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Reducing the Risk of Sudden Unexpected Death in Epilepsy (SUDEP)

  • Epilepsy (E Waterhouse, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Abstract

Purpose of Review

Recent reports have highlighted an increase in the number of epilepsy-related deaths. Sudden unexpected death in epilepsy (SUDEP) is thought to be the number one cause of death in chronic epilepsy. This review provides a summary of the current evidence of how to communicate, stratify, and mitigate known risk factors for SUDEP.

Recent Findings

There is now a clearer understanding of the possible pathological mechanisms that contribute to SUDEP. SUDEP is the culmination of multifactorial predisposing and precipitating factors and has been linked to particular candidate genes. A number of static and modifiable risk factors for SUDEP have been consistently identified. Recent guidance has emphasised the importance of communicating SUDEP risk to individuals at the earliest appropriate time.

Summary

SUDEP risk assessment should be integral to the care of individuals with epilepsy. The use of evidence-based risk assessment tools may provide an opportunity to communicate identified risks in a person-centred holistic way. There is increasing evidence to support the use of wearable seizure monitoring devices to help reduce the frequency and impact of convulsive seizures, perhaps the number one risk factor for SUDEP.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. De Boer HM, Mula M, Sander JW. The global burden and stigma of epilepsy. Epilepsy Behav. 2008;12(4):540–6.

    Article  PubMed  Google Scholar 

  2. Office for National Statistics Death registrations summary table, England and Wales. 2013

  3. Deaths associated with neurological conditions in England 2001 to 2014 Data analysis report. Public Health England. 2018. This recent publication highlights an alarming trend of increased mortality rates associated with neurological conditions including epilepsy.

  4. Sander JW, Bell GS. Reducing mortality: an important aim of epilepsy management. J Neurol Neurosurg Psychiatry. 2004;75:349–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Nashef L, So EL, Ryvlin P, Tomson T. Unifying the definitions of sudden unexpected death in epilepsy. Epilepsia. 2012;53(2):227–33.

    Article  PubMed  Google Scholar 

  6. Hesdorffer DC, Tomson T, Benn E, Sander JW, Nilsson L, Langan Y, et al. Combined analysis of risk factors for SUDEP. Epilepsia. 2011;52(6):1150–9.

    Article  PubMed  Google Scholar 

  7. •• Tomson T, Surges R, Delamont R, Haywood S, Hesdorffer DC. Who to target in sudden unexpected death in epilepsy prevention and how? Risk factors, biomarkers, and intervention study designs. Epilepsia. 2016;57(S1):4–16. This paper summarises the current evidence on identified SUDEP risk factors.

    Article  PubMed  Google Scholar 

  8. Surges R, Sander JW. Sudden unexpected death in epilepsy: mechanisms, prevalence, and prevention. Curr Opin Neurol. 2012;25(2):201–7.

    Article  PubMed  Google Scholar 

  9. Shmuely S, Van der Lende M, Lamberts RJ, Sander JW, Thijs RD. The heart of epilepsy: current views and future concepts. Seizure. 2017;44:176–83.

    Article  CAS  PubMed  Google Scholar 

  10. Devinsky O, Hesdorffer DC, Thurman DJ, Lhatoo S, Richerson G. Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention. Lancet Neurol. 2016;15(10):1075–88.

    Article  PubMed  Google Scholar 

  11. Ryvlin P, Nashef L, Lhatoo SD, Bateman LM, Bird J, Bleasel A, et al. Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study. Lancet Neurol. 2013;12(10):966–77.

    Article  PubMed  Google Scholar 

  12. Goldman AM, Behr ER, Semsarian C, Bagnall RD, Sisodiya S, Cooper PN. Sudden unexpected death in epilepsy genetics: molecular diagnostics and prevention. Epilepsia. 2016;57(S1):17–25.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Tu E, Bagnall RD, Duflou J, Semsarian C. Post-mortem review and genetic analysis of sudden unexpected death in epilepsy (SUDEP) cases. Brain Pathol. 2011;21(2):201–8.

    Article  CAS  PubMed  Google Scholar 

  14. Bagnall RD, Crompton DE, Petrovski S, Lam L, Cutmore C, Garry SI, et al. Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy. Ann Neurol. 2016;79(4):522–34.

    Article  CAS  PubMed  Google Scholar 

  15. Hodges MR, Wehner M, Aungst J, Smith JC, Richerson GB. Transgenic mice lacking serotonin neurons have severe apnea and high mortality during development. J Neurosci. 2009;29(33):10341–10,349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. •• Harden C, Tomson T, Gloss D, Buchhalter J, Cross JH, Donner E, et al. 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. 2017;88(17):1674–80. Guidance on good practice and communication of risk.

    Article  PubMed  Google Scholar 

  17. The National Institute for Health and Care Excellence (NICE). The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care. NICE clinical guideline 137. 2012. guidance.nice.org.uk/cg137

  18. Mclean B, Shankar R, et al. SUDEP – measures to reduce risk. Pract Neurol. 2017;17:13–20.

    Article  PubMed  Google Scholar 

  19. Shankar R, Donner EJ, McLean B, Nashef L, Tomson T. Sudden unexpected death in epilepsy (SUDEP): what every neurologist should know. Epileptic Disord. 2017;19(1):1–9.

    PubMed  Google Scholar 

  20. Shankar R, Newman C, Gales A, McLean BN, Hanna J, Ashby S, et al. Has the time come to stratify and score SUDEP risk to inform people with epilepsy of their changes in safety? Front Neurol. 2018;9. https://doi.org/10.3389/fneur.2018.00281.

  21. •• Maguire MJ, Jackson CF, Marson AG, Nolan SJ. Treatments for the prevention of sudden unexpected death in epilepsy (SUDEP). Cochrane Database Syst Rev. 2016;7:CD011792. Cochrane review of current SUDEP prevention evidence

    PubMed  Google Scholar 

  22. Shankar R, Cox D, Jalihal V, Brown S, Hanna J, McLean B. Sudden unexpected death in epilepsy (SUDEP): development of a safety checklist. Seizure. 2013;22(10):812–7.

    Article  PubMed  Google Scholar 

  23. •• Shankar R, Walker M, McLean B, Laugharne R, Ferrand F, Hanna J, et al. Steps to prevent SUDEP: the validity of risk factors in the SUDEP and seizure safety checklist: a case control study. J Neurol. 2016;263(9):1840–6. Evidence to support the use of an evidence-based, structured risk assessment tool to communicate risk.

    Article  PubMed  Google Scholar 

  24. Shankar R, Newman C, McLean B, Anderson T, Obe JH. Can technology help reduce risk of harm in patients with epilepsy? Br J Gen Pract. 2015;65(638):448–9. https://doi.org/10.3399/bjgp15X686413.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shankar R, Henley W, Boland C, Laugharne R, McLean BN, Newman C, et al. Decreasing the risk of SUDEP: structured communication of risk factors for premature mortality in people with epilepsy. Eur J Neurol. 2018; https://doi.org/10.1111/ene.13651.

    Article  CAS  PubMed  Google Scholar 

  26. Newman C, Shankar R, Hanna J, McLean B, Osland A, Milligan C, et al. Developing an evidence-based epilepsy risk assessment ehealth solution: from concept to market. JMIR Res Protoc. 2016;5(2):e82.

    Article  PubMed  PubMed Central  Google Scholar 

  27. DeGiorgio CM, Miller P, Meymandi S, Chin A, Epps J, Gordon S, et al. RMSSD, a measure of vagus-mediated heart rate variability, is associated with risk factors for SUDEP: the SUDEP-7 Inventory. Epilepsy Behav. 2010;19(1):78–81.

    Article  PubMed  PubMed Central  Google Scholar 

  28. DeGiorgio CM, Markovic D, Mazumder R, Moseley BD. Ranking the leading risk factors for sudden unexpected death in epilepsy. Front Neurol. 2017;8:473.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Langan Y, Nashef L, Sander JW. Case-control study of SUDEP. Neurology. 2005;64(7):1131–3.

    Article  CAS  PubMed  Google Scholar 

  30. Ryvlin P, Cucherat M, Rheims S. 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 Neurol. 2011;10(11):961–8.

    Article  PubMed  Google Scholar 

  31. Lamberts RJ, Thijs RD, Laffan A, Langan Y, Sander JW. Sudden unexpected death in epilepsy: people with nocturnal seizures may be at highest risk. Epilepsia. 2012;53(2):253–7.

    Article  PubMed  Google Scholar 

  32. Liebenthal JA, Wu S, Rose S, Ebersole JS, Tao JX. Association of prone position with sudden unexpected death in epilepsy. Neurology. 2015;84(7):703–9.

    Article  PubMed  Google Scholar 

  33. Shmuely S, Surges R, Sander JW, Thijs RD. Prone sleeping and SUDEP risk: the dynamics of body positions in nonfatal convulsive seizures. Epilepsy Behav. 2016;62:176–9.

    Article  PubMed  Google Scholar 

  34. Sperling MR, Feldman H, Kinman J, Liporace JD, O’Connor MJ. Seizure control and mortality in epilepsy. Ann Neurol. 1999;46(1):45–50.

    Article  CAS  PubMed  Google Scholar 

  35. Annegers JF, Coan SP, Hauser WA, Leestma J. Epilepsy, vagal nerve stimulation by the NCP system, all-cause mortality, and sudden, unexpected, unexplained death. Epilepsia. 2000;41(5):549–53.

    Article  CAS  PubMed  Google Scholar 

  36. Granbichler CA, Nashef L, Selway R, Polkey CE. Mortality and SUDEP in epilepsy patients treated with vagus nerve stimulation. Epilepsia. 2015;56(2):291–6.

    Article  PubMed  Google Scholar 

  37. Ryvlin P, So EL, Gordon CM, Hesdorffer DC, Sperling MR, Devinsky O, et al. Long-term surveillance of SUDEP in drug-resistant epilepsy patients treated with VNS therapy. Epilepsia. 2018;59:562–72. https://doi.org/10.1111/epi.14002.

    Article  CAS  PubMed  Google Scholar 

  38. Devinsky O, Friedman D, Duckrow RB, Fountain NB, Gwinn RP, Leiphart JW, et al. Sudden unexpected death in epilepsy in patients treated with brain-responsive neurostimulation. Epilepsia. 2018; https://doi.org/10.1111/epi.13998.

    Article  PubMed  Google Scholar 

  39. •• Jory C, Shankar R, Coker D, McLean B, Hanna J, Newman C. Safe and sound? A systematic literature review of seizure detection methods for personal use. Seizure. 2016;36:4–15. Systematic review of technology-based seizure detection devices.

    Article  PubMed  Google Scholar 

  40. Arends J, Van Hoek D, Van Mierlo P, Van Dorp J, Kramer N, Van Der Vorst D, et al. Diagnostic accuracy of audio based seizure detection in patients with severe epilepsy and a mental impairment. Epilepsy Behav. 2016;62:180–5.

    Article  PubMed  Google Scholar 

  41. Narechania AP, Garić II, Sen-Gupta I, Macken MP, Gerard EE, Schuele SU. Assessment of a quasi-piezoelectric mattress monitor as a detection system for generalized convulsions. Epilepsy Behav. 2013;28(2):172–6.

    Article  PubMed  Google Scholar 

  42. Poppel KV, Fulton SP, McGregor A, Ellis M, Patters A, Wheless J. Prospective study of the Emfit movement monitor. J Child Neurol. 2013;28(11):1434–6.

    Article  PubMed  Google Scholar 

  43. Fulton S, Poppel KV, McGregor A, Ellis M, Patters A, Wheless J. Prospective study of 2 bed alarms for detection of nocturnal seizures. J Child Neurol. 2013;28(11):1430–3.

    Article  PubMed  Google Scholar 

  44. Carlson C, Arnedo V, Cahill M, Devinsky O. Detecting nocturnal convulsions: efficacy of the MP5 monitor. Seizure-European Journal of Epilepsy. 2009;18(3):225–7.

    Article  PubMed  Google Scholar 

  45. Shankar R, Jory C, Tripp M, Cox D, Hagenow K. Monitoring nocturnal seizure in vulnerable patients. Learn Disabil Pract. 2013;16(9):36.

    Article  Google Scholar 

  46. Cuppens K, Chen CW, Wong KBY, Van de Vel A, Lagae L, Ceulemans B, Tuytelaars T, Van Huffel S, Vanrumste B, Aghajan H. Integrating video and accelerometer signals for nocturnal epileptic seizure detection. In Proceedings of the 14th ACM international conference on Multimodal interaction. 2012; (pp. 161–164). ACM.

  47. Lockman J, Fisher RS, Olson DM. Detection of seizure-like movements using a wrist accelerometer. Epilepsy Behav. 2011;20(4):638–41.

    Article  PubMed  Google Scholar 

  48. Beniczky S, Polster T, Kjaer TW, Hjalgrim H. Detection of generalized tonic–clonic seizures by a wireless wrist accelerometer: a prospective, multicenter study. Epilepsia. 2013:54(4).

    Article  PubMed  Google Scholar 

  49. Cuppens K, Karsmakers P, Van de Vel A, Bonroy B, Milosevic M, Luca S, et al. Accelerometry-based home monitoring for detection of nocturnal hypermotor seizures based on novelty detection. IEEE J Biomed Health Informatics. 2014;18(3):1026–33.

    Article  Google Scholar 

  50. Onorati F, Regalia G, Caborni C, Migliorini M, Bender D, Poh MZ, et al. Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors. Epilepsia. 2017;58(11):1870–9.

    Article  PubMed  Google Scholar 

  51. Massé F, Penders J, Serteyn A, van Bussel M, Arends J. Miniaturized wireless ECG-monitor for real-time detection of epileptic seizures. In Wireless Health. 2010; (pp. 111–117). ACM.

  52. Vandecasteele K, De Cooman T, Gu Y, Cleeren E, Claes K, Paesschen WV, et al. Automated epileptic seizure detection based on wearable ECG and PPG in a hospital environment. Sensors. 2017;17(10):2338.

    Article  Google Scholar 

  53. Rodriguez-Villegas E, Chen G, Radcliffe J, Duncan J. A pilot study of a wearable apnea detection device. BMJ open. 2014;4(10):e005299.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Cavazos J, Girouard M, Whitmire L. Novel ambulatory EMG-based GTC seizure detection device for home & hospital use (I6-4B). Neurology. 2015;84(14 Supplement):I6–4B.

    Google Scholar 

  55. Graves J, Arjona J, Gourraud PA. Wearable electromyogram device associated with disability outcomes in adults with multiple sclerosis (P1.377). Neurology. 2017;88(16 Supplement)

  56. Poh MZ, Loddenkemper T, Reinsberger C, Swenson NC, Goyal S, Sabtala MC, Madsen JR, Picard RW. Convulsive seizure detection using a wrist-worn electrodermal activity and accelerometry biosensor. Epilepsia, 2012; 53(5).

    Article  PubMed  Google Scholar 

  57. Picard RW, Migliorini M, Caborni C, Onorati F, Regalia G, Friedman D, et al. Wrist sensor reveals sympathetic hyperactivity and hypoventilation before probable SUDEP. Neurology. 2017;89(6):633–5.

    Article  PubMed  Google Scholar 

  58. Ge A, Gonzalez E, Lee SW, Carmenate Y, Collard M, Dixon-Salazar T, Crone N, Krauss G. Seizure triggers in epilepsy patients: a national perspective, American Academy of Neurology 69th Annual Meeting. 2017; (S37. 002).

  59. Hampel KG, Jahanbekam A, Elger CE, Surges R. Seizure-related modulation of systemic arterial blood pressure in focal epilepsy. Epilepsia. 2016;57(10):1709–18.

    Article  CAS  PubMed  Google Scholar 

  60. Hampel KG, Elger CE, Surges R. Impaired baroreflex sensitivity after bilateral convulsive seizures in patients with focal epilepsy. Front Neurol. 2017;8:210.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Dupuis M, Van Rijckevorsel K, Evrard F, Dubuisson N, Dupuis F, Van Robays P. Takotsubo syndrome (TKS): a possible mechanism of sudden unexplained death in epilepsy (SUDEP). Seizure. 2012;21(1):51–4.

    Article  CAS  PubMed  Google Scholar 

  62. Monté CPJA, Arends JBAM, Tan IY, Aldenkamp AP, Limburg M, De Krom MCTFM. Sudden unexpected death in epilepsy patients: risk factors: a systematic review. Seizure. 2007;16(1):1–7.

    Article  PubMed  Google Scholar 

  63. Sveinsson O, Andersson T, Carlsson S, Tomson T. The incidence of SUDEP: a nationwide population-based cohort study. Neurology. 2017:10–1212.

  64. Faingold CL, Tupal S, Randall M. Prevention of seizure-induced sudden death in a chronic SUDEP model by semichronic administration of a selective serotonin reuptake inhibitor. Epilepsy Behav. 2011;22(2):186–90.

    Article  PubMed  Google Scholar 

  65. Watkins L, Shankar R, Sander JW. Identifying and mitigating sudden unexpected death in epilepsy (SUDEP) risk factors. Expert Rev Neurother. 2018;18(4):265–74.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Neath Port Talbot CLDT, Mental Health & Learning Disability Delivery Unit, Abertawe Bro Morgannwg University Health Board, LLwyneryr Unit, 151 Clasemont Road, Morriston, Swansea, SA6 6AH, UK

    Lance Watkins MRCPsych, MSc

  2. Cornwall Partnership NHS Foundation Trust, Threemilestone Industrial Estate, Truro, TR4 9LD, UK

    Rohit Shankar MBE, FRCPsych

  3. Exeter Medical School, Knowledge Spa, Royal Cornwall Hospital, Truro, Cornwall, TR1 3HD, UK

    Rohit Shankar MBE, FRCPsych

Authors
  1. Lance Watkins MRCPsych, MSc
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Correspondence to Rohit Shankar MBE, FRCPsych.

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Conflict of Interest

Rohit Shankar is a stakeholder of the ‘SUDEP and Seizure Safety Checklist’. Rohit Shankar is a principal developer and key stakeholder of EpSMon. Rohit Shankar has received institutional and research support and personal fees from LivaNova, UCB, Eisai, Special Products, Bial and Desitin.

Lance Watkins has no disclosures to report.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Epilepsy

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Watkins, L., Shankar, R. Reducing the Risk of Sudden Unexpected Death in Epilepsy (SUDEP). Curr Treat Options Neurol 20, 40 (2018). https://doi.org/10.1007/s11940-018-0527-0

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