Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Oct 1;6(5):fcae309.
doi: 10.1093/braincomms/fcae309. eCollection 2024.

Sudden death in epilepsy: the overlap between cardiac and neurological factors

Nathan A Shlobin  1   2   3 , Roland D Thijs  2   3   4 , David G Benditt  5 , Katja Zeppenfeld  6 , Josemir W Sander  2   4   7   8
Affiliations
Review

Sudden death in epilepsy: the overlap between cardiac and neurological factors

Nathan A Shlobin et al. Brain Commun. .

Abstract

People with epilepsy are at risk of premature death, of which sudden unexpected death in epilepsy (SUDEP), sudden cardiac death (SCD) and sudden arrhythmic death syndrome (SADS) are the primary, partly overlapping, clinical scenarios. We discuss the epidemiologies, risk factors and pathophysiological mechanisms for these sudden death events. We reviewed the existing evidence on sudden death in epilepsy. Classification of sudden death depends on the presence of autopsy and expertise of the clinician determining aetiology. The definitions of SUDEP, SCD and SADS lead to substantial openings for overlap. Seizure-induced arrhythmias constitute a minority of SUDEP cases. Comorbid cardiovascular conditions are the primary determinants of increased SCD risk in chronic epilepsy. Genetic mutations overlap between the states, yet whether these are causative, associated or incidentally present is often unclear. Risk stratification for sudden death in people with epilepsy requires a multidisciplinary approach, including a review of clinical history, toxicological analysis and complete autopsy with histologic and, preferably, genetic examination. We recommend pursuing genetic testing of relatives of people with epilepsy who died suddenly, mainly if a post-mortem genetic test contained a Class IV/V (pathogenic/likely pathogenic) gene variant. Further research may allow more precise differentiation of SUDEP, SCD and SADS and the development of algorithms for risk stratification and preventative strategies.

Keywords: epidemiology; seizure; sudden arrhythmic death syndrome; sudden cardiac death; sudden unexpected death in epilepsy.

PubMed Disclaimer

Conflict of interest statement

N.A.S., D.G.B. and K.Z. report no conflicts of interest. R.D.T. has received personal compensation for serving on the Advisory Boards or Speaker’s Bureau for Xenon, Theravance, Novartis, Esai, Angelini Pharma and UCB. J.W.S. or his department has received grants from Esai, Angelini Pharma and UCB. He has received personal compensation for serving on the Advisory Boards or Speaker’s Bureau for UCB and Angelini Pharma.

Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Similarities and differences in SUDEP, SADS and SCD.
Figure 2
Figure 2
Flow chart for the work-up of sudden death in people with epilepsy.
See this image and copyright information in PMC

References

    1. Sillanpää M, Shinnar S. Long-term mortality in childhood-onset epilepsy. N Engl J Med. 2010;363(26):2522–2529. - PubMed
    1. Neligan A, Bell GS, Johnson AL, Goodridge DM, Shorvon SD, Sander JW. The long-term risk of premature mortality in people with epilepsy. Brain. 2011;134(2):388–395. - PubMed
    1. Gaitatzis A, Johnson AL, Chadwick DW, Shorvon SD, Sander JW. Life expectancy in people with newly diagnosed epilepsy. Brain. 2004;127(11):2427–2432. - PubMed
    1. Surges R, Shmuely S, Dietze C, Ryvlin P, Thijs RD. Identifying patients with epilepsy at high risk of cardiac death: Signs, risk factors and initial management of high risk of cardiac death. Epileptic Disord. 2021;23(1):17–39. - PubMed
    1. Nashef L, So EL, Ryvlin P, Tomson T. Unifying the definitions of sudden unexpected death in epilepsy. Epilepsia. 2012;53(2):227–233. - PubMed

LinkOut - more resources