Hypocretin (orexin) levels in cerebrospinal fluid of patients with narcolepsy: relationship to cataplexy and HLA DQB1*0602 status.
OBJECTIVE
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
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.


METHODS
Data were collected at a sleep disorders center.


METHODS
Twenty-six patients with narcolepsy, with and without HLA DQB1*0602 and with and without cataplexy, as well as 15 neurologic controls.


METHODS
N/A.


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.


CONCLUSIONS
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.
Krahn
Lois E
LE
Mayo Clinic, Department of Psychiatry & Psychology, Rochester, MN 55905, USA. krahn.lois@mayo.edu
Pankratz
V Shane
VS
Oliver
Lawrence
L
Boeve
Bradley F
BF
Silber
Michael H
MH
D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002352:Carrier Proteins / Q000134:cerebrospinal fluid* / Q000276:immunology; D002385:Cataplexy / Q000134:cerebrospinal fluid / Q000276:immunology; D005260:Female; D006683:HLA-DQ Antigens / Q000276:immunology*; D059866:HLA-DQ beta-Chains; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009290:Narcolepsy / Q000134:cerebrospinal fluid* / Q000276:immunology*; D009479:Neuropeptides / Q000134:cerebrospinal fluid* / Q000172:deficiency* / Q000276:immunology; D000068797:Orexins; D011863:Radioimmunoassay
D002352:Carrier Proteins; C000596229:HCRT protein, human; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D000068797:Orexins