Remarkable effect of transdermal nicotine in children with CHRNA4-related autosomal dominant sleep-related hypermotor epilepsy.

Autor: Lossius K; National Centre for Epilepsy, Division for Clinical Neuroscience, Oslo University Hospital, Oslo, Norway., de Saint Martin A; Pediatric Neurology, Reference Center for Rare Epilepsies, Strasbourg University Hospital, France., Myren-Svelstad S; Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, St. Olav University Hospital, Trondheim, Norway. Electronic address: s@myren-svelstad.no., Bjørnvold M; National Centre for Epilepsy, Division for Clinical Neuroscience, Oslo University Hospital, Oslo, Norway., Minken G; National Centre for Epilepsy, Division for Clinical Neuroscience, Oslo University Hospital, Oslo, Norway., Seegmuller C; Pediatric Neurology, Reference Center for Rare Epilepsies, Strasbourg University Hospital, France; Neurology Department, Reference Center for Rare Epilepsies, Strasbourg University Hospital, France., Valenti Hirsch MP; Neurology Department, Reference Center for Rare Epilepsies, Strasbourg University Hospital, France., Chelly J; Genetic Department, Strasbourg University, Hospital, IGBMC, INSERM, CNRS, Strasbourg University, France., Steinlein O; Institute of Human Genetics, University Hospital, Ludwig Maximillian University of Munich, Munich, Germany., Picard F; EEG and Epilepsy Unit, Department of Neurology, University Hospitals and Medical School of Geneva, Geneva, Switzerland., Brodtkorb E; Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, St. Olav University Hospital, Trondheim, Norway.
Jazyk: angličtina
Zdroj: Epilepsy & behavior : E&B [Epilepsy Behav] 2020 Apr; Vol. 105, pp. 106944. Date of Electronic Publication: 2020 Feb 22.
DOI: 10.1016/j.yebeh.2020.106944
Abstrakt: Objective: Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is characterized by hypermotor seizures and may be caused by gain-of-function mutations affecting the nicotinic acetylcholine receptor (nAChR). Benefit from nicotine consumption has been reported in adult patients with this disorder. For the first time, the effect of transdermal nicotine is evaluated in children.
Methods: Transdermal nicotine was applied to three boys, two aged 10 years (7 mg/24 h) and one six years (3.5 mg/24 h). Autosomal dominant sleep-related hypermotor epilepsy was caused by the p.S280F-CHRNA4 (cholinergic receptor, nicotinic, alpha polypeptide 4) mutation. The children suffered from frequent, persistent nocturnal seizures and had developed educational and psychosocial problems. Seizure frequency and cognitive and behavioral parameters were assessed before and after treatment.
Results: A striking seizure reduction was reported soon after treatment onset. Hypermotor seizures disappeared; only sporadic arousals, sometimes with minor motor elements, were observed. Psychometric testing documented improvement in cognitive domains such as visuospatial ability, processing speed, memory, and some areas of executive functions.
Significance: Nicotine appears to be a mechanistic treatment for this specific disorder, probably because of desensitization of the mutated receptors. It may control seizures resistant to conventional drugs for epilepsy and impact socioeducational function in children. This mode of precision therapy should receive more attention and should be available to more patients with uncontrolled CHRNA4-related ADSHE across the age span.
Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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