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

Autor: Jamel Chelly, Fabienne Picard, Kristine Lossius, Caroline Seegmuller, Sverre Myren-Svelstad, Marit Bjørnvold, Guro Minken, Anne de Saint Martin, Maria Paola Valenti Hirsch, Ortrud K. Steinlein, Eylert Brodtkorb
Přispěvatelé: Oslo University Hospital [Oslo], CHU Strasbourg, Norwegian University of Science and Technology (NTNU), St. Olavs Hospital HF (St. Olav's University Hospital), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ludwig-Maximilians-Universität München (LMU), University Hospital and Medical School of Geneva
Rok vydání: 2019
Předmět:
Male
Pediatrics
Mutation / genetics
medicine.medical_treatment
Autosomal dominant sleep-related hypermotor epilepsy (ADSHE)
Receptors
Nicotinic
Nicotine
Behavioral Neuroscience
Epilepsy
0302 clinical medicine
Receptors
Nicotinic / genetics
030212 general & internal medicine
Child
Epilepsy
Reflex / genetics
Cognition
Executive functions
Sleep / drug effects
Tobacco Use Cessation Devices
Desensitization (psychology)
Nicotinic acetylcholine receptor
Nicotinic agonist
Treatment Outcome
Neurology
medicine.drug
medicine.medical_specialty
Adolescent
Alpha (ethology)
Epilepsy
Reflex
03 medical and health sciences
p.S280F-CHRNA4
medicine
Nicotine / administration & dosage
Humans
[SDV.GEN]Life Sciences [q-bio]/Genetics
Precision therapy
business.industry
P.S280F-CHRNA4
medicine.disease
ddc:616.8
Epilepsy
Reflex / drug therapy
Epilepsy
Reflex / diagnosis
Mutation
Sleep / genetics
Neurology (clinical)
business
Sleep
030217 neurology & neurosurgery
Zdroj: Epilepsy & Behavior
Epilepsy & Behavior, [San Diego CA]: Elsevier B.V., 2020, 105, ⟨10.1016/j.yebeh.2020.106944⟩
Epilepsy & behavior, Vol. 105 (2020) P. 106944
ISSN: 1525-5069
1525-5050
Popis: 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. © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
Databáze: OpenAIRE
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