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

Eur J Paediatr Neurol. 2021 May 26;33:75-85. doi: 10.1016/j.ejpn.2021.05.010. Online ahead of print.ABSTRACTCACNA1A 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 refracto...

Source: European Journal of Paediatric Neurology - June 8, 2021 Category: Neurology Authors: Marie Le Roux Magalie Barth Sophie Gueden Patrick Desbordes de Cepoy Alec Aeby Catheline Vilain Edouard Hirsch Anne de Saint Martin Vincent des Portes Ga ëtan Lesca Audrey Riquet Laurence Chaton Nathalie Villeneuve Laurent Villard Claude Cances Luc Valto Source Type: research