title: Nocturnal rapid eye movement sleep latency for identifying patients with narcolepsy/hypocretin deficiency.
abstract: OBJECTIVE
  Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically.
  
  
  OBJECTIVE
  To determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency.
  
  
  METHODS
  Observational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels.
  
  
  METHODS
  Sensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal fluid hypocretin-1 results available) or narcolepsy with documented low (≤ 110 pg/mL) cerebrospinal fluid hypocretin-1 level.
  
  
  RESULTS
  Short REML (≤15 minutes) during NPSG was highly specific (99.2% [95% CI, 98.5%-100.0%] of 516 and 99.6% [95% CI, 99.1%-100.0%] of 735) but not sensitive (50.6% [95% CI, 46.3%-54.9%] of 516 and 35.7% [95% CI, 10.6%-60.8%] of 14) for patients with narcolepsy/hypocretin deficiency vs population-based controls or all patients with sleep disorders undergoing a nocturnal sleep study (area under the curve, 0.799 [95% CI, 0.771-0.826] and 0.704 [95% CI, 0.524-0.907], respectively). In patients with central hypersomnia and thus a high pretest probability for narcolepsy, short REML remained highly specific (95.4% [95% CI, 90.4%-98.3%] of 132) and similarly sensitive (57.4% [95% CI, 48.1%-66.3%] of 122) for narcolepsy/hypocretin deficiency (area under the curve, 0.765 [95% CI, 0.707-0.831]). Positive predictive value in this high pretest probability sample was 92.1% (95% CI, 83.6%-97.0%).
  
  
  CONCLUSIONS
  Among patients being evaluated for possible narcolepsy, short REML (≤15 minutes) at NPSG had high specificity and positive predictive value and may be considered diagnostic without the use of an MSLT; absence of short REML, however, requires a subsequent MSLT.
authors: Center for Sleep Sciences and Medicine and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
authors: Olivier
authors: O
authors: Andlauer
authors: Hyatt
authors: H
authors: Moore
authors: Laura
authors: L
authors: Jouhier
authors: Christopher
authors: C
authors: Drake
authors: Paul E
authors: PE
authors: Peppard
authors: Fang
authors: F
authors: Han
authors: Seung-Chul
authors: SC
authors: Hong
authors: Francesca
authors: F
authors: Poli
authors: Giuseppe
authors: G
authors: Plazzi
authors: Ruth
authors: R
authors: O'Hara
authors: Emmanuel
authors: E
authors: Haffen
authors: Thomas
authors: T
authors: Roth
authors: Terry
authors: T
authors: Young
authors: Emmanuel
authors: E
authors: Mignot
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002385:Cataplexy / Q000175:diagnosis; D005260:Female; D059866:HLA-DQ beta-Chains / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid / Q000172:deficiency*; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics; D009479:Neuropeptides / Q000134:cerebrospinal fluid / Q000172:deficiency*; D000068797:Orexins; D017286:Polysomnography / Q000379:methods*; D012372:ROC Curve; D012042:Registries; D012893:Sleep Wake Disorders / Q000134:cerebrospinal fluid / Q000145:classification / Q000175:diagnosis*; D012895:Sleep, REM / Q000502:physiology*; D055815:Young Adult
chemical_list: C000596229:HCRT protein, human; D059866:HLA-DQ beta-Chains; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins
references: Sleep. 2002 Jun 15;25(4):440-4
references: 12071546
references: Lancet. 1998 Mar 7;351(9104):727
references: 9504524
references: Electroencephalogr Clin Neurophysiol. 1963 Aug;15:599-609
references: 14161512
references: Arch Neurol. 2002 Oct;59(10):1553-62
references: 12374492
references: Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):426-31
references: 10673181
references: Sleep. 1997 Nov;20(11):1012-20
references: 9456467
references: J Clin Sleep Med. 2007 Apr 15;3(3):301-11
references: 17561602
references: Lancet. 2000 Jan 1;355(9197):39-40
references: 10615891
references: Sleep. 1995 Jul;18(6):463-9
references: 7481418
references: Sleep Med. 2009 Dec;10(10):1146-50
references: 19464232
references: Sleep. 2006 Jul;29(7):890-5
references: 16895255
references: J Clin Neurophysiol. 2008 Aug;25(4):218-21
references: 18677186
references: Sleep. 1984;7(2):115-25
references: 6740056
references: Sleep. 2000 Nov 1;23(7):911-3
references: 11083600
references: Sleep. 1997 Aug;20(8):620-9
references: 9351129
references: Nat Genet. 2009 Jun;41(6):708-11
references: 19412176
references: Sleep Med Rev. 2008 Apr;12(2):129-41
references: 18342261
references: Clin Neurophysiol. 2000 Mar;111(3):428-33
references: 10699402
references: Sleep. 1991 Jun;14(3):267-9
references: 1896729
references: Sleep. 2010 Jun;33(6):745-52
references: 20550014
references: Arch Gen Psychiatry. 1960 Oct;3:421-8
references: 13781811
references: J Sleep Res. 2011 Mar;20(1 Pt 1):45-9
references: 20642748
references: Sleep. 1999 Feb 1;22(1):77-87
references: 9989368
references: Lancet Neurol. 2008 Jul;7(7):649-62
references: 18565458
references: Sleep. 2005 Jan;28(1):123-44
references: 15700728
references: J Neurol Neurosurg Psychiatry. 2006 Mar;77(3):402-4
references: 16484654
references: Sleep Med. 2010 Jan;11(1):93-5
references: 19699146
references: Sleep. 1986 Dec;9(4):519-24
references: 3809866
references: Biol Psychiatry. 1999 Mar 15;45(6):764-70
references: 10188007
references: J Sleep Res. 2003 Mar;12(1):43-52
references: 12603786
references: Sleep. 2012 Sep 01;35(9):1247-55F
references: 22942503
references: Electroencephalogr Clin Neurophysiol. 1989 Aug;73(2):107-16
references: 2473877
references: Sleep. 2005 Apr;28(4):499-521
references: 16171294
references: Sleep. 2004 Nov 1;27(7):1255-73
references: 15586779
references: Arch Neurol. 2009 Dec;66(12):1563-6
references: 20008665
references: Biol Psychiatry. 1996 Aug 1;40(3):208-14
references: 8830954
references: Sleep Med Clin. 2009 Mar 1;4(1):37-46
references: 20161300
references: Brain. 2006 Jun;129(Pt 6):1609-23
references: 16597649
references: Neurology. 2004 Jan 13;62(1):46-50
references: 14718696
references: Am J Hum Genet. 2001 Mar;68(3):686-99
references: 11179016
references: J Sleep Res. 2002 Mar;11(1):53-9
references: 11869427
references: Sleep. 2005 Jan;28(1):113-21
references: 15700727