Decreased CSF histamine in narcolepsy with and without low CSF hypocretin-1 in comparison to healthy controls

Sleep. 2009 Feb;32(2):175-80. doi: 10.1093/sleep/32.2.175.


Study objective: To examine whether cerebrospinal fluid (CSF) histamine contents are altered in human narcolepsy and whether these alterations are specific to hypocretin deficiency, as defined by low CSF hypocretin-1.

Methods: Patients meeting the ICSD-2 criteria for narcolepsy with and without cataplexy and who had CSF hypocretin-1 results available were selected from the Stanford Narcolepsy Database on the basis of CSF availability and adequate age and sex matching across 3 groups: narcolepsy with low CSF hypocretin-1 (n=34, 100% with cataplexy), narcolepsy without low CSF hypocretin-1 (n=24, 75% with cataplexy), and normal controls (n=23). Low CSF hypocretin-1 was defined as CSF < or =110 pg/mL (1/3 of mean control values). Six of 34 patients with low CSF hypocretin-1, six of 24 subjects with normal CSF hypocretin-1, and all controls were unmedicated at the time of CSF collection. CSF histamine was measured in all samples using a fluorometric HPLC system.

Results: Mean CSF histamine levels were: 133.2 +/- 20.1 pg/mL in narcoleptic subjects with low CSF hypocretin-1, 233.3 +/- 46.5 pg/mL in patients with normal CSF hypocretin-1 (204.9 +/- 89.7 pg/mL if only patients without cataplexy are included), and 300.5 +/- 49.7 pg/mL in controls, reaching statistically significant differences between the 3 groups.

Conclusion: CSF histamine levels are reduced in human narcolepsy. The reduction of CSF histamine levels was more evident in the cases with low CSF hypocretin-1, and levels were intermediate in other narcolepsy cases. As histamine is a wake-promoting amine known to decrease during sleep, decreased histamine could either passively reflect or partially mediate daytime sleepiness in these pathologies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cataplexy / cerebrospinal fluid*
  • Cataplexy / diagnosis
  • Disorders of Excessive Somnolence / cerebrospinal fluid
  • Female
  • Histamine / cerebrospinal fluid*
  • Histamine / deficiency*
  • Humans
  • Intracellular Signaling Peptides and Proteins / cerebrospinal fluid*
  • Intracellular Signaling Peptides and Proteins / deficiency*
  • Male
  • Narcolepsy / cerebrospinal fluid*
  • Narcolepsy / diagnosis
  • Neuropeptides / cerebrospinal fluid*
  • Neuropeptides / deficiency*
  • Orexins
  • Polysomnography
  • Reference Values
  • Wakefulness


  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Histamine