Severe peri-ictal respiratory dysfunction is common in Dravet syndrome
| Autor: | Xiuqiong Zhou, YuJaung Kim, Se Hee Kim, George B. Richerson, Eduardo Bravo, Brian K. Gehlbach, Douglas R. Nordli, Linda Laux, Caitlin K. Thirnbeck, Lori A. Smith-Mellecker |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Bradycardia medicine.medical_specialty Genotype Central apnea Video Recording Epilepsies Myoclonic Muscarinic Antagonists Hypoxemia Death Sudden Electrocardiography Mice 03 medical and health sciences Epilepsy 0302 clinical medicine Dravet syndrome Parasympathetic Nervous System Seizures Internal medicine Animals Humans Medicine Ictal Child Mice Inbred C3H Electromyography business.industry Apnea Electroencephalography Hypoventilation General Medicine Respiration Disorders medicine.disease Receptors Muscarinic Respiration Artificial NAV1.1 Voltage-Gated Sodium Channel Plethysmography 030104 developmental biology Mutation Cardiology Female medicine.symptom business 030217 neurology & neurosurgery Research Article |
| Zdroj: | Journal of Clinical Investigation. 128:1141-1153 |
| ISSN: | 1558-8238 0021-9738 |
| DOI: | 10.1172/jci94999 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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