Orexin A (hypocretin-1) levels are not reduced while cocaine/amphetamine regulated transcript levels are increased in the cerebrospinal fluid of patients with multiple sclerosis: no correlation with fatigue and sleepiness

J Neurol Sci. 2011 Aug 15;307(1-2):127-31. doi: 10.1016/j.jns.2011.04.024. Epub 2011 May 24.


Background: Fatigue and sleep disturbance are common features of multiple sclerosis (MS). Our objectives were to determine cerebrospinal fluid levels of orexin A (hypocretin-1), a hypothalamic peptide involved in sleep, in patients with MS, and correlate them with fatigue, sleepiness, and levels of cocaine and amphetamine regulated transcript (CART) another neuropeptide regulating metabolism with wider nervous system distribution.

Methods: Consecutive patients with MS (n=34), other inflammatory (n=24) or non-inflammatory (n=42) neurological diseases, undergoing lumbar puncture were investigated. Orexin and CART were measured by RIA by investigators unaware of the patients' diagnosis.

Results: Orexin A was slightly decreased in the cerebrospinal fluid of patients with inflammatory disease. There was no evidence of orexin A deficiency in MS, although there was a non-significant trend toward a decrease compared to non-inflammatory neurological diseases (p=0.06). CART levels were increased in MS compared to the non-inflammatory disease group (p=0.03). There were no significant correlations between CSF levels of orexin A and CART, fatigue, and hypersomnolence.

Conclusions: Cerebrospinal fluid orexin A is decreased in CNS inflammatory diseases other than MS, where it shows a trend toward reduction, but does not correlate significantly with CART or with measures of fatigue and hypersomnolence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Disorders of Excessive Somnolence / cerebrospinal fluid*
  • Disorders of Excessive Somnolence / etiology
  • Disorders of Excessive Somnolence / physiopathology
  • Down-Regulation* / drug effects
  • Down-Regulation* / physiology
  • Fatigue Syndrome, Chronic / cerebrospinal fluid*
  • Fatigue Syndrome, Chronic / etiology
  • Fatigue Syndrome, Chronic / physiopathology
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / cerebrospinal fluid*
  • Male
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / physiopathology
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / cerebrospinal fluid*
  • Nerve Tissue Proteins / genetics
  • Neuropeptides / antagonists & inhibitors
  • Neuropeptides / cerebrospinal fluid*
  • Orexins
  • Sleep / drug effects
  • Sleep / physiology
  • Up-Regulation* / drug effects
  • Up-Regulation* / physiology


  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Orexins
  • cocaine- and amphetamine-regulated transcript protein