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Severe peri-ictal respiratory dysfunction is common in Dravet syndrome.

Authors
 YuJaung Kim  ;  Eduardo Bravo  ;  Caitlin K. Thirnbeck  ;  Lori A. Smith-Mellecker  ;  Se Hee Kim  ;  Brian K. Gehlbach  ;  Linda C. Laux  ;  Xiuqiong Zhou  ;  Douglas R. Nordli  ;  George B. Richerson 
Citation
 JOURNAL OF CLINICAL INVESTIGATION, Vol.128(3) : 1141-1153, 2018 
Journal Title
 JOURNAL OF CLINICAL INVESTIGATION 
ISSN
 0021-9738 
Issue Date
2018
Keywords
Epilepsy ; Neuroscience ; Respiration
Abstract
Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly due to mutations of the sodium channel gene SCN1A. Patients with DS have a high risk of sudden unexplained death in epilepsy (SUDEP), widely believed to be due to cardiac mechanisms. Here we show that patients with DS commonly have peri-ictal respiratory dysfunction. One patient had severe and prolonged postictal hypoventilation during video EEG monitoring and died later of SUDEP. Mice with an Scn1aR1407X/+ loss-of-function mutation were monitored and died after spontaneous and heat-induced seizures due to central apnea followed by progressive bradycardia. Death could be prevented with mechanical ventilation after seizures were induced by hyperthermia or maximal electroshock. Muscarinic receptor antagonists did not prevent bradycardia or death when given at doses selective for peripheral parasympathetic blockade, whereas apnea, bradycardia, and death were prevented by the same drugs given at doses high enough to cross the blood-brain barrier. When given via intracerebroventricular infusion at a very low dose, a muscarinic receptor antagonist prevented apnea, bradycardia, and death. We conclude that SUDEP in patients with DS can result from primary central apnea, which can cause bradycardia, presumably via a direct effect of hypoxemia on cardiac muscle.
Files in This Item:
T201800508.pdf Download
DOI
10.1172/JCI94999
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Hee(김세희) ORCID logo https://orcid.org/0000-0001-7773-1942
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162027
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