The Crucial Interplay Between the Lungs, Brain, and Heart to Understand Epilepsy-Linked SUDEP: A Literature Review : Brain Sciences
Mir, Mohd Y. LU
; Seh, Bilal A.
; Zahra, Shabab
and Legradi, Adam
(2025)
In Brain Sciences
15(8).
- Abstract
- Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective of this review is to elucidate how seizures disrupt critical physiological systems, especially the brainstem, heart, and lungs, contributing to SUDEP, with emphasis on respiratory control failure and autonomic instability. Methods: The literature from experimental models, clinical observations, neuroimaging studies, and genetic analyses was systematically examined. Results: SUDEP is frequently... (More)
- Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective of this review is to elucidate how seizures disrupt critical physiological systems, especially the brainstem, heart, and lungs, contributing to SUDEP, with emphasis on respiratory control failure and autonomic instability. Methods: The literature from experimental models, clinical observations, neuroimaging studies, and genetic analyses was systematically examined. Results: SUDEP is frequently preceded by generalized tonic–clonic seizures, which trigger central and obstructive apnea, hypoventilation, and cardiac arrhythmias. Brainstem dysfunction, particularly in areas such as the pre-Bötzinger complex and nucleus tractus solitarius, plays a central role. Genetic mutations affecting ion channels (e.g., SCN1A, KCNQ1) and neurotransmitter imbalances (notably serotonin and GABA) exacerbate autonomic dysregulation. Risk is compounded by a prone sleeping position, reduced arousal capacity, and impaired ventilatory responses. Conclusions: SUDEP arises from a cascade of interrelated failures in respiratory and cardiac regulation initiated by seizure activity. The recognition of modifiable risk factors, implementation of monitoring technologies, and targeted therapies such as serotonergic agents may reduce mortality. Multidisciplinary approaches integrating neurology, cardiology, and respiratory medicine are essential for effective prevention strategies. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/a4730f16-88b9-4be8-b4f5-6dc1261038b7
- author
- Mir, Mohd Y.
LU
; Seh, Bilal A.
; Zahra, Shabab
and Legradi, Adam
- publishing date
- 2025
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- SUDEP, epilepsy, autonomic nervous system, central apnea, hypoventilation, neurodegeneration
- in
- Brain Sciences
- volume
- 15
- issue
- 8
- article number
- 809
- publisher
- MDPI AG
- ISSN
- 2076-3425
- DOI
- 10.3390/brainsci15080809
- language
- English
- LU publication?
- no
- id
- a4730f16-88b9-4be8-b4f5-6dc1261038b7
- date added to LUP
- 2025-08-04 13:12:49
- date last changed
- 2025-08-04 13:12:49
@article{a4730f16-88b9-4be8-b4f5-6dc1261038b7,
abstract = {{Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective of this review is to elucidate how seizures disrupt critical physiological systems, especially the brainstem, heart, and lungs, contributing to SUDEP, with emphasis on respiratory control failure and autonomic instability. Methods: The literature from experimental models, clinical observations, neuroimaging studies, and genetic analyses was systematically examined. Results: SUDEP is frequently preceded by generalized tonic–clonic seizures, which trigger central and obstructive apnea, hypoventilation, and cardiac arrhythmias. Brainstem dysfunction, particularly in areas such as the pre-Bötzinger complex and nucleus tractus solitarius, plays a central role. Genetic mutations affecting ion channels (e.g., SCN1A, KCNQ1) and neurotransmitter imbalances (notably serotonin and GABA) exacerbate autonomic dysregulation. Risk is compounded by a prone sleeping position, reduced arousal capacity, and impaired ventilatory responses. Conclusions: SUDEP arises from a cascade of interrelated failures in respiratory and cardiac regulation initiated by seizure activity. The recognition of modifiable risk factors, implementation of monitoring technologies, and targeted therapies such as serotonergic agents may reduce mortality. Multidisciplinary approaches integrating neurology, cardiology, and respiratory medicine are essential for effective prevention strategies.}},
author = {{Mir, Mohd Y. and Seh, Bilal A. and Zahra, Shabab and Legradi, Adam}},
issn = {{2076-3425}},
keywords = {{SUDEP; epilepsy; autonomic nervous system; central apnea; hypoventilation; neurodegeneration}},
language = {{eng}},
number = {{8}},
publisher = {{MDPI AG}},
series = {{Brain Sciences}},
title = {{The Crucial Interplay Between the Lungs, Brain, and Heart to Understand Epilepsy-Linked SUDEP: A Literature Review : Brain Sciences}},
url = {{http://dx.doi.org/10.3390/brainsci15080809}},
doi = {{10.3390/brainsci15080809}},
volume = {{15}},
year = {{2025}},
}