Challenging Sleep Homeostasis in Narcolepsy-Cataplexy: Implications for Non-REM and REM Sleep Regulation

Abstract

We recently proposed insufficient non-rapid eye movement sleep (NREMS) intensity to contribute to disturbed nocturnal sleep in patients with narcolepsy-cataplexy (NC). To test this hypothesis, we investigated the effect of physiologically intensified NREMS in recovery sleep following sleep deprivation. Nocturnal baseline and recovery sleep architecture, and the sleep electroencephalogram (EEG) before and after 40 hours of sustained wakefulness were compared between 6 drug-free patients with NC (age range: 19-37 years) and 6 individually matched, healthy control subjects (18-43 years). Sleep and sleep EEG power spectra (C3A2 derivation). The dynamics of the homeostatic Process S were estimated from the time course of slow-wave activity (SWA, spectral power within 0.75-4.5 Hz) across consecutive NREMS episodes. Sleep research laboratory. In baseline, SWA decreased across consecutive NREMS episodes in patients with NC and control subjects. The build-up of SWA, however, was attenuated in NC in the second episode (P = 0.01) due to a higher number of short wake periods (P = 0.02). Prolonged wakefulness increased initial SWA in both groups (P = 0.003) and normalized the baseline differences between patients and control subjects in the time course of SWA in NREMS. The changed dynamics of SWA in the patients in recovery sleep when compared with baseline were associated with reduced numbers of intermittent wake periods in the first (P = 0.01) and second (P = 0.04) NREMS episodes. All patients, but no control subjects, showed a sleep-onset rapid eye movement period (SOREMP) in both baseline and recovery sleep. Sleep deprivation increased SOREMP duration (P = 0.03). Increased SWA after sleep deprivation indicates that sleep homeostasis is functional in NC. Increased NREMS intensity in recovery sleep postpones sleep fragmentation, supporting our concept that sleep fragmentation is directly related to insufficient NREMS intensity in NC. The persistence of SOREMP despite enhanced NREMS pressure suggests an abnormal interaction between NREMS and REMS regulatory processes.