Differences in the neuropsychological profiles of high-functioning TSC adults with and without epilepsy

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder often accompanied by neuropsychiatric symptoms, including epilepsy and cognitive impairments. While the cognitive impact of epilepsy in TSC is well documented in children, there is a paucity of studies examining neuropsychological functioning in high-functioning adults, particularly in relation to epilepsy status.

This study aimed to investigate cognitive functioning in adults with clinically or molecularly confirmed TSC, without intellectual disability or autism spectrum disorder (ASD), with a specific focus on the impact of epilepsy.

Fifty-six adults were divided into three groups: individuals with TSC and epilepsy (EpiTSC; n = 18), individuals with TSC without epilepsy (NEpiTSC; n = 19), and healthy controls (n = 37). Participants underwent a comprehensive neuropsychological assessment targeting executive functions, attention, memory, and visuospatial abilities. Statistical analyses included ANOVA, Tukey's post-hoc tests, and Mann-Whitney U tests, with additional analyses limited to participants with confirmed TSC2 pathogenic variants.

Individuals with TSC and epilepsy exhibited significantly poorer performance on tasks assessing psychomotor speed, attention shifting, and executive control, including the Colour Trail Test and Trail Making Test. They also demonstrated lower scores in verbal memory and learning tasks, with a higher frequency of perseverative and intrusion errors on the California Verbal Learning Test (CVLT). Adults without epilepsy showed a distinct profile, characterized mainly by deficits in executive functioning and verbal fluency compared to controls. No significant group differences were observed in demographic variables.

This study highlights the existence of two distinct cognitive phenotypes among high-functioning adults with TSC, based on epilepsy status. Epilepsy in this cohort is associated with global cognitive dysfunction, particularly affecting attention, executive control, and memory. These findings underscore the need for individualized cognitive assessment and targeted intervention strategies, especially in individuals with a history of epilepsy.