Abstracts

Rationale: Seizures represent a core symptom of genetic epilepsies that can impact cognitive function. This impact is exacerbated by interictal epileptiform activity and the neurobiological process behind the epilepsy. This is referred to as developmental and epileptic encephalopathy (DEE), which is often related to gene variants and mostly childhood-onset.

In VNS, electrical stimulation of the vagus nerve modulates activity of the nucleus tractus solitarius which via the vagal afferent network seems to interrupt the hypersynchronous cortical activity of seizures. VNS has shown positive effects for the treatment of some well-known genetic DEE such as Dravet Syndrome and Lennox Gastaut Syndrome; however, more data is needed on how and when clinicians integrate VNS into treatment approaches for genetic epilepsies around the world.

Aim of this analysis is to provide an updated description of a cohort of patients with genetic epilepsies treated with VNS in order to offer greater insight into the status quo of genetic testing in drug-resistant epilepsy and genetic basis of patients treated with VNS around the world.

Methods: We collected and analyzed clinical data of patients with genetic or suspected genetic epilepsies enrolled in the Comprehensive Outcomes Registry in Subjects with Epilepsy Treated with Vagus Nerve Stimulation Therapy (CORE-VNS, NCT 03529045). CORE-VNS is a registry collecting data related to patients with drug-resistant epilepsies treated with VNS. The registry enrolled patients between May 2018 and May 2021 in 61 centers in 15 countries.

Results: A total of 810 patients consented to participate in this study as of May 13, 2021 and had epilepsy and seizure history data reported. 244 (30.1%) patients underwent genetic testing and within this group with suspected genetic epilepsy, 116 (47.5%) were carrying a genetic variant which was likely correlated with the epilepsy phenotype (genetic epilepsy group) and a further 8 (3.3%) carried a genetic variant of uncertain significance. Mutations of SCN1A (n=15, 6.1%) and TSC2 (n=11, 4.5%) genes were the most frequent. In the genetic epilepsy group, epilepsy diagnosis was made before age 4 in 75.9 % of patients and at an average age of 3 ±4.2 years. 26.7% of patients in the genetic epilepsy group were classified as having genetic non-syndromic epilepsy. The most frequently reported epilepsy syndromes confirmed by genetic testing were Tuberous Sclerosis (n=15, 12.9%), Dravet Syndrome (n=12, 10.3%), Lennox Gastaut Syndrome (n=11, 9.5%) and Infantile Spasms/West Syndrome (n=9, 7.8%). All patients diagnosed with Dravet Syndrome had a mutation in the SCN1A gene. 12 different genetic mutations were identified for patients with Lennox Gastaut Syndrome.

Conclusions: VNS is a therapeutic approach that is frequently considered in patients with presumed or confirmed genetic epilepsies. Data coming from clinical practice in highly specialized centers around the world confirm that VNS is part of the therapeutic algorithm in severe DEE and drug resistant epilepsies.

Funding: Please list any funding that was received in support of this abstract.: Livanova supported this study.