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Hypocretin (orexin) deficiency in narcolepsy and primary hypersomnia
  1. I O Ebrahim1,4,
  2. M K Sharief1,2,
  3. S de Lacy1,
  4. Y K Semra2,
  5. R S Howard3,
  6. M D Kopelman4,
  7. A J Williams1
  1. 1Sleep Disorders Centre, St Thomas’s Hospital, London UK
  2. 2Department of Neuroimmunology, GKT School of Medicine, King’s College, London, UK
  3. 3Department of Neurology, St Thomas’s Hospital
  4. 4Department of Neuropsychiatry, GKT School of Medicine, London, UK
  1. Correspondence to:
 Dr I Ebrahim, Sleep Disorders Centre, Lane Fox Unit, St Thomas’ Hospital, Lambeth Palace Road, London, SE1 7EH, UK;


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.

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

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  • Competing interests: none declared.