Phenotyping sleep and sleep–wake rhythms in pediatric epilepsy

Sleep disturbances are frequently reported in children with epilepsy, yet the 24-hour organization of rest–activity rhythms remains poorly characterized in the pediatric population. This study aimed to phenotype sleep and sleep–wake rhythms in children with epilepsy using wrist actigraphy, with a focus on circadian and ultradian rhythm metrics beyond conventional sleep macrostructure. Children and adolescents aged 4–17 years with a diagnosis of epilepsy (n=95) were consecutively recruited at the Epilepsy Unit of the Gaslini Institute, Genoa, and compared with an age-matched group of typically developing controls (n=51). All participants wore a wrist actigraph for 7–10 days under real-life conditions. Actigraphic sleep parameters, cosinor-derived circadian indices, and non-parametric rest–activity rhythm metrics (interdaily stability, IS; intradaily variability, IV; relative amplitude, RA; L5; M10) were extracted. Functional Linear Model (FLM) analysis was applied to explore time-specific group differences across the 24-hour activity profile. Despite the absence of significant differences in actigraphic sleep macrostructure and sleep timing, children with epilepsy showed significantly higher IV (β=+0.0806, p=0.001) and lower IS (β=−0.0588, p=0.008), alongside a reduced cosinor goodness-of-fit (R²; β=−0.0888, p=0.001). The increased IV persisted after adjustment for sleep efficiency and daytime activity levels, indicating that rhythm fragmentation was not secondary to altered nocturnal sleep continuity. FLM did not reveal significant global differences but identified localized time windows of pointwise significance during daytime and early evening hours. Subjectively, parents of children with epilepsy reported higher sleep disturbance scores on the SDSC. These findings indicate that pediatric epilepsy is associated with a disruption of rest–activity rhythm stability—manifested by increased intradaily fragmentation and reduced day-to-day regularity—in the context of preserved sleep macrostructure and circadian phase. Rhythm instability may represent a functional marker of network dysregulation in pediatric epilepsy, warranting future integration with electrophysiological measures and longitudinal designs.