Abstracts

Rationale: Epilepsy is one of the most common chronic neurological disorders in pediatric patients. Approximately one-third suffer from treatment-resistant epilepsies (TRE), causing neurological, cognitive, behavioral, and psychosocial impairments. The underlying etiologies of TRE could be infectious, immunological, metabolic, structural, genetic, and unknown causes. With advances in bioinformatics and biotechnologies, genetic factors have been recognized as a vital role. Vagus nerve stimulation (VNS) therapy is an add-on neuromodulation treatment designed for people with TRE, leading to fewer and shorter seizures and better recovery after seizures. This study aims to describe the efficacy of VNS in genetic and non-genetic TRE in pediatric patients.

Methods: From January 2021 to January 2024, 41 TRE patients who received VNS therapy were enrolled. The definition of TRE was a failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules with or without combination of epilepsy surgery to achieve sustained seizure freedom. Genetic TRE referred to patients who were diagnosed with TRE having chromosomal disorders confirmed by karyotyping or chromosomal microarray analysis or carrying single gene variants identified by single gene testing, whole exome sequencing, or whole-genome sequencing; while non-genetic TRE originated from infectious, structural, or unknown causes. The clinical efficacy of genetic and non-genetic TRE was analyzed.


Results: Seventeen TRE patients were classified as genetic origins, including SCN1A-related Dravet syndrome (6), TSC1-related tuberous sclerosis complex (3), CHD2-related developmental and epileptic encephalopathy (DEE) 94 (2), ATP1A3-related DEE 99 (1), KCNT1-related DEE 14 (1), SCN2A-related DEE 11 (1), DHPR-related TRE (1), FOXG1-related TRE (1), and chromosomal microdeletion disorder (1). Twenty-four TRE resulted from post-encephalitis (6), structural anomalies (3), and unknown cause (15). The duration of clinical follow-up after VNS therapy ranged from 3 months to 3 years. Eleven of 17 (65%) genetic TRE patients achieved a greater than 50% seizure reduction; among them, one with CHD2-related DEE 94 and one with FOXG1-related TRE had a greater then 90% seizure reduction. Thirteen of 24 (54%) non-genetic TRE patients could exhibit a greater than 50% seizure reduction, but none of them had a greater then 90% seizure reduction and one was off VNS setting due to obvious auditory hallucination.

Conclusions: VNS therapy showed clinical efficacy in both genetic and non-genetic TRE and supported its role in this pediatric patient group.


Funding: No.