Head Epilepsy Unit, Department of Neuroscience Bambino Gesu' Children's Hospital, IRCCS
Rationale: Genetic epilepsies result directly from a known or presumed genetic mutation. Seizures in these conditions are a core symptom of the disorder. A causative genetic variant can be disclosed in 30–50% of infants, often presenting with severe DEE. In several cases with suspected or confirmed severe genetic epilepsies seizures, conventional anti-seizure medications (ASMs) are ineffective, and resective surgery is not feasible. VNS has shown positive effects for the treatment of some well-known genetic DEE as Dravet syndrome, Lennox Gastaut syndrome, and epilepsy with myoclonic-atonic seizures. VNS is supposed to act through a modulation of electrical stimuli to the nucleus tractus solitarius and the brainstem reticular formation, and it seems to interrupt the synchronous activity of seizures. Aim of this study is to describe a cohort of patients with genetic DEE treated with VNS. Methods: Comprehensive Outcomes Registry in Subjects with Epilepsy Treated with Vagus Nerve Stimulation Therapy (CORE-VNS, NCT 03529045) is a registry collecting data related to patients with drug-resistant epilepsies treated with VNS. The registry started in 2018 and is up and running in 63 centers in 18 countries around the world. In this specific analysis we collected clinical data of patients with genetic or suspected genetic epilepsies enrolled in the CORE-VNS study in order to profile trends in VNS option in patients with genetic DEE. Results: A total of 558 patients consented to participate in this study as of June 10, 2020 and had epilepsy and seizure history data reported. Within this number, 157 (28.1%) underwent genetic testing. Out of these 157 patients with suspected genetic epilepsy, 72 (45.9%) were carrying a genetic abnormality which was likely correlated with the epilepsy phenotype. In this group, epilepsy diagnosis was made before age 1 in 41.7% of patients and at an average age of 3.1±4.3 years (Interquartile range 0.5-5). The most frequently reported epilepsy syndromes confirmed by genetic testing included Lennox Gastaut syndrome (n=7), Dravet syndrome (n=6), Tuberous Sclerosis (n=5) and Infantile Spasms/West Syndrome (n=4). All patients diagnosed with Dravet syndrome had a mutation in the SCN1A gene. Seven different genetic mutations were identified for patients with Lennox Gastaut syndrome. Other syndromes included outside DEE were, Juvenile Absence Epilepsy (n=2), and Juvenile Myoclonic Epilepsy (n=1), in 47 patients epileptic syndrome was unknown or unclassified. Updated description of the population’s characteristics (including age at diagnosis of epilepsy, age at VNS implantation, epilepsy syndromes, type of seizures, genetic variant, number of ASMs at VNS implantation will be presented. Moreover, data following the most frequent epileptic syndromes will be grouped. Conclusions: VNS is a therapeutic approach that is frequently considered in patients with genetic DEE, and in patients with non-surgical severe epilepsies. Data coming from clinical practice in highly specialized centers around the world confirm that VNS is part of therapeutic algorithm in severe DEE and drug resistant epilepsies. Funding: Please list any funding that was received in support of this abstract.: LivaNova provided statistical support and medical writing assistance.