Circadian Modulation of Sleep-Wake Behavior in Patients with Narcolepsy Type 1 and Idiopathic Hypersomnia

Approximately 4.7 million subjects worldwide suffer from narcolepsy (type 1 and 2) and idiopathic hypersomnia and are impaired in their sleep and wakefulness behavior. However, the role of the circadian rhythm in their sleep-wake behavior remains largely unknown. With this study, we investigated the influence of the internal clock on vigilance and sleep in central disorders of hypersomnolence.

We implemented a nap protocol with 10 cycles of 80 minutes sleep and 160 minutes wake time and compared various sleep and wake parameters (vigilance, subjective sleepiness, sleep efficiency, stages of sleep, slow wave activity) of patients with idiopathic hypersomnia (N=12, ∅25.8 ± 4.1 years, 10 females) and narcolepsy type 1 (N=12, ∅25.0 ± 4.4 years, 8 females) with a healthy control group (N=12, ∅26.8 ± 4.7 years, 6 females) using a linear mixed-model analysis.

Our protocol successfully disentangled the circadian rhythm from homeostatic sleep pressure and revealed an intact circadian melatonin pattern as assessed by dim light melatonin onset and offset in both patient groups. Patients with narcolepsy showed high sleep efficiencies of ∅94.3 ± 5.3% over all naps (group effect p < 0.001) and responded positively to the short sleep episodes with an increase in vigilance in the late afternoon (PVT speed @wake seven 2.5 ± 1.0 vs @wake ten 3.9 ± 0.6, p < 0.001). Patients with idiopathic hypersomnia showed an increased subjective sleepiness (group effect p < 0.001), yet practically no statistically significant differences in sleep parameters compared to healthy controls. Surprisingly, we observed a high number of SOREMPs in the healthy control group under low sleep pressure - a finding not previously reported in literature.

These findings argue against circadian disruption as a primary mechanism in idiopathic hypersomnia and point toward other underlying causes, such as altered sleep homeostasis or neurochemical dysregulation.