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* [http://www.aesnet.org/pame/ Partners Against Mortality in Epilepsy 3-day conference (22-24 June 2012)]
* [http://www.aesnet.org/pame/ Partners Against Mortality in Epilepsy 3-day conference (22-24 June 2012)]
* [http://www.sudepglobalconversation.com/ Online book "SUDEP: continuing the global conversation"]
* [http://www.sudepglobalconversation.com/ Online book "SUDEP: continuing the global conversation"]
* [http://www.patient.co.uk/showdoc/27001047/ SUDEP described] at patient.co.uk
* [http://patient.info/health/sudden-unexpected-death-in-epilepsy SUDEP described] at patient.info
* [http://www.cureepilepsy.org/aboutepilepsy/facts.asp Citizens United for Research in Epilepsy: epilepsy facts]
* [http://www.cureepilepsy.org/aboutepilepsy/facts.asp Citizens United for Research in Epilepsy: epilepsy facts]
* [http://www.epilepsy.com/epilepsy/sudep_intro/ Defining SUDEP] at epilepsy.com
* [http://www.epilepsy.com/epilepsy/sudep_intro/ Defining SUDEP] at epilepsy.com

Revision as of 14:37, 27 October 2015

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] 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 to 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] Instances of death as a result of prolonged seizures (status epilepticus) are not classified as SUDEP.[6]

Risk factors

Consistent risk factors include:

  • Severity of seizures, increased refractoriness of epilepsy and presence of generalized tonic-clonic seizures:[4] the most consistent risk factor is an increased frequency of tonic–clonic seizures.[5]
  • Poor compliance.[4] Lack of therapeutic levels of anti-epileptic drugs, non-adherence to treatment regimens, and frequent changes in regimens are risk factors for sudden death.[5]
  • Young age, and early age of seizures onset.[4]
  • Male gender[4]
  • Poly-therapy of epilepsy. If this is an independent risk factor or a surrogate marker for severity of epilepsy remains unclear.[7]
  • The use of lamotrigine in idiopathic generalized epilepsy cases.[7]
  • Being asleep during a seizure is likely to favour SUDEP occurrence.[8]

Causes

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.[9]

  • Cardiac factors: cardiac arrhythmias and other cardiac events are known to be involved in some cases of SUDEP.[5] Such arrhythmias are defined as ictal arrhythmias and include the ictal asystole which is a rare occurrence mostly in people that have temporal lobe epilepsy.[10][11]
  • Respiratory factors: impaired respiration and seizure induced pulmonary dysfunction as well as central apnea as a result of brain-stem respiratory centers suppression are known to play a role in some cases of SUDEP.[5]
  • Cerebral and autonomic nervous system dysregulation: cardiac arrhythmia and respiratory failure as a result of seizure related changes to brain function and dysfunction of the autonomic nervous system have been described in cases of SUDEP. These include cases of post-ictal generalized EEG suppression described as cerebral shutdown, but its significance remains unclear.[7]
  • Genetic factors: mutations in several genes have been associated with an increased susceptibility to SUDEP. Over 33% of these are related to mutations which lead to increased susceptibility for arrhythmia. Genes involved include the hyperpolarization-activated cyclic nucleotide-gated channels genes (HCN1, HCN2, HCN3, and HCN4).[2]
  • Anti epileptic drugs: most evidence suggests that antiepileptic drugs are not associated with an increased risk for SUDEP, but rather reduce its incidence.[12] Some studies however indicate that some antiepileptic drugs such as lamotrigine and carbamazepine, may increase the risk of SUDEP in certain individuals.[13] It is unclear if this is because of the potential cardio-respiratory adverse effects such as lengthening of the QT interval and reduction of heart rate known to be associated with these drugs under certain circumstances,[9] or because a high drug dosage could be a surrogate marker for poor seizure control.[14]
  • Vagal nerve stimulation: concerns have been raised that vagal nerve stimulation may induce bradycardia or cardiac arrest, and may exacerbate sleep apnoea common in people with epilepsy.[9]

Management

The lack of generally recognized clinical recommendations available are a reflection of the dearth of data on the effectiveness of any particular clinical strategy,[9] but on the basis of present evidence, the following may be relevant:

  • Epileptic seizure control with the appropriate use of medication and lifestyle counseling is the focus of prevention.[5]
  • Reduction of stress, participation in physical exercises, and night supervision might minimize the risk of SUDEP.[2]
  • Knowledge of how to perform the appropriate first-aid responses to seizure by persons who live with epileptic people may prevent death.[5]
  • People associated with arrhythmias during seizures should be submitted to extensive cardiac investigation[2] with a view to determining the indication for on-demand cardiac pacing.[9]
  • Successful epilepsy surgery may reduce the risk of SUDEP, but this depends on the outcome in terms of seizure control.[9]
  • The use of anti suffocation pillows have been advocated by some practitioners to improve respiration while sleeping, but their effectiveness remain unproven because experimental studies are lacking.[5]
  • Providing information to individuals and relatives about SUDEP is beneficial.[7]

Epidemiology

  • Approximately 50,000 people die each year in the USA from status epilepticus (prolonged seizures), SUDEP, and other seizure-related causes. SUDEP accounts for 8-17% of deaths in people with epilepsy.[15]
  • The risk of sudden death in young adults with epilepsy is increased 24-fold compared to the general population.[7]
  • SUDEP is the number one cause of epilepsy related death in people with pharmaco-resistant epilepsy.[7]
  • Children with epilepsy have a cumulative risk of dying suddenly of 7% within 40 years.[7]
  • In children, SUDEP accounts for 34% of all sudden deaths.[16]

References

  1. ^ Ryvlin, P; Nashef, L; Tomson, T (May 2013). "Prevention of sudden unexpected death in epilepsy: a realistic goal?". Epilepsia. 54 Suppl 2: 23–8. doi:10.1111/epi.12180. PMID 23646967.
  2. ^ a b c d e f Terra, VC; Cysneiros, R; Cavalheiro, EA; Scorza, FA (Mar 2013). "Sudden unexpected death in epilepsy: from the lab to the clinic setting". Epilepsy & behavior : E&B. 26 (3): 415–20. doi:10.1016/j.yebeh.2012.12.018. PMID 23402930.
  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.
  4. ^ a b c d e f Tolstykh, GP; Cavazos, JE (Mar 2013). "Potential mechanisms of sudden unexpected death in epilepsy". Epilepsy & behavior : E&B. 26 (3): 410–4. doi:10.1016/j.yebeh.2012.09.017. PMID 23305781.
  5. ^ a b c d e f g h i Devinsky, Orrin (10 November 2011). "Sudden, Unexpected Death in Epilepsy". New England Journal of Medicine. 365 (19): 1801–1811. doi:10.1056/NEJMra1010481.
  6. ^ Tomson T, Nashef L, Ryvlin P (November 2008). "Sudden unexpected death in epilepsy: current knowledge and future directions". Lancet Neurology. 7 (11): 1021–31. doi:10.1016/S1474-4422(08)70202-3. PMID 18805738.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ a b c d e f g 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.
  8. ^ Nobili, L; Proserpio, P; Rubboli, G; Montano, N; Didato, G; Tassinari, CA (Aug 2011). "Sudden unexpected death in epilepsy (SUDEP) and sleep". Sleep medicine reviews. 15 (4): 237–46. doi:10.1016/j.smrv.2010.07.006. PMID 20951616.
  9. ^ a b c d e f Shorvon, S; Tomson, T (Dec 10, 2011). "Sudden unexpected death in epilepsy". Lancet. 378 (9808): 2028–38. doi:10.1016/S0140-6736(11)60176-1. PMID 21737136.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ Hesdorffer, DC; Tomson, T (Feb 2013). "Sudden unexpected death in epilepsy. Potential role of antiepileptic drugs". CNS Drugs. 27 (2): 113–9. doi:10.1007/s40263-012-0006-1. PMID 23109241.
  14. ^ Surges, R; Thijs, RD; Tan, HL; Sander, JW (Sep 2009). "Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms". Nature reviews. Neurology. 5 (9): 492–504. doi:10.1038/nrneurol.2009.118. PMID 19668244.
  15. ^ eMedicine - Sudden Unexpected Death in Epilepsy : Article by Shahin Nouri
  16. ^ "Epilepsy Facts". Citizens United for Research in Epilepsy. Retrieved 18 March 2014.
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