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Severe peri-ictal respiratory dysfunction is common in Dravet syndrome.
Kim, YuJaung; Bravo, Eduardo; Thirnbeck, Caitlin K; Smith-Mellecker, Lori A; Kim, Se Hee; Gehlbach, Brian K; Laux, Linda C; Zhou, Xiuqiong; Nordli, Douglas R; Richerson, George B.
Afiliação
  • Kim Y; Department of Neurology and.
  • Bravo E; Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA.
  • Thirnbeck CK; Department of Neurology and.
  • Smith-Mellecker LA; Department of Neurology and.
  • Kim SH; Department of Neurology and.
  • Gehlbach BK; Division of Pediatric Neurology, Northwestern University, Chicago, Illinois, USA.
  • Laux LC; Department of Internal Medicine and.
  • Zhou X; Division of Pediatric Neurology, Northwestern University, Chicago, Illinois, USA.
  • Nordli DR; Department of Neurology and.
  • Richerson GB; Division of Pediatric Neurology, Northwestern University, Chicago, Illinois, USA.
J Clin Invest ; 128(3): 1141-1153, 2018 03 01.
Article em En | MEDLINE | ID: mdl-29329111
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Epilepsias Mioclônicas / Morte Súbita / Epilepsia Limite: Animals / Child / Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Epilepsias Mioclônicas / Morte Súbita / Epilepsia Limite: Animals / Child / Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article