Long-Term Impact of Cenobamate on Cognition, Adaptive Behavior, and Quality of Life in Patients with Tuberous Sclerosis Complex

Introduction: Cenobamate is a recent therapeutic option for epilepsy, but few studies have investigated its impact on cognitive and emotional/behavioral functioning. The aim of our study was to assess cognitive function, adaptive behavior, quality of life, and parental stress in late adolescents and young adults with tuberous sclerosis complex (TSC) and drug-resistant epilepsy, treated with add-on cenobamate over a 12-month period using standardized neuropsychological tests. Methods: Our prospective observational study included 22 patients, aged 18 to 24 years with a diagnosis of TSC and drug-resistant epilepsy who started cenobamate add-on therapy for improving seizure control. At baseline and after 3- and 12-month follow-ups, participants completed a neuropsychological standardized assessment of executive functions (Epitrack©), adaptive behavior (VABS-II), quality of life (QOL), and parental stress (PSI). Cognitive functions (WAIS-IV) were reassessed only at the 12-month follow-up. Changes in standardized scores over time were analyzed using Friedman's two-way analysis of variance and post hoc analysis. Relationships between demographic/clinical variables and neuropsychological scores were analyzed using correlation analysis. Results: Our study highlighted a statistically significant improvement in Epitrack, PSI-4-SF, and QOL scores after 3- or 12-month follow-ups (p < 0.05). Stability was maintained for the WAIS and VABS-II scores. The subjects with TSC2 mutations showed significantly lower IQ scores than those carrying TSC1 mutations (p < 0.001). Total parental stress (PSI) was significantly related to the total score of VABS-II at both baseline (p = 0.003) and 12 months (p = 0.001). Conclusion: Our study suggested that cenobamate add-on therapy was effective and generally well tolerated in this cohort. Neuropsychological assessments suggest beneficial effects on executive functions, emotional well-being, social functioning, and quality of life. Furthermore, an improvement in parental stress also emerged. These findings could support clinicians in the decision-making process, evaluating cenobamate as an early treatment option in drug-resistant epilepsy.