CSF histamine contents in narcolepsy, idiopathic hypersomnia and obstructive sleep apnea syndrome

Sleep. 2009 Feb;32(2):181-7. doi: 10.1093/sleep/32.2.181.


Study objective: To (1) replicate our prior result of low cerebrospinal fluid (CSF) histamine levels in human narcolepsy in a different sample population and to (2) evaluate if histamine contents are altered in other types of hypersomnia with and without hypocretin deficiency.

Design: Cross sectional studies.

Setting and patients: Sixty-seven narcolepsy subjects, 26 idiopathic hypersomnia (IHS) subjects, 16 obstructive sleep apnea syndrome (OSAS) subjects, and 73 neurological controls were included. All patients were Japanese. Diagnoses were made according to ICSD-2.

Results: We found significant reductions in CSF histamine levels in hypocretin deficient narcolepsy with cataplexy (mean +/- SEM; 176.0 +/- 25.8 pg/mL), hypocretin non-deficient narcolepsy with cataplexy (97.8 +/- 38.4 pg/mL), hypocretin non-deficient narcolepsy without cataplexy (113.6 +/- 16.4 pg/mL), and idiopathic hypersomnia (161.0 +/- 29.3 pg/ mL); the levels in OSAS (259.3 +/- 46.6 pg/mL) did not statistically differ from those in the controls (333.8 +/- 22.0 pg/mL). Low CSF histamine levels were mostly observed in non-medicated patients; significant reductions in histamine levels were evident in non-medicated patients with hypocretin deficient narcolepsy with cataplexy (112.1 +/- 16.3 pg/ mL) and idiopathic hypersomnia (143.3 +/- 28.8 pg/mL), while the levels in the medicated patients were in the normal range.

Conclusion: The study confirmed reduced CSF histamine levels in hypocretin-deficient narcolepsy with cataplexy. Similar degrees of reduction were also observed in hypocretin non-deficient narcolepsy and in idiopathic hypersomnia, while those in OSAS (non central nervous system hypersomnia) were not altered. The decrease in histamine in these subjects were more specifically observed in non-medicated subjects, suggesting CSF histamine is a biomarker reflecting the degree of hypersomnia of central origin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / therapeutic use
  • Cataplexy / cerebrospinal fluid*
  • Cataplexy / diagnosis
  • Cataplexy / drug therapy
  • Central Nervous System Stimulants / therapeutic use
  • Cross-Sectional Studies
  • Disorders of Excessive Somnolence / cerebrospinal fluid*
  • Disorders of Excessive Somnolence / diagnosis
  • Disorders of Excessive Somnolence / drug therapy
  • Female
  • Histamine / cerebrospinal fluid*
  • Histamine / deficiency*
  • Humans
  • Intracellular Signaling Peptides and Proteins / cerebrospinal fluid*
  • Intracellular Signaling Peptides and Proteins / deficiency*
  • Male
  • Middle Aged
  • Narcolepsy / cerebrospinal fluid*
  • Narcolepsy / diagnosis
  • Narcolepsy / drug therapy
  • Nervous System Diseases / cerebrospinal fluid
  • Nervous System Diseases / diagnosis
  • Neuropeptides / cerebrospinal fluid*
  • Neuropeptides / deficiency*
  • Orexins
  • Reference Values
  • Sleep Apnea, Obstructive / cerebrospinal fluid*
  • Sleep Apnea, Obstructive / diagnosis
  • Sleep Apnea, Obstructive / drug therapy
  • Young Adult


  • Antidepressive Agents
  • Central Nervous System Stimulants
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Histamine