Diagnosis and Management of Narcolepsy

Logan Schneider; Emmanuel Mignot

doi:10.1055/s-0037-1605554

Seminars in Neurology, Table of Contents

Semin Neurol 2017; 37(04): 446-460
DOI: 10.1055/s-0037-1605554

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Diagnosis and Management of Narcolepsy

Logan Schneider

¹Stanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University Medical School, Palo Alto, California

,

Emmanuel Mignot

¹Stanford Department of Psychiatry and Behavioral Medicine, Center for Sleep Sciences and Medicine, Stanford University Medical School, Palo Alto, California

› Author Affiliations

Abstract

Type 1 narcolepsy is caused by deficient hypocretin signaling in the central nervous system (CNS), and is distinct from other primary CNS hypersomnias, which seem to lay along a spectrum from type 2 narcolepsy to idiopathic hypersomnia. There appears to be a strong autoimmune diathesis to the development of type 1 narcolepsy, as evidenced by the near universal presence of HLA-DQB1*06:02 in patients. Growing knowledge of the immunogenetic basis of the disease is supported by genetic studies and seasonal variation of type 1 narcolepsy incidence following winter upper respiratory infections (e.g., strep throat and influenza). Despite improved diagnostic accuracy of adding cerebrospinal fluid hypocretin measurement to the traditional workup, recognition of the disorder remains limited by its moderate prevalence and atypical manifestations in different ethnic groups. Treatments are currently symptom-based, and have been extended to other hypersomnias with mixed results.

Keywords

narcolepsy - hypersomnia - neuroimmunology - sleep

Full Text

References

References
1 Lennox WG. Thomas Willis on narcolepsy. Arch Neurol Psychiatry 1939; 41 (02) 348-351
2 Dewhurst K. Thomas Willis and the foundation of British neurology. In: Rose FC, Bynum WF. , eds. Historical Aspects of the Neurosciences: A Festschrift for Macdonald Critchley. New York: Raven Press; 1982: 327-346
3 Fischer F. Epileptoide schlafzustände. Arch Psychiatr Nervenkr 1878; 8 (01) 200-203
4 Guilleminault C, Dement WC, Passouant P. Narcolepsy: Proceedings of the First International Symposium on Narcolepsy, July 1975, Montpellier, France. Richmond, Victoria, Australia:SP Boods division of Spectrum Publications; 1976
5 Furukawa T. Heinrich Bruno Schindler's description of narcolepsy in 1829. Neurol (Tokyo) 1987; 37 (01) 146
6 Schenck CH, Bassetti CL, Arnulf I, Mignot E. English translations of the first clinical reports on narcolepsy and cataplexy by Westphal and Gélineau in the late 19th century, with commentary. J Clin Sleep Med 2007; 3 (03) 301-311
7 Binns E. The Anatomy of Sleep: Or, The Art of Procuring Sound and Refreshing Slumber at Will. London: Churchill; 1842
8 Daniels LE. Narcolepsy. Medicine (Baltimore) 1934; 13 (Feb): 1-122
9 ADIE WJ. Idiopathic narcolepsy: a disease sui generis; with remarks on the mechanism of sleep. Brain 1926; 49 (03) 257-306 abstract
10 Vogel G. Studies in psychophysiology of dreams. III. The dream of narcolepsy. Arch Gen Psychiatry 1960; 3 (04) 421-428
11 Rechtschaffen A, Wolpert EA, Dement WC, Mitchell SA, Fisher C, Dament WC, Mitchell SA, Fisher C. Nocturnal sleep of narcoleptics. Electroencephalogr Clin Neurophysiol 1963; 15 (04) 599-609
12 Mignot E. Genetic and familial aspects of narcolepsy. Neurology 1998; 50 (02) (Suppl. 01) S16-S22
13 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). 5th ed. Arlington, VA: American Psychiatric Association; 2013
14 American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014
15 Mignot EJM. A practical guide to the therapy of narcolepsy and hypersomnia syndromes. Neurotherapeutics 2012; 9 (04) 739-752
16 Nishino S, Mignot E. Pharmacological aspects of human and canine narcolepsy. Prog Neurobiol 1997; 52 (01) 27-78
17 Crocker A, España RA, Papadopoulou M. , et al. Concomitant loss of dynorphin, NARP, and orexin in narcolepsy. Neurology 2005; 65 (08) 1184-1188
18 Peyron C, Faraco J, Rogers W. , et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 2000; 6 (09) 991-997
19 Thannickal TC, Moore RY, Nienhuis R. , et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron 2000; 27 (03) 469-474
20 Chemelli RM, Willie JT, Sinton CM. , et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 1999; 98 (04) 437-451
21 Peyron C, Tighe DK, van den Pol AN. , et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 1998; 18 (23) 9996-10015
22 Sakurai T, Amemiya A, Ishii M. , et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998; 92 (04) 573-585
23 Bourgin P, Huitrón-Résendiz S, Spier AD. , et al. Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. J Neurosci 2000; 20 (20) 7760-7765
24 España RA, Baldo BA, Kelley AE, Berridge CW. Wake-promoting and sleep-suppressing actions of hypocretin (orexin): basal forebrain sites of action. Neuroscience 2001; 106 (04) 699-715
25 Hagan JJ, Leslie RA, Patel S. , et al. Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc Natl Acad Sci U S A 1999; 96 (19) 10911-10916
26 Lee MG, Hassani OK, Jones BE. Discharge of identified orexin/hypocretin neurons across the sleep-waking cycle. J Neurosci 2005; 25 (28) 6716-6720
27 Mileykovskiy BY, Kiyashchenko LI, Siegel JM. Behavioral correlates of activity in identified hypocretin/orexin neurons. Neuron 2005; 46 (05) 787-798
28 Adamantidis AR, Zhang F, Aravanis AM, Deisseroth K, de Lecea L. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 2007; 450 (7168): 420-424
29 Carter ME, Adamantidis A, Ohtsu H, Deisseroth K, de Lecea L. Sleep homeostasis modulates hypocretin-mediated sleep-to-wake transitions. J Neurosci 2009; 29 (35) 10939-10949
30 Ranson SW. Somnolence caused by hypothalamic lesions in the monkey. Arch Neurol Psychiatry 1939; 41 (01) 1
31 Gerashchenko D, Kohls MD, Greco M. , et al. Hypocretin-2-saporin lesions of the lateral hypothalamus produce narcoleptic-like sleep behavior in the rat. J Neurosci 2001; 21 (18) 7273-7283
32 Verret L, Goutagny R, Fort P. , et al. A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep. BMC Neurosci 2003; 4: 19
33 Nauta WJ. Hypothalamic regulation of sleep in rats; an experimental study. J Neurophysiol 1946; 9: 285-316
34 Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, Scammell TE. Behavioral state instability in orexin knock-out mice. J Neurosci 2004; 24 (28) 6291-6300
35 Baumann CR, Bassetti CL, Valko PO. , et al. Loss of hypocretin (orexin) neurons with traumatic brain injury. Ann Neurol 2009; 66 (04) 555-559
36 Benarroch EE, Schmeichel AM, Sandroni P, Low PA, Parisi JE. Involvement of hypocretin neurons in multiple system atrophy. Acta Neuropathol 2007; 113 (01) 75-80
37 Fronczek R, Baumann CR, Lammers GJ, Bassetti CL, Overeem S. Hypocretin/orexin disturbances in neurological disorders. Sleep Med Rev 2009; 13 (01) 9-22
38 Fronczek R, Overeem S, Lee SYY. , et al. Hypocretin (orexin) loss in Parkinson's disease. Brain 2007; 130 (Pt 6): 1577-1585
39 Thannickal TC, Lai Y-Y, Siegel JM. Hypocretin (orexin) cell loss in Parkinson's disease. Brain 2007; 130 (Pt 6): 1586-1595
40 Bourgin P, Zeitzer JM, Mignot E. CSF hypocretin-1 assessment in sleep and neurological disorders. Lancet Neurol 2008; 7 (07) 649-662
41 Aston-Jones G, Smith RJ, Moorman DE, Richardson KA. Role of lateral hypothalamic orexin neurons in reward processing and addiction. Neuropharmacology 2009; 56 (Suppl. 01) 112-121
42 Borgland SL, Chang S-J, Bowers MS. , et al. Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers. J Neurosci 2009; 29 (36) 11215-11225
43 Burdakov D, Gerasimenko O, Verkhratsky A. Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ. J Neurosci 2005; 25 (09) 2429-2433
44 España RA, Melchior JR, Roberts DCS, Jones SR. Hypocretin 1/orexin A in the ventral tegmental area enhances dopamine responses to cocaine and promotes cocaine self-administration. Psychopharmacology (Berl) 2011; 214 (02) 415-426
45 España RA, Oleson EB, Locke JL, Brookshire BR, Roberts DCS, Jones SR. The hypocretin-orexin system regulates cocaine self-administration via actions on the mesolimbic dopamine system. Eur J Neurosci 2010; 31 (02) 336-348
46 Moriguchi T, Sakurai T, Nambu T, Yanagisawa M, Goto K. Neurons containing orexin in the lateral hypothalamic area of the adult rat brain are activated by insulin-induced acute hypoglycemia. Neurosci Lett 1999; 264 (1-3): 101-104
47 Honda Y, Juji T. , Eds. HLA in Narcolepsy . Heidelberg: Springer; 1988
48 Juji T, Satake M, Honda Y, Doi Y. HLA antigens in Japanese patients with narcolepsy. All the patients were DR2 positive. Tissue Antigens 1984; 24 (05) 316-319
49 Billiard M, Seignalet J, Juji T. , et al. Extraordinary association between HLA-DR2 and narcolepsy. Lancet 1985; 1 (8422): 226-227
50 Marcadet A, Gebuhrer L, Betuel H. , et al. DNA polymorphism related to HLA-DR2 Dw2 in patients with narcolepsy. Immunogenetics 1985; 22 (06) 679-683
51 Mueller-Eckhardt G, Meier-Ewert K, Schendel DJ, Reinecker FB, Multhoff G, Mueller-Eckhardt C. HLA and narcolepsy in a German population. Tissue Antigens 1986; 28 (03) 163-169
52 Roth B, Nevsímalová S, Sonka K. , et al. A study of the occurrence of HLA DR2 in 124 narcoleptics: clinical aspects. Schweiz Arch Neurol Psychiatr (1985) 1988; 139 (04) 41-51
53 Poirier G, Montplaisir J, Décary F, Momège D, Lebrun A. HLA antigens in narcolepsy and idiopathic central nervous system hypersomnolence. Sleep 1986; 9 (1 Pt 2): 153-158
54 Guilleminault C, Grumet C. HLA-DR2 and narcolepsy: not all narcoleptic-cataplectic patients are DR2. Hum Immunol 1986; 17 (01) 1-2
55 Neely S, Rosenberg R, Spire JP, Antel J, Arnason BG. HLA antigens in narcolepsy. Neurology 1987; 37 (12) 1858-1860
56 Matsuki K, Grumet FC, Lin X. , et al. DQ (rather than DR) gene marks susceptibility to narcolepsy. Lancet 1992; 339 (8800): 1052
57 Rogers AE, Meehan J, Guilleminault C, Grumet FC, Mignot E. HLA DR15 (DR2) and DQB1*0602 typing studies in 188 narcoleptic patients with cataplexy. Neurology 1997; 48 (06) 1550-1556
58 Mignot E, Kimura A, Lattermann A. , et al. Extensive HLA class II studies in 58 non-DRB1*15 (DR2) narcoleptic patients with cataplexy. Tissue Antigens 1997; 49 (04) 329-341
59 Mignot E, Lin X, Arrigoni J. , et al. DQB1*0602 and DQA1*0102 (DQ1) are better markers than DR2 for narcolepsy in Caucasian and black Americans. Sleep 1994; 17 (8, Suppl) S60-S67
60 Pelin Z, Guilleminault C, Risch N, Grumet FC, Mignot E. ; US Modafinil in Narcolepsy Multicenter Study Group. HLA-DQB1*0602 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups. Tissue Antigens 1998; 51 (01) 96-100
61 Han F, Lin L, Li J. , et al. HLA-DQ association and allele competition in Chinese narcolepsy. Tissue Antigens 2012; 80 (04) 328-335
62 Hohjoh H, Terada N, Nakayama T. , et al. Case-control study with narcoleptic patients and healthy controls who, like the patients, possess both HLA-DRB1*1501 and -DQB1*0602. Tissue Antigens 2001; 57 (03) 230-235
63 Hong S-C, Lin L, Lo B. , et al. DQB1*0301 and DQB1*0601 modulate narcolepsy susceptibility in Koreans. Hum Immunol 2007; 68 (01) 59-68
64 Hor H, Kutalik Z, Dauvilliers Y. , et al. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. Nat Genet 2010; 42 (09) 786-789
65 Mignot E, Lin L, Rogers W. , et al. Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. Am J Hum Genet 2001; 68 (03) 686-699
66 Ollila HM, Fernandez-Vina M, Mignot E. HLA-DQ allele competition in narcolepsy: a comment on Tafti et al. DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe. Sleep 2015; 38 (01) 147-151
67 Han F, Faraco J, Dong XS. , et al. Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic. PLoS Genet 2013; 9 (10) e1003880
68 Black III JL, Avula RK, Walker DL. , et al. HLA DQB1*0602 positive narcoleptic subjects with cataplexy have CSF lgG reactive to rat hypothalamic protein extract. Sleep 2005; 28 (09) 1191-1192
69 Black III JL, Silber MH, Krahn LE. , et al. Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602-positive narcoleptic subjects with cataplexy. Biol Psychiatry 2005; 58 (06) 504-509
70 Tanaka S, Honda Y, Inoue Y, Honda M. Detection of autoantibodies against hypocretin, HCRTRL, and HCRTR2 in narcolepsy: anti-HCRT system antibody in narcolepsy. Sleep 2006; 29 (05) 633-638
71 Bergman P, Adori C, Vas S. , et al. Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns. Proc Natl Acad Sci U S A 2014; 111 (35) E3735-E3744
72 Graus F, Saiz A, Dalmau J. Antibodies and neuronal autoimmune disorders of the CNS. J Neurol 2010; 257 (04) 509-517
73 Fontana A, Gast H, Reith W, Recher M, Birchler T, Bassetti CL. Narcolepsy: autoimmunity, effector T cell activation due to infection, or T cell independent, major histocompatibility complex class II induced neuronal loss?. Brain 2010; 133 (Pt 5): 1300-1311
74 Overeem S, Dalmau J, Bataller L. , et al. Hypocretin-1 CSF levels in anti-Ma2 associated encephalitis. Neurology 2004; 62 (01) 138-140
75 Dauvilliers Y, Bauer J, Rigau V. , et al. Hypothalamic immunopathology in anti-Ma-associated diencephalitis with narcolepsy-cataplexy. JAMA Neurol 2013; 70 (10) 1305-1310
76 Faraco J, Lin L, Kornum BR. , et al. ImmunoChip study implicates antigen presentation to T cells in narcolepsy. PLoS Genet 2013; 9 (02) e1003270
77 Hallmayer J, Faraco J, Lin L. , et al. Narcolepsy is strongly associated with the T-cell receptor alpha locus. Nat Genet 2009; 41 (06) 708-711
78 Bernard-Valnet R, Yshii L, Quériault C. , et al. CD8 T cell-mediated killing of orexinergic neurons induces a narcolepsy-like phenotype in mice. Proc Natl Acad Sci U S A 2016; 113 (39) 10956-10961
79 Julkunen I, Partinen M. Neuroimmunology: disease mechanisms in narcolepsy remain elusive. Nat Rev Neurol 2014; 10 (11) 616-617
80 Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet 2007; 369 (9560): 499-511
81 Hor H, Bartesaghi L, Kutalik Z. , et al. A missense mutation in myelin oligodendrocyte glycoprotein as a cause of familial narcolepsy with cataplexy. Am J Hum Genet 2011; 89 (03) 474-479
82 Aran A, Lin L, Nevsimalova S. , et al. Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset. Sleep 2009; 32 (08) 979-983
83 Longstreth Jr WT, Ton TGN, Koepsell TD. Narcolepsy and streptococcal infections. Sleep 2009; 32 (12) 1548
84 Mancardi GL, Del Sette M, Primavera A, Farinelli M, Fumarola D. A prospective study of acute idiopathic neuropathy II antecedent events. J Neurol Neurosurg Psychiatry 1989; 52 (03) 424-425
85 Lehmann HC, Hartung H-P, Kieseier BC, Hughes RAC. Guillain-Barré syndrome after exposure to influenza virus. Lancet Infect Dis 2010; 10 (09) 643-651
86 Vincent A. Encephalitis lethargica: part of a spectrum of post-streptococcal autoimmune diseases?. Brain 2004; 127 (Pt 1): 2-3
87 Von Economo C. Sleep as a problem of localization. J Nerv Ment Dis 1930; 71 (march): 249-259
88 Han F, Lin L, Warby SC. , et al. Narcolepsy onset is seasonal and increased following the 2009 H1N1 pandemic in China. Ann Neurol 2011; 70 (03) 410-417
89 Oberle D, Drechsel-Bäuerle U, Schmidtmann I, Mayer G, Keller-Stanislawski B. Incidence of narcolepsy in Germany. Sleep 2015; 38 (10) 1619-1628
90 Partinen M, Saarenpää-Heikkilä O, Ilveskoski I. , et al. Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PLoS One 2012; 7 (03) e33723
91 Dauvilliers Y, Montplaisir J, Cochen V. , et al. Post-H1N1 narcolepsy-cataplexy. Sleep 2010; 33 (11) 1428-1430
92 Dauvilliers Y, Arnulf I, Lecendreux M. , et al; Narcoflu-VF study group. Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France. Brain 2013; 136 (Pt 8): 2486-2496
93 Partinen M, Saarenpää-Heikkilä O, Ilveskoski I. , et al. Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PLoS One 2012; 7 (03) e33723
94 Heier MS, Gautvik KM, Wannag E. , et al. Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A. Sleep Med 2013; 14 (09) 867-871
95 Winstone AM, Stellitano L, Verity C. , et al. Clinical features of narcolepsy in children vaccinated with AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine in England. Dev Med Child Neurol 2014; 56 (11) 1117-1123
96 O'Flanagan D, Barret AS, Foley M. , et al. Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010. Euro Surveill 2014; 19 (17) 15-25
97 Mendes MFSG, Valladares Neto DdeC, Azevedo RA, Caramelli P. Narcolepsy after A/H1N1 vaccination. Clinics (Sao Paulo) 2012; 67 (01) 77-78
98 Jacob L, Leib R, Ollila HM, Bonvalet M, Adams CM, Mignot E. Comparison of Pandemrix and Arepanrix, two pH1N1 AS03-adjuvanted vaccines differentially associated with narcolepsy development. Brain Behav Immun 2015; 47: 44-57
99 Leroux-Roels I, Roman F, Forgus S. , et al. Priming with AS03 A-adjuvanted H5N1 influenza vaccine improves the kinetics, magnitude and durability of the immune response after a heterologous booster vaccination: an open non-randomised extension of a double-blind randomised primary study. Vaccine 2010; 28 (03) 849-857
100 Gadroen K, Straus SMJM, Pacurariu A, Weibel D, Kurz X, Sturkenboom MCJM. Patterns of spontaneous reports on narcolepsy following administration of pandemic influenza vaccine; a case series of individual case safety reports in Eudravigilance. Vaccine 2016; 34 (41) 4892-4897
101 Vaarala O, Vuorela A, Partinen M. , et al. Antigenic differences between AS03 adjuvanted influenza A (H1N1) pandemic vaccines: implications for pandemrix-associated narcolepsy risk. PLoS One 2014; 9 (12) e114361
102 Mignot E, Lammers GJ, Ripley B. , et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 2002; 59 (10) 1553-1562
103 Kawai M, O'Hara R, Einen M, Lin L, Mignot E. Narcolepsy in African Americans. Sleep 2015; 38 (11) 1673-1681
104 Broughton R, Dunham W, Newman J, Lutley K, Duschesne P, Rivers M. Ambulatory 24 hour sleep-wake monitoring in narcolepsy-cataplexy compared to matched controls. Electroencephalogr Clin Neurophysiol 1988; 70 (06) 473-481
105 Frauscher B, Ehrmann L, Mitterling T. , et al. Delayed diagnosis, range of severity, and multiple sleep comorbidities: a clinical and polysomnographic analysis of 100 patients of the Innsbruck narcolepsy cohort. J Clin Sleep Med 2013; 9 (08) 805-812
106 Taddei RN, Werth E, Poryazova R, Baumann CR, Valko PO. Diagnostic delay in narcolepsy type 1: combining the patients' and the doctors' perspectives. J Sleep Res 2016; 25 (06) 709-715
107 Mignot E, Hayduk R, Black J, Grumet FC, Guilleminault C. HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients. Sleep 1997; 20 (11) 1012-1020
108 Silber MH, Krahn LE, Olson EJ, Pankratz VS. The epidemiology of narcolepsy in Olmsted County, Minnesota: a population-based study. Sleep 2002; 25 (02) 197-202
109 Okun ML, Lin L, Pelin Z, Hong S, Mignot E. Clinical aspects of narcolepsy-cataplexy across ethnic groups. Sleep 2002; 25 (01) 27-35
110 Anic-Labat S, Guilleminault C, Kraemer HC, Meehan J, Arrigoni J, Mignot E. Validation of a cataplexy questionnaire in 983 sleep-disorders patients. Sleep 1999; 22 (01) 77-87
111 Cornes SB, Shih T. Evaluation of the patient with spells. Continuum (Minneap Minn) 2011; 17 (5 Neurologic Consultation in the Hospital): 984-1009
112 St Louis EK, Cascino GD. Diagnosis of epilepsy and related episodic disorders. Continuum (minneap minn) 2016; 22 (1 epilepsy): 15-37
113 Serra L, Montagna P, Mignot E, Lugaresi E, Plazzi G. Cataplexy features in childhood narcolepsy. Mov Disord 2008; 23 (06) 858-865
114 Ohayon MM, Dauvilliers Y, Reynolds III CF. Operational definitions and algorithms for excessive sleepiness in the general population: implications for DSM-5 nosology. Arch Gen Psychiatry 2012; 69 (01) 71-79
115 Bixler EO, Vgontzas AN, Lin H-M, Calhoun SL, Vela-Bueno A, Kales A. Excessive daytime sleepiness in a general population sample: the role of sleep apnea, age, obesity, diabetes, and depression. J Clin Endocrinol Metab 2005; 90 (08) 4510-4515
116 Gonçalves R, Togeiro S. Drug-induced sleepiness and insomnia: an update. Sleep Sci 2013; 6 (01) 36-43
117 Dyken ME, Afifi AK, Lin-Dyken DC. Sleep-related problems in neurologic diseases. Chest 2012; 141 (02) 528-544
118 Sharpless BA, Barber JP. Lifetime prevalence rates of sleep paralysis: a systematic review. Sleep Med Rev 2011; 15 (05) 311-315
119 Ohayon MM, Zulley J, Guilleminault C, Smirne S. Prevalence and pathologic associations of sleep paralysis in the general population. Neurology 1999; 52 (06) 1194-1200
120 Roth T, Dauvilliers Y, Mignot E. , et al. Disrupted nighttime sleep in narcolepsy. J Clin Sleep Med 2013; 9 (09) 955-965
121 Fraigne JJ, Torontali ZA, Snow MB, Peever JH. REM Sleep at its Core - Circuits, Neurotransmitters, and Pathophysiology. Front Neurol 2015; 6: 123
122 Pizza F, Tartarotti S, Poryazova R, Baumann CR, Bassetti CL. Sleep-disordered breathing and periodic limb movements in narcolepsy with cataplexy: a systematic analysis of 35 consecutive patients. Eur Neurol 2013; 70 (1-2): 22-26
123 Pizza F, Bassetti CL. Reply to Comments on ‘Sleep Disordered Breathing and Periodic Limb Movements in Patients with Narcolepsy with Cataplexy’. Eur Neurol 2015; 74 (3-4): 170
124 Sethi NK. Comments on ‘Sleep Disordered Breathing and Periodic Limb Movements in Patients with Narcolepsy with Cataplexy’. Eur Neurol 2015; 74 (3-4): 169
125 Kotagal S, Krahn LE, Slocumb N. A putative link between childhood narcolepsy and obesity. Sleep Med 2004; 5 (02) 147-150
126 Pagel JF. Excessive daytime sleepiness. Am Fam Physician 2009; 79 (05) 391-396
127 Martínez-Orozco FJ, Vicario JL, Villalibre-Valderrey I, De Andrés C, Fernández-Arquero M, Peraita-Adrados R. Narcolepsy with cataplexy and comorbid immunopathological diseases. J Sleep Res 2014; 23 (04) 414-419
128 Kanbayashi T, Sagawa Y, Takemura F. , et al. The pathophysiologic basis of secondary narcolepsy and hypersomnia. Curr Neurol Neurosci Rep 2011; 11 (02) 235-241
129 Haddad F, Anouti S, Maalouly G, Koussa S. [Narcolepsy associated with systemic lupus erythematosus]. Rev Med Interne 2011; 32 (11) e114-e115
130 Pablos JL, del Rincon E, Francisco F, Mateo I. Narcolepsy in systemic lupus erythematosus. J Rheumatol 1993; 20 (02) 375-376
131 Winkelmann J, Lin L, Schormair B. , et al. Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. Hum Mol Genet 2012; 21 (10) 2205-2210
132 Parkes JD. Genetic factors in human sleep disorders with special reference to Norrie disease, Prader-Willi syndrome and Moebius syndrome. J Sleep Res 1999; 8 (Suppl. 01) 14-22
133 Tyagi A, Harrington H. Cataplexy in association with Moebius syndrome. J Neurol 2003; 250 (01) 110-111
134 Krämer S, Goldammer U, Sindern E. [Moebius syndrome and narcolepsy]. Nervenarzt 2014; 85 (12) 1569-1572
135 Nelson GB, Hahn JS. Stimulus-induced drop episodes in Coffin-Lowry syndrome. Pediatrics 2003; 111 (03) e197-e202
136 Vankova J, Stepanova I, Jech R. , et al. Sleep disturbances and hypocretin deficiency in Niemann-Pick disease type C. Sleep 2003; 26 (04) 427-430
137 Oyama K, Takahashi T, Shoji Y. , et al. Niemann-Pick disease type C: cataplexy and hypocretin in cerebrospinal fluid. Tohoku J Exp Med 2006; 209 (03) 263-267
138 Pedroso JL, Fusão EF, Ladeia-Frota C. , et al. Teaching video neuroimages: gelastic cataplexy as the first neurologic manifestation of Niemann-Pick disease type C. Neurology 2012; 79 (22) e189
139 Vossler DG, Wyler AR, Wilkus RJ, Gardner-Walker G, Vlcek BW. Cataplexy and monoamine oxidase deficiency in Norrie disease. Neurology 1996; 46 (05) 1258-1261
140 Smit LS, Lammers GJ, Catsman-Berrevoets CE. Cataplexy leading to the diagnosis of Niemann-Pick disease type C. Pediatr Neurol 2006; 35 (01) 82-84
141 Martínez-Rodríguez JE, Lin L, Iranzo A. , et al. Decreased hypocretin-1 (Orexin-A) levels in the cerebrospinal fluid of patients with myotonic dystrophy and excessive daytime sleepiness. Sleep 2003; 26 (03) 287-290
142 Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991; 14 (06) 540-545
143 Drake C, Nickel C, Burduvali E, Roth T, Jefferson C, Pietro B. The Pediatric Daytime Sleepiness Scale (PDSS): sleep habits and school outcomes in middle-school children. Sleep 2003; 26 (04) 455-458
144 Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The Fatigue Severity Scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 1989; 46 (10) 1121-1123
145 Carskadon MA, Dement WC. Normal sleep and its variations. In: Kryger MH, Roth T, Dement WC. , eds. Principles and Practice of Sleep Medicine. 2nd ed. Saunders; 1994: 1-13
146 Littner MR, Kushida C, Wise M. , et al; Standards of Practice Committee of the American Academy of Sleep Medicine. Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test. Sleep 2005; 28 (01) 113-121
147 Andlauer O, Moore H, Jouhier L. , et al. Nocturnal rapid eye movement sleep latency for identifying patients with narcolepsy/hypocretin deficiency. JAMA Neurol 2013; 70 (07) 891-902
148 Carskadon MA, Dement WC, Mitler MM, Roth T, Westbrook PR, Keenan S. Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness. Sleep 1986; 9 (04) 519-524
149 Goldbart A, Peppard P, Finn L. , et al. Narcolepsy and predictors of positive MSLTs in the Wisconsin Sleep Cohort. Sleep 2014; 37 (06) 1043-1051
150 Chervin RD, Aldrich MS. Sleep onset REM periods during multiple sleep latency tests in patients evaluated for sleep apnea. Am J Respir Crit Care Med 2000; 161 (2 Pt 1): 426-431
151 Trotti LM, Staab BA, Rye DB. Test-retest reliability of the multiple sleep latency test in narcolepsy without cataplexy and idiopathic hypersomnia. J Clin Sleep Med 2013; 9 (08) 789-795
152 Bassetti C, Aldrich MS. Idiopathic hypersomnia. A series of 42 patients. Brain 1997; 120 (Pt 8): 1423-1435
153 Han F, Lin L, Schormair B. , et al. HLA DQB1*06:02 negative narcolepsy with hypocretin/orexin deficiency. Sleep 2014; 37 (10) 1601-1608
154 Andlauer O, Moore IV H, Hong S-C. , et al. Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy. Sleep 2012; 35 (09) 1247-55F
155 Lin L, Hungs M, Mignot E. Narcolepsy and the HLA region. J Neuroimmunol 2001; 117 (1-2): 9-20
156 Adenuga O, Attarian H. Treatment of disorders of hypersomnolence. Curr Treat Options Neurol 2014; 16 (09) 302
157 Morgenthaler TI, Kapur VK, Brown T. , et al; Standards of Practice Committee of the American Academy of Sleep Medicine. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep 2007; 30 (12) 1705-1711
158 Wise MS, Arand DL, Auger RR, Brooks SN, Watson NF. ; American Academy of Sleep Medicine. Treatment of narcolepsy and other hypersomnias of central origin. Sleep 2007; 30 (12) 1712-1727
159 Snead III OC. Evidence for a G protein-coupled gamma-hydroxybutyric acid receptor. J Neurochem 2000; 75 (05) 1986-1996
160 Alshaikh MK, Tricco AC, Tashkandi M, Mamdani M, Straus SE, BaHammam AS. Sodium oxybate for narcolepsy with cataplexy: systematic review and meta-analysis. J Clin Sleep Med 2012; 8 (04) 451-458
161 Sebban C, Tesolin-Decros B, Millan MJ, Spedding M. Contrasting EEG profiles elicited by antipsychotic agents in the prefrontal cortex of the conscious rat: antagonism of the effects of clozapine by modafinil. Br J Pharmacol 1999; 128 (05) 1055-1063
162 Volkow ND, Fowler JS, Logan J. , et al. Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. JAMA 2009; 301 (11) 1148-1154
163 Mignot E, Nishino S, Guilleminault C, Dement WC. Modafinil binds to the dopamine uptake carrier site with low affinity. Sleep 1994; 17 (05) 436-437
164 Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM. Dopaminergic role in stimulant-induced wakefulness. J Neurosci 2001; 21 (05) 1787-1794
165 Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR. New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol 2007; 47 (01) 681-698
166 Tilley MR, Gu HH. The effects of methylphenidate on knockin mice with a methylphenidate-resistant dopamine transporter. J Pharmacol Exp Ther 2008; 327 (02) 554-560
167 McCarter SJ, St Louis EK, Sandness DJ. , et al. Antidepressants increase REM sleep muscle tone in patients with and without REM sleep behavior disorder. Sleep 2015; 38 (06) 907-917
168 Winkelman JW, James L. Serotonergic antidepressants are associated with REM sleep without atonia. Sleep 2004; 27 (02) 317-321
169 Knudsen S, Mikkelsen JD, Bang B, Gammeltoft S, Jennum PJ. Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy. Neuropediatrics 2010; 41 (05) 217-222
170 Fujiki N, Yoshida Y, Ripley B, Mignot E, Nishino S. Effects of IV and ICV hypocretin-1 (orexin A) in hypocretin receptor-2 gene mutated narcoleptic dogs and IV hypocretin-1 replacement therapy in a hypocretin-ligand-deficient narcoleptic dog. Sleep 2003; 26 (08) 953-959
171 Mieda M, Willie JT, Hara J, Sinton CM, Sakurai T, Yanagisawa M. Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proc Natl Acad Sci U S A 2004; 101 (13) 4649-4654
172 Leu-Semenescu S, Louis P, Arnulf I. Benefits and risk of sodium oxybate in idiopathic hypersomnia versus narcolepsy type 1: a chart review. Sleep Med 2016; 17: 38-44
173 Trotti LM, Saini P, Bliwise DL, Freeman AA, Jenkins A, Rye DB. Clarithromycin in γ-aminobutyric acid-related hypersomnolence: a randomized, crossover trial. Ann Neurol 2015; 78 (03) 454-465
174 Khan Z, Trotti LM. Central disorders of hypersomnolence: focus on the narcolepsies and idiopathic hypersomnia. Chest 2015; 148 (01) 262-273
175 Rye DB, Bliwise DL, Parker K. , et al. Modulation of vigilance in the primary hypersomnias by endogenous enhancement of GABAA receptors. Sci Transl Med 2012; 4 (161) 161ra151
176 Bassetti C, Gugger M, Bischof M. , et al. The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexin A). Sleep Med 2003; 4 (01) 7-12
177 Hong S-C, Lin L, Jeong J-H. , et al. A study of the diagnostic utility of HLA typing, CSF hypocretin-1 measurements, and MSLT testing for the diagnosis of narcolepsy in 163 Korean patients with unexplained excessive daytime sleepiness. Sleep 2006; 29 (11) 1429-1438