title: Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy.
abstract: OBJECTIVE
  To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110-200 pg/ml), and normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1.
  
  
  METHODS
  University-based sleep clinics and laboratories.
  
  
  METHODS
  Narcolepsy without cataplexy (n = 171) and control patients (n = 170), all with available CSF hypocretin-1.
  
  
  METHODS
  Retrospective comparison and receiver operating characteristics curve analysis. Patients were also recontacted to evaluate if they developed cataplexy by survival curve analysis.
  
  
  RESULTS
  The optimal cutoff of CSF hypocretin-1 for narcolepsy without cataplexy diagnosis was 200 pg/ml rather than 110 pg/ml (sensitivity 33%, specificity 99%). Forty-one patients (24%), all HLA DQB1*06:02 positive, had low concentrations (≤ 110 pg/ml) of CSF hypocretin-1. Patients with low concentrations of hypocretin-1 only differed subjectively from other groups by a higher Epworth Sleepiness Scale score and more frequent sleep paralysis. Compared with patients with normal hypocretin-1 concentration (n = 117, 68%), those with low hypocretin-1 concentration had higher HLA DQB1*06:02 frequencies, were more frequently non-Caucasians (notably African Americans), with lower age of onset, and longer duration of illness. They also had more frequently short rapid-eye movement (REM) sleep latency (≤ 15 min) during polysomnography (64% versus 23%), and shorter sleep latencies (2.7 ± 0.3 versus 4.4 ± 0.2 min) and more sleep-onset REM periods (3.6 ± 0.1 versus 2.9 ± 0.1 min) during the Multiple Sleep Latency Test (MSLT). Patients with intermediate concentrations of CSF hypocretin-1 (n = 13, 8%) had intermediate HLA DQB1*06:02 and polysomnography results, suggesting heterogeneity. Of the 127 patients we were able to recontact, survival analysis showed that almost half (48%) with low concentration of CSF hypocretin-1 had developed typical cataplexy at 26 yr after onset, whereas only 2% had done so when CSF hypocretin-1 concentration was normal. Almost all patients (87%) still complained of daytime sleepiness independent of hypocretin status.
  
  
  CONCLUSIONS
  Objective (HLA typing, MSLT, and sleep studies) more than subjective (sleepiness and sleep paralysis) features predicted low concentration of CSF hypocretin-1 in patients with narcolepsy without cataplexy.
authors.affiliation: Center for Sleep Sciences and Medicine, and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Andlauer
authors.forename: Hyatt
authors.initials: H
authors.lastname: Moore
authors.forename: Seung-Chul
authors.initials: SC
authors.lastname: Hong
authors.forename: Yves
authors.initials: Y
authors.lastname: Dauvilliers
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanbayashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Nishino
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.forename: Michael H
authors.initials: MH
authors.lastname: Silber
authors.forename: Tom
authors.initials: T
authors.lastname: Rico
authors.forename: Mali
authors.initials: M
authors.lastname: Einen
authors.forename: Birgitte R
authors.initials: BR
authors.lastname: Kornum
authors.forename: Poul
authors.initials: P
authors.lastname: Jennum
authors.forename: Stine
authors.initials: S
authors.lastname: Knudsen
authors.forename: Sona
authors.initials: S
authors.lastname: Nevsimalova
authors.forename: Francesca
authors.initials: F
authors.lastname: Poli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Plazzi
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mignot
mesh_terms: D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid* / Q000172:deficiency*; D008297:Male; D009290:Narcolepsy / Q000134:cerebrospinal fluid*; D009479:Neuropeptides / Q000134:cerebrospinal fluid* / Q000172:deficiency*; D000068797:Orexins; D017286:Polysomnography / Q000379:methods; D011237:Predictive Value of Tests; D012372:ROC Curve; D044469:Racial Groups / Q000706:statistics & numerical data; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012894:Sleep Stages; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins