title: Normal levels of cerebrospinal fluid hypocretin-1 and daytime sleepiness during attacks of relapsing-remitting multiple sclerosis and monosymptomatic optic neuritis.
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.
authors.affiliation: Danish Center of Sleep Medicine, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark. stine.knudsen@dadlnet.dk
authors.forename: S
authors.initials: S
authors.lastname: Knudsen
authors.forename: P J
authors.initials: PJ
authors.lastname: Jennum
authors.forename: K
authors.initials: K
authors.lastname: Korsholm
authors.forename: S P
authors.initials: SP
authors.lastname: Sheikh
authors.forename: S
authors.initials: S
authors.lastname: Gammeltoft
authors.forename: J L
authors.initials: JL
authors.lastname: Frederiksen
mesh_terms: D000328:Adult; D006970:Disorders of Excessive Somnolence / Q000134:cerebrospinal fluid / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000150:complications / Q000503:physiopathology*; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D009902:Optic Neuritis / Q000134:cerebrospinal fluid / Q000209:etiology / Q000503:physiopathology*; D000068797:Orexins; D012008:Recurrence; D012894:Sleep Stages / Q000502:physiology*
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins