Sudden unexpected death in epilepsy (SUDEP): what every neurologist should know

Shankar, Rohit; Donner, Elizabeth; McLean, Brendan; Nashef, Lina; Tomson, Torbjörn

doi:10.1684/epd.2017.0891

Cited by 90 publications

(95 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…difference in the ictal sympathetic and parasympathetic response [42,43] may account for potentially distinct manifestations and compensatory mechanisms in the two populations. However, additional studies assessing the occurrence of seizure-related respiratory disfunctions in comparable groups of children and adults are needed, as interestingly, children also have a reduced risk of SUDEP (0.2/1,000) [44] as compared with adults (4/1,000) [45].…”

Section: Discussionmentioning

confidence: 99%

Ictal hypoxemia: A systematic review and meta-analysis

Bruno

Maira

Biondi

et al. 2018

Seizure

View full text Add to dashboard Cite

A B S T R A C TPurpose: To estimate the incidence of ictal hypoxemia (IH) and to identify clinical and study-related factors modulating the estimate. Methods: We searched articles recording concurrent peri-ictal and ictal EEG and Sp02 in adults and children with epilepsy. Studies reporting the total number of seizures recorded and the number of seizures with IH were included in a random-effects meta-analysis. A random-effects meta-regression was used to identify variables affecting study heterogeneity. Results: Twenty-one studies, including 917 participants and 1840 with SpO2 data available were included. The meta-analysis showed a pooled incidence of IH of 35/100 seizures (95% CI 27-44). Sp02 desaturation threshold was associated with the incidence of IH, with less severe desaturations resulting in higher IH frequencies. The incidence of IH was 41/100 seizures (95% CI 29-54) for adults and 47/100 seizures (95% CI 15-78) for tonicclonic seizures. The meta-regression showed that SpO2 desaturation severity was the sole variable significantly correlated with the incidence of ictal hypoxemia (p = 0.00). Conclusion: In a population with refractory epilepsy IH is a frequent phenomenon, especially in adults and in patients presenting with tonic-clonic seizures. The severity of IH appeared independent from the age group and from seizure type and is probably the major clinical concern for its correlation with potentially life-threatening cardiorespiratory alterations and sudden unexpected death in epilepsy (SUDEP). factors on its occurrence, severity, duration and association with apnea https://doi.

show abstract

Section: Discussionmentioning

confidence: 99%

Ictal hypoxemia: A systematic review and meta-analysis

Bruno

Maira

Biondi

et al. 2018

Seizure

View full text Add to dashboard Cite

show abstract

“…1,2 A major cause for this premature mortality increase is sudden unexpected death in epilepsy (SUDEP), which occurs under benign circumstances associated with terminal seizures but excludes drowning, trauma, toxicologic effect, or status epilepticus-related deaths. 1,2 A major cause for this premature mortality increase is sudden unexpected death in epilepsy (SUDEP), which occurs under benign circumstances associated with terminal seizures but excludes drowning, trauma, toxicologic effect, or status epilepticus-related deaths.…”

Section: Introductionmentioning

confidence: 99%

“…Epilepsy is associated with a two-to threefold increase in premature mortality compared to the general population. 1,2 A major cause for this premature mortality increase is sudden unexpected death in epilepsy (SUDEP), which occurs under benign circumstances associated with terminal seizures but excludes drowning, trauma, toxicologic effect, or status epilepticus-related deaths. 3 The lifetime risk of SUDEP among patients with epilepsy is estimated to be up to 8%, and young persons with epilepsy are at a 24-to 28fold higher risk of sudden unexpected death than the general population.…”

Section: Introductionmentioning

confidence: 99%

Fenfluramine, a serotonin‐releasing drug, prevents seizure‐induced respiratory arrest and is anticonvulsant in the DBA/1 mouse model of SUDEP

Tupal

Faingold

2019

Epilepsia

View full text Add to dashboard Cite

Summary Objective Prevention of sudden unexpected death in epilepsy (SUDEP) is a critical goal for epilepsy therapy. The DBA/1 mouse model of SUDEP exhibits an elevated susceptibility to seizure‐induced death in response to electroconvulsive shock, hyperthermia, convulsant drug, and acoustic stimulation. The serotonin hypothesis of SUDEP is based on findings that treatments which modify serotonergic function significantly alter susceptibility to seizure‐induced sudden death in several epilepsy models, including DBA/1 mice. Serotonergic abnormalities have also recently been observed in human SUDEP. Fenfluramine is a drug that enhances serotonin release in the brain. Recent studies have found that the addition of fenfluramine improved seizure control in patients with Dravet syndrome, which has a high incidence of SUDEP. Therefore, we investigated the effects of fenfluramine on seizures and seizure‐induced respiratory arrest (S‐IRA) in DBA/1 mice. Methods The dose and time course of the effects of fenfluramine (i.p.) on audiogenic seizures (Sz) induced by an electric bell in DBA/1 mice were determined. Videos of Sz‐induced behaviors were recorded for analysis. Statistical significance (P < 0.05) was evaluated using the chi‐square test. Results Sixteen hours after administration of 15 mg/kg of fenfluramine, a high incidence of selective block of S‐IRA susceptibility (P < 0.001) occurred in DBA/1 mice without blocking any convulsive behavior. Thirty minutes after 20‐40 mg/kg of fenfluramine, significant reductions of seizure incidence and severity, as well as S‐IRA susceptibility occurred, which were long‐lasting (≥48 hours). The median effective dose (ED50) of fenfluramine for significantly reducing Sz at 30 minutes was 21 mg/kg. Significance This study presents the first evidence for the effectiveness of fenfluramine in reducing seizure incidence, severity, and S‐IRA susceptibility in a mammalian SUDEP model. The ability of fenfluramine to block S‐IRA selectively suggests the potential usefulness of fenfluramine in prophylaxis of SUDEP. These results further confirm and extend the serotonin hypothesis of SUDEP.

show abstract

“…Although no data have been collected, one can speculate concerning other adverse consequences that might occur, recognizing that these would probably vary between individuals. Certainly, the possibilities cannot be ignored that accidents involving mother or offspring, or physical injury to either or both, or even unexpected death during or in relation to seizures,17 may occur. Until more extensive information becomes available, it is hoped that data such as that provided in this paper may help inform those responsible for advising women on issues relating to the question of valproate and existing or future pregnancy.…”

mentioning

confidence: 99%

Valproate-associated foetal malformations-Rates of occurrence, risks in attempted avoidance

et al. 2018

View full text Add to dashboard Cite

Avoiding valproate intake during pregnancy is likely to reduce the incidence of foetal malformation, but at a cost of worsened maternal epilepsy control. Individualization of treatment is particularly important in considering withdrawal of valproate in the light of the fact that it is much more widely used in generalized epilepsy, there being fewer alternative drugs than for focal epilepsy and withdrawal is not without risk for both mother and baby. This study may provide a quantitative basis for assessing the balance between benefit and disadvantage for individual women with valproate-treated epilepsy who are considering pregnancy.

show abstract

Sudden unexpected death in epilepsy (SUDEP): what every neurologist should know

Cited by 90 publications

References 61 publications

Ictal hypoxemia: A systematic review and meta-analysis

Ictal hypoxemia: A systematic review and meta-analysis

Fenfluramine, a serotonin‐releasing drug, prevents seizure‐induced respiratory arrest and is anticonvulsant in the DBA/1 mouse model of SUDEP

Valproate-associated foetal malformations-Rates of occurrence, risks in attempted avoidance

Contact Info

Product

Resources

About