Abstract | STUDY 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: 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:
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Authors | Olivier 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 |
Journal | Sleep
(Sleep)
Vol. 35
Issue 9
Pg. 1247-55F
(Sep 01 2012)
ISSN: 1550-9109 [Electronic] United States |
PMID | 22942503
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- HCRT protein, human
- Intracellular Signaling Peptides and Proteins
- Neuropeptides
- Orexins
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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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