IN adults with tuberous sclerosis complex, add-on cenobamate improved executive function, quality of life, and stress.
Cenobamate in Drug-Resistant Epilepsy With TSC
Cenobamate is a newer therapeutic option for epilepsy, but its longer-term effects beyond seizure control remain less well described, particularly in complex neurogenetic conditions. A prospective observational study evaluated neuropsychological and psychosocial outcomes in late adolescents and young adults with tuberous sclerosis complex (TSC) and drug-resistant epilepsy who initiated cenobamate as add-on therapy.
The cohort included 22 patients aged 18–24 years who began cenobamate to improve seizure control. Participants completed standardized assessments at baseline and again at 3 and 12 months, focusing on executive function, adaptive behavior, quality of life, and parental stress. Broader cognitive testing was repeated at 12 months to assess stability over time.
Executive Function and Quality of Life Improve Over 12 Months
Over follow-up, the study reported statistically significant improvements in executive function (as measured by Epitrack), quality of life scores, and parental stress measures after 3 months or 12 months of cenobamate add-on therapy. In contrast, broader cognitive performance and adaptive behavior scores remained stable, suggesting no overall decline across the observation period.
The analysis also identified meaningful clinical context within the cohort. Patients with TSC2 mutations had significantly lower IQ scores than those with TSC1 mutations. In addition, parental stress showed significant relationships with adaptive behavior scores at baseline and at 12 months, highlighting how day-to-day functioning may intersect with caregiver burden in this population.
Why These Findings Matter for Practice
Taken together, the findings suggest cenobamate add-on therapy was effective and generally well tolerated in this small cohort, with signals of benefit across executive functioning, emotional well-being, social functioning, quality of life, and caregiver stress. The authors note these outcomes may help inform clinical decision-making when considering cenobamate earlier in drug-resistant epilepsy for patients with TSC.
Reference: Operto FF et al. Long-Term Impact of Cenobamate on Cognition, Adaptive Behavior, and Quality of Life in Patients with Tuberous Sclerosis Complex. Neurol Ther. 2026; doi:10.1007/s40120-026-00894-3.
