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  • Title: Hypocretin (orexin) levels in cerebrospinal fluid of patients with narcolepsy: relationship to cataplexy and HLA DQB1*0602 status.
    Author: Krahn LE, Pankratz VS, Oliver L, Boeve BF, Silber MH.
    Journal: Sleep; 2002 Nov 01; 25(7):733-6. PubMed ID: 12405608.
    Abstract:
    STUDY OBJECTIVES: Hypocretin (orexin) deficiency (< 40 pg/ml) is highly associated with narcolepsy with cataplexy (89.5%) and more specifically with patients with cataplexy who are HLA DQB1*0602 positive (95.7%). The relationship between hypocretin-1 levels and narcolepsy without cataplexy or the DQB1*0602 allele is less clear. METHODS/DESIGN: This study compared cerebrospinal (CSF) hypocretin-1 in 13 patients with HLA DQB1*0602 allele and cataplexy to 4 HLA negative patients with cataplexy, 3 HLA positive patients without cataplexy, and 6 HLA negative patients without cataplexy, plus 15 neurologic controls. SETTING: Data were collected at a sleep disorders center. PATIENTS/PARTICIPANTS: Twenty-six patients with narcolepsy, with and without HLA DQB1*0602 and with and without cataplexy, as well as 15 neurologic controls. INTERVENTIONS: N/A. MEASUREMENT & RESULTS: Using analysis of variance techniques, statistically significant differences were found between the CSF hypocretin-1 levels in HLA positive patients and all other groups (P < 0.01). Although the sample size was small, subjects with the DQB1*0602 allele without cataplexy had lower hypocretin-1 levels than did other groups (other than the HLA and cataplexy positive group). Hypocretin-1 levels were not associated with age at diagnosis, age at lumbar puncture, body mass index at time of diagnosis, or body mass index at time of lumbar puncture. CONCLUSION: This data confirms the previous finding that undetectable hypocretin-1 levels are highly specific for HLA positive narcolepsy with cataplexy. The data suggests that the pathophysiology and, by extension, etiology of this disorder are distinctly different from the other conditions studied. The relationship of the DQB1*0602 allele and reduced hypocretin-1 levels needs further study.
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