Lack of effectiveness and seizure worsening with cenobamate in pediatric patients with Dravet syndrome.

Abstract

Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy primarily caused by loss-of-function (LoF) variants in the SCN1A gene. Despite advancements in precision medicine, seizure control remains challenging. Cenobamate, a novel antiseizure medication, has shown positive results in a small case series of adults with DS, but its efficacy in children is unclear. This retrospective and single-center study analyzed the therapeutic response to cenobamate in six pediatric patients (median age = 8.5 years) with DS and SCN1A LoF variants. Patients were treated with cenobamate for a median follow-up of 7 months. Baseline seizure frequency was assessed over 3 months prior to treatment initiation. Response was defined as a ≥50% reduction in seizure frequency and worsening as a ≥25% increase compared to baseline. No patient met the responder criteria. Three patients experienced seizure worsening, including one patient who started presenting status epilepticus after a long status epilepticus-free period, and the remaining three showed no improvement. Adverse effects included sleepiness, restlessness, and loss of appetite, and cenobamate was discontinued in all patients due to lack of effectiveness or seizure worsening. Our findings suggest that cenobamate lacks effectiveness in pediatric DS and may exacerbate seizures in some cases. These results highlight the need for age-specific approaches in treatment decisions for genetic epilepsies.