0951 Sleep Stabilization Patterns Define Pediatric CNS Hypersomnia Conditions

Abstract Introduction Narcolepsy type 1 (NT1) is caused by loss of hypocretins, neuropeptides that promote consolidated nocturnal sleep and sustain daytime wakefulness. In mouse models of NT1, sleep in the light period is characterized by more brief wake bouts, fewer long wake bouts, and longer REM sleep bouts. It is unknown if this sleep pattern is present in NT1 patients and whether it can distinguish NT1 sleep from other CNS hypersomnia conditions [narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH)]. Methods Participants (6-18 years of age, drug -naïve or drug free) had diagnostic PSG/MSLT testing at Boston Children’s Hospital between 2009-2018. PSG records were rescored blinded to diagnosis. We calculated Kaplan Meier survival curves for nocturnal wake and sleep stages extracted from the nocturnal PSGs. To adjust for differences in survival related to age, sex, and race, we used Cox proportional hazards models. In total, we performed survival analysis and compared wake/sleep stages for 4 groups: NT1 (n=46), NT2 (n=12), IH (n=18) and subjective sleepy controls (n=48). Results NT1 patients had worse survival of wake bouts compared to controls (p<0.001). In addition, NT1 patients had decreased survival of both NREM 2 and REM sleep bouts compared to all groups (all p<0.001), and, the survival of REM sleep bouts decreased with age (p=0.006). Compared to controls, NREM 2 bouts survived longer in IH patients and whereas NREM 1 bouts survived longer in the NT2 group (p’s<0.006). There were no group effects for NREM 3, but survival of NREM 3 was less in the older IH patients compared to older controls (p<0.02). Conclusion Pediatric NT1 patients have unique sleep fragmentation characterized by unstable wake, NREM 2 and REM bouts. Though less severe as NT1, NT2 patients sustain lighter sleep. In contrast, IH patients show overly stable NREM stage 2 sleep and plausibly this contributes to their characteristic sleep inertia. Further research is needed to determine if sleep stability patterns can be used to diagnose CNS hypersomnia conditions and differentiate treatment responsiveness. Support K23 National Institutes of Health (NINDS, K23 NS104267-01A1) and Investigator Initiated Research grants from Jazz Pharmaceuticals, Inc. (Dr. Maski)