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Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy.

AbstractSTUDY OBJECTIVES:
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.
SETTING:
University-based sleep clinics and laboratories.
PATIENTS:
Narcolepsy without cataplexy (n = 171) and control patients (n = 170), all with available CSF hypocretin-1.
DESIGN AND INTERVENTIONS:
Retrospective comparison and receiver operating characteristics curve analysis. Patients were also recontacted to evaluate if they developed cataplexy by survival curve analysis.
MEASUREMENTS AND 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.
CONCLUSION:
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.
AuthorsOlivier Andlauer, Hyatt Moore 4th, Seung-Chul Hong, Yves Dauvilliers, Takashi Kanbayashi, Seiji Nishino, Fang Han, Michael H Silber, Tom Rico, Mali Einen, Birgitte R Kornum, Poul Jennum, Stine Knudsen, Sona Nevsimalova, Francesca Poli, Giuseppe Plazzi, Emmanuel Mignot
JournalSleep (Sleep) Vol. 35 Issue 9 Pg. 1247-55F (Sep 01 2012) ISSN: 1550-9109 [Electronic] United States
PMID22942503 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers
  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
Topics
  • Adult
  • Age of Onset
  • Biomarkers (cerebrospinal fluid)
  • Female
  • Follow-Up Studies
  • Humans
  • Intracellular Signaling Peptides and Proteins (cerebrospinal fluid, deficiency)
  • Male
  • Narcolepsy (cerebrospinal fluid)
  • Neuropeptides (cerebrospinal fluid, deficiency)
  • Orexins
  • Polysomnography (methods)
  • Predictive Value of Tests
  • ROC Curve
  • Racial Groups (statistics & numerical data)
  • Retrospective Studies
  • Sensitivity and Specificity
  • Sleep Stages
  • Survival Analysis

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