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Sleep. 2013 Aug 1;36(8):1173-7. doi: 10.5665/sleep.2880.

Sleep transitions in hypocretin-deficient narcolepsy.

Author information

1
Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Glostrup Hospital, Copenhagen, Denmark.

Abstract

STUDY OBJECTIVES:

Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain's sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype.

DESIGN:

We measured the frequency of transitions in patients with narcolepsy between sleep-wake states and to/from REM and NREM sleep stages. Patients were subdivided by the presence of +/- cataplexy and +/- hypocretin-1 deficiency.

SETTING:

Sleep laboratory studies conducted from 2001-2011.

PATIENTS:

In total 63 narcolepsy patients were included in the study. Cataplexy was present in 43 of 63 patients and hypocretin-1 deficiency was present in 37 of 57 patients.

MEASUREMENTS AND RESULTS:

Hypocretin-deficient patients with narcolepsy had a significantly higher frequency of sleep-wake transitions (P = 0.014) and of transitions to/from REM sleep (P = 0.044) than patients with normal levels of hypocretin-1. Patients with cataplexy had a significantly higher frequency of sleep-wake transitions (P = 0.002) than those without cataplexy. A multivariate analysis showed that transitions to/from REM sleep were predicted mainly by hypocretin-1 deficiency (P = 0.011), whereas sleep-wake transitions were predicted mainly by cataplexy (P = 0.001).

CONCLUSIONS:

In human narcolepsy, hypocretin deficiency and cataplexy are both associated with signs of destabilized sleep-wake and REM sleep control, indicating that the disorder may serve as a human model for the sleep-wake and REM sleep flip-flop switches.

KEYWORDS:

Flip-flop; hypocretin; narcolepsy; sleep transition

PMID:
23904677
PMCID:
PMC3700714
DOI:
10.5665/sleep.2880
[Indexed for MEDLINE]
Free PMC Article

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