Download PDF
Aktuelle Neurologie 2016; 43(04): 230-236
DOI: 10.1055/s-0041-110668
Neues in der Neurologie
© Georg Thieme Verlag KG Stuttgart · New York

Epidemiologie, Pathophysiologie und Prävention des SUDEP

Epidemiology, Pathophysiology and Prevention of SUDEP
K. G. Hampel
1   Klinik für Epileptologie, Universitätsklinik Bonn, Bonn
,
C. E. Elger
1   Klinik für Epileptologie, Universitätsklinik Bonn, Bonn
,
R. Surges
1   Klinik für Epileptologie, Universitätsklinik Bonn, Bonn
› Author Affiliations
Further Information

Publication History

Publication Date:
18 May 2016 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Der plötzliche und unerwartete Tod bei Epilepsie (SUDEP) ist eine häufige Ursache für das vorzeitige Versterben von Menschen mit Epilepsie. Die meisten SUDEP-Fälle ereignen sich nachts bzw. sind oft unbeobachtet, sodass die zugrundeliegenden Pathomechanismen nicht abschließend geklärt sind. Es wird jedoch vermutet, dass der SUDEP in den meisten Fällen eine tödliche Komplikation epileptischer Anfälle ist. Nach den bisherigen Erkenntnissen beruht er auf einer Suppression der Herz- und Atmungstätigkeit in der frühen Phase nach generalisierten tonisch-klonischen Anfällen, welche schließlich in einem terminalen Herzkreislaufstillstand endet. Verschiedene Faktoren scheinen das SUDEP-Risiko zu erhöhen. So sind junge männliche Erwachsene mit unkontrollierten generalisierten tonisch-klonischen Anfällen besonders gefährdet, an einem SUDEP zu versterben. Gegenstand derzeitiger Forschung sind u. a. mögliche genetische Ursachen sowie strukturelle und funktionelle Hirnfunktionsstörungen, woraus künftig ggf. Biomarker abgeleitet werden, die zur individuellen Risikoeinschätzung beitragen können. Die effektive medikamentöse Therapie ist die bisher einzige evidenzbasierte Präventionsmaßnahme. Wahrscheinlich kann eine nächtliche Supervision das SUDEP-Risiko reduzieren und eine frühzeitig einsetzende kardiopulmonale Reanimation den SUDEP verhindern. In dieser Übersichtsarbeit werden wichtige Erkenntnisse zusammengefasst, neue Forschungsansätze kritisch diskutiert und ein für den klinischen Alltag relevantes Fazit gezogen.

Abstract

Sudden unexpected death in epilepsy (SUDEP) is a frequent cause of premature death in people with epilepsy. Most SUDEP cases occur at night and are often unobserved, so that its underlying pathomechanisms are not fully understood. Most SUDEP cases, however, are most likely a fatal complication of epileptic seizures. According to recent studies, SUDEP is caused by a suppression of cardiorespiratory activity in the early phase following generalized tonic-clonic seizures that finally leads to death. Several factors appear to increase the risk of SUDEP; for instance, young male epilepsy patients with uncontrolled generalized tonic-clonic seizures die more frequently from SUDEP than other patients. Recent research aims at identifying genetic causes as well as structural and functional cerebral dysfunction, which may enable the future development of biomarkers for increased SUDEP risk. So far, effective anticonvulsive drug therapy is the only evidence-based preventive measure. Nocturnal supervision of people with epilepsy may reduce the risk of SUDEP, and early cardiopulmonary resuscitation may also prevent SUDEP. This review summarizes important facts, critically discusses new findings in SUDEP research and draws conclusions that are relevant for the daily clinical practice.

Schlüsselwörter

plötzlicher Tod bei Epilepsie - Biomarker - Mortalität - SUDEP - Epilepsie

Keywords

sudden death in epilepsy - SUDEP - biomarker - epilepsy - mortality
 

  • Literatur

  • 1 Forsgren L, Beghi E, Oun A et al. The epidemiology of epilepsy in Europe – a systematic review. Eur J Neurol 2005; 12: 245-253
    CrossrefPubMedGoogle Scholar
  • 2 Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342: 314-319
    CrossrefPubMedGoogle Scholar
  • 3 Ficker DM, So EL, Shen WK et al. Population-based study of the incidence of sudden unexplained death in epilepsy. Neurology 1998; 51: 1270-1274
    CrossrefPubMedGoogle Scholar
  • 4 Mohanraj R, Norrie J, Stephen LJ et al. Mortality in adults with newly diagnosed and chronic epilepsy: a retrospective comparative study. Lancet Neurol 2006; 5: 481-487
    CrossrefPubMedGoogle Scholar
  • 5 Thurman DJ, Hesdorffer DC, French JA. Sudden unexpected death in epilepsy: assessing the public health burden. Epilepsia 2014; 55: 1479-1485
    CrossrefPubMedGoogle Scholar
  • 6 Krämer G, Wieser HG, Tuxhorn I et al. Königsteiner Arbeitskreis für Epilepsie. Plötzlicher, unerwarteter Tod bei Epilepsie (SUDEP). Zeitschrift für Epileptologie 2007; 20: 72-75
    CrossrefPubMedGoogle Scholar
  • 7 Nashef L. Sudden unexpected death in epilepsy: terminology and definitions. Epilepsia 1997; 38: S6-S8
    PubMedGoogle Scholar
  • 8 Nashef L, So EL, Ryvlin P et al. Unifying the definitions of sudden unexpected death in epilepsy. Epilepsia 2012; 53: 227-233
    CrossrefPubMedGoogle Scholar
  • 9 Surges R, Thijs RD, Tan HL et al. Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms. Nat Rev Neurol 2009; 5: 492-504
    CrossrefPubMedGoogle Scholar
  • 10 Téllez-Zenteno JF, Ronquillo LH, Wiebe S. Sudden unexpected death in epilepsy: evidence-based analysis of incidence and risk factors. Epilepsy Res 2005; 65: 101-115
    CrossrefPubMedGoogle Scholar
  • 11 Holst AG, Winkel BG, Risgaard B et al. Epilepsy and risk of death and sudden unexpected death in the young: a nationwide study. Epilepsia 2013; 54: 1613-1620
    CrossrefPubMedGoogle Scholar
  • 12 Sillanpää M, Shinnar S. Long-term mortality in childhood-onset epilepsy. N Engl J Med 2010; 363: 2522-2529
    CrossrefPubMedGoogle Scholar
  • 13 Ryvlin P, Nashef L, Lhatoo SD et al. Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study. Lancet Neurol 2013; 12: 966-977
    CrossrefPubMedGoogle Scholar
  • 14 Langan Y, Nashef L, Sander JW. Sudden unexpected death in epilepsy: a series of witnessed deaths. J Neurol Neurosurg Psychiatry 2000; 68: 211-213
    CrossrefPubMedGoogle Scholar
  • 15 Surges R, Taggart P, Sander JW et al. Too long or too short? New insights into abnormal cardiac repolarization in people with chronic epilepsy and its potential role in sudden unexpected death. Epilepsia 2010; 51: 738-744
    CrossrefPubMedGoogle Scholar
  • 16 Lhatoo SD, Faulkner HJ, Dembny K et al. An electroclinical case-control study of sudden unexpected death in epilepsy. Ann Neurol 2010; 68: 787-796
    CrossrefPubMedGoogle Scholar
  • 17 Surges R, Sander JW. Sudden unexpected death in epilepsy: mechanisms, prevalence, and prevention. Curr Opin Neurol 2012; 25: 201-207
    CrossrefPubMedGoogle Scholar
  • 18 Hirsch M, Altenmüller D-M, Schulze-Bonhage A. Latencies from intracranial seizure onset to ictal tachycardia: A comparison to surface EEG patterns and other clinical signs. Epilepsia 2015; 56: 1639-1647
    CrossrefPubMedGoogle Scholar
  • 19 Surges R, Scott CA, Walker MC. Enhanced QT shortening and persistent tachycardia after generalized seizures. Neurology 2010; 74: 421-426
    CrossrefPubMedGoogle Scholar
  • 20 Surges R, Jordan A, Elger CE. Ictal modulation of cardiac repolarization, but not of heart rate, is lateralized in mesial temporal lobe epilepsy. PloS One 2013; 8: e64765
    CrossrefPubMedGoogle Scholar
  • 21 Duplyakov D, Golovina G, Lyukshina N et al. Syncope, seizure-induced bradycardia and asystole: two cases and review of clinical and pathophysiological features. Seizure 2014; 23: 506-511
    CrossrefPubMedGoogle Scholar
  • 22 van der Lende M, Surges R, Sander JW et al. Cardiac arrhythmias during or after epileptic seizures. J Neurol Neurosurg Psychiatry 2015; DOI: 10.1136/jnnp-2015-310559. (im Druck)
    PubMedGoogle Scholar
  • 23 Surges R, Adjei P, Kallis C et al. Pathologic cardiac repolarization in pharmacoresistant epilepsy and its potential role in sudden unexpected death in epilepsy: a case-control study. Epilepsia 2010; 51: 233-242
    CrossrefPubMedGoogle Scholar
  • 24 Lamberts RJ, Blom MT, Wassenaar M et al. Sudden cardiac arrest in people with epilepsy in the community: Circumstances and risk factors. Neurology 2015; 85: 212-218
    CrossrefPubMedGoogle Scholar
  • 25 Stöllberger C, Wegner C, Finsterer J. Seizure-associated Takotsubo cardiomyopathy. Epilepsia 2011; 52: e160-e167
    CrossrefPubMedGoogle Scholar
  • 26 Finsterer J, Bersano A. Seizure-triggered Takotsubo syndrome rarely causes SUDEP. Seizure 2015; 31: 84-87
    CrossrefPubMedGoogle Scholar
  • 27 Nashef L, Walker F, Allen P et al. Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy. J Neurol Neurosurg Psychiatry 1996; 60: 297-300
    CrossrefPubMedGoogle Scholar
  • 28 Bateman LM, Li C-S, Seyal M. Ictal hypoxemia in localization-related epilepsy: analysis of incidence, severity and risk factors. Brain 2008; 131: 3239-3245
    CrossrefPubMedGoogle Scholar
  • 29 Seyal M, Bateman LM, Albertson TE et al. Respiratory changes with seizures in localization-related epilepsy: analysis of periictal hypercapnia and airflow patterns. Epilepsia 2010; 51: 1359-1364
    CrossrefPubMedGoogle Scholar
  • 30 Aiba I, Noebels JL. Spreading depolarization in the brainstem mediates sudden cardiorespiratory arrest in mouse SUDEP models. Sci Transl Med 2015; 7 282ra46
    PubMedGoogle Scholar
  • 31 Hesdorffer DC, Tomson T, Benn E et al. Do antiepileptic drugs or generalized tonic-clonic seizure frequency increase SUDEP risk? A combined analysis. Epilepsia 2012; 53: 249-252
    CrossrefPubMedGoogle Scholar
  • 32 Lamberts RJ, Thijs RD, Laffan A et al. Sudden unexpected death in epilepsy: people with nocturnal seizures may be at highest risk. Epilepsia 2012; 53: 253-257
    CrossrefPubMedGoogle Scholar
  • 33 Hesdorffer DC, Tomson T, Benn E et al. Combined analysis of risk factors for SUDEP. Epilepsia 2011; 52: 1150-1159
    CrossrefPubMedGoogle Scholar
  • 34 Liebenthal JA, Wu S, Rose S et al. Association of prone position with sudden unexpected death in epilepsy. Neurology 2015; 84: 703-709
    CrossrefPubMedGoogle Scholar
  • 35 Clark D, Riney K. A population-based post mortem study of sudden unexpected death in epilepsy. J Clin Neurosci 2015; DOI: 10.1016/j.jocn.2015.04.027.
    PubMedGoogle Scholar
  • 36 George JR, Davis GG. Comparison of anti-epileptic drug levels in different cases of sudden death. J Forensic Sci 1998; 43: 598-603
    PubMedGoogle Scholar
  • 37 Beecham GW, Dickson DW, Scott WK et al. PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease. Neurology 2015; 84: 972-980
    CrossrefPubMedGoogle Scholar
  • 38 Glasscock E. Genomic biomarkers of SUDEP in brain and heart. Epilepsy Behav 2014; 38: 172-179
    CrossrefPubMedGoogle Scholar
  • 39 Loy CT, Schofield PR, Turner AM et al. Genetics of dementia. Lancet 2014; 383: 828-840
    CrossrefPubMedGoogle Scholar
  • 40 Goldman AM, Glasscock E, Yoo J et al. Arrhythmia in heart and brain: KCNQ1 mutations link epilepsy and sudden unexplained death. Sci Transl Med 2009; 1 2ra6
    PubMedGoogle Scholar
  • 41 Johnson JN, Hofman N, Haglund CM et al. Identification of a possible pathogenic link between congenital long QT syndrome and epilepsy. Neurology 2009; 72: 224-231
    CrossrefPubMedGoogle Scholar
  • 42 Tiron C, de Llano CT, Campuzano O et al. Further evidence of the association between LQT syndrome and epilepsy in a family with KCNQ1 pathogenic variant. Seizure 2015; 25: 65-67
    CrossrefPubMedGoogle Scholar
  • 43 Sakauchi M, Oguni H, Kato I et al. Retrospective multiinstitutional study of the prevalence of early death in Dravet syndrome. Epilepsia 2011; 52: 1144-1149
    CrossrefPubMedGoogle Scholar
  • 44 Auerbach DS, Jones J, Clawson BC et al. Altered cardiac electrophysiology and SUDEP in a model of Dravet syndrome. PloS One 2013; 8: e77843
    CrossrefPubMedGoogle Scholar
  • 45 Coll M, Allegue C, Partemi S et al. Genetic investigation of sudden unexpected death in epilepsy cohort by panel target resequencing. Int J Legal Med 2015; DOI: 10.1007/s00414-015-1269-0. (im Druck)
    PubMedGoogle Scholar
  • 46 Bagnall RD, Crompton DE, Cutmore C et al. Genetic analysis of PHOX2B in sudden unexpected death in epilepsy cases. Neurology 2014; 83: 1018-1021
    CrossrefPubMedGoogle Scholar
  • 47 Klassen TL, Bomben VC, Patel A et al. High-resolution molecular genomic autopsy reveals complex sudden unexpected death in epilepsy risk profile. Epilepsia 2014; 55: e6-e12
    CrossrefPubMedGoogle Scholar
  • 48 Leu C, Balestrini S, Maher B et al. Genome-wide Polygenic Burden of Rare Deleterious Variants in Sudden Unexpected Death in Epilepsy. EBioMedicine 2015; 2: 1063-1070
    CrossrefPubMedGoogle Scholar
  • 49 Surges R, Strzelczyk A, Scott CA et al. Postictal generalized electroencephalographic suppression is associated with generalized seizures. Epilepsy Behav 2011; 21: 271-274
    CrossrefPubMedGoogle Scholar
  • 50 Lamberts RJ, Gaitatzis A, Sander JW et al. Postictal generalized EEG suppression: an inconsistent finding in people with multiple seizures. Neurology 2013; 81: 1252-1256
    CrossrefPubMedGoogle Scholar
  • 51 Tang Y, Chen Q, Yu X et al. A resting-state functional connectivity study in patients at high risk for sudden unexpected death in epilepsy. Epilepsy Behav 2014; 41: 33-38
    CrossrefPubMedGoogle Scholar
  • 52 Mueller SG, Bateman LM, Laxer KD. Evidence for brainstem network disruption in temporal lobe epilepsy and sudden unexplained death in epilepsy. NeuroImage Clin 2014; 5: 208-216
    CrossrefPubMedGoogle Scholar
  • 53 Wandschneider B, Koepp M, Scott C et al. Structural imaging biomarkers of sudden unexpected death in epilepsy. Brain 2015; 138: 2907-2919
    CrossrefPubMedGoogle Scholar
  • 54 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: 961-968
    CrossrefPubMedGoogle Scholar
  • 55 Bell GS, Sinha S, de Tisi J et al Premature mortality in refractory partial epilepsy: does surgical treatment make a difference?. J Neurol Neurosurg Psychiatry 2010; 81: 716-718
    CrossrefPubMedGoogle Scholar
  • 56 Ryvlin P, Gilliam FG, Nguyen DK et al. The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long-term Effectiveness) trial. Epilepsia 2014; 55: 893-900
    CrossrefPubMedGoogle Scholar
  • 57 Morris GL, Gloss D, Buchhalter J et al. Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2013; 81: 1453-1459
    CrossrefPubMedGoogle Scholar
  • 58 Granbichler CA, Nashef L, Selway R et al. Mortality and SUDEP in epilepsy patients treated with vagus nerve stimulation. Epilepsia 2015; 56: 291-296
    CrossrefPubMedGoogle Scholar
  • 59 Langan Y, Nashef L, Sander JW. Case-control study of SUDEP. Neurology 2005; 64: 1131-1133
    CrossrefPubMedGoogle Scholar
  • 60 Seyal M, Bateman LM, Li CS. Impact of periictal interventions on respiratory dysfunction, postictal EEG suppression, and postictal immobility. Epilepsia 2013; 54: 377-382
    CrossrefPubMedGoogle Scholar
  • 61 Hoppe C, Feldmann M, Blachut B et al. Novel techniques for automated seizure registration: Patients’ wants and needs. Epilepsy Behav 2015; 52: 1-7
    CrossrefPubMedGoogle Scholar
  • 62 Ramgopal S, Thome-Souza S, Jackson M et al. Seizure detection, seizure prediction, and closed-loop warning systems in epilepsy. Epilepsy Behav 2014; 37: 291-307
    CrossrefPubMedGoogle Scholar
  • 63 Schmidt D, Surges R, May T et al. Bestimmung des Nutzens und des Zusatznutzens von Antiepileptika: eine kritische Übersicht. Aktuelle Neurol 2015; 42: 323-334
    Article in Thieme ConnectPubMedGoogle Scholar
  • 64 Beniczky S, Polster T, Kjaer TW et al. Detection of generalized tonic-clonic seizures by a wireless wrist accelerometer: a prospective, multicenter study. Epilepsia 2013; 54: e58-e61
    CrossrefPubMedGoogle Scholar
  • 65 Faught RE, Weiner JR, Guérin A et al. Impact of nonadherence to antiepileptic drugs on health care utilization and costs: findings from the RANSOM study. Epilepsia 2009; 50: 501-509
    PubMedGoogle Scholar
  • 66 Zhuo L, Zhang Y, Zielke HR et al. Sudden unexpected death in epilepsy: Evaluation of forensic autopsy cases. Forensic Sci Int 2012; 223: 171-175
    CrossrefPubMedGoogle Scholar
  • 67 Brodie MJ, Holmes GL. Should all patients be told about sudden unexpected death in epilepsy (SUDEP)? Pros and Cons. Epilepsia 2008; 49 (Suppl. 09) 99-101
    CrossrefPubMedGoogle Scholar
  • 68 Tonberg A, Harden J, McLellan A et al. A qualitative study of the reactions of young adults with epilepsy to SUDEP disclosure, perceptions of risks, views on the timing of disclosure, and behavioural change. Epilepsy Behav 2015; 42: 98-106
    CrossrefPubMedGoogle Scholar
  • 69 Kroner BL, Wright C, Friedman D et al. Characteristics of epilepsy patients and caregivers who either have or have not heard of SUDEP. Epilepsia 2014; 55: 1486-1494
    CrossrefPubMedGoogle Scholar
  • 70 Xu Z, Ayyappan S, Seneviratne U. Sudden unexpected death in epilepsy (SUDEP): what do patients think?. Epilepsy Behav 2015; 42: 29-34
    CrossrefPubMedGoogle Scholar
  • 71 Friedman D, Donner EJ, Stephens D et al. Sudden unexpected death in epilepsy: knowledge and experience among US and Canadian neurologists. Epilepsy Behav 2014; 35: 13-18
    CrossrefPubMedGoogle Scholar
  • 72 Gayatri NA, Morrall MCHJ, Jain V et al. Parental and physician beliefs regarding the provision and content of written sudden unexpected death in epilepsy (SUDEP) information. Epilepsia 2010; 51: 777-782
    CrossrefPubMedGoogle Scholar
  • 73 Stevenson MJ, Stanton TF. Knowing the risk of SUDEP: two family’s perspectives and The Danny Did Foundation. Epilepsia 2014; 55: 1495-1500
    CrossrefPubMedGoogle Scholar