Timothy J. Young, MD; and Michael H. Silber, MBChB. disorder; REM = rapid eye movement; SOREM = sleep onset rapid eye movement sleep

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1 CHEST Timothy J. Young, MD; and Michael H. Silber, MBChB CNS CNS (hypersomnia); (idiopathic hypersomnia); (narcolepsy); (recurrent hypersomnia) CSF = cerebrospinal fluid; EDS = excessive daytime sleepiness; HLA = human leukocyte antigen; IH = idiopathic hypersomnia; MSLT = multiple sleep latency test; RBD = rapid eye movement sleep behavior disorder; REM = rapid eye movement; SOREM = sleep onset rapid eye movement sleep 9% [1] (EDS) From the Sleep Disorders Center, Mayo Clinic College of Medicine, Rochester, MN. This research was supported by Mayo Piscopo Funds. Correspondence to: Michael H. Silber, MBChB, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905; ( 1) msilber@mayo.edu CHEST

2 1 (1) [5] REM NREM 5-1 ( 2) CNS 1 2 (1) REM NREM y Yoss [6] 1957 EDS [2] 5-10 y (REM) REM 5- REM EDS EDS [7] [8] 1 2 (Orexin) A B [3] [7] 64% 80% [9] 2min γ - (galanin) [10] [4] ( ) 86% [11, 12] 25% 38

3 (prodynorphin) REM [22, 23] 63% 6% [12, 13] [14] 24 h [15] (HLA) DQB1*0602 [24] REM 85% 93% [25] (RBD) RBD 36% [15] RBD (35% 56%) [26] 12% 38% % 2% [27] [16] [17] [28] (CSF) CSF [18] [29] 1 IgG [19] [30] [31] CNS 20 HLA DQB1*0602 N- CSF IgG [20] / [21] 10% 86% CSF 2 [12] CSF C [12] CSF Kleine-Levin ( ) 2wk 1wk (MSLT) CHEST

4 3 (1) (2) mg 400 mg 500mg/mL 9g mg 100 mg 20 mg CNS (Concerta mg 100 mg McNeil Fort Washing- CNS ton, PA) 5 10 mg 100 mg CNS (Dexedrine mg 100 mg Spansules GlaxoSmith- CNS Kline) mg 100 mg (Adderall Shire Phar- CNS maceuticals Basingstoke, UK) mg 100mg (Adderall XR Shire CNS Pharmaceuticals) 5mg 80 mg CNS (1) Richardson [69] (2) Littner [70] 4 5 EDS 15 min REM MSLT SOREM MSLT [32] 4 HLA 10.4 min s DQB1*0602 [12, 34] 4.2 min CSF ( ) min 8 min 2 REM (SOREM) [33] REM ( ) [35 37] HLA CSF CSF 40

5 [38] [39] [46 49] 1 [46] 1 [47] EDS 5 Ig [48, 49] 3 1 [40] ( 3) (IH) [41] (von Economo ) 20 Roth [50] [51, 52] IH [5] IH [42] 10 h EDS ( ) IH EDS 10 h [50] 25% 60% [43, 44] γ - 21% γ - -B h 1 IH [45] 2005 MSLT EDS 8 min 2 γ - SOREM MSLT h IH CHEST

6 [58] MSLT 10 h MSLT 4 8 y [59, 60] 8min 2 SOREM IH EDS 5- [61] Kleine- Levin [53] 4 : 1 4 [54] Kleine-Levin CNS [55] 61% mo 1 4y 18 h MSLT 2 SOREM [62] CSF 1 [56] CSF [53] 1 MRI CT [57] 4 3 [53] CNS 42

7 [63] [64] [65] [66] C 10 Krahn LE, et al. Sleep Med 2000;1: [67] Ohayon MM. Psychiatry Res 2000;97: (47%) 12 Mignot E, et al. Arch Neurol 2002;59: % EDS EDS 1988;70: Nightingale S, et al. Sleep Med 2005;6: Lin L, et al. Cell 1999;98: Chemelli RM, et al. Cell 1999;98: Ripley B, et al. Neurology 2001;57: ( ) ( 19 Peyron C, et al. Nat Med 2000;6: ) ( 20 Lodi R, et al. Neurology 2004;63: Thannickal TC, et al. Neuron 2000;27: ) 28 Black JL, et al. Sleep 2002;25: Black JL, et al. Sleep 2005; 28: Smith AJ, et al. Lancet 2004; 364: Black JL, et al. Sleep 2005;28: Arand D, et al. Sleep 2005;28: Littner MR, et al. Sleep 2005;28: [68] MSLT 34 Krahn LE, et al. Sleep 2002;25: ( ) 1 Hublin C, et al. J Intern Med 1996;239: Jones BE. Basic mechanisms of sleep-wake states. In: Kryger MH, et al, eds. Principles and practice of sleep medcine. 4th ed. Philadelphia, PA: Elsevier Saunders, 2005; Eggermann E, et al. Neuroscience 2001;108: Saper CB, et al. Trends Neurosci 2005;28: American Academy of Sleep Medicine. International classification of sleep disorders: diagnostic and coding manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine, Yoss RE, et al. Proc Staff Meet Mayo Clin 1957;32: Silber MH, et al. Sleep 2002;25: Beusterien KM, et al. Sleep 1999;22: Krahn LE, et al. J Neuropsychiatry Clin Neurosci 2005;17: 13 Ohayon MM, et al. Neurology 1999;52: Broughton R, et al. Electroencephalogr Clin Neurophysiol 22 Crocker A, et al. Neurology 2005;65: Blouin AM, et al. Neurology 2005;65: Mignot E, et al. Sleep 1997;20: Mignot E. Neurology 1998;50:S16 S22 26 Roger AE, et al. Neurology 1997;48: Guilleminault C, et al. Lancet 1989;2: Lankford DA, et al. Sleep 1994;17(Suppl):S25 S Autret A, et al. Sleep 1994;17:S21 S24 37 Malik S, et al. Neurology 2001;57: Scammel TE, et al. Neurology 2001;56: Melberg A, et al. Neurology 1999;53: Rogers AE, et al. Sleep 2001;24: Mitler MM, et al. Sleep Med 2000;1: Auger RR, et al. Sleep 2005;28: Lammers GJ, et al. Sleep 1993;16: US Xyrem Multicenter Study Group. Sleep 2002;25: Lapierre O, et al. Sleep 1990;13: Hecht M, et al. Sleep 2003;26: Chen W, et al. Ann Neurol 2005;58: Lecendreaux M, et al. J Sleep Res 2003;12: Dauvilliers Y, et al. Ann Neurol 2004;56: Roth B. Schweiz Arch Neurol Neurochir Psych 1976;119: Bassetti C, et al. Brain 1997;120: Billiard M, et al. Sleep Med Rev 2001;5: Kesler A, et al. Sleep 2000;23: CHEST

8 54 Gadoth N, et al. J Sleep Res 2001;10: Arnulf I, et al. Brain 2005;128: Dauvilliers Y, et al. J Neurol Neurosurg Psychiatry 2003;74: Huang YS, et al. Sleep 2005;28: Dauvilliers Y, et al. Neurology 2002;59: Landtblom AM, et al. Acta Neurol Scand 2003;108: Fontenelle LF, et al. Acta Neurol Scand 2003;107: Poppe M, et al. Neuropediatrics 2003;34: Bonnet MH, et al. Sleep 2005;28: Arnulf I. Sleep Med Rev 2005;9: Laberge L, et al. J Sleep Res 2004;13: Vankova J, et al. Sleep 2003;26: Manni R, et al. Clin Neurophysiol 2001;112: Masel BE, et al. Arch Phys Med Rehabil 2001;82: Vgontzas AN, et al. Psychosom Med 2000;62: Richardson JR, et al. Sleep disorders. In: Levenson JL,ed. Textbook of psychosomatic medicine. Washington, DC:American Psychiatric Publishing, Littner M, et al. Sleep 2001;24: CHEST 2006;130:

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