Sudden unexplained death in epilepsy

Laura Vilella Bertran MD (

Dr. Vilella of University of Texas Health Science Center at Houston has no relevant financial relationships to disclose.

)
Samden D Lhatoo MD FRCP (

Dr. Lhatoo of the University of Texas Health Science Center at Houston has no relevant financial relationships to disclose.

)
Jerome Engel Jr MD PhD, editor. (Dr. Engel of the David Geffen School of Medicine at the University of California, Los Angeles, has no relevant financial relationships to disclose.)
Originally released May 13, 2020; expires May 13, 2023

This article includes discussion of sudden unexplained death in epilepsy, sudden unexpected death in epilepsy, and SUDEP. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Epilepsy affects 6.38 per 1000 persons (95% CI 5.57-7.30), with a lifetime prevalence of 7.60 per 1000 persons (95% CI 6.1-9.38) (Fiest et al 2017). Persons with epilepsy face an increased risk of premature death 2- to 3-fold greater than the risk of the general population (Trinka et al 2013). Cause-specific mortality in persons with epilepsy can be divided into epilepsy-related and nonepilepsy-related categories (Trinka et al 2013; Devinsky et al 2016). Epilepsy-related causes can be further classified as indirect, such as suicide, or direct causes such as status epilepticus and sudden unexpected death in epilepsy (Trinka et al 2013; Devinsky et al 2016). Sudden unexplained death in epilepsy refers to sudden death in persons with epilepsy in whom postmortem examination is negative for toxicological or pathological causes of death (Nashef et al 2012). Sudden unexplained death in epilepsy excludes deaths resulting from accidents, such as trauma or drowning, and documented status epilepticus (Nashef et al 2012). Evidence points to critical failure of breathing and/or cardiac function in the periictal period (Ryvlin et al 2013), although similar failure may occur rarely without a preceding seizure (Lhatoo et al 2016). This article aims to provide a comprehensive review of current knowledge of sudden unexplained death in epilepsy, including epidemiology, pathophysiology, and strategies for prevention.

Key points

 

• Sudden unexplained death in epilepsy is the principal cause of premature mortality in persons with epilepsy.

 

• Sudden unexplained death in epilepsy typically occurs in patients with longstanding, early-onset epilepsy who have frequent (more than 3 per year) generalized convulsive seizures.

 

• Most sudden unexplained death in epilepsy cases occur at night, following generalized convulsive seizures, although sudden unexplained death in epilepsy without preceding seizure can occur, suggesting sudden unexplained death in epilepsy is a heterogeneous phenomenon.

 

• Seizure-induced respiratory dysfunction in the setting of impaired protective arousal mechanisms in the postictal state may trigger terminal cardiorespiratory collapse.

 

• The ultimate physiopathology behind cardiorespiratory collapse is poorly understood, although there is circumstantial, neuroimaging, and neuropathological evidence of compromised brainstem function.

 

• Sudden unexplained death in epilepsy preventive measures are currently focused on achieving adequate seizure control and seizure detection to ensure lifesaving interventions.

Historical note and terminology

One of the first scientific descriptions of sudden unexplained death in epilepsy dates back to 1910 (Munson 1910) when Munson described not only an increased risk of premature death in persons with epilepsy for all causes, but also identified a subset of patients who suffered nonaccidental death. He reported 4 such patients in whom sudden death was witnessed, with breathing compromise as a common feature, occurring mainly at night. He pointed out an “intrinsic” rather than “extrinsic” etiology behind these deaths and raised concerns about counseling, medicolegal aspects, and mechanisms for prevention, such as close supervision and the use of hair pillows. Finally, he provided a detailed guideline for examination in case of sudden death in order to maximize the amount of information regarding circumstances of death.

The availability of information or lack thereof regarding circumstances of death and postmortem examination limit definition of sudden unexplained death in epilepsy. In order to harmonize diagnostic criteria for sudden unexplained death in epilepsy, the following categories have been suggested (Nashef et al 2012):

 

• Definite sudden unexplained death in epilepsy: sudden, unexpected witnessed or unwitnessed and nondrowning 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 a cause of death.

 

• Definite sudden unexplained death in epilepsy plus: satisfies the definition of definite sudden unexplained death in epilepsy but a concurrent condition other than epilepsy is identified before or after death, death may have been due to the combined effect of both conditions, and autopsy or direct observations/recordings of terminal event did not prove the concurrent condition caused death.

 

• Probable sudden unexplained death in epilepsy/probable sudden unexplained death in epilepsy plus: same as definite sudden unexplained death in epilepsy/sudden unexplained death in epilepsy plus but without autopsy.

 

• Possible sudden unexplained death in epilepsy: a competing cause of death is present.

 

• Near- sudden unexplained death in epilepsy/near-sudden unexplained death in epilepsy plus: a patient with epilepsy survives resuscitation for more than 1 hour after a cardiorespiratory arrest that has no structural cause identified after investigation.

 

• Not sudden unexplained death in epilepsy: a clear cause of death is known.

 

• Unclassified: incomplete information available; not possible to classify.

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