Preview

Epilepsy and paroxysmal conditions

Advanced search

Sudden unexpected death in genetic epileptic encephalopathies: a role of neurocardiac genes

https://doi.org/10.17749/2077-8333.2018.10.3.063-070

Full Text:

Abstract

It is well known that sudden unexpected death in epilepsy (SUDEP) is one of the most significant factors of mortality in epileptic patients. There is an increased risk of SUDEP in genetic epileptic encephalopathies (EE), partly because those syndromes are associated with mutations in the “neurocardiac” genes, which have been implicated in both epilepsy and cardiac arrhythmias. In these clinical conditions, functions of ion selective channels (sodium, potassium and etc.) are affected; for example, in children with Dravet syndrome, the risk of SUDEP is 40 times higher than that in children with common epilepsy syndromes. In a murine model of SCN1A epilepsy, a prolongation of QT interval coincided with a seizure; in addition, an excessive excitability of cultured cardiomyocytes was demonstrated. A high risk of SUDEP is characteristic for EE caused by mutation in the SCN8A gene. Other prognostic biomarkers of SUDEP may include mutations in sodium channel genes, such as SCN4A, SCN10A, and SCN11A. Our knowledge about SUDEP associated with potassium channel dysfunctions is still very limited. There are likely some mutations in other genes, that can modify (increase or decrease) the risk of SUDEP in EE. If patients with genetic EE are indeed at a high risk for SUDEP, they must be followed up by cardiologists alongside with neurologists. Provided this hypothesis is proved, any newly diagnosed arrhythmia should be carefully monitored and treated (with medications and/or interventions), in order to improve the survival rate in genetic EE.

About the Authors

E. D. Belousova
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation

Belousova Elena Dmitrievna – MD, PhD (Med. Sciences), Professor, Head of the Department of Psychoneurology and Epileptology.

1 Ostrovityanova Str., Moscow 117997



M. A. Shkolnikova
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation

Shkolnikova Mariya Aleksandrovna – MD, PhD (Med. Sciences), Scientific Director of the Pediatric Scientific and Clinical Center of Cardiac Arrhythmias; Head of the Research and Clinical Institute of Pediatrics, Pirogov RNRMU.

Ул. Островитянова, д. 1, Москва 117997, tel.: +7(495)484-02-92



References

1. Jones L. A., Thomas R. H. Sudden death in epilepsy: Insights from the last 25 years. Seizure. 2017 Jan; 44: 232-236. DOI: 10.1016/j.seizure.2016.10.002.

2. Nashef L., So E. L., Ryvlin P., Tomson T. Unifying the definitions of sudden unexpected death in epilepsy. Epilepsia. 2012; 53 (2): 227-33. DOI: 10.1111/j.528-67.2011.03358.x4.

3. Bagnall R. D., Crompton D. E., Semsarian C. Genetic Basis of Sudden Unexpected Death in Epilepsy. Front Neurol. 2017 Jul 20; 8: 348. DOI: 10.3389/fneur.2017.00348.

4. Scheffer I. E., Berkovic S., Capovilla G., Connolly M. B., French J., Guilhoto L., Hirsch E., Jain S., Mathern G. W., Moshé S. L., Nordli D. R., Perucca E., Tomson T., Wiebe S., Zhang Y. H., Zuberi S. M. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr; 58 (4): 512-521. DOI: 10.1111/epi.13709.

5. OMIM (On-line mendelian inheritance of man). Website: https://www.omim.org/search/?index=entry&sort=score+desc%2C+prefix_sort+desc&start=1&limit=10&search=Early+infantile+epileptic+encephalopathy. Accessed: 14.06.2018.

6. Cooper M. S., Mcintosh A., Crompton D. E., McMahon J.M., Schneider A., Farrell K., Ganesan V., Gill D., Kivity S., Lerman-Sagie T., McLellan A., Pelekanos J., Ramesh V., Sadleir L., Wirrell E., Scheffer I. E. Mortality in Dravet syndrome. Epilepsy Res. 2016 Dec; 128: 43-47. DOI: 10.1016/j.eplepsyres.2016.10.006.

7. Nei M., Sperling M. R., Mintzer S., Ho R. T. Long-term cardiac rhythm and repolarization abnormalities in refractory focal and generalized epilepsy. Epilepsia. 2012; 53: e137-40.

8. Schuele S. U. Effects of seizures on cardiac function. Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society. 2009; 26: 302-8.

9. Shmuely S., Sisodiya S. M., Gunning W. B., Sander J. W., Thijs R. D. Mortality in Dravet syndrome: A review. Epilepsy Behav. 2016 Nov; 64 (Pt A): 69-74. DOI: 10.1016/j.yebeh.2016.09.007.

10. Harden C., Tomson T., Gloss D., Buchhalter J., Cross J. H., Donner E., French J. A., Gil-Nagel A., Hesdorffer D. C., Smithson W. H., Spitz M. C., Walczak T. S. Sander J. W., Ryvlin P. 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 Apr 25; 88 (17): 1674-1680. DOI: 10.1212/WNL.0000000000003685.

11. Auerbach D. S., Jones J., Clawson B. C., Offord J., Lenk G. M., Ogiwara I., Yamakawa K., Meisler M. H., Parent J. M., Isom L. L. Altered cardiac electrophysiology and SUDEP in a model of Dravet syndrome. PLoS One. 2013 Oct 14; 8 (10): e77843. DOI: 10.1371/journal.pone.0077843.

12. Glasscock E. Genomic biomarkers of SUDEP in brain and heart. Epilepsy Behav. 2014 Sep; 38: 172-9. DOI: 10.1016/j.yebeh.2013.09.019.

13. Coll M., Allegue C., Partemi S., Mates J., Del Olmo B., Campuzano O., Pascali V., Iglesias A., Striano P., Oliva A., Brugada R. Genetic investigation of sudden unexpected death in epilepsy cohort by panel target resequencing. Int J Legal Med. 2016 Mar; 130 (2): 331-9. DOI: 10.1007/s00414-015-1269-0.

14. Coll M., Striano P., Ferrer-Costa C., Campuzano O., Matés J., Del Olmo B., Iglesias A., Pérez-Serra A., Mademont I., Picó F., Oliva A., Brugada R. Targeted next generation sequencing provides novel clues for associated epilepsy and cardiac conduction dis-order/SUDEP. PLoS One. 2017 Dec 19; 12 (12): e0189618. DOI: 10.1371/journal.pone.0189618.

15. Parisi P., Oliva A., Coll Vidal M., Partemi S., Campuzano O., Iglesias A., Pisani D., Pascali V.L, Paolino M. C., Villa M. P., Zara F., Tassinari C. A., Striano P., Brugada R. Coexistence of epilepsy and Brugada syndrome in a family with SCN5Amutation. Epilepsy Res. 2013 Aug; 105 (3): 415-8. DOI: 10.1016/j.eplepsyres.2013.02.024.

16. Tiron C., Campuzano O., Pérez-Serra A., Mademont I., Coll M., Allegue C., Iglesias A., Partemi S., Striano P., Oliva A., Brugada R. Further evidence of the association between LQT syndrome and epilepsy in a family with KCNQ1pathogenic variant. Seizure. 2015 Feb; 25: 65-7. DOI: 10.1016/j.seizure.2015.01.003.

17. Chanséaume A., Millat G., Roux A. KCNH2 gene new mutation in a patient with prior diagnosis of epilepsy. Rev Neurol (Paris). 2014 Apr; 170 (4): 304-5. DOI: 10.1016/j.neurol.2013.12.006.

18. Goldman A. M., Behr E. R., Semsarian C., Bagnall R. D., Sisodiya S., Cooper P. N. Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention. Epilepsia. 2016 Jan; 57 Suppl 1: 17-25. DOI: 10.1111/epi.13232.

19. Dongli Zhang, Xiaoming Liu, Xingqiang Deng. Genetic basis of pediatric epilepsy syndromes (review). Experimental and therapeutic medicine. 2017; 13: 2129-2133. DOI: 10.3892/etm.2017.4267.

20. Shbarou R., Mikati M. A. The Expanding Clinical Spectrum of Genetic Pediatric Epileptic Encephalopathies. Semin Pediatr Neurol. 2016 May; 23 (2): 134-42. DOI: 10.1016/j.spen.2016.06.002.

21. Surges R., Taggart P., Sander J. W., Walker M. C. 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. DOI: 10.1111/j.1528-1167.2010.02571.x.

22. Ergul Y., Ekici B. Tatli B. Nisli K. Ozmen M. QT and P wave dispersion and heart rate variability in patients with Dravet syndrome. Acta Neurol Belg. 2013 Jun; 113 (2): 161-6. DOI: 10.1007/s13760-012-0140-z.

23. Auerbach D. S., Jones J., Clawson B. C., Offord J., Lenk G. M., Ogiwara I., Yamakawa K., Meisler M. H., Parent J. M., Isom L. L. Altered cardiac electrophysiology and SUDEP in a model of Dravet syndrome. PLoS One. 2013 Oct 14; 8 (10): e77843. DOI: 10.1371/journal.pone.0077843.

24. Frasier C. R., Wagnon J. L., Bao Y. O., McVeigh L.G., Lopez-Santiago L.F., Meisler M. H., Isom L. L. Сarrhythmia ina mouse model of sodium channel SCN8A epileptic encephalopathy. Proc Natl Acad Sci U S A. 2016 Oct 26; PII: 201612746.

25. Mishra V., Karumuri B. K., Gautier N. M., Liu R., Hutson T. N., Vanhoof-Villalba S.L., Vlachos I., Iasemidis L., Glasscock E. Scn2a deletion improves survival and brain-heart dynamics in the Kcna1null mouse model of sudden unexpected death in epilepsy (SUDEP). Hum Mol Genet. 2017 Jun 1; 26 (11): 2091-2103. DOI: 10.1093/hmg/ddx104.


For citation:


Belousova E.D., Shkolnikova M.A. Sudden unexpected death in genetic epileptic encephalopathies: a role of neurocardiac genes. Epilepsy and paroxysmal conditions. 2018;10(3):63-70. (In Russ.) https://doi.org/10.17749/2077-8333.2018.10.3.063-070

Views: 120


ISSN 2077-8333 (Print)
ISSN 2311-4088 (Online)