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Unifying the definitions of sudden unexpected death in epilepsy
Open accessAbstract
Summary: Sudden unexpected death in epilepsy (SUDEP) is a category of death in people with epilepsy occurring in the absence of a known structural cause of death and is most likely heterogeneous with regard to mechanisms and circumstances. SUDEP is particularly difficult to investigate in research studies for several reasons, including its relatively low incidence, its unpredictable occurrence often in unwitnessed settings, and its low rate of complete autopsy examinations. Over the past two decades, two complementary definitions have been used in most SUDEP studies, but often with variations. We propose here a unified SUDEP definition and classification to resolve current ambiguities and to retrieve cases that would not have been further studied if the previous definitions were used. The proposed Unified SUDEP Definition and Classification contains, in addition to concepts inherent in the previous definitions, nine main recommendations. (1) The word “unexpected,” and not the word “unexplained,” should be uniformly used in the term SUDEP . (2) The SUDEP category should be applied when appropriate, whether or not a terminal seizure is known to have occurred. (3) The “Possible SUDEP” category should be used only for cases with competing causes of death, with cases left unclassified when data are insufficient to reasonably permit their classification. (4) Cases that would otherwise fulfill the definition of SUDEP should be designated as “SUDEP Plus” when evidence indicates that a preexisting condition, known before or after autopsy, could have contributed to the death, which otherwise is classified as SUDEP (e.g., coronary insufficiency with no evidence of myocardial infarction or long‐QT syndrome with no documented primary ventricular arrhythmia leading to death). (5) To be considered SUDEP, the death should have occurred within 1 h from the onset of a known terminal event. (6) For status epilepticus as an exclusion criterion for SUDEP, the duration of seizure activity should be 30 min or more. (7) A specific category of SUDEP due to asphyxia should not be designated, the distinction being largely impractical on circumstantial or autopsy evidence, with more than one mechanism likely to be contributory in many cases. (8) Death occurring in water but without circumstantial or autopsy evidence of submersion should be classified as “Possible SUDEP.” If any evidence of submersion is present, the death should not be classified as SUDEP. (9) A category of “Near‐SUDEP” should be agreed to include cases in which cardiorespiratory arrest was reversed by resuscitation efforts with subsequent survival for more than 1 h. Scenarios that demonstrate the basis for each SUDEP category are described. If disagreement exists about which category fits a particular case, we suggest the use of consensus decision by a panel of informed reviewers to adjudicate the classification of the case.
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“The primary cause of death is sudden unexpected death in epilepsy (SUDEP) 17 ; other causes include cerebral oedema following status epilepticus 18 , chest infections and accidental causes 19 .”
From Developmental and epileptic encephalopathies (2024) · cites this paper as [17]
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“Sudden Unexpected Death in Epilepsy (SUDEP) is defined as a sudden, unexpected death in a person with epilepsy, with or without evidence for a seizure preceding the death, in which there is no evidence of other disease, injury, or drowning that caused the death[3].”
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“same essence with the original definition (2).”
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“Deathmay ormay not coincidewith a seizure, excluding status epilepticus, which if longer than 30 minutes is an exclusion criterion (Nashef et al., 2012).”
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“…or unwitnessed, non-traumatic, and non-drowning death that occurs in benign circumstances in an individual with epilepsy, with or without evidence for a seizure, and excludes documented status epilepticus, in which post-mortem examination does not reveal a cause of death (Nashef et al. 2012).”
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“Sudden unexpected death in epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, nontraumatic, and nondrowning death in patients with epilepsy, with or without evidence of a seizure and excluding documented status epilepticus, in which postmortem examination does not reveal a toxicologic or anat…”
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“70 Inferences from these associations suggest that dysregulated Pi from impaired renal function might cause SERCA2a dysfunction related to sudden unexpected death in epilepsy (SUDEP), 71 and Pi-induced SERCA2a dysfunction may be associated with dead- in-bed syndrome in type 1 diabetes.”
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Pack, A. M. (2014) · Epiliepsy currents/Epilepsy currents · doi:10.5698/1535-7597-14.2.78 · Cited by 8
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“, trauma, drowning, status epilepticus, burns, or accident [11,12].”
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Addressing the gap: SUDEP knowledge and communication among patients and neurologists
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“…witnessed or unwitnessed, nontraumatic and non-drowning death, occurring in benign circumstances, in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus (SE), in which postmortem examination does not reveal a cause of death” [6].”
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“SUDEP is defined as the sudden, unexpected death of a person with epilepsy, who was otherwise reasonably healthy and for which no obvious anatomical or toxicological cause of death is found upon postmortem examination (Nashef et al., 2012; Sveinsson et al., 2020).”
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“[43] indicated the possibility of a coexisting susceptibility to sudden cardiac death—independent of or related to the epilepsy—that becomes symptomatic in the presence of uncontrolled seizures.”
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“Similar to the definition of definite SUDEP, but without postmortem and toxicologic data, death can be categorized as probable SUDEP (16).”
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“…unexpected, witnessed or unwitnessed, nontraumatic and nondrowning death in patients with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus, in which postmortem examination does not reveal a structural or toxicologic cause for death’ (Nashef et al., 2012).”
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“…sudden, unexpected, witnessed or unwitnessed, nontraumatic and non-drowning death, occurring in benign circumstances, in an individual with Epilepsy, with or without evidence for a seizure after excluding status epi-lepticus, in which post-mortem examination does not reveal a cause of death ” [1].”
BackgroundIncidence and risk factors of sudden unexpected death in epilepsy in rural Northeast China
Li, R., Zhao, D., Hu, B., Li, N., Li, J., & Lin, W. (2025) · Seizure · doi:10.1016/j.seizure.2025.02.011 · Cited by 5
Exploring transcriptomic signatures in sudden unexplained death (SUD) cases
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Mortality in patients with refractory temporal lobe epilepsy at a tertiary center in Cuba
Andrade-Machado, R., Cuartas, V. B., Santos, A. S., Sosa-Dubón, M. A., Espinosa, A. G., & Andrade-Gutierrez, G. (2015) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2015.08.038 · Cited by 5
“Sudden unexpected death on epilepsy (SUDEP) was defined as: “Sudden, unexpected, witnessed or un-witnessed, non-traumatic or/and non-drowning deaths in an individual with epilepsy, with or without evidence of a seizure and excluding documented status epilepticus where postmortem examination did not reveal a cause of d…”
Aljumah, T. K., Al-Attas, A. A., Alqahtani, A. A., Masuadi, E., Al-Dahi, A. S., AlShammary, M. A., Heji, A., & Alanazi, A. F. (2023) · Epileptic Disorders · doi:10.1002/epd2.20079 · Cited by 5
Eilbes, M., Gallo, A., Osmani, W. A., Bittencourt‐Silva, P. G., Manis, A. D., & Hodges, M. R. (2025) · Epilepsia · doi:10.1111/epi.18360 · Cited by 5
“22,23 ,24–26 Here, we utilized SS Kcnj16−/− rats 14–16, 27– 30 to determine 31–34 Most changes in these physiological systems occur in the immediate postictal period and combine to create a life-threatening situation.”
Iyengar, S. S., O'Loughlin, E. K., Harte‐Hargrove, L. C., Holmay, M., Lubbers, L. S., & Working Group Members (2025) · Epilepsia Open · doi:10.1002/epi4.70103 · Cited by 5
Papacostas, S. (2015) · PubMed Central · Cited by 5
SUDEP: A steep increase in publication since its definition
Scorza, F. A., do Carmo, A. C. F., Scorza, C. A., & FIORINI, A. C. (2017) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2017.05.006 · Cited by 5
Cardiac Autonomic Changes in Epilepsy
Romigi, A., & Toschi, N. (2017) · Springer eBooks · doi:10.1007/978-3-319-58709-7_14 · Cited by 5
Sudden cardiac death of arrhythmic origin: Value of post-mortem genetic analysis
Campuzano, Ó., Sanchez-Molero, O., Fernandez, A., Iglesias, A., & Brugada, R. (2018) · Revista Española de Medicina Legal · doi:10.1016/j.remle.2017.08.001 · Cited by 5
“No conclusive cause of death or of traumatic death secondary to an epileptic seizure is discovered in the autopsy.(19) In recent epidemiological studies in this SUDEP group, it has been observed that SUD is the main cause of death in young epileptic patients.”
BackgroundParkinson's disease, epileptic seizures, and sudden death: Three faces of the same coin
Scorza, F. A., de Almeida, A.-C. G., FIORINI, A. C., Scorza, C. A., & Finsterer, J. (2018) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2018.03.023 · Cited by 5
When the brain hurts the heart: status epilepticus inducing tako‐tsubo cardiomyopathy
Giovannini, G., Grassi, L., Vincenzi, C., Mirandola, L., & Meletti, S. (2019) · Epileptic Disorders · doi:10.1684/epd.2019.1068 · Cited by 5
Bounajem, M. T., Cole, K. L., & Menacho, S. T. (2021) · Cureus · doi:10.7759/cureus.19186 · Cited by 5
“With concomitant APXA and LDM with multiple strokes, the described case would be classified as probable SUDEP plus, which indicates that a pre-existing condition could have contributed to the patient’s death; without an autopsy, it was not possible to rule out a cardiac event as a potential contributor [13].”
BackgroundPaediatric sudden unexpected death in epilepsy (SUDEP): is it truly unexplained?
Abdel‐Mannan, O., Venkatesan, T., & Sutcliffe, A. G. (2022) · Paediatrics and Child Health · doi:10.1016/j.paed.2022.07.010 · Cited by 5
Esmaeili, B., Weisholtz, D. S., Tobochnik, S. D., Dworetzky, B. A., Friedman, D. J., Kaffashi, F., Cash, S. S., Cha, B., Laze, J., Reich, D., et al. (2022) · Clinical Neurophysiology · doi:10.1016/j.clinph.2022.12.002 · Cited by 5
Intellectual Disability and Epilepsy
Shankar, R., Watkins, L. V., & Brown, S. (2018) · Springer eBooks · doi:10.1007/978-3-319-90083-4_10 · Cited by 5
Sudden Death Due to Calcifying Pseudoneoplasm of the Neuraxis
Conway, K. S., Jentzen, J. M., Pratt, D. W., & Camelo-Piragua, S. I. (2019) · American Journal of Forensic Medicine & Pathology · doi:10.1097/paf.0000000000000520 · Cited by 5
Sudden infant death with dysgenesis of the testes syndrome in a non‐Amish infant: A case report
Slater, B. A., Glinton, K. E., Dai, H., Lay, E. J., Karaviti, L. P., Mizerik, E. A., Murali, C. N., Lalani, S. R., Bacino, C. A., & Rossetti, L. Z. (2020) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61842 · Cited by 5
Muerte súbita en epilepsia: casuística de una unidad médica de epilepsia española
Muñoz, M. I. C., López-Hidalgo, E., Martín, G. G., Rodríguez-Belli, A. O., & Gutiérrez‐Bedmar, M. (2017) · Neurología · doi:10.1016/j.nrl.2017.10.003 · Cited by 5
Maternal deaths with epilepsy: A population-based study in Turkey
Yücel, A., Tanaçan, A., Atalay, F., Altınboğa, O., Köksal, Z., Baydilli, M. B., Esen, M., Karabacak, Y., Ongun, V., Şahlar, T. E., et al. (2020) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2020.12.045 · Cited by 5
Seizures with Autonomic Symptoms and Sudden Unexpected Death in Epilepsy (SUDEP)
Çelik, R. G. G., & Özkara, Ç. (2019) · Turkish Journal Of Neurology · doi:10.4274/tnd.2019.56254 · Cited by 5
Jehi, L. E., & Schuele, S. (2015) · Neurology · doi:10.1212/wnl.0000000000001768 · Cited by 5
Buchhalter, J., & Cascino, G. D. (2017) · Neurology · doi:10.1212/wnl.0000000000004099 · Cited by 5
“, SUDEP probable/plus.(3) During the last 20 years, SUDEP has become recognized as an important cause of premature mortality in the epilepsy population and is second only to stroke as the most common neurologic disorder responsible for the most potential years of life lost due its occurrence prior to late adulthood.”
BackgroundThe epilepsy deaths register: Third-party reports of SUDEP in adults and older adolescents
Grundmann, A., Brolly, J., Craig, D. P., Osland, K., Hanna, J., Hughes, E., Kerr, M. P., Donovan, B., & Thomas, R. H. (2025) · Seizure · doi:10.1016/j.seizure.2025.08.031 · Cited by 4
“To improve comparability with previously published work, we excluded cases where no post-mortem results or certified cause of death were provided by the reporting individual [20,21].”
Saranti, A., Dragoumi, P., Pavlogiannis, K., Pavlou, E., & Zafeiriou, D. (2025) · Seizure · doi:10.1016/j.seizure.2025.10.001 · Cited by 4
Michele, A. B. D., Onofri, V., Melchionda, F., Fiordelmondo, L., Ciarimboli, E., Palpacelli, M., Sablone, S., Turchi, C., & Pesaresi, M. (2025) · Genes · doi:10.3390/genes16111272 · Cited by 4
Muerte súbita cardiaca de origen arrítmico: valor del análisis genético post mortem
Campuzano, Ó., Sanchez-Molero, O., Fernandez, A., Iglesias, A., & Brugada, R. (2017) · Revista Española de Medicina Legal · doi:10.1016/j.reml.2017.08.002 · Cited by 4
Age-Specific Mechanisms of Sudden Death Associated With Epilepsy
Holmström, L. T. A., Uy‐Evanado, A., Sargsyan, A. S., Chugh, H. S., Aziz, H., Calsavara, V. F., Bui, A. A. T., Salvucci, A., Jui, J., Reinier, K., et al. (2025) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2025.04.028 · Cited by 4
SUDEP risk is influenced by longevity genomics: a polygenic risk score study
Custodio, H. M., Mills, J. D., Pagni, S., Gulcebi, M. I., Vakrinou, A., Moloney, P. B., Clayton, L. M. S., Bellampalli, R., Stamberger, H., Weckhuysen, S., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.105841 · Cited by 4
Byard, R. W., & Collins, K. (2014) · Springer eBooks · doi:10.1007/978-1-61779-403-2_48 · Cited by 4
Burton, E. C., & Singer, N. (2014) · Forensic Pathology of Infancy and Childhood · doi:10.1007/978-1-61779-403-2_36 · Cited by 6
“It has been proposed that if investigation of the circumstances surrounding death indicates status epilepticus, for SUDEP to be excluded as the cause of death, the duration of the seizure activity should be more than 30 min (Nashef et al. 2012).”
BackgroundInfluentialIype, M., Anish, T. S., Saradakutty, G., Kunju, P. A. M., Sreedharan, M., & Ahamed, S. M. (2023) · Seizure · doi:10.1016/j.seizure.2023.09.005 · Cited by 4
Makino, Y., Kojima, M., Inokuchi, G., Motomura, A., Arai, N., Inoue, H., Kabasawa, H., Iwase, H., & Yajima, D. (2023) · Legal Medicine · doi:10.1016/j.legalmed.2023.102342 · Cited by 4
Metadata
- Authors
- Nashef, L., So, E. L., Ryvlin, P., & Tomson, T.
- Affiliations
- King's College Hospital (GB)
- Mayo Clinic (US)
- Lyon 1 Université (FR)
- Karolinska Institutet (SE)
- Corresponding author
- So, Elson L.
- Venue
- Epilepsia
- Publisher
- Wiley
- Published
- 2011-12-22
- Volume
- 53
- Issue
- 2
- Pages
- 227-233
- ISSN
- 0013-9580 (ISSN-L)
- 1528-1167
- OpenAlex
- W1549808427
- Cited by
- 632
- References
- 26
- Citations by year
- 2026: 34 · 2025: 54 · 2024: 39 · 2023: 57 · 2022: 38 · 2021: 70 · 2020: 69 · 2019: 59 · 2018: 55 · 2017: 39 · 2016: 30 · 2015: 35 · 2014: 24 · 2013: 20 · 2012: 8
- FWCI
- 11.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epilepsia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Emergency Medicine › Cardiac Arrest and Resuscitation
- Keywords
- sudden unexpected death in epilepsy, status epilepticus, cardiac arrest, SUDEP incidence, SUDEP risk factors, SUDEP prevention
- MeSH terms
- Death, Sudden, Epilepsy, Humans
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