title: CSF hypocretin/orexin levels in narcolepsy and other neurological conditions.
abstract: OBJECTIVE
  To examine the specificity of low CSF hypocretin-1 levels in narcolepsy and explore the potential role of hypocretins in other neurologic disorders.
  
  
  METHODS
  A method to measure hypocretin-1 in 100 microL of crude CSF sample was established and validated. CSF hypocretin-1 was measured in 42 narcolepsy patients (ages 16-70 years), 48 healthy controls (ages 22-77 years,) and 235 patients with various other neurologic conditions (ages 0-85 years).
  
  
  RESULTS
  As previously reported, CSF hypocretin-1 levels were undetectably low (<100 pg/mL) in 37 of 42 narcolepsy subjects. Hypocretin-1 levels were detectable in all controls (224-653 pg/mL) and all neurologic patients (117-720 pg/mL), with the exception of three patients with Guillain-Barré syndrome (GBS). Hypocretin-1 was within the control range in most neurologic patients tested, including patients with AD, PD, and MS. Low but detectable levels (100-194 pg/mL) were found in a subset of patients with acute lymphocytic leukemia, intracranial tumors, craniocerebral trauma, CNS infections, and GBS.
  
  
  CONCLUSIONS
  Undetectable CSF hypocretin-1 levels are highly specific to narcolepsy and rare cases of GBS. Measuring hypocretin-1 levels in the CSF of patients suspected of narcolepsy is a useful diagnostic procedure. Low hypocretin levels are also observed in a large range of neurologic conditions, most strikingly in subjects with head trauma. These alterations may reflect focal lesions in the hypothalamus, destruction of the blood brain barrier, or transient or chronic hypofunction of the hypothalamus. Future research in this area is needed to establish functional significance.
authors.affiliation: Stanford University Center for Narcolepsy, Palo Alto, CA 94304, USA.
authors.forename: B
authors.initials: B
authors.lastname: Ripley
authors.forename: S
authors.initials: S
authors.lastname: Overeem
authors.forename: N
authors.initials: N
authors.lastname: Fujiki
authors.forename: S
authors.initials: S
authors.lastname: Nevsimalova
authors.forename: M
authors.initials: M
authors.lastname: Uchino
authors.forename: J
authors.initials: J
authors.lastname: Yesavage
authors.forename: D
authors.initials: D
authors.lastname: Di Monte
authors.forename: K
authors.initials: K
authors.lastname: Dohi
authors.forename: A
authors.initials: A
authors.lastname: Melberg
authors.forename: G J
authors.initials: GJ
authors.lastname: Lammers
authors.forename: Y
authors.initials: Y
authors.lastname: Nishida
authors.forename: F W
authors.initials: FW
authors.lastname: Roelandse
authors.forename: M
authors.initials: M
authors.lastname: Hungs
authors.forename: E
authors.initials: E
authors.lastname: Mignot
authors.forename: S
authors.initials: S
authors.lastname: Nishino
mesh_terms: D002352:Carrier Proteins / Q000134:cerebrospinal fluid*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009290:Narcolepsy / Q000134:cerebrospinal fluid*; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid*; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D000068797:Orexins; D011863:Radioimmunoassay; D012680:Sensitivity and Specificity
chemical_list: D002352:Carrier Proteins; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins