Quantifying the impact of age, sleepiness and hypocretin on activity profile in pediatric NT1

Study Objectives: Pediatric type 1 Narcolepsy (NT1) is a chronic neurological disorder characterized by hypersomnolence, cataplexy, and dissociated rapid eye movement sleep manifestations. Recently several studies highlighted a peculiar nycthemeral profile, characterized by enhanced motor activity throughout the nocturnal period and blunted motor activity in the first afternoon, which is already detectable in children close to disease onset [1]. In the present study we analyzed the features of motor activity profile of pediatric NT1 patients applying of a novel statistical framework to stratify the motor profile with respect to demographical, clinical and biomedical data. Methods: Fifty drug-naïve NT1 children and adolescents (mean age = 12.31 ± 3.41) underwent seven days of actigraphy prior to the hospitalization finalized to diagnosis. Activity profiles were processed by mean of functional linear modeling (FLM) to analyze raw activity values with respect to age, BMI, ESS-CHAD scores and Hcrt-1 levels [2]. Results: FLM showed that age display a significant impact on NT1 children activity profile with younger children presenting with higher nocturnal motor activity from 2:00 to 6:00 (global F values on permutations <0.05) coupled with higher diurnal motor activity from 11:00 to 22:00 (point-wise F values on permutations <0.05). Higher ESS-CHAD scores are associated with lower motor activity from 10:00 to 12:00 (critical F) and from 16:00 to 18:00 (point-wise F). Conversely, higher sleep latency at MSLT are associated with higher motor activity during morning (7:30-10:00) and early afternoon (14:00-16:00). ESS-CHAD scores also significantly impact children activity profile, with higher scores associated with higher motor activity during the first part of nocturnal period (24:00-3:00, global F) and lower motor activity from 9:00-12:00 and from 16:00-18:00 (global F). Finally higher Hctr-1 values were associated with higher motor activity from 14:00-18:00 (global F) and lower motor activity levels throughout the nocturnal period (point-wise F). BMI does not significantly impact on children’s nycthemeral profile. Conclusion: Results highlight that subjective and objective sleepiness severity influence NT1 children’s activity profile in specific time windows corresponding to the morning and the first afternoon. The influence of age on circadian activity profile appears to be especially evident during the nocturnal period, which suggests that in younger NT1 children the nocturnal sleep disruption is more severe.