Define an objective measure of DNS in pediatric NT1 compared to controls and other CNS hypersomnia conditions. 

Disrupted nighttime sleep (DNS) is a core narcolepsy symptom and reflects the instability of wake and sleep resulting from hypocretin neuronal loss. It is unknown how to objectively define DNS and whether it is present in pediatric narcolepsy.

Retrospective, cross-sectional study of consecutive polysomnograms (PSGs) and multiple sleep latency tests (MSLTs) from 2010-2018 at Boston Children’s Hospital Pediatric Sleep Laboratory ordered for the evaluation of hypersomnia. Participants were drug-free, ages 6-18 years.  Patients were diagnosed based on 3^rd International Classification of Sleep Disorders criteria. The study included narcolepsy type 1 (NT1, n=44), narcolepsy type 2 (n=12), idiopathic hypersomnia  (n=25), and subjectively sleepy controls (n=49). We defined the DNS index as number of transitions from stable sleep (NREM 2, NREM 3 or REM sleep) to Wake or NREM stage 1 sleep normalized by total sleep time. 

Mean age of participants was 11.3+/-1.1 years. Mean DNS index was nearly 2x higher in NT1 compared to other groups adjusted for age and gender [NT1: 3.9(+/-13.1), NT2: 1.8(+/-8.8), IH: 1.9(+/-8.8), controls: 2.1(+/-10.2)]; ANOVA p<0.0005]. Overall, the AUC of the ROC curve of the DNS index was 0.79 [95% CI: 0.70 to 0.87] and a DNS cutoff score of 3.3 transitions/hour yielded a specificity of 92% and sensitivity of 51% for NT1. We detected a weak correlation between DNS and objective daytime sleepiness on the Multiple Sleep Latency Test (r=-0.28, p=0.002).

DNS is present in pediatric NT1 patients despite the known higher sleep pressure of children compared to adults. The DNS index is an objective biomarker that captures the unique sleep pathology of NT1 and its underlying hypocretin neuronal degeneration. Lastly, DNS may contribute to problematic daytime sleepiness.