Julie Anja Engelhard Christensen1, Oscar Carrillo2, Eileen B Leary2, Paul E Peppard3, Terry Young3, Helge Bjarrup Dissing Sorensen4, Poul Jennum5, Emmanuel Mignot6. 1. Department of Electrical Engineering, Technical University of Denmark, Orsteds Plads 349, DK-2800 Kongens Lyngby, Denmark; Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Glostrup Hospital, Nordre Ringvej 57, DK-2600 Glostrup, Denmark; Stanford Center for Sleep Sciences and Medicine, Stanford University, 3165 Porter Drive, Palo Alto, CA 94304, USA. 2. Stanford Center for Sleep Sciences and Medicine, Stanford University, 3165 Porter Drive, Palo Alto, CA 94304, USA. 3. School of Medicine and Public Health, Health Sciences Learning Center, University of Wisconsin, 750 Highland Ave., Madison, WI 53705, USA. 4. Department of Electrical Engineering, Technical University of Denmark, Orsteds Plads 349, DK-2800 Kongens Lyngby, Denmark. 5. Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Glostrup Hospital, Nordre Ringvej 57, DK-2600 Glostrup, Denmark; Center for Healthy Aging, University of Copenhagen, Norregade 10, DK-1017 Copenhagen, Denmark. 6. Stanford Center for Sleep Sciences and Medicine, Stanford University, 3165 Porter Drive, Palo Alto, CA 94304, USA. Electronic address: mignot@stanford.edu.
Abstract
OBJECTIVE: Type 1 narcolepsy/hypocretin deficiency is characterized by excessive daytime sleepiness, sleep fragmentation, and cataplexy. Short rapid eye movement (REM) latency (≤15 min) during nocturnal polysomnography (PSG) or during naps of the multiple sleep latency test (MSLT) defines a sleep-onset REM sleep period (SOREMP), a diagnostic hallmark. We hypothesized that abnormal sleep transitions other than SOREMPs can be identified in type 1 narcolepsy. METHODS: Sleep-stage transitions (one to 10 epochs to one to five epochs of any other stage) and bout length features (one to 10 epochs) were extracted from PSGs. The first 15 min of sleep were excluded when a nocturnal SOREMP was recorded. F(0.1) measures and receiver operating characteristic curves were used to identify specific (≥98%) features. A data set of 136 patients and 510 sex- and age-matched controls was used for the training. A data set of 19 cases and 708 sleep-clinic patients was used for the validation. RESULTS: (1) ≥5 transitions from ≥5 epochs of stage N1 or W to ≥2 epochs of REM sleep, (2) ≥22 transitions from ≥3 epochs of stage N2 or N3 to ≥2 epochs of N1 or W, and (3) ≥16 bouts of ≥6 epochs of N1 or W were found to be highly specific (≥98%). Sensitivity ranged from 16% to 30%, and it did not vary substantially with and without medication or a nocturnal SOREMP. In patients taking antidepressants, nocturnal SOREMPs occurred much less frequently (16% vs. 36%, p < 0.001). CONCLUSIONS: Increased sleep-stage transitions notably from ≥2.5 min of W/N1 into REM are specifically diagnostic for narcolepsy independent of a nocturnal SOREMP.
OBJECTIVE: Type 1 narcolepsy/hypocretin deficiency is characterized by excessive daytime sleepiness, sleep fragmentation, and cataplexy. Short rapid eye movement (REM) latency (≤15 min) during nocturnal polysomnography (PSG) or during naps of the multiple sleep latency test (MSLT) defines a sleep-onset REM sleep period (SOREMP), a diagnostic hallmark. We hypothesized that abnormal sleep transitions other than SOREMPs can be identified in type 1 narcolepsy. METHODS: Sleep-stage transitions (one to 10 epochs to one to five epochs of any other stage) and bout length features (one to 10 epochs) were extracted from PSGs. The first 15 min of sleep were excluded when a nocturnal SOREMP was recorded. F(0.1) measures and receiver operating characteristic curves were used to identify specific (≥98%) features. A data set of 136 patients and 510 sex- and age-matched controls was used for the training. A data set of 19 cases and 708 sleep-clinic patients was used for the validation. RESULTS: (1) ≥5 transitions from ≥5 epochs of stage N1 or W to ≥2 epochs of REM sleep, (2) ≥22 transitions from ≥3 epochs of stage N2 or N3 to ≥2 epochs of N1 or W, and (3) ≥16 bouts of ≥6 epochs of N1 or W were found to be highly specific (≥98%). Sensitivity ranged from 16% to 30%, and it did not vary substantially with and without medication or a nocturnal SOREMP. In patients taking antidepressants, nocturnal SOREMPs occurred much less frequently (16% vs. 36%, p < 0.001). CONCLUSIONS: Increased sleep-stage transitions notably from ≥2.5 min of W/N1 into REM are specifically diagnostic for narcolepsy independent of a nocturnal SOREMP.
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