دورية أكاديمية
أعرض في EDS

CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients.

التفاصيل البيبلوغرافية
العنوان: CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients.
المؤلفون: Le Roux M; Department of Pediatric Neurology and Neurosurgery, CHU Angers, France. Electronic address: Marie.Le-Roux@chu-angers.fr., Barth M; Department of Medical Genetics, CHU Angers, France., Gueden S; Department of Pediatric Neurology and Neurosurgery, CHU Angers, France., Desbordes de Cepoy P; Department of Pediatric Radiology, CHU Angers, France., Aeby A; Department of Pediatric Neurology, HUDERF, Bruxelles, Belgium., Vilain C; Department of Medical Genetics, Erasme Hospital, Bruxelles, Belgium., Hirsch E; Department of Neurology, CHU Strasbourg, France., de Saint Martin A; Department of Pediatrics, CHU Strasbourg, France., Portes VD; Department of Pediatric Neurology, Hospices civils de Lyon, Bron, France., Lesca G; Department of Genetics, Hospices civils de Lyon, Bron, France., Riquet A; Department of Pediatric Neurology, CHRU Lille, France., Chaton L; Department of Neurophysiology, CHRU Lille, France., Villeneuve N; Department of Pediatric Neurology, Hôpital de La Timone, AP-HM, Marseille, France., Villard L; Department of Medical Genetics, Hôpital de La Timone, AP-HM, Marseille, France; Aix Marseille Univ, Inserm, Marseille Medical Genetics, U1251, Marseille, France., Cances C; Department of Pediatric Neurology, CHU Purpan, Toulouse, France., Valton L; Explorations Neurophysiologiques, CHU Purpan, Toulouse, France; Centre de Recherche Cerveau et Cognition (CerCo), University of Toulouse, Toulouse F, 31300, France., Renaldo F; Department of Pediatric Neurology, Hôpital Trousseau, Assistance publique-Hôpitaux de Paris, France., Vermersch AI; Department of Neurophysiology, Hôpital Trousseau, Assistance publique-Hôpitaux de Paris, France., Altuzarra C; Department of Pediatrics, CHU Besançon, France., Nguyen-Morel MA; Department of Pediatric Neurology, CHU Grenoble Alpes, France., Van Gils J; Department of Medical Genetics, CHU Bordeaux Pellegrin, Bordeaux, France., Angelini C; Department of Medical Genetics, CHU Bordeaux Pellegrin, Bordeaux, France., Biraben A; Department of Neurology, CHU Rennes Pontchaillou, Rennes, France., Arnaud L; Department of Genetics, Hôpital de la Pitie Salpetrière, Assistance publique-Hôpitaux de Paris, France., Riant F; Department of Genetics, Groupe hospitalier Saint Louis-Lariboisière, Assistance publique-Hôpitaux de Paris, France., Van Bogaert P; Department of Pediatric Neurology and Neurosurgery, CHU Angers, France; Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers, France.
المصدر: European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society [Eur J Paediatr Neurol] 2021 Jul; Vol. 33, pp. 75-85. Date of Electronic Publication: 2021 May 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Saunders Country of Publication: England NLM ID: 9715169 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-2130 (Electronic) Linking ISSN: 10903798 NLM ISO Abbreviation: Eur J Paediatr Neurol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London ; Philadelphia : Saunders, c1997-
مواضيع طبية MeSH: Epilepsy*/drug therapy , Epilepsy*/genetics , Seizures*/etiology , Seizures*/genetics, Calcium Channels/*genetics, Ataxia ; Child, Preschool ; Female ; Humans ; Male ; Spinocerebellar Ataxias
مستخلص: CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly documented. We studied 18 patients (10 males) carrying de novo or inherited CACNA1A mutations, with median age of 2,5 years at epilepsy onset. Eight mutations were novel. Two variants known leading to gain of function (GOF) were found in 5 patients. Five other patients had non-sense variants leading to loss of function (LOF). Seizures were most often revealed by either status epilepticus (SE) (n = 8), eventually triggered by fever (n = 5), or absences/behavioural arrests (n = 7). Non-epileptic paroxysmal events were frequent and consisted in recurrent hemiplegic accesses (n = 9), jitteriness in the neonatal period (n = 6), and ocular paroxysmal events (n = 9). Most of the patients had early permanent cerebellar dysfunction (n = 16) and early moderate to severe global developmental delay (GDD)/intellectual deficiency (ID) (n = 17). MRI was often abnormal, with cerebellar (n = 8) and/or cerebral (n = 6) atrophy. Stroke-like occurred in 2 cases. Some antiepileptic drugs including topiramate, levetiracetam, lamotrigine and valproate were effective on seizures. Acetazolamide and calcium channel blockers were often effective when used. More than half of the patients had refractory epilepsy. CACNA1A mutation should be evoked in front of 2 main electro-clinical phenotypes that are associated with permanent cerebellar dysfunction and moderate to severe GDD/ID. The first one, found in all 5 patients with GOF variants, is characterized by intractable seizures, early and recurrent SE and hemiplegic accesses. The second, less severe, found in 5 patients with LOF variants, is characterized by refractory early onset absence seizures.
Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose.
(Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)
فهرسة مساهمة: Keywords: Absence seizure; CACNA1A; Drug-resistance; Lennox-gastaut syndrome; Status epilepticus; Stroke-like
المشرفين على المادة: 0 (CACNA1A protein, human)
0 (Calcium Channels)
تواريخ الأحداث: Date Created: 20210608 Date Completed: 20211012 Latest Revision: 20211012
رمز التحديث: 20240628
DOI: 10.1016/j.ejpn.2021.05.010
PMID: 34102571
قاعدة البيانات: MEDLINE
الوصف
تدمد:1532-2130
DOI:10.1016/j.ejpn.2021.05.010