SHORT REPORT

Hypocretin (orexin) deficiency in narcolepsy and primary hypersomnia

I O Ebrahim^1,4, M K Sharief^1,2, S de Lacy¹, Y K Semra², R S Howard³, M D Kopelman⁴ and A J Williams¹

¹ Sleep Disorders Centre, St Thomas’s Hospital, London UK
² Department of Neuroimmunology, GKT School of Medicine, King’s College, London, UK
³ Department of Neurology, St Thomas’s Hospital
⁴ Department of Neuropsychiatry, GKT School of Medicine, London, UK

Correspondence to:
Correspondence to:
Dr I Ebrahim, Sleep Disorders Centre, Lane Fox Unit, St Thomas’ Hospital, Lambeth Palace Road, London, SE1 7EH, UK;
irshaadoebrahim{at}aol.com

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.

Keywords: hypocretin; orexin; narcolepsy; primary hypersomnia

Abbreviations: Hcrt, hypocretin; EDS, excessive daytime sleep; NC, narcolepsy-cataplexy; CBF, cerobrospinal fluid; MN, monosymptomatic narcolepsy; PH, primary hypersomnia; MSLT, multiple sleep latency test

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Fronczek, R., Overeem, S., Lee, S. Y. Y., Hegeman, Ingrid. M., van Pelt, J., van Duinen, Sjoerd. G., Lammers, G. J., Swaab, D. F. (2007). Hypocretin (orexin) loss in Parkinson's disease. Brain 130: 1577-1585 [Abstract] [Full Text]  
• Dilley, M., Fleminger, S. (2006). Advances in neuropsychiatry: clinical implications. Adv. Psychiatr. Treat. 12: 23-34 [Abstract] [Full Text]  
• Dauvilliers, Y, Baumann, C., Carlander, B, Bischof, M, Blatter, T, Lecendreux, M, Maly, F, Besset, A, Touchon, J, Billiard, M, Tafti, M, Bassetti, C L (2003). CSF hypocretin-1 levels in narcolepsy, Kleine-Levin syndrome, and other hypersomnias and neurological conditions. J. Neurol. Neurosurg. Psychiatry 74: 1667-1673 [Abstract] [Full Text]