Normative modeling of brain morphometry in self-limited epilepsy with centrotemporal spikes

Self-limited epilepsy with centrotemporal spikes is the most common pediatric epilepsy, characterized by an age-dependent onset that typically arises during childhood brain development and is followed by remission at puberty. However, the heterogeneity in children's brain development at the individual level complicates the challenge of personalized treatment. Our goal is to quantify individual deviations from the normative range of brain morphometric variation in children with Self-limited epilepsy with centrotemporal spikes and to assess their associations with clinical manifestations and cognitive functions. We have developed sex-specific normative models on regional subcortical volume, cortical thickness, and surface area data from 457 healthy children sourced from two datasets. These models were then utilized to map the brain morphometric deviations of children with Self-limited epilepsy with centrotemporal spikes (n = 187) and sex- and age-matched healthy controls (n = 108) from another dataset. In the Self-limited epilepsy with centrotemporal spikes group, children exhibited a higher proportion of regions with infra-normal deviations in subcortical volumes, the number of regions with normative deviations correlated with disease duration, seizure frequency, and Raven's total score. Our findings suggest that a few extreme distributions of heterogeneous brain morphometric deviations are present in a minority of individuals, emphasizing the need to monitor brain abnormalities throughout the course of the disease.