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Normal levels of cerebrospinal fluid hypocretin-1 and daytime sleepiness during attacks of relapsing-remitting multiple sclerosis and monosymptomatic optic neuritis

¹ Danish Center of Sleep Medicine, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark
² Glostrup Research Institute, Glostrup, Denmark
³ Danish Research Centre for Magnetic Resonance, University of Copenhagen, Hvidovre Hospital, Hvidovre, Denmark
⁴ Department of Clinical Biochemistry, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark
⁵ Department of Biochemistry, Pharmacology and Genetics, University of Southern Denmark, Odense Hospital, Odense, Denmark
⁶ Department of Neurology, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark

^* To whom correspondence should be addressed.

	Abstract

There is emerging evidence that multiple sclerosis (MS), the hypothalamic sleep-wake regulating neuropeptide hypocretin-1 (hcrt-1) and the sleep disorder narcolepsy may be connected. Thus, the major pathophysiological component of narcolepsy is lack of hcrt-1. Dysfunction of the hypocretin system has been reported in MS case reports with attacks of hypothalamic lesions, undetectable cerebrospinal fluid (CSF) hcrt-1 and hypersomnia, but not found during remission in small samples. Finally, daytime sleepiness, the major symptom of narcolepsy, is reported in several MS populations, and there are case reports of co-existent narcolepsy and MS. However, it is unknown whether hcrt-1 and daytime sleepiness generally change during MS attacks. We therefore analyzed whether daytime sleepiness (using the Epworth Sleepiness Scale (ESS)) and CSF hcrt-1 levels differed between MS attack and remission, in 48 consecutively referred patients with relapsing–remitting MS (RRMS) or monosymptomatic optic neuritis (MON). Twenty-seven patients were in attack and 21 in remission. ESS was normal both during attacks (5.4 ± 3.0) and remission (5.8 ± 2.6), and mean CSF hcrt-1 was normal (456 ± 41 pg/ml). No statistically significant differences were found between attack and remission. MRI scans revealed no hypothalamic lesions. The results show that the hypocretin system is intact and sleepiness is not typical in RRMS and MON without hypothalamic lesions on MRI.

Key Words: multiple sclerosis, narcolepsy, optic neuritis, excessive daytime sleepiness, CSF hypocretin-1

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