Sudden unexpected death in epilepsy: a review of literature and own observations

Authors

  • L. B. Marienko Danylo Halytsky Lviv National Medical University of the Ministry of Health of Ukraine, Lviv,
  • K. M. Marienko Danylo Halytsky Lviv National Medical University of the Ministry of Health of Ukraine, Lviv,

DOI:

https://doi.org/10.14739/2310-1210.2019.6.186718

Keywords:

epilepsy, sudden death, epidemiology, risk factors, biomarkers, prevention.

Abstract

 

The purpose. To analyze the current state of scientific data related to sudden unexpected death in epilepsy (SUDEP) based on the study of recent investigations presented in the sources of scientific information about definition and classification of SUDEP, its risk factors, epidemiological data, pathophysiology, validity of proposed biomarkers, results of post-mortem examinations, measures of SUDEP prevention and also to present own observations of deaths with their classification.

Numerous studies of the recent years have demonstrated the high medical and social significance of the problem of sudden unexpected death in epilepsy, the prevalence of which in patients with epilepsy is 20 times higher than in the general population. The proven association of such a death with a generalized tonic-clonic seizure (GTCS) indicates a real potential threat to life of patients with an unfavorable pharmacoresistant course of the disease. Possible, but not definitively evident, risk factors for SUDEP could be nighttime seizures during sleep, absence of witnesses who could help, prone position during sleep, male gender, age of epilepsy onset before 16 years and its duration more than 15 years, psychiatric comorbidity, simultaneous use of several anti-epileptic drugs (AEDs) or absence of any treatment, symptomatic etiology of epilepsy, use of lamotrigine in idiopathic epilepsy. The exact pathophysiology of SUDEP is unknown. The proposed clinical, genetic, electrophysiological, radiological SUDEP biomarkers for the purpose of identifying individuals with an increased risk of sudden death also do not have sufficient evidence base. Possible preventive SUDEP measures include monitoring of patients’ night sleep with the use of acoustic and biosensor devices, special smart-watches, usage of oxygen mask during or immediately after GTCS. There is a need to inform patients, especially those with unsatisfactory adherence to treatment, about the possibility of sudden death in order to improve their compliance. The main measure of prevention is the search for effective treatment with the best seizure control and minimal AEDs side effects. At present, only this way has an evidence base for reducing the risk of SUDEP. Own observations that meet the criteria for different types of SUDEP are presented.

 

References

  1. Thurman, D., Logroscino, G., Beghi, E., Hauser, W., Hesdorffer, D., & Newton, C. et al. (2017). The burden of premature mortality of epilepsy in high-income countries: a systematic review from the mortality task force of the international league against epilepsy. Epilepsia, 58(1), 17-26. doi: 10.1111/epi.13604
  2. Levira, F., Thurman, D., Sander, J., Hauser, W., Hesdorffer, D., & Masanja, H. et al. (2017). Premature mortality of epilepsy in low- and middle-income countries: a systematic review from the mortality task force of the international league against epilepsy. Epilepsia, 58(1), 6-16. doi: 10.1111/epi.13603
  3. Greenlund, S., Croft, J., & Kobau, R. (2017). Epilepsy by the numbers. Epilepsy & Behavior, 69, 28-30. doi: 10.1016/j.yebeh.2017.01.016
  4. Tomson, T., Surges, R., Delamont, R., Haywood, S., & Hesdorffer, D. (2016). Who to target in sudden unexpected death in epilepsy prevention and how? Risk factors, biomarkers, and intervention study designs. Epilepsia, 57(S.1), 4-16. doi: 10.1111/epi.13234
  5. Holst, A., Winkel, B., Risgaard, B., Nielsen, J., Rasmussen, P., & Haunsø, S. et al. (2013). Epilepsy and risk of death and sudden unexpected death in the young: A nationwide study. Epilepsia, 54(9), 1613-1620. doi: 10.1111/epi.12328
  6. Devinsky, O., Spruill, T., Thurman, D., & Friedman, D. (2016). Recognizing and preventing epilepsy-related mortality. Neurology, 86(8), 779-786. doi: 10.1212/wnl.0000000000002253
  7. Gorton, H., Webb, R., Carr, M., DelPozo-Banos, M., John, A., & Ashcroft, D. (2018). Risk of unnatural mortality in people with epilepsy. JAMA Neurology, 75(8), 929-938. doi: 10.1001/jamaneurol.2018.0333
  8. Nashef, L., So, E., Ryvlin, P., & Tomson, T. (2012). Unifying the definitions of sudden unexpected death in epilepsy. Epilepsia, 53(2), 227-233. doi: 10.1111/j.1528-1167.2011.03358.x
  9. Maguire, M. J., Jackson, C. F., Marson, A. G., & Nevitt, S. J. (2016). Treatments for the prevention of Sudden Unexpected Death in Epilepsy (SUDEP). Cochrane Database of Systematic Reviews, 7, CD011792. doi: 10.1002/14651858.CD011792.pub2
  10. Chapman, D., Panelli, R., Hanna, J., & Jeffs, T. (2011). Sudden unexpected death in epilepsy (pp. 7, 11-15). Camberwell, Vic.: Epilepsy Australia.
  11. Ryvlin, P., & Cascino, G. (2017). Sudden unexpected death in epilepsy patients is often misdiagnosed as sudden cardiac death. Neurology, 89(9), 878-879. doi: 10.1212/wnl.0000000000004301
  12. Thom, M., Michalak, Z., Wright, G., Dawson, T., Hilton, D., & Joshi, A. et al. (2016). Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings. Neuropathology And Applied Neurobiology, 42(5), 463-476. doi: 10.1111/nan.12265
  13. Shankar, R., Cox, D., Jalihal, V., Brown, S., Hanna, J., & McLean, B. (2013). Sudden unexpected death in epilepsy (SUDEP): Development of a safety checklist. Seizure, 22(10), 812-817. doi: 10.1016/j.seizure.2013.07.014
  14. Devinsky, O., Friedman, D., & Besag, F. (2018). Nocturnal monitoring in epilepsy: Evidence mounts. Neurology, 91(16), 731-732. doi: 10.1212/wnl.0000000000006345
  15. Novak, J., Miller, P., Markovic, D., Meymandi, S., & DeGiorgio, C. (2015). Risk assessment for sudden death in epilepsy: The SUDEP-7 Inventory. Frontiers In Neurology, 6, 252. doi: 10.3389/fneur.2015.00252
  16. Shankar, R., Donner, E., McLean, B., Nashef, L., & Tomson, T. (2017). Sudden unexpected death in epilepsy (SUDEP): what every neurologist should know. Epileptic Disorders, 19(1), 1-9. doi: 10.1684/epd.2017.0891
  17. Harden, C., Tomson, T., Gloss, D., Buchhalter, J., Cross, J., & Donner, E. et al. (2017). Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors. Neurology, 88(17), 1674-1680. doi: 10.1212/wnl.0000000000003685
  18. Keller, A., Whitney, R., Li, S., Pollanen, M., & Donner, E. (2018). Incidence of sudden unexpected death in epilepsy in children is similar to adults. Neurology, 91(2), e107-111. doi: 10.1212/wnl.0000000000005762
  19. Devinsky, O., Friedman, D., Cheng, J., Moffatt, E., Kim, A., & Tseng, Z. (2017). Underestimation of sudden deaths among patients with seizures and epilepsy. Neurology, 89(9), 886-892. doi: 10.1212/wnl.0000000000004292
  20. Annegers, J. (1997). United States perspective on definitions and classifications. Epilepsia, 38(S.11), S9-12. doi: 10.1111/j.1528-1157.1997.tb06137.x
  21. Nashef, L. (1997). Sudden unexpected death in epilepsy: terminology and definitions. Epilepsia, 38(S.11), S6-8. doi: 10.1111/j.1528-1157.1997.tb06130.x
  22. Devinsky, O., Bundock, E., Hesdorffer, D., Donner, E., Moseley, B., & Cihan, E. et al. (2018). Resolving ambiguities in SUDEP classification. Epilepsia, 59(6), 1220-1233. doi: 10.1111/epi.14195
  23. Nass, R., Meiling, S., Andrié, R., Elger, C., & Surges, R. (2017). Laboratory markers of cardiac and metabolic complications after generalized tonic-clonic seizures. BMC Neurology, 17(187). doi: 10.1186/s12883-017-0965-4
  24. Ryvlin, P., Nashef, L., Lhatoo, S., Bateman, L., Bird, J., & Bleasel, A. et al. (2013). Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study. The Lancet Neurology, 12(10), 966-977. doi: 10.1016/s1474-4422(13)70214-x
  25. van der Lende, M., Hesdorffer, D., Sander, J., & Thijs, R. (2018). Nocturnal supervision and SUDEP risk at different epilepsy care settings. Neurology, 91(16), e1508-1518. doi: 10.1212/wnl.0000000000006356
  26. Hesdorffer, D., Tomson, T., Benn, E., Sander, J., Nilsson, L., & Langan, Y. et al. (2012). Do antiepileptic drugs or generalized tonic-clonic seizure frequency increase SUDEP risk? A combined analysis. Epilepsia, 53(2), 249-252. doi: 10.1111/j.1528-1167.2011.03354.x
  27. Ali, A., Wu, S., Issa, N., Rose, S., Towle, V., Warnke, P., & Tao, J. (2017). Association of sleep with sudden unexpected death in epilepsy. Epilepsy & Behavior, 76, 1-6. doi: 10.1016/j.yebeh.2017.08.021
  28. Sveinsson, O., Andersson, T., Carlsson, S., & Tomson, T. (2018). Circumstances of SUDEP: A nationwide population‐based case series. Epilepsia, 59(5), 1074-1082. doi: 10.1111/epi.14079
  29. Donner, E., Waddell, B., Osland, K., Leach, J., Duncan, S., Nashef, L., & Picot, M. (2016). After sudden unexpected death in epilepsy: Lessons learned and the road forward. Epilepsia, 57(S.1), 46-53. doi: 10.1111/epi.13235
  30. Devinsky, O., Friedman, D., Duckrow, R., Fountain, N., Gwinn, R., & Leiphart, J. et al. (2018). Sudden unexpected death in epilepsy in patients treated with brain-responsive neurostimulation. Epilepsia, 59(3), 555-561. doi: 10.1111/epi.13998
  31. Hesdorffer, D., Tomson, T., Benn, E., Sander, J., Nilsson, L., & Langan, Y. et al. (2011). Combined analysis of risk factors for SUDEP. Epilepsia, 52(6), 1150-1159. doi: 10.1111/j.1528-1167.2010.02952.x
  32. Sethi, N., Lhatoo, S., Tao, J., Nashef, L., Tomson, T., & Ryvlin, P. et al. (2015). Association of prone position with sudden unexpected death in epilepsy. Neurology, 85(13), 1185-1186. doi: 10.1212/wnl.0000000000002011
  33. Fazel, S., Wolf, A., Långström, N., Newton, C., & Lichtenstein, P. (2013). Premature mortality in epilepsy and the role of psychiatric comorbidity: a total population study. The Lancet, 382(9905), 1646-1654. doi: 10.1016/s0140-6736(13)60899-5
  34. Sveinsson, O., Andersson, T., Carlsson, S., & Tomson, T. (2017). The incidence of SUDEP. Neurology, 89(2), 170-177. doi: 10.1212/wnl.0000000000004094
  35. St. Louis, E., & Dworetzky, B. (2019). Postconvulsive central apnea and asystole. Neurology, 92(3), 115-116. doi: 10.1212/wnl.0000000000006765
  36. Ryvlin, P., Tomson, T., & Devinsky, O. (2018). Prevention of Sudden Unexpected Death in Epilepsy. European Neurological Review, 13(2), 72-77. doi: 10.17925/enr.2018.13.2.72
  37. DeGiorgio, C., Curtis, A., Hertling, D., & Moseley, B. (2018). Sudden unexpected death in epilepsy: Risk factors, biomarkers, and prevention. Acta Neurologica Scandinavica, 139(3), 220-230. doi: 10.1111/ane.13049
  38. Manolis, T., Manolis, A., Melita, H., & Manolis, A. (2019). Sudden unexpected death in epilepsy: The neuro-cardio-respiratory connection. Seizure, 64, 65-73. doi: 10.1016/j.seizure.2018.12.007
  39. Peng, W., Danison, J., & Seyal, M. (2017). Postictal generalized EEG suppression and respiratory dysfunction following generalized tonic-clonic seizures in sleep and wakefulness. Epilepsia, 58(8), 1409-1414. doi: 10.1111/epi.13805
  40. Devinsky, O., Hesdorffer, D., Thurman, D., Lhatoo, S., & Richerson, G. (2016). Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention. The Lancet Neurology, 15(10), 1075-1088. doi: 10.1016/s1474-4422(16)30158-2
  41. Mueller, S. (2018). Brainstem Network Disruption in Focal Epilepsy and Sudden Unexplained Death in Epilepsy (SUDEP). US Neurology, 14(1), 27-28. doi: 10.17925/usn.2018.14.1.27
  42. Nakase, K., Kollmar, R., Lazar, J., Arjomandi, H., Sundaram, K., & Silverman, J. et al. (2016). Laryngospasm, central and obstructive apnea during seizures: Defining pathophysiology for sudden death in a rat model. Epilepsy Research, 128, 126-139. doi: 10.1016/j.eplepsyres.2016.08.004
  43. Lacuey, N., Zonjy, B., Hampson, J., Rani, M., Zaremba, A., & Sainju, R. et al. (2018). The incidence and significance of periictal apnea in epileptic seizures. Epilepsia, 59(3), 573-582. doi: 10.1111/epi.14006
  44. Vilella, L., Lacuey, N., Hampson, J., Rani, M., Sainju, R., & Friedman, D. et al. (2018). Postconvulsive central apnea as a biomarker for sudden unexpected death in epilepsy (SUDEP). Neurology, 92(3), e171-182. doi: 10.1212/wnl.0000000000006785
  45. Alexandre, V., Mercedes, B., Valton, L., Maillard, L., Bartolomei, F., & Szurhaj, W. et al. (2015). Risk factors of postictal generalized EEG suppression in generalized convulsive seizures. Neurology, 85(18), 1598-1603. doi: 10.1212/wnl.0000000000001949
  46. McCarter, A., Timm, P., Shepard, P., Sandness, D., Luu, T., & McCarter, S. et al. (2018). Obstructive sleep apnea in refractory epilepsy: A pilot study investigating frequency, clinical features, and association with risk of sudden unexpected death in epilepsy. Epilepsia, 59(10), 1973-1981. doi: 10.1111/epi.14548
  47. Leu, C., Balestrini, S., Maher, B., Hernández-Hernández, L., Gormley, P., & Hämäläinen, E. et al. (2015). Genome-wide Polygenic Burden of Rare Deleterious Variants in Sudden Unexpected Death in Epilepsy. Ebiomedicine, 2(9), 1063-1070. doi: 10.1016/j.ebiom.2015.07.005
  48. Bagnall, R., Crompton, D., & Semsarian, C. (2017). Genetic Basis of Sudden Unexpected Death in Epilepsy. Frontiers In Neurology, 8, 348. doi: 10.3389/fneur.2017.00348
  49. Kishk, N., Sharaf, Y., Ebraheim, A., Baghdady, Y., Alieldin, N., Afify, A., & Eldamaty, A. (2018). Interictal cardiac repolarization abnormalities in people with epilepsy. Epilepsy & Behavior, 79, 106-111. doi: 10.1016/j.yebeh.2017.10.028
  50. Auerbach, D., McNitt, S., Gross, R., Zareba, W., Dirksen, R., & Moss, A. (2016). Genetic biomarkers for the risk of seizures in long QT syndrome. Neurology, 87(16), 1660-1668. doi: 10.1212/wnl.0000000000003056
  51. Friedman, D., Kannan, K., Faustin, A., Shroff, S., Thomas, C., & Heguy, A. et al. (2018). Cardiac arrhythmia and neuroexcitability gene variants in resected brain tissue from patients with sudden unexpected death in epilepsy (SUDEP). Npj Genomic Medicine, 3(9). doi: 10.1038/s41525-018-0048-5
  52. Odom, N., & Bateman, L. (2018). Sudden unexpected death in epilepsy, periictal physiology, and the SUDEP-7 Inventory. Epilepsia, 59(10), e157-160. doi: 10.1111/epi.14552
  53. Moseley, B., So, E., Wirrell, E., Nelson, C., Lee, R., Mandrekar, J., & Britton, J. (2013). Characteristics of postictal generalized EEG suppression in children. Epilepsy Research, 106(1-2), 123-127. doi: 10.1016/j.eplepsyres.2013.05.007
  54. Devinsky, O., Kim, A., Friedman, D., Bedigian, A., Moffatt, E., & Tseng, Z. (2018). Incidence of cardiac fibrosis in SUDEP and control cases. Neurology, 91(1), e55-61. doi: 10.1212/wnl.0000000000005740
  55. Clark, D., & Riney, K. (2016). A population-based post mortem study of sudden unexpected death in epilepsy. Journal Of Clinical Neuroscience, 23, 58-62. doi: 10.1016/j.jocn.2015.04.027
  56. Afandi, D. & Romus, I. (2018). Autopsy findings of SUDEP in adolescence. The Malaysian Journal of Pathology, 40(2), 185-189.
  57. Nascimento, F., Tseng, Z., Palmiere, C., Maleszewski, J., Shiomi, T., McCrillis, A., & Devinsky, O. (2017). Pulmonary and cardiac pathology in sudden unexpected death in epilepsy (SUDEP). Epilepsy & Behavior, 73, 119-125. doi: 10.1016/j.yebeh.2017.05.013
  58. Middleton, O., Atherton, D., Bundock, E., Donner, E., Friedman, D., & Hesdorffer, D. et al. (2018). National Association of Medical Examiners position paper: Recommendations for the investigation and certification of deaths in people with epilepsy. Epilepsia, 59(3), 530-543. doi: 10.1111/epi.14030
  59. Ryvlin, P., So, E., Gordon, C., Hesdorffer, D., Sperling, M., & Devinsky, O. et al. (2018). Long-term surveillance of SUDEP in drug-resistant epilepsy patients treated with VNS therapy. Epilepsia, 59(3), 562-572. doi: 10.1111/epi.14002
  60. Devinsky, O., Friedman, D., Duckrow, R., Fountain, N., Gwinn, R., & Leiphart, J. et al. (2018). Sudden unexpected death in epilepsy in patients treated with brain-responsive neurostimulation. Epilepsia, 59(3), 555-561. doi: 10.1111/epi.13998
  61. Rheims, S., Alvarez, B., Alexandre, V., Curot, J., Maillard, L., & Bartolomei, F. et al. (2018). Hypoxemia following generalized convulsive seizures. Neurology, 92(3), e183-193. doi: 10.1212/wnl.0000000000006777
  62. Elzawahry, H., Do, C., Lin, K., & Benbadis, S. (2010). The diagnostic utility of the ictal cry. Epilepsy & Behavior, 18(3), 306-307. doi: 10.1016/j.yebeh.2010.04.041
  63. Ryvlin, P., Ciumas, C., Wisniewski, I., & Beniczky, S. (2018). Wearable devices for sudden unexpected death in epilepsy prevention. Epilepsia, 59(S.1), 61-66. doi: 10.1111/epi.14054
  64. Beniczky, S., Conradsen, I., & Wolf, P. (2018). Detection of convulsive seizures using surface electromyography. Epilepsia, 59(S.1), 23-29. doi: 10.1111/epi.14048
  65. Arends, J. (2018). Movement-based seizure detection. Epilepsia, 59(S.1), 30-35. doi: 10.1111/epi.14053
  66. Bartlam, R., & Mohanraj, R. (2016). Ictal bradyarrhythmias and asystole requiring pacemaker implantation: Combined EEG–ECG analysis of 5 cases. Epilepsy & Behavior, 64(Pt.A), 212-215. doi: 10.1016/j.yebeh.2016.06.026
  67. Arends, J., Thijs, R., Gutter, T., Ungureanu, C., Cluitmans, P., & Van Dijk, J. et al. (2018). Multimodal nocturnal seizure detection in a residential care setting. Neurology, 91(21), e2010-2019. doi: 10.1212/wnl.0000000000006545
  68. Jory, C., Shankar, R., Coker, D., McLean, B., Hanna, J., & Newman, C. (2016). Safe and sound? A systematic literature review of seizure detection methods for personal use. Seizure, 36, 4-15. doi: 10.1016/j.seizure.2016.01.013
  69. Xu, Z., Ayyappan, S., & Seneviratne, U. (2015). Sudden unexpected death in epilepsy (SUDEP): What do patients think?. Epilepsy & Behavior, 42, 29-34. doi: 10.1016/j.yebeh.2014.11.007
  70. Radhakrishnan, D., Ramanujam, B., Srivastava, P., Dash, D., & Tripathi, M. (2018). Effect of providing sudden unexpected death in epilepsy (SUDEP) information to persons with epilepsy (PWE) and their caregivers-Experience from a tertiary care hospital. Acta Neurologica Scandinavica, 138(5), 417-424. doi: 10.1111/ane.12994
  71. Farrell, K. (2018). SUDEP Challenge Initiative. Retreived from https://www.epilepsy.com/living-epilepsy/our-programs/sudep-institute/sudep-challenge-initiative

How to Cite

1.
Marienko LB, Marienko KM. Sudden unexpected death in epilepsy: a review of literature and own observations. Zaporozhye Medical Journal [Internet]. 2019Dec.11 [cited 2026May15];21(6). Available from: https://zmj.zsmu.edu.ua/article/view/186718

Issue

Section

Review