Sudden Unexplained Death in Epilepsy: Observations from a Large Clinical Development Program

Leestma, Jan E.; Annegers, John F.; Brodie, Martin J.; Brown, Stephen; Schraeder, Paul L.; Siscovick, David S.; Wannamaker, Braxton B.; Tennis, Patricia; Cierpial, Mark A.; Earl, N.

doi:10.1111/j.1528-1157.1997.tb01076.x

Cited by 212 publications

(169 citation statements)

References 18 publications

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“…Terrence et al, in a comparable study, reported a figure of 32 years 4 . Leestma et al reported a mean age of death of 28 years 10 . The two peak decades of SUDEP in our study were the third and fourth decades, while in Terrence s study the second and fifth decades were the highest 4 .…”

Section: Discussionmentioning

confidence: 99%

Sudden unexpected, unexplained death in epilepsy autopsied patients

Antoniuk

Oliva

Bruck

et al. 2001

Arq. Neuro-Psiquiatr.

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Sudden unexpected, unexplained death in epilepsy (SUDEP) has been reported to be responsible for 2 to 17% of all deaths in patients with epilepsy. This study was conducted to determine the circumstances of SUDEP and the autopsy findings in these patients. Fifty-three individuals whose cause of death was related to epilepsy were identified and in 30 cases relatives or friends were interviewed about the circumstances of death and other information which allowed to classify the patients as SUDEP or not. The death certificates were also reviewed. We found 20 cases of SUDEP. Most of them were found dead lying on the bed with no evidence of seizure event, and most of them had pulmonary and/or cerebral edema as the cause of death. The incidence and the risk of SUDEP can only be fully ascertained if all sudden deaths had postmortem examination. Consensus in certifying SUDEP cases would allow better accuracy in national mortality rate.KEY WORDS: sudden death, epilepsy, circumstances of death, pulmonary edema.Morte súbita, inexplicada e inesperada em epilepsia: pacientes autopsiados RESUMO Morte súbita inexplicada e inesperada em epilepsia (SUDEP) é responsável por 2 a 17% das mortes em pacientes epilépticos. Este estudo visa determinar as circunstâncias de SUDEP e os achados de autópsia destes pacientes. Foram identificados 53 pacientes cuja causa de morte foi associada a crise epiléptica; em 30 destes, parentes ou amigos foram entrevistados quanto às circunstâncias das mortes e outros aspectos. Também foram revisados os certificados de óbito destes pacientes. Foram encontrados 20 casos de SUDEP. A maioria foi encontrada morta na sua cama por parentes, sem evidência de crise convulsiva, e a causa de morte foi edema cerebral e\ou pulmonar. A incidência e o risco relativo de SUDEP só podem ser adequadamente definidos se houver autópsia em todas as pessoas que morrem subitamente. Um consenso sobre SUDEP permitiria maior acurácia aos dados de mortalidade nacional. PALAVRAS-CHAVE: morte súbita, epilepsia, circunstâncias de morte, edema pulmonar.

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Section: Discussionmentioning

confidence: 99%

Sudden unexpected, unexplained death in epilepsy autopsied patients

Antoniuk

Oliva

Bruck

et al. 2001

Arq. Neuro-Psiquiatr.

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“…Following this reasoning, postmortem examinations in people dying of SUDEP have found hearts that are dilated and heavier than expected 16,29,31,32 and pulmonary edema in approximately 50-86% of cases 16,26,29,32,33 . Furthermore, others have described pathological changes in the hearts of those dying with SUDEP, including fibrosis of the walls of small coronary arteries, atrophy of cardiomyocytes, myofibrillar degeneration, edema of the conductive tissue and morphological abnormalities of the cardiac conduction system 26,29,31,34,35 .…”

Section: Sudden Unexpected Death In Epilepsymentioning

confidence: 97%

“…Comparisons of incidence estimates for SUDEP are difficult, since different definitions of SUDEP have been used, not all patients have a postmortem examination, and case ascertainment methods and source populations have varied 15 . The incidence of SUDEP has been estimated to be 3.5/1000 person-years in a lamotrigine clinical trial 16 , 0.5-1.4/1000 person-years in people with treated epilepsy 17 , 5.9/1000 person-years in outpatients with epilepsy at a tertiary referral centre 18 and 0.35/1000 person-years in a population-based study 19 . The National General Practice Study of Epilepsy (NGPSE), a community-based study in the United Kingdom, saw the first case of SUDEP after 11,000 person-years of follow-up 20 , and the results of the Medical research Council Antiepileptic Drug withdrawal Study showed that SUDEP is a rare event among patients with epilepsy in remission 21 .…”

Section: Sudden Unexpected Death In Epilepsymentioning

confidence: 99%

“…The National General Practice Study of Epilepsy (NGPSE), a community-based study in the United Kingdom, saw the first case of SUDEP after 11,000 person-years of follow-up 20 , and the results of the Medical research Council Antiepileptic Drug withdrawal Study showed that SUDEP is a rare event among patients with epilepsy in remission 21 . Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: early adulthood 16 , early onset of epilepsy 22 , long duration of epilepsy 23 , uncontrolled seizures (mainly in those with TlE) 23,24 , high seizure frequency [23][24][25] , certain seizure types 23,26 , higher numbers of antiepileptic drug (AED) 22,23,27 and winter temperatures 28 . Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures, electrolyte disturbances, arrhythmogenic drugs or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role 29,30 .…”

Section: Sudden Unexpected Death In Epilepsymentioning

confidence: 99%

“…SUDEP is mainly, but not exclusively, a problem for patients with chronic uncontrolled epilepsy 49 . Accordingly, among the rarely witnessed cases of SUDEP, the majority of patients proved to suffer a partial or generalized seizure immediately prior to death, suggesting a seizure-related cardiac or respiratory dysfunction 16,30 . In an elegant largest case-control study, Nilsson and colleagues 22 demonstrated that seizure frequency is a strongest risk factor for SUDEP.…”

Section: Gustave Flaubert: Death Due Epilepsy?mentioning

confidence: 99%

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The mistery of Gustave Flaubert's death: could sudden unexpected death in epilepsy be part of the context?

Albuquerque

Scorza

Arida

et al. 2009

Arq. Neuro-Psiquiatr.

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-Epilepsy is the most common serious neurological condition and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but high seizure frequency is a potential risk factor. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role. More than two decades ago, temporal lobe epilepsy was suggested as having been the ''nervous disease'' of Gustave Flaubert, one of the most important French novelists. In these lines, as the circumstances of his death were the subject of fabulous and mysterious speculations, we postulated in this paper that Falubert's death could be due SUDEP phenomenon.KEy worDS: epilepsy, Gustave Flaubert, SUDEP, seizure. O mistério da morte de Gustave Flaubert: pode a morte súbita em epilepsia fazer parte o contexto ?Resumo -A epilepsia é a condição neurológica crônica grave mais comum e a morte súbita em epilepsia (SUDEP) é a mais importante causa de morte diretamente relacionada à epilepsia. Informações sobre fatores de risco para SUDEP são conflitantes, porém, a alta freqüência de crises epilépticas é um fator de risco em potencial. Além disso, os mecanismos causais para SUDEP ainda não estão conhecidos, mas é muito provável que arritmias cardíacas durante e entre as crises epilépticas ou a transmissão da atividade epiléptica para o coração via sistema nervoso autônomo desempenhem um importante papel. Mais de duas décadas atrás, foi proposto que a "doença nervosa" de Gustave Flaubert, um dos mais importantes novelistas franceses, era epilepsia do lobo temporal. Nesse sentido, como a morte de Gustave Flaubert ainda seja motivo de misteriosa especulação, nosso artigo propõe que a mesma poderia estar relacionada ao fenômeno de SUDEP.

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Seizure control and mortality in epilepsy

et al. 1999

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Mortality rates are increased among people with epilepsy, and may be highest in those with uncontrolled seizures. Because epilepsy surgery eliminates seizures in some people, we used an epilepsy surgery population to examine how seizure control influences mortality. We tested the hypothesis that patients with complete seizure relief after surgery would have a lower mortality rate than those who had persistent seizures. Three hundred ninety‐three patients who had epilepsy surgery between January 1986 and January 1996 were followed after surgery to assess long‐term survival; 347 had focal resection or transection, and 46 had anterior or complete corpus callosotomy. A multivariate survival analysis was performed, contrasting survival in those who had seizure recurrence with survival of those who remained seizure free. Standardized mortality ratios and 95% confidence intervals were calculated. Overall, seizure‐free patients had a lower mortality rate than those with persistent seizures. This was true for the subset of patients with localized resection or multiple subpial transection. No patients died among 199 with no seizure recurrence, whereas of 194 patients with seizure recurrence, 11 died. Six of the deaths were sudden and unexplained. Most patients who died had a substantial reduction in postoperative seizure frequency. The standardized mortality ratio for patients with recurrent seizures was 4.69, and the risk of death in these patients was 1.37 in 100 person‐years, whereas among patients who became seizure free, there was no difference in mortality rate compared with the age‐ and sex‐matched population of the United States. Elimination of seizures after surgery reduces mortality rates in people with epilepsy to a level indistinguishable from that of the general population, whereas patients with recurrent seizures continue to suffer from high mortality rates. This suggests that uncontrolled seizures are a major risk factor for excess mortality in epilepsy. Achieving complete seizure control with epilepsy surgery in refractory patients reduces the risk of death, so the long‐term risk of continuing medical treatment appears to be higher than the risk of epilepsy surgery in suitable candidates. Ann Neurol 1999;46:45–50

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Sudden Unexplained Death in Epilepsy: Observations from a Large Clinical Development Program

Cited by 212 publications

References 18 publications

Sudden unexpected, unexplained death in epilepsy autopsied patients

Sudden unexpected, unexplained death in epilepsy autopsied patients

The mistery of Gustave Flaubert's death: could sudden unexpected death in epilepsy be part of the context?

Seizure control and mortality in epilepsy

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