sudden infant death syndrome (SIDS) or sudden unexplained death in childhood (SUDC) (Hesdorffer et al 2015).…”

Sudden Unexpected Death in Epilepsy (SUDEP): an overview

“…Cases where SUDEP cannot be excluded, either because of limited information regarding death circumstances or there is a plausible competing explanation for death have been classified as "possible SUDEP" in a definition proposed by Annegers. [7] Slightly refined definitions have recently been proposed [8] to resolve some ambiguities with previous definitions. This inovolves the introduction of the category of "SUDEP plus" where evidence indicates that a preexisting condition could have contributed to the death, which otherwise is SUDEP.…”

“…[9] The new proposal has set an arbitrary time limit of one hour [8] recognizing that deaths do not always occur instantaneously during the postictal phase. The proposal introduced the term "Near-SUDEP" for cases with a cardio-respiratory arrest where resuscitation reversed the condition so that the patient survived for more than one hour.…”