Neurodevelopmental and Behavioral Profiles in Children with Tuberous Sclerosis Complex: Exploratory Associations with Epilepsy Onset and Cortical Tuber Burden

Objective: To characterize neurodevelopmental disorders in children and adolescents with Tuberous Sclerosis Complex (TSC) and explore associations with epilepsy onset and cortical tuber burden. Methods: This exploratory cross-sectional study included 18 children and adolescents with TSC followed at a tertiary pediatric neurology center in Brazil. Standardized neuropsychological, behavioral, and neuroimaging assessments were performed. Participants were stratified according to epilepsy onset and cortical tuber burden. Results: Epilepsy was present in 94.4% of participants, and pharmacoresistance in 52.9%. Neurodevelopmental disorders were highly prevalent, particularly autism spectrum disorder and attention-deficit/hyperactivity disorder, frequently occurring as comorbidities. Children with earlier epilepsy onset demonstrated exploratory trends toward poorer cognitive outcomes, whereas greater cortical tuber burden showed exploratory trends toward greater behavioral and emotional dysregulation, although these differences did not reach statistical significance. Conclusions: Neurodevelopmental disorders are highly prevalent in pediatric TSC. Exploratory findings suggest that epilepsy characteristics and lesion burden may be related to cognitive and behavioral outcomes. These exploratory findings support systematic multidisciplinary neurodevelopmental monitoring in children with TSC.