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Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms

Nature Reviews Neurology volume 5, pages 492–504 (2009)Cite this article

Abstract

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death directly related to epilepsy, and most frequently occurs in people with chronic epilepsy. The main risk factors for SUDEP are associated with poorly controlled seizures, suggesting that most cases of SUDEP are seizure-related events. Dysregulation in cardiac and respiratory physiology, dysfunction in systemic and cerebral circulation physiology, and seizure-induced hormonal and metabolic changes might all contribute to SUDEP. Cardiac factors include bradyarrhythmias and asystole, as well as tachyarrhythmias and alterations to cardiac repolarization. Altered electrolytes and blood pH, as well as the release of catecholamines, modulate cardiac excitability and might facilitate arrhythmias. Respiratory symptoms are not uncommon during seizures and comprise central apnea or bradypnea, and, less frequently, obstruction of the airways and neurogenic pulmonary edema. Alterations to autonomic function, such as a reduction in heart rate variability or disturbed baroreflex sensitivity, can impair the body's capacity to cope with challenging situations of elevated stress, such as seizures. Here, we summarize data on the incidence of and risk factors for SUDEP, and consider the pathophysiological aspects of chronic epilepsy that might lead to sudden death. We suggest that SUDEP is caused by the fatal coexistence of several predisposing and triggering factors.

Key Points

  • Sudden unexpected death in epilepsy (SUDEP) is the most frequent cause of death directly related to epilepsy, and most often occurs in individuals with chronic epilepsy

  • The most important risk factors for SUDEP are related to poorly controlled seizures, suggesting that SUDEP is a seizure-related event

  • Cardiac arrhythmia, respiratory dysfunction, dysregulation of systemic or cerebral circulation, and seizure-induced hormonal and metabolic changes have all been suggested as potential pathomechanisms in SUDEP

  • SUDEP is most probably triggered by the peri-ictal concurrence of a number of predisposing and precipitating factors

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Figure 1: Factors that might affect SUDEP.

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Acknowledgements

R. Surges and J. W. Sander are based at University College London (UCL) and UCL Hospitals NHS Trust, which receive a proportion of their funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. J. W. Sander is partly supported by the Marvin Weil Epilepsy Research Fund. R. D. Thijs is supported by the Dutch Epilepsy Foundation. H. L. Tan is supported by the Royal Netherlands Academy of Arts and Sciences and the Netherlands Organization for Scientific Research (grant ZonMW-Vici 918.86.616). Charles P. Vega, University of California, Irvine, CA is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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  1. Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK

    Rainer Surges & Josemir W. Sander

  2. Epilepsy Institute in the Netherlands Foundation, Heemstede, The Netherlands

    Roland D. Thijs

  3. Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

    Hanno L. Tan

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Surges, R., Thijs, R., Tan, H. et al. Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms. Nat Rev Neurol 5, 492–504 (2009). https://doi.org/10.1038/nrneurol.2009.118

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