Hypocretin (orexin) deficiency in narcolepsy and primary hypersomnia.
The discovery that hypocretins are involved in narcolepsy, a disorder associated with excessive daytime sleepiness, cataplexy, and unusually rapid transitions to rapid eye movement sleep, opens a new field of investigation in the area of disorders of sleep and activation. Hypocretin-1 (hcrt-1) and hypocretin-2 (hcrt-2) (also called orexin-A and orexin-B) are newly discovered neuropeptides processed from a common precursor. Hypocretin containing cells are located exclusively in the lateral hypothalamus, with widespread projections within the central nervous system. The role of the hypocretin system in other disorders causing excessive daytime sleepiness is more uncertain. This study reports the findings of a prospective study measuring cerebrospinal fluid concentrations of hypocretin-1 and hypocretin-2 in HLA DQB1*0602 positive narcolepsy with cataplexy, monosymptomatic narcolepsy, and primary hypersomnia. The results confirmed the previous observations, that hcrt-1 is deficient in narcolepsy and for the first time report very low levels of hcrt-1 in primary hypersomnia. It is also reported for the first time that there is a generalised defect in hcrt-2 transmission in all three of these clinical entities compared with controls.
Ebrahim
I O
IO
Sleep Disorders Centre, Lane Fox Unit, St Thomas's Hospital, Lambeth Palace Road, London, SE1 7EH, UK. irshaadoebrahim@aol.com
Sharief
M K
MK
de Lacy
S
S
Semra
Y K
YK
Howard
R S
RS
Kopelman
M D
MD
Williams
A J
AJ
D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000134:cerebrospinal fluid*; D002385:Cataplexy / Q000134:cerebrospinal fluid* / Q000276:immunology; D006970:Disorders of Excessive Somnolence / Q000134:cerebrospinal fluid* / Q000276:immunology; D005260:Female; D006683:HLA-DQ Antigens / Q000032:analysis; D059866:HLA-DQ beta-Chains; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000134:cerebrospinal fluid* / Q000276:immunology; D009479:Neuropeptides / Q000134:cerebrospinal fluid* / Q000172:deficiency*; D000068797:Orexins; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012016:Reference Values
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; D009479:Neuropeptides; D000068797:Orexins