Background/Objectives: Juvenile myoclonic epilepsy (JME) is characterized by seizures clustering in the early morning hours, reflecting circadian modulation of cortical excitability. To the best of our knowledge, circadian rest-activity rhythms have not previously been objectively characterized in adolescents with JME, a gap that may be relevant to understanding seizure timing in this population. This study aimed to characterize circadian rest-activity rhythms and sleep parameters in adolescents with JME compared to healthy controls (HCs) and to explore whether chronotype relates to the strength of circadian rhythm. Methods: This pilot case-control study analyzed data from 11 adolescents with JME and 10 age- and sex-matched HCs who underwent 14-day continuous wrist actigraphy. Non-parametric circadian rhythm analysis (NPCRA) and cosinor analysis were conducted, and conventional sleep-wake parameters and night-to-night variability were derived. Subjective data from the Morningness-Eveningness Questionnaire (MEQ), the Pittsburgh Sleep Quality Index, a modified Epworth Sleepiness Scale, and the Pediatric Sleep Questionnaire were included. Between-group comparisons used the Mann-Whitney U test with an effect size of r. Results: Patients showed significantly lower interdaily stability (p = 0.002, r = 0.692), higher intradaily variability (p = 0.022, r = 0.500), reduced peak daytime activity (p = 0.002, r = 0.672), and attenuated cosinor (p = 0.013, r = 0.544) and mesor (p = 0.001, r = 0.754) amplitude, all with large effect sizes. Night-to-night variability was significantly greater for sleep efficiency (p = 0.010, r = 0.561), the fragmentation index (p = 0.003, r = 0.653), and mean sleep-bout duration (p = 0.020, r = 0.509). The MEQ score correlated positively with cosinor amplitude (rho = 0.679, p = 0.022) and peak daytime activity (rho = 0.615, p = 0.044). No significant group differences were found in conventional sleep-wake parameters. Given the exploratory nature of this pilot study, no correction for multiple comparisons was applied, and these findings should be considered hypothesis-generating. Conclusions: This pilot study provides preliminary evidence of circadian rest-activity rhythm disruption in a small and clinically heterogeneous adolescent cohort, with large effect sizes in JME, despite preserved conventional sleep parameters, underscoring the potential value of NPCRA-based actigraphy monitoring in this population and the need for replication in larger cohorts.
