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

Эпилепсия и пароксизмальные состояния

E. D. Belousova¹  M. A. Shkolnikova¹ 

[1] N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia;

关键词: sudden unexpected death in epilepsy;    sudep;    genetic epileptic encephalopathies;    “neurocardiac” genes;    arrhythmias;    dravet syndrome;   

DOI  :  10.17749/2077-8333.2018.10.3.063-070

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown