title: Decreased CSF histamine in narcolepsy with and without low CSF hypocretin-1 in comparison to healthy controls.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Sleep and Circadian Neurobiology Laboratory, Center for Narcolepsy, Stanford Sleep Research Center, Stanford University, MSLS Bldg Room P213, 1201 Welch Road, Palo Alto CA 94305, USA. nishino@stanford.edu
authors.forename: Seiji
authors.initials: S
authors.lastname: Nishino
authors.forename: Eiko
authors.initials: E
authors.lastname: Sakurai
authors.forename: Sona
authors.initials: S
authors.lastname: Nevsimalova
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Takehiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mignot
mesh_terms: D000328:Adult; D002385:Cataplexy / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D006970:Disorders of Excessive Somnolence / Q000134:cerebrospinal fluid; D005260:Female; D006632:Histamine / Q000134:cerebrospinal fluid* / Q000172:deficiency*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid* / Q000172:deficiency*; D008297:Male; D009290:Narcolepsy / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D009479:Neuropeptides / Q000134:cerebrospinal fluid* / Q000172:deficiency*; D000068797:Orexins; D017286:Polysomnography; D012016:Reference Values; D014851:Wakefulness
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D006632:Histamine