Sudden unexpected death in epilepsy

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Sudden unexpected death in epilepsy
Specialty Neurology

Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy. [1] It is defined as the sudden and unexpected, non-traumatic and non-drowning death of a person with epilepsy, without a toxicological or anatomical cause of death detected during the post-mortem examination. [2] [3]

Contents

While the mechanisms underlying SUDEP are still poorly understood, it is possibly the most common cause of death as a result of complications from epilepsy, accounting for between 7.5 and 17% of all epilepsy-related deaths [2] and 50% of all deaths in refractory epilepsy. [4] [5] The causes of SUDEP seem to be multifactorial [2] and include respiratory, cardiac, and cerebral factors as well as the severity of epilepsy and seizures. [5] Proposed pathophysiological mechanisms include seizure-induced cardiac and respiratory arrests. [4]

Among epileptics, SUDEP occurs in about 1 in 1,000 adults and 1 in 4,500 children annually. [6] Rates of death as a result of prolonged seizures (status epilepticus) are not classified as SUDEP. [7]

Categories

The overarching term SUDEP can be subdivided into four different categories: Definite, Probably, Possible, and Unlikely. [8]

  1. Definite SUDEP: a non-traumatic and non-drowning death in an individual with epilepsy, without a cause of death after postmortem examination.
    • Definite SUDEP Plus: includes the presence of a concomitant condition other than epilepsy, where death may be due to the combined effects of both epilepsy and the other condition.
  2. Probably SUDEP: all the same criteria for Definite SUDEP are met, but no postmortem examination is performed.
  3. Possible SUDEP: insufficient information is available regarding the death, with no postmortem examination.
  4. Unlikely SUDEP: an alternate cause of death has been determined, ruling out the possibility of SUDEP being the cause.

Risk factors

Consistent risk factors include:

Genetic mutations have been identified that increase a person's risk for SUDEP (some are discussed below), but ultimately their genetic risk is determined by the function of multiple genes that is not yet well understood. Overlap is seen between these ion channel genes and the different sudden death disorders, including SUDEP, [12] SIDS, [13] sudden unexpected death (SUD), [14] and sudden unexplained death in childhood (SUDC). [15] Many of the genes are involved in long QT syndrome.

Mechanism

The mechanisms underlying SUDEP are not well understood but probably involve several pathophysiological mechanisms and circumstances. The most commonly involved are seizure-induced hypoventilation and cardiac arrhythmias, but different mechanisms may be involved in different individuals, and more than one mechanism may be involved in any one individual. [17]

Management

Currently, the most effective strategy to protect against SUDEP in childhood epilepsy is seizure control, but this approach is not completely effective and is particularly challenging in cases of intractable epilepsy. The lack of generally recognized clinical recommendations available are a reflection of the dearth of data on the effectiveness of any particular clinical strategy, [17] but based on present evidence, the following may be relevant:

Epidemiology

See also

Related Research Articles

<span class="mw-page-title-main">Epilepsy</span> Group of neurological disorders causing seizures

Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. An epileptic seizure is the clinical manifestation of an abnormal, excessive, and synchronized electrical discharge in the neurons. The occurrence of two or more unprovoked seizures defines epilepsy. The occurrence of just one seizure may warrant the definition in a more clinical usage where recurrence may be able to be prejudged. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical activity in the brain. These episodes can result in physical injuries, either directly, such as broken bones, or through causing accidents. In epilepsy, seizures tend to recur and may have no detectable underlying cause. Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy. People with epilepsy may be treated differently in various areas of the world and experience varying degrees of social stigma due to the alarming nature of their symptoms.

<span class="mw-page-title-main">Seizure</span> Period of symptoms due to excessive or synchronous neuronal brain activity

A seizure is a sudden change in behavior, movement, and/or consciousness due to abnormal electrical activity in the brain. Seizures can look different in different people. It can be uncontrolled shaking of the whole body or a person spacing out for a few seconds. Most seizures last less than two minutes. They are then followed by confusion/drowsiness before the person returns to normal. If a seizure lasts longer than 5 minutes, it is a medical emergency and needs immediate treatment.

A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term convulsion is often used as a synonym for seizure. However, not all epileptic seizures result in convulsions, and not all convulsions are caused by epileptic seizures. Non-epileptic convulsions have no relation with epilepsy, and are caused by non-epileptic seizures.

Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.

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Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung disease, and kidney disease.

<span class="mw-page-title-main">Lennox–Gastaut syndrome</span> Rare form of childhood-onset epilepsy

Lennox–Gastaut syndrome (LGS) is a complex, rare, and severe childhood-onset epilepsy syndrome. It is characterized by multiple and concurrent seizure types including tonic seizure, cognitive dysfunction, and slow spike waves on electroencephalogram (EEG), which are very abnormal. Typically, it presents in children aged 3–5 years and most of the time persists into adulthood with slight changes in the electroclinical phenotype. It has been associated with perinatal injuries, congenital infections, brain malformations, brain tumors, genetic disorders such as tuberous sclerosis and numerous gene mutations. Sometimes LGS is observed after infantile epileptic spasm syndrome. The prognosis for LGS is marked by a 5% mortality in childhood and persistent seizures into adulthood.

Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy (SMEI), is an autosomal dominant genetic disorder which causes a catastrophic form of epilepsy, with prolonged seizures that are often triggered by hot temperatures or fever. It is very difficult to treat with anticonvulsant medications. It often begins before one year of age, with six months being the age that seizures, char­ac­ter­ized by prolonged convulsions and triggered by fever, usually begin.

Benign familial neonatal seizures (BFNS), also referred to as benign familial neonatal epilepsy (BFNE), is a rare autosomal dominant inherited form of seizures. This condition manifests in newborns as brief and frequent episodes of tonic-clonic seizures with asymptomatic periods in between. Characteristically, seizure activity spontaneously ends during infancy and does not affect childhood development. However, some studies have reported that a minority of children with BFNS consequently develop intellectual disability. Additionally, BFNS increases lifetime susceptibility to seizures as approximately 14% of those afflicted go on to develop epilepsy later in life. There are three known genetic causes of BFNE, two being the voltage-gated potassium channels KCNQ2 (BFNC1) and KCNQ3 (BFNC2) and the third being a chromosomal inversion (BFNC3). There is no obvious correlation between most of the known mutations and clinical variability seen in BFNE.

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Juvenile myoclonic epilepsy (JME), also known as Janz syndrome or impulsive petit mal, is a form of hereditary, idiopathic generalized epilepsy, representing 5–10% of all epilepsy cases. Typically it first presents between the ages of 12 and 18 with myoclonic seizures. These events typically occur after awakening from sleep, during the evening or when sleep-deprived. JME is also characterized by generalized tonic–clonic seizures, and a minority of patients have absence seizures. It was first described by Théodore Herpin in 1857. Understanding of the genetics of JME has been rapidly evolving since the 1990s, and over 20 chromosomal loci and multiple genes have been identified. Given the genetic and clinical heterogeneity of JME some authors have suggested that it should be thought of as a spectrum disorder.

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References

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  3. ↑ Nashef, L; So, EL; Ryvlin, P; Tomson, T (Feb 2012). "Unifying the definitions of sudden unexpected death in epilepsy". Epilepsia. 53 (2): 227–33. doi: 10.1111/j.1528-1167.2011.03358.x . PMID   22191982. S2CID   19119225.
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  6. ↑ Harden, C; Tomson, T; Gloss, D; Buchhalter, J; Cross, JH; Donner, E; French, JA; Gil-Nagel, A; Hesdorffer, DC; Smithson, WH; Spitz, MC; Walczak, TS; Sander, JW; Ryvlin, P (25 April 2017). "Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society". Neurology. 88 (17): 1674–1680. doi: 10.1212/WNL.0000000000003685 . PMID   28438841.
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  14. ↑ Wang, Dawei; Shah, Krunal R.; Um, Sung Yon; Eng, Lucy S.; Zhou, Bo; Lin, Ying; Mitchell, Adele A.; Nicaj, Leze; Prinz, Mechthild; McDonald, Thomas V.; Sampson, Barbara A. (April 2014). "Cardiac channelopathy testing in 274 ethnically diverse sudden unexplained deaths". Forensic Science International. 237: 90–99. doi:10.1016/j.forsciint.2014.01.014. ISSN   1872-6283. PMID   24631775.
  15. ↑ Winkel, Bo Gregers; Larsen, Maiken Kudahl; Berge, Knut Erik; Leren, Trond Paul; Nissen, Peter Henrik; Olesen, Morten Salling; Hollegaard, Mads Vilhelm; Jespersen, Thomas; Yuan, Lei; Nielsen, Nikolaj; Haunsø, Stig (October 2012). "The prevalence of mutations in KCNQ1, KCNH2, and SCN5A in an unselected national cohort of young sudden unexplained death cases". Journal of Cardiovascular Electrophysiology. 23 (10): 1092–1098. doi:10.1111/j.1540-8167.2012.02371.x. ISSN   1540-8167. PMID   22882672. S2CID   12365657.
  16. ↑ Klassen, Tara L.; Bomben, Valerie C.; Patel, Ankita; Drabek, Janice; Chen, Tim T.; Gu, Wenli; Zhang, Feng; Chapman, Kevin; Lupski, James R.; Noebels, Jeffrey L.; Goldman, A. M. (February 2014). "High-resolution molecular genomic autopsy reveals complex sudden unexpected death in epilepsy risk profile". Epilepsia. 55 (2): e6–12. doi:10.1111/epi.12489. ISSN   1528-1167. PMC   4195652 . PMID   24372310.
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  18. ↑ So, N. K.; Sperling, M. R. (31 July 2007). "Ictal asystole and SUDEP". Neurology. 69 (5): 423–424. doi:10.1212/01.wnl.0000268698.04032.bc. PMID   17664399. S2CID   35395982.
  19. ↑ Schuele, SU; Bermeo, AC; Alexopoulos, AV; Locatelli, ER; Burgess, RC; Dinner, DS; Foldvary-Schaefer, N (Jul 31, 2007). "Video-electrographic and clinical features in patients with ictal asystole". Neurology. 69 (5): 434–41. doi:10.1212/01.wnl.0000266595.77885.7f. PMID   17664402. S2CID   8130846.
  20. 1 2 3 4 5 Surges, R; Sander, JW (Apr 2012). "Sudden unexpected death in epilepsy: mechanisms, prevalence, and prevention". Current Opinion in Neurology. 25 (2): 201–7. doi:10.1097/WCO.0b013e3283506714. PMID   22274774.
  21. ↑ Ryvlin, P; Cucherat, M; Rheims, S (Nov 2011). "Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials". Lancet Neurology. 10 (11): 961–8. doi:10.1016/S1474-4422(11)70193-4. PMID   21937278. S2CID   21266860.
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  25. ↑ "New sleep seizure detection device may help against sudden unexpected death in epilepsy (SUDEP)". epilepsytoday. Epilepsy Action. 19 Nov 2018. Retrieved 11 June 2021.
  26. ↑ Picard, Rosalind (5 April 2019). "An AI smartwatch that detects seizures". Ted - ideas worth spreading. Retrieved 11 June 2021.
  27. ↑ Gutiérrez-Viedma, Álvaro; Sanz-Graciani, Isabel; Romeral-Jiménez, María; Parejo-Carbonell, Beatriz; Serrano-García, Irene; Cuadrado, María-Luz; Aledo-Serrano, Ángel; Gil-Nagel, Antonio; Toledano, Rafael; García-Morales, Irene (2019-10-01). "Patients' knowledge on epilepsy and SUDEP improves after a semi-structured health interview". Epilepsy & Behavior. 99: 106467. doi:10.1016/j.yebeh.2019.106467. ISSN   1525-5050. PMID   31421520. S2CID   199577310.
  28. ↑ Thurman, David J.; Hesdorffer, Dale C.; French, Jacqueline A. (October 2014). "Sudden unexpected death in epilepsy: assessing the public health burden". Epilepsia. 55 (10): 1479–1485. doi: 10.1111/epi.12666 . ISSN   1528-1167. PMID   24903551.
  29. ↑ Lynge, Thomas Hadberg; Jeppesen, Alexander Gade; Winkel, Bo Gregers; Glinge, Charlotte; Schmidt, Michael Rahbek; Søndergaard, Lars; Risgaard, Bjarke; Tfelt-Hansen, Jacob (June 2018). "Nationwide Study of Sudden Cardiac Death in People With Congenital Heart Defects Aged 0 to 35 Years". Circulation: Arrhythmia and Electrophysiology. 11 (6): e005757. doi: 10.1161/CIRCEP.117.005757 . ISSN   1941-3084. PMID   29858381. S2CID   46924064.
  30. ↑ Goldstein, Richard D.; Trachtenberg, Felicia L.; Sens, Mary Ann; Harty, Brian J.; Kinney, Hannah C. (January 2016). "Overall Postneonatal Mortality and Rates of SIDS". Pediatrics. 137 (1): e20152298. doi: 10.1542/peds.2015-2298 . ISSN   1098-4275. PMID   26634772.
  31. ↑ Nouri, Shahin (December 3, 2015). "Sudden Unexpected Death in Epilepsy" . Medscape.
  32. ↑ Shorvon, Simon; Tomson, Torbjorn (2011-12-10). "Sudden unexpected death in epilepsy". Lancet. 378 (9808): 2028–2038. doi:10.1016/S0140-6736(11)60176-1. ISSN   1474-547X. PMID   21737136. S2CID   6947573.
  33. ↑ Annegers, J. F.; Coan, S. P. (September 1999). "SUDEP: overview of definitions and review of incidence data". Seizure. 8 (6): 347–352. doi: 10.1053/seiz.1999.0306 . ISSN   1059-1311. PMID   10512776. S2CID   7522458.
  34. ↑ Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo; de Albuquerque, Marly; Scattolini, Marcello; Arida, Ricardo Mario (June 2011). "Sudden unexpected death in epilepsy: an important concern". Clinics. 66 (Suppl 1): 65–69. doi:10.1590/S1807-59322011001300008. ISSN   1807-5932. PMC   3118439 . PMID   21779724.
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