Unraveling SUDEP: Mechanisms of Seizure-Induced Cardiac and Respiratory Impairment

Ian C Wenker; Brian K. Gehlbach; Lori L. Isom; Brian J. Dlouhy; David S. Auerbach; Jamie L. Maguire; Carie R. Boychuk

doi:10.1177/15357597261416723

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Unraveling SUDEP: Mechanisms of Seizure-Induced Cardiac and Respiratory Impairment

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Unraveling SUDEP: Mechanisms of Seizure-Induced Cardiac and Respiratory Impairment

Ian C Wenker, Brian K. Gehlbach, Lori L. Isom, Brian J. Dlouhy, David S. Auerbach, Jamie L. Maguire and Carie R. Boychuk

Epilepsy currents

01/21/2026

DOI: 10.1177/15357597261416723

PMCID: PMC12823373

PMID: 41584903

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Abstract

People with epilepsy have a markedly increased risk of premature mortality, with sudden unexpected death in epilepsy (SUDEP) accounting for approximately half of epilepsy-related deaths. Although rarely witnessed, converging evidence indicates that SUDEP arises from seizure-triggered cardiorespiratory failure mediated by central and peripheral mechanisms. In this article, we explore mechanisms of SUDEP related to respiratory, cardiac, and autonomic control of vital functions. Specifically, we examine how seizure propagation to a discrete amygdala subregion can induce profound ictal and postictal apnea; how complementary genetic and animal studies reveal that ion channelopathies affecting genes expressed in both brain and heart produce intrinsic neuronal and cardiac electrical dysfunction; and how emerging evidence implicates stress physiology and hypothalamic–pituitary–adrenal axis dysfunction as underrecognized contributors to SUDEP risk. Together, these findings support a multifactorial model in which respiratory suppression, cardiac vulnerability, autonomic dysregulation, and stress-responsive mechanisms converge to produce fatal outcomes.

Stress

apnea

arrhythmia

autonomic

brainstem

SUDEP

Details

Title: Subtitle: Unraveling SUDEP: Mechanisms of Seizure-Induced Cardiac and Respiratory Impairment
Creators: Ian C Wenker - University of Virginia Health System
Brian K. Gehlbach - University of Iowa Health Care
Lori L. Isom - University of Michigan
Brian J. Dlouhy - University of Iowa Health Care
David S. Auerbach - SUNY Upstate Medical University
Jamie L. Maguire - Tufts University
Carie R. Boychuk - University of Missouri
Resource Type: Journal article
Publication Details: Epilepsy currents
DOI: 10.1177/15357597261416723
PMID: 41584903
PMCID: PMC12823373
NLM abbreviation: Epilepsy Curr
ISSN: 1535-7597
eISSN: 1535-7511
Publisher: Sage
Language: English
Electronic publication date: 01/21/2026
Academic Unit: Neurology; Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurosurgery; Health, Sport, and Human Physiology ; Internal Medicine
Record Identifier: 9985132083102771

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