Subjective reporting of disrupted nighttime sleep and associated functional outcomes in nt1 youth

Abstract Introduction In people with NT1, Disrupted Nighttime sleep (DNS) can be measured using the Wake/N1 Index, the number of transitions from sleep to wake or N1 sleep per hour of sleep. However, it remains unknown if this DNS measure correlates with sleep quality and daytime symptom burden. We compared the Wake/N1 Index with perceptions of sleep quality in young NT1 patients and healthy controls (HC) and determined its relationships with subjective sleep quality, daytime behavior, and cognition across groups. Methods 25 HC (mean age 13.4 years) and 23 NT1 participants (mean age 15.8 years) completed a 15-item survey after sleeping a minimum of 6 hours during an in-lab polysomnogram. The survey included questions from validated surveys on habitual sleep quality, fatigue, sleepiness and cognitive function. We dichotomized survey responses into frequent or infrequent concerns. We compared responses using Fisher Exact tests and logistic regression to determine associations with the Wake/N1 Index. NT1 participants could take SSRI/SNRI medication for cataplexy but were weaned off wake-promoting medications and excluded if on an oxybate. Results Compared to HC, NT1 participants reported more frequent restless sleep, nighttime moaning/groaning/talking, tossing and turning, and waking more than once during the night (p’s < 0.02) and showed a trend for more leg kicking during sleep (p=0.06). NT1 and HC groups did not differ in falling asleep quickly and returning back to sleep quickly after waking. NT1 subjects reported more frequent fatigue, difficulty keeping thoughts focused, difficulty thinking clearly and making decisions, problems remembering things, and dozing/napping inadvertently. Across groups and controlling for age, the Wake/N1 Index was associated with subjective reporting of waking more than once (OR=3.2) as well as problems with daytime alertness (OR 1.5) and fatigue (OR 1.4). Conclusion Young NT1 patients describe DNS as a multi-factorial complaint comprising problems with sleep maintenance, restless sleep, parasomnia-like behaviors, and periodic limb movements. The Wake/N1 Index is associated with perceptions of waking at night as well as daytime alertness and fatigue across groups. This work suggests that Wake/N1 Index could be a useful measure of sleep instability and inform future research on DNS impact on daytime function. Support (if any) NIH 5K23NS104267-2, Jazz Pharmaceuticals