ABSTRACT
Hypersomnia and excessive daytime sleepiness are commonly encountered by physicians dealing with sleep medicine. Although these are common symptoms associated with sleep disorders, they can be ignored. The tendency of excessive daytime sleepiness, which might be caused by sleep deprivation that continues for a while in our society, makes it difficult to diagnose diseases with hypersomnia. Hypersomnia is used as a comprehensive definition for excessive daytime sleepiness and/or excessive need for sleep or increased amount of sleep. Clinically, it presents with prolonged sleep times at night, falling asleep easily and everywhere, recurrent sleep attacks, and excessive daytime sleepiness. Hypersomnia can be either a symptom of neurological and metabolic diseases, especially sleep disorders, or develop due to substance, drug use, and trauma. Sleep attacks occurring during the day can affect individuals’ academic or professional performance, disrupt their cognitive functions and social relations, and cause life-threatening traffic or work accidents. It is crucial to examine this symptom, which causes a significant deterioration in the quality of life of people, and to diagnose and treat the diseases causing it. This review article plans to address the epidemiological, pathophysiological, clinical aspects of sleep disorders that cause hypersomnia, treatment and emphasize the critical points in the differential diagnosis.
Keywords:
Hypersomnia, excessive daytime sleepiness, clinic, diagnosis
References
1Vaughn BV, D’Cruz O’NF. Cardinal Manifestations of sleep Disorders. In: Kryger M, Roth T, Dement W (eds). Principles and practice of sleep medicine. 5th ed. Philadelphia, WB Saunders Co, 2011;647-57.
2Hirshkowitz M, Whiton K, Albert SM, Alessi C, Bruni O, DonCarlos L, Hazen N, Herman J, Adams Hillard PJ, Katz ES, Kheirandish-Gozal L, Neubauer DN, O’Donnell AE, Ohayon M, Peever J, Rawding R, Sachdeva RC, Setters B, Vitiello MV, Ware JC. National Sleep Foundation’s updated sleep duration recommendations: final report. Sleep Health 2015;1:233-43.
3American Academy of Sleep Medicine (AASM). The International Classification of Sleep Disorders, Third Edition (ICSD-3). Darien, IL: American Academy of Sleep Medicine 2014.
4Friedman NS. Determinants and measurements of daytime sleepiness. In: Pagel JF, Pandi-Perumal SR, (eds). Primary Care Sleep Medicine: A Practical Guide. Totowa NJ, Humana Press, 2007;61-82.
5Malhotra RK. Evaluating the sleepy and sleepless patient. Continuum (Minneap Minn) 2020;26:871-89.
6Ohayon MM. From wakefulness to excessive sleepiness: what we know and still need to know. Sleep Med Rev 2008;12:129-41.
7Markowitz AJ, Rabow MW. Palliative management of fatigue at the close of life: “it feels like my body is just worn out”. JAMA 2007;298:217.
8Archontogeorgis K, Nena E, Papanas N, Steiropoulos P. The role of vitamin D in obstructive sleep apnoea syndrome. Breathe (Sheff) 2018;14:206-15.
9Tonon C, Vetrugno R, Lodi R, Gallassi R, Provini F, Iotti S, Plazzi G, Montagna P, Lugaresi E, Barbiroli B. Proton Magnetic Resonance Spectroscopy Study of Brain Metabolism in Obstructive Sleep Apnoea Syndrome before and after Continuous Positive Airway Pressure Treatment. Sleep 2007;30:305-11.
10Türk Toraks Derneği. Obstrüktif Uyku Apne Sendromu Tanı ve Tedavi Uzlaşı Raporu. Turk Thorac J 2012;13:1-44.
11Kraus MA, Hamburger RJ. Sleep apnea in renal failure. Adv Perit Dial 1997;13:88-92.
12Bassetti C, Aldrich MS. Sleep apnea in acute cerebrovascular diseases: Final report on 128 patients. Sleep 1999;22:217-23.
13Malow BA, Levy K, Maturen K, Bowes R. Obstructive sleep apnea is common in medically refractory epilepsy patients. Neurology 2000;55:1002-7.
14Elmasry A, Lindberg E, Berne C, Janson C, Gislason T, Awad Tageldin M, Boman G. Sleep-disordered breathing and glucose metabolism in hypertensive men: A populatiorı-based study. J Intern Med 2001;249:153-61.
15Young T, Peppard PE, Taheri S. Excess weight and sleep-disordered breathing. J Appl Physiol 2005;99:1592-9.
16Stradling JR. Sleep-related breathing disorders. 1. Obstructive sleep apnoea: definitions, epidemiology, and natural history. Thorax 1995;50:683-9.
17Mindy BC, Christian G. Obstructive sleep apnea syndrome. In: Sudhansu C (ed). Sleep disorders medicine: Basic science, technical considerations and clinical aspects. Butterworth-Heinneman, 1995;199-219.
18Trois MS, Capone GT, Lutz JA, Melendres MC, Schwartz AR, Collop NA, Marcus CL. Obstructive sleep apnea in adults with Down syndrome. J Clin Sleep Med 2009;5:317-23.
19Guilleminault C, Tilkian A, Dement WC. The sleep apnea syndromes. Annu Rev Med 1976;27:465-84.
20Kales A, Cadieux RJ, Bixler EO, Soldatos CR, Vela-Bueno A, Misoul CA, Locke TW. Severe obstructive sleep apnea: I: Onset, clinical course, and characteristics. J Chron Dis 1985;38:419-25.
21Coverdale SG, Read DJ, Woolcock AJ, Schoeffel RE. The importance of suspecting sleep apnea as a common cause of excessive daytime sleepiness: Further experience from the diagnosis and management of 19 patients. Aust N Z J Med 1980;10:284-8.
22Hoffstein V, Szala JP. Predictive value of clinical features in diagnosing obstructive sleep apnea. Sleep 1993;16:118-22.
23Hajduk IA, Strollo PJ Jr, Jasani RR, Atwood CW Jr, Houck PR, Sanders M. Prevalence and prediction of nocturi a in obstructi ve sleep apnea-hypopne a syndr me: A retrospective study. Sleep 2003;26:61-4.
24Krieger J, Laks L, Wilcox I, Grunstein RR, Costas LJ, McDougall JG, Sullivan CE. Atrial natriuretic peptide release during sleep in patients with obstructive sleep apnoea before and during treatment with nasal continuous positi ve airway pressure. Clin Sci (Lond) 1989;77:407-11.
25Ohayon MM, Li KK, Guilleminault C. Risk factors for sleep bruxism in the general population. Chest 2001;119:53-61.
26Strohl KP, Redline S. Recognition of obstructive sleep apnea. Am J Respir Crit Care Med 1996;154:279-89.
27Colten HR, Altevogt BM. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem Committee on Sleep Medicine and Research, 2006. https://www.ncbi.nlm.nih.gov/books/NBK19960/
28Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A. Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med 2013;188:996-1004.
29Edwards BA, Eckert DJ, Jordan AS. Obstructive sleep apnoea pathogenesis from mild to severe: Is it all the same? Respirology 2017;22:33-42.
30Lee-Chi ong T. Monitoring respirati on during sleep. In: Lee-Chiong T, Sateia M, Cars kadon M (eds). Sleep Medicine. Philadelphia, Hanley & Belfus, 2002;639-6.
31Chesson AL Jr, Ferber RA, Fry JM, Grigg-Damberger M, Hartse KM, Hurwitz TD, Johnson S, Kader GA, Littner M, Rosen G, Sangal RB, Schmidt-Nowara W, Sher A. The in dications for polysomnography and related procedures. Sleep 1997;20:423-87.
32No authors listed. Practice parameters for the indications for polysomnography and related procedures. Polysomnography Task Force, American Sleep Disorders Association Standards of Practice Committee. Sleep 1997;20:406-22.
33Morgenthaler TI, Kapen S, Lee-Chiong T, Alessi C, Boehlecke B, Brown T, Coleman J, Friedman L, Kapur V, Owens J, Pancer J, Swick T; Standards of Practice Committee; American Academy of Sleep Medicine. Practice parameters for the medical therapy of obstructive sleep apnea. Sleep 2006;29:1031-5.
34Chung JW, Enciso R, Levendowski DJ, Morgan TD, Westbrook PR, Clark GT. Treatment out comes of mandibular advancement devices in positional and nonpositional OSA patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:724-31.
35Thurnheer R. Obstructive sleep apnea and cardiovascular disease -time to act! Swiss Med Wkly 2007;137:217-22.
36Weaver T. Adherence to continuous positive airway pressure treatment and functional status in adult obstructive sleep apnea. In: Pack A (ed). Sleep Apnea Pathogenesis Diagnosis and Treatment. New York, Marcel Dekker, Inc, 2002;523-54.
37Grunstein R, Sullivan C. Continuous positive airway pressure for sleep breathing disorders. In: Kryger M, Roth T, Dement W (eds). Principles and Practice of Sleep Medicine, 3rd ed. Philadelphia, W.B. Saunders Company, 2000;894-912.
38Epstein LJ, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, Ramar K, Rogers R, Schwab RJ, Weaver EM, Weinstein MD; Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med 2009;5:263-76.
39Hirshkowitz M, Sarwar A, Sharafkhaneh A. Evaluating Sleepiness. In: Kryger M, Roth T, Dement W, (eds). Principles and practice of sleep medicine. 5th ed. Philadelphia, WB Saunders Co, 2011;1624-31.
40Izci B, Ardic S, Firat H, Sahin A, Altinors M, Karacan I. Reliability and validity studies of the Turkish version of the Epworth Sleepiness Scale. Sleep Breath 2008;12:161-8.
41Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991;14:540-5.
42Scammell TE. Narcolepsy. N Engl J Med 2015;373:2654-62.
43Gélineau JBE. De la narcolepsie. Gazette des Hôpitaux 1880;53:626-8.
44Löwenfeld L. Uber Narkolepsie. Munch Med Wochenschr 1902;49:1041-5.
45Adie WJ. Idiopatic narcolepsy: A disease sui generis, with remarks on the mechanisms of sleep. Brain 1926;49:257-306.
46Ohayon MM, Priest RG, Zulley J, Smirne S, Paiva T. Prevalence of narcolepsy symptomatology and diagnosis in the European general population. Neurology 2002;58:1826-33.
47DelRosso LM, Hoque R. Central Nervous System hypersomnias. In: Malhotra RK (ed). Sleepy or sleepless. Clinic approach to the sleep patient. Switzerland, Springer International Publishing, 2015;53-8.
48Aldrich MS. Narcolepsy and related disorders. Medicine. Oxford University Press, Net, 1999;152-74.
49Okun ML, Lin L, Pelin Z, Hong S, Mignot E. Clinical aspects of narcolepsy-cataplexy across ethnic groups. Sleep 2002;25:27-35.
50Schoch SF, Werth E, Poryazova R, Scammell TE, Baumann CR, Imbach LL. Dysregulation of Sleep Behavioral States in Narcolepsy. Sleep 2017. doi: 10.1093/sleep/zsx17
51Trotti ML. Central Disorders of Hypersomnolence. Continuum (Minneap Minn) 2020;26:890-907.
52Bayer L, Eggermann E, Serafin M, Saint-Mleux B, Machard D, Jones B, Mühlethaler M. Orexins (hypocretins) directly excite tuberomammillary neurons. Eur J Neurosci 2001;14:1571-5.
53Sansa G, Iranzo A, Santamaria J. Obstructive sleep apnea in narcolepsy. Sleep Med 2010;11:93-5.
54Ohayon MM. Narcolepsy is complicated by high medical and psychiatric comorbidities: a comparison with the general population. Sleep Med 2013;14:488-92.
55Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998;92:573-85.
56Inutsuka A, Yamanaka A. The regulation of sleep and wakefulness by the hypothalamic neuropeptide orexin/hypocretin. Nagoya J Med Sci 2013;75:29-36.
57Ganjavi H, Shapiro CM. Hypocretin/orexin: a molecular link between sleep, energy regulation, and pleasure. J Neuropsychiatry Clin Neurosci 2007;19:413-9.
58Zhou J, Zhang J, Lam SP, Chan JW, Mok V, Chan A, Li SX, Liu Y, Tang X, Yung WH, Wing YK. Excessive daytime sleepiness predicts neurodegeneration in idiopathic REM sleep behavior disorder. Sleep 2017. doi:10.1093/sleep/zsx041.
59Arango MT, Kivity S, Shoenfeld Y. Is narcolepsy a classical autoimmune disease? Pharmacol Res 2015;92:6-12.
60Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E. Hypocretln (orexin) deficiency in human narcolepsy. Lancet 2000;355:39-40.
61Nakayama J, Miura M, Honda M, Miki T, Honda Y, Arinami T. Linkage of human narcolepsy with HLA association to chromosome 4p13-q21. Genomics 2000;65:84-6.
62Andlauer O, Moore H, Jouhier L, Drake C, Peppard PE, Han F, Hong SC, Poli F, Plazzi G, O’Hara R, Haffen E, Roth T, Young T, Mignot E. Nocturnal rapid eye movement sleep latency for identifying patients with narcolepsy/hypocretin deficiency. JAMA Neurol 2013;70:891-902.
63Guilleminault C, Mignot E, Grumet FC. Familial pattems of narcolepsy. Lancet 1989;2:1376-9.
64Jara CO, Popp R, Zulley J, Hajak G, Geisler P. Determinants of depressive symptoms in narcoleptic patients with and without cataplexy. J Nerv Ment Dis 2011;199:329-34.
65Sasai-Sakuma T, Kinoshita A, Inoue Y. Polysomnographic Assessment of Sleep Comorbidities in Drug-Naîve Narcolepsy- Spectrum Disorders--A Japanese Cross- Sectional Study. PLoS One 2015. doi: 10.1371/journal.pone.0136988.
66Koepsell TD, Longstreth WT, Ton TG. Medical exposures in youth and the frequency of narcolepsy with cataplexy: a population-based case-control study in genetically predisposed people. J Sleep Res 2010;19:80-6.
67Johansen K, Brasseur D, MacDonald N, Nohynek H, Vandeputte J, Wood D, Neels P; Scientific Committee. Where are we in our understanding of the association between narcolepsy and onset the 2009 adjuvanted influenza A (H1N1) vaccines? Biologicals 2016;44:276-80.
68Nalbantoğlu M, Benbir G, Karadeniz D, Altıntaş A, Savran Oğuz F. Cases of Narcolepsy-Cataplexy Syndrome Following H1N1 Vaccination. Noro Psikiyatr Ars 2014;51:283-7.
69Watson NF, Ton TG, Koepsell TD, Longstreth WT Jr. Birth order and narcolepsy risk among genetically susceptible individuals: a population-based case-control study. Sleep Med 2012;13:310-3.
70Arii J, Kanbayashi T, Tanabe Y, Ono J, Nishino S, Kohno Y. A hypersomnolent girl with decreased CSF hypocretin level after removal of a hypothalamic tumor. Neurology 2001;56:1775-6.
71Kandt RS, Emerson RG, Singer HS, Valle DL, Moser HW. Cataplexy in variant forms of Niemann-Pick disease. Ann Neurol 1982;12:284-8.
72Jennum P, Thorstensen EW, Pickering L, Ibsen R, Kjellberg J. Morbidity and mortality of middle-aged and elderly narcoleptics. Sleep Med 2017;36:23-8.
73Black J, Reaven NL, Funk SE, McGaughey K, Ohayon MM, Guilleminault C, Ruoff C. Medical comorbidity in narcolepsy: findings from the Bıırden of Narcolepsy Disease (BOND) study. Sleep Med 2017;33:13-8.
74Peacock J, Benca RM. Narcolepsy: clinical features, co-morbidities & treatment. Indian J Med Res. 2010;131:338-49.
75Didato G, Nobili L. Treatment of narcolepsy. Expert Rev Neurother 2009;9:897-910.
76De la Herrán-Arita AK, García-García F. Current and emerging options for the drug treatment of narcolepsy. Drugs 2013;73:1771-81.
77Baklan B. Narcolepsy and the Other Central Hypersomnias. Türkiye Klinikleri J Neurol-Special Topics 2010;3:65-75.
78Husain AM, Yancy WS Jr, Carwile ST, Miller PP, Westman EC. Diet therapy for narcolepsy. Neurology 2004;62:2300-2.
79Yılmaz H, Tuncel D. Uyku Bozukluklarında Tedavi Rehberi. Türk Nöroloji Derneği, Ankara, 2014.
80Mitler MM, Shafor R, Hajdukovich R, Timms RM, Browman CP. Treatment of narcolepsy: objective studies on methylphenidate, pemoline, and protriptyline. Sleep 1986;9:260-4.
81Schwartz JR, Feldman NT, Fry JM, Harsh J. Efficacy and safety of modafinil for improving daytime wakefulness in patients treated previously with psychostimulants. Sleep Med 2003;4:43-9.
82Berry RB. Fundamentals of Sleep Medicine. Chapter 24: Hypersomnias of Central originb Philadelphia, PA: Elsevier Saunders, 2012;451-79.
83Lavault S, Dauvilliers Y, Drouot X, Leu-Semenescu S, Golmard JL, Lecendreux M, Franco P, Arnulf I. Benefit and risk of modafinil in idiopathic hypersomnia vs. narcolepsy with cataplexy. Sleep Med 2011;12:550-6.
84Volkow ND, Fowler JS, Logan J, Alexoff D, Zhu W, Telang F, Wang GJ, Jayne M, Hooker JM, Wong C, Hubbard B, Carter P, Warner D, King P, Shea C, Xu Y, Muench L, Apelskog-Torres K. Effects of modafinil on dopamine and dopamine transporters in the male human brain: Clinical implications. JAMA 2009;301:1148-54.
85Huang Q, Zhang L, Tang H, Wang L, Wang Y. Modafinil modulates GABA-activated currents in rat hippocampal pyramidal neurons. Brain Res 2008;1208:74-8.
86Billiard M. Narcolepsy: Current treatment options and future approaches. Neuropsychiatr Dis Treat 2008;4:557-66.
87No authors listed. Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy: US Modafinil in Narcolepsy Multicenter Study Group. Neurology 2000;54:1166-75.
88Modafinil package insert. 2004; Available from: https://www. modafinil.com/prescribe/index.html.
89Schwartz JR, Feldman NT, Bogan RK. Dose effects of modafinil in sustaining wakefulness in narcolepsy patients with residual evening sleepiness. J Neuropsychiatry Clin Neurosci 2005;17:405-12.
90Mamelak M, Black J, Montplaisir J, Ristanovic R. A pilot study on the effects of sodium oxybate on sleep architecture and daytime alertness in narcolepsy. Sleep 2004;27:1327-34.
91Xyrem International Study Group. A double-blind, placebo-controlled study demonstrates sodium oxybate is effective for the treatment of excessive daytime sleepiness in narcolepsy. J Clin Sleep Med 2005;1:391-7.
92Black J, Pardi D, Hornfledt CS, Inhaber N. The nightly administration of sodium oxybate results in signifıcant reduction in the nocturnal sleep disruption of patients with narcolepsy. Sleep Med 2009;10:829-35.
93Morgenthaler TI, Kapur VK, Brown T, Swick TJ, Alessi C, Aurora RN, Boehlecke B, Chesson AL Jr, Friedman L, Maganti R, Owens J, Pancer J, Zak R; 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;30:1705-11.
94Black J, Houghton WC. Sodium oxybate improves excessive daytime sleepiness in narcolepsy. Sleep 2006;29:939-46.
95Trotti LM, Arnuf I. Idiopathic Hypersomnia and Other Hypersomnia Syndromes. Neurotherapeutics 2021;18:20-31.
96Sunosi (solriamfetol) package insert. 2019; Available from: https:// sunosihcp.com
97Leu-Semenescu S, Nittur N, Golmard JL, Arnulf I. Effects of pitolisant, a histamine H3 inverse agonist, in drug-resistant idiopathic and symptomatic hypersomnia: a chart review. Sleep Med 2014;15:681-7.
98Robert P, Schwartz JC. Hormonal Contraceptive and Pitolisant CYP3A4 Induction. Neurology 2019;92(Suppl 15):6-35.
99Nittur N, Konofal E, Dauvilliers Y, Franco P, Leu-Semenescu S, Cock VC, Inocente CO, Bayard S, Scholtz S, Lecendreux M, Arnulf I. Mazindol in narcolepsy and idiopathic and symptomatic hypersomnia refractory to stimulants: a long-term chart review. Sleep Med 2013;14:30-6.
100Mayer G, Ewert Meier K, Hephata K. Selegiline hydrochloride treatment in narcolepsy-a double-blind placebo-controlled study. Clin Neuropharmacol 1995;18:306-19.
101Honda Y, Hishikawa Y. A long-term treatment of narcolepsy and excessive daytime sleepiness with pemoline (Bentanamin). Curr Ther Res 1980;27:429-41.
102Alvarez B, Dahlitz M, Grimshaw J, Parkes JD. Mazindol in long-term treatment of narcolepsy. Lancet 1991;337:1293-4.
103Ryan DH, Bray GA, Helmcke F, Sander G, Volaufova J, Greenway F, Subramaniam P, Glancy DL. Serial echocardiographic and clinical evaluation of valvular regurgitation before, during, and after treatment with fenfl uramine or dexfenfluramine and mazindol or phentermine. Obes Res 1999;7:313-22.
104Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet 2007;369:499-511.
105Thorpy MJ. Cataplexy associated with narcolepsy: epidemiology, pathophysiology and management. CNS Drugs 2006;20:43-50.
106Dauvilliers Y, Billiard M, Montplaisir J. Clinical aspects and pathophysiology of narcolepsy. Clin Neurophysiol 2003;114:2000-17.
107Langdon N, Shindler J, Parkes JD, Bandak S. Fluoxetine in the treatment of cataplexy. Sleep 1986;9:371-3.
108Abad VC, Guilleminault C. Emerging drugs for narcolepsy. Expert Opin Emerg Drugs 2004;9:281-91.
109Mignot E, Nishino S. Emerging therapies in narcolepsy-cataplexy. Sleep 2005;28:754-63.
110Iijima S, Sugita Y, Teshima Y, Hishikawa Y. Therapeutic eff ects of mazindol on narcolepsy. Sleep 1986;9:265-8.
111Chen W, Black J, Call P, Mignot E. Late-onset narcolepsy presenting as rapidly progressing muscle weakness: response to plasmapheresis. Ann Neurol 2005;58:489-90.
112Hecht M, Lin L, Kushida CA, Umetsu DT, Taheri S, Einen M, Mignot E. Report of a case of immunosuppression with prednisone in an 8-year-old boy with an acute onset of hypocretin-deficiency narcolepsy. Sleep 2003;26:809-10.
113Lecendreux M, Maret S, Bassetti C, Mouren MC, Tafti M. Clinical efficacy of high-dose intravenous immunoglobulins near the onset of narcolepsy in a 10-year-old boy. J Sleep Res 2003;12:347-88.
114Valko PO, Khatami R, Baumann CR, Bassetti CL. No persistent effect of intravenous immunoglobulins in patients with narcolepsy with cataplexy. J Neurol 2008;255:1900-3.
115Mochizuki T, Arrigoni E, Marcus JN, Clark EL, Yamamoto M, Honer M, Borroni E, Lowell BB, Elmquist JK, Scammell TE. Orexin receptor 2 expression in the posterior hypothalamus rescues sleepiness in narcoleptic mice. Proc Natl Acad Sci USA 2011;108:4471-6.
116Weinhold SL, Seeck-Hirschner M, Nowak A, Hallschmid M, Göder R, Baier PC. The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy. Behav Brain Res 2014;262:8-13.
117Roth B, Bruhova`S. A clinical and polygraphic study of dreams in polygraphic and clinical data for 100 patients. Sleep 1981;4:23-37.
118Öztura İ. İdiyopatik hipersomni. Uyku Fizyolojisi ve Hastalıkları. Birinci Baskı, İçinde: Kaynak H, Ardıç S (editörler). İstanbul, Türk Uyku Tıbbı Yayını, Nobel Tıp Kitabevi, 2011;317-9.
119Billiard M, Besset A. Idiopathic hypersomnia. Sleep: physiology, investigations, and medicine. 1st ed. In: Billiard M (ed). Newyork, Kluwer Academic Plenum Publishers, 2003;429-35.
120Trotti LM. Idiopathic hypersomnia. Sleep Med Clin 2017;12:331-44.
121Vernet C, Arnulf I. Idiopathic hypersomnia with and without long sleep time: a controlled series of 75 patients. Sleep 2009;32:753-9.
122Barateau L, Lopez R, Arnulf I, Lecendreux M, Franco P, Drouot X, Leu-Semenescu S, Jaussent I, Dauvilliers Y. Comorbidity between Central disorders of hypersomnolence and immune-based disorders. Neurology 2017;88:93-100.
123Bassetti C, Aldrich MS. Idiopathic hypersomnia. A series of 42 patients. Brain 1997;120:1423-35.
124Poirier G, Montplaisir J, Décary F, Momège D, Lebrun A. HLA antigens in narcolepsy and idiopathic Central nervous system hypersomnolence. Sleep 1986;9:153-8.
125Faull KF, Thiemann S, King RJ, Guilleminault C. Monoamine interactions in narcolepsy and hypersomnia: reanalysis. Sleep 1989;12:185-6.
126Dauvilliers Y, Evangelista E, Lopez R, Barateau L, Jaussent I, Cens T, Rousset M, Charnet P. Absence of y-aminobutyric acid-a receptor potentiation in Central hypersomnolence disorders. Ann Neurol 2016;80:259-68.
127Rye DB, Bliwise DL, Parker K, Trotti LM, Saini P, Fairley J, Freeman A, Garcia PS, Owens MJ, Ritchie JC, Jenkins A. Modulation of vigilance in the primary hypersomnias by endogenous enhancement of GABA A receptors. Sci Transl Med 2012. doi: 10.1126/scitranslmed.3004685.
128Trotti LM, Saini P, Bliwise DL, Freeman AA, Jenkins A, Rye DB. Clarithromycin in y -aminobutyric acid-Related hypersomnolence: A randomized, crossover trial. Ann Neurol 2015;78:454-65.
129Billiard M, Sonka K. Idiopathic hypersomnia. Sleep Med Rev 2016;29:23-33.
130Dauvilliers Y, Lopez R, Ohayon M, Bayard S. Hypersomnia and depressive symptoms: methodological and clinical aspects. BMC Med 2013;11:78.
131Aldrich MS. The clinical spectrum of narcolepsy and idiopathic hypersomnia. Neurology 1996;46:393-401.
132Aydın H. Uyku ve Bozuklukları. Ankara, HYB Basım Yayın, 2007;86-90.
133Ali M, Auger RR, Slocumb NL, Morgenthaler TI. Idiopathic hypersomnia: clinical features and response to treatment. J Clin Sleep Med 2009;5:562-8.
134Arnulf I, Lin L, Gadoth N, File J, Lecendreux M, Franco P, Zeitzer J, Lo B, Faraco JH, Mignot E. Kleine-Levin Syndrome: a systematic study of 108 patients. Ann Neurol 2008;63:482-92.
135Dauvilliers Y, Mayer G, Lecendreux M, Neidhart E, Peraita-Adrados R, Sonka K, Billiard M, Tafti M. Kleine-Levin syndrome: an autoimmune hypothesis based on clinical and genetic analyses. Neurology 2002;59:1739-45.
136Arnulf I. Zeitzer JM, File J, Farber N, Mignot E. Kleine-Levin syndrome: a systematic review of 186 cases in the literature. Brain 2005;128:2763-76.
137Lavault S, Golmard JL, Groos E, Brion A, Dauvilliers Y, Lecendreux M, Franco P, Arnulf I. Kleine- Levin syndrome in 120 patients: differential diagnosis and long episodes. Ann Neurol 2015;77:529-40.
138Arnulf I, Rico TJ, Mignot E. Diagnosis, disease course, and management of patients with Kleine-Levin syndrome. Lancet Neurol 2012;11:918-28.
139Léotard A, Groos E, Chaumereuil C, Peter-Derex L, Rossetti AO, Leu-Semenescu S, Arnulf I. IV steroids during long episodes of Kleine-Levin syndrome. Neurology 2018;90:1488-92.
140Rezvanian E, Watson NF. Kleine-levin syndrome treated with clarithromycin. J Clin Sleep Med 2013;9:1211-2.
141Trotti LM, Bliwise DL, Rye DB. Further Experience using Clarithromycin in Patients with Kleine-Levin Syndrome. J Clin Sleep Med 2014;10:457-8.
142Carpenter S, Yassa R, Ochs R. A pathologic basis for Kleine-Levin syndrome. Arch Neurol 1982;39:25-8.
143Aggarwal A, Garg A, Jiloha RC. Kleine-Levine syndrome in an adolescent female and response to modafinil. Ann Indian Acad Neurol 2011;14:50-2.
144Huang YS, Lakkis C, Guilleminault C. Kleine-Levin syndrome: current status. Med Clin North Am 2010;94:557-62.
145Muratori F, Bertini N, Masi G. Efficacy of lithium treatment in Kleine-Levin syndrome. Eur Psychiatry 2002;17:232-3.
146Leu-Semenescu S, Le Corvec T, Groos E, Lavault S, Golmard JL, Arnulf I. Lithium therapy in Kleine-Levin syndrome: an open-label, controlled study in 130 patients. Neurology 2015;85:1655-62.
147Damkier P, Broe A. First-Trimester Pregnancy Exposure to Modafinil and Risk of Congenital Malformations. JAMA 2020;323:374-6.
148Crumley FE. Valproic acid for Kleine-Levin syndrome. J Am Acad Child Adolesc Psychiatry 1997;36:868-9.
149Mukaddes NM, Kora ME, Bilge S. Carbamazepine for Kleine-Levin syndrome. J Am Acad Child Adolesc Psychiatry 1999;38:791-2.
150Itokawa K, Fukui M, Ninomiya M, Yamamoto T, Imabayashi E, Tamura N, Matsuda H, Araki N. Gabapentin for Kleine-Levin Syndrome. Intern Med 2009;48:1183-5.
151Billiard M, Guilleminault C, Dement WC. A menstruation-linked periodic hypersomnia. Kleine-Levin syndrome or new clinical entity? Neurology 1975;25:436-43.
152Ortega-Albás JJ, Díaz JR, López-Bernabé R, Vera JF, Alós M, Serrano AL. Treatment of Kleine-Levin syndrome with sodium oxybate. Sleep Med 2011;12:730.
153de Oliveira MM, Conti C, Prado GF. Pharmacological treatment for Kleine-Levin syndrome. Cochrane Database Syst Rev 2016. doi: 10.1002/14651858.CD006685.pub4.
154Guilleminault C, Brooks SN. Excessive daytime sleepiness: a challenge for the practising neurologist. Brain 2001;124:1482-91.
155Guilleminault C, Yuen KM, Gulevich MG, Karadeniz D, Leger D, Philip P. Hypersomnia after head-neck trauma: a medicolegal dilemma. Neurology 2000;54:653-9.
156Fernandez-Mendoza J, Vgontzas AN, Kritikou I, Calhoun SL, Liao D, Bixler EO. Natural history of excessive daytime sleepiness: role of obesity, weight loss, depression, and sleep propensity. Sleep 2015;38:351-60.
157Murray BJ. A Practical Approach to Excessive Daytime Sleepiness: A Focused Review. Can Respir J 2016. doi: 10.1155/2016/4215938.
158Gandhi KD, Mansukhani MP, Silber MH, Kolla BP. Excessive Daytime Sleepiness: A Clinical Review. Mayo Clin Proc 2021;96:1288-301.
159Pagel JF. Excessive Daytime Sleepiness Am Fam Physician 2009;79:391-6.
160Maestri M, Romigi A, Schirru A, Fabbrini M, Gori S, Bonuccelli U, Bonanni E. Excessive daytime sleepiness and fatigue in neurological disorders. Sleep Breath 2020;24:413-24.
161Benjamin S. Sleep in Patients with Neurologic Disease. Continuum (Minneap Minn) 2020;26:1016-33.
162Ju YS, Videnovic A, Vaughn BV. Comorbid Sleep Disturbances in neurologic disorders. Continuum (Minneap Minn) 2017;23:1117-31.
163Kingshott RN, Vennelle M, Coleman EL, Engleman HM, Mackay TW, Douglas NJ. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 2001;163:918-23.
164Roth T, White D, Schmidt-Nowara W, Wesnes KA, Niebler G, Arora S, Black J. Effects of armodafinil in the treatment of residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome: a 12-week, multicenter, double-blind, randomized, placebo-controlled study in nCPAP-adherent adults. Clin Ther 2006;28:689-706.
165Schweitzer PK, Rosenberg R, Zammit GK, Gotfried M, Chen D, Carter LP, Wang H, Lu Y, Black J, Malhotra A, Strohl KP; TONES 3 Study Investigators. Solriamfetol for Excessive Sleepiness in Obstructive Sleep Apnea (TONES 3). A Randomized Controlled Trial. Am J Respir Crit Care Med 2019;199:1421-31.
166Sheng P, Hou L, Wang X, Wang X, Huang C, Yu M, Han X, Dong Y. Efficacy of modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: a systematic review and meta-analysis. PLoS One 2013. doi: 10.1371/journal.pone.0081802.
167Trotti LM, Bliwise DL. Treatment of the sleep disorders associated with Parkinson’s disease. Neurotherapeutics 2014;11:68-77.
168Büchele F, Hackius M, Schreglmann SR, Omlor W, Werth E, Maric A, Imbach LL, Hägele-Link S, Waldvogel D, Baumann CR. Sodium Oxybate for Excessive Daytime Sleepiness and Sleep Disturbance in Parkinson Disease: A Randomized Clinical Trial JAMA Neurol 2018;75:114-8.
169Menn SJ, Yang R, Lankford A. Armodafinil for the treatment of excessive sleepiness associated with mild or moderate closed traumatic brain injury: a 12-week, randomized, double-blind study followed by a 12-month open-label extension. J Clin Sleep Med 2014;10:1181-91.
170Annane D, Moore DH, Barnes PR, Miller RG. Psychostimulants for hypersomnia (excessive daytime sleepiness) in myotonic dystrophy. Cochrane Database Syst Rev 2006. doi: 10.1002/14651858.CD003218.
171Billiard M, Dolenc L, Aldaz C, Ondze B, Besset A. Hypersomnia associated with mood disorders: a new perspective. J Psychosom Res 1994;38(Suppl):41-7.
172Buysse DJ, Germain A, Nofzinger EA Kupfer D. Mood disorders and sleep. The American Psychiatric Publishing Textbook of Mood Disorders, 1st ed. In: Stein DJ, Kupfer DJ, Schatzberg AF (eds). Arlington, American Psychiatric Publishing, 2006;717-37.
173Bixler EO, Vgontzas AN, Lin HM, 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;90:4510-5.
174Palagini L, Baglioni C, Ciapparelli A, Gemignani A, Riemann D. REM sleep dysregulation in depression: state of the art. Sleep Med Rev 2013;17:377-90.
175Zee PC, Attarian H, Videnovic A. Circadian Rhythm Abnormalities. Continuum (Minneap Minn) 2013;19:132-47.
176Vgontzas AN, Bixler EO, Kales A, Criley C, Vela-Bueno A. Differences in nocturnal and daytime sleep between primary and psychiatric hypersomnia: diagnostic and treatment implications. Psychosom Med 2000;62:220-6.
177Gulec M, Ozcan H, Oral E, Selvi Y, Aydin A. The relationship between insomnia and major depressive disorder: a chicken and egg situation? J Mood Disord 2012;2:28-33.
178Geoffroy PA, Hoertel N, Etain B, Bellivier F, Delorme R, Limosin F, Peyre H. Insomnia and hypersomnia in majör depressive episode: Prevalence, sociodemographic characteristics and psychiatric comorbidity in a populatıon- based study. J Affect Disord 2018;226:132-41.
179Nofzinger EA, Thase ME, Reynolds CF 3rd, Himmelhoch JM, Mallinger A, Houck P, Kupfer DJ. Hypersomnia in bipolar depression: a comparison with narcolepsy using the multiple sleep latency test. Am J Psychiatry 1991;148:1177-81.
180Dunlop BW, Crits-Christoph P, Evans DL, Hirschowitz J, Solvason HB, Rickels K, Garlow SJ, Gallop RJ, Ninan PT. Coadministration of modafinil and a selective serotonin reuptake inhibitor from the initiation of treatment of major depressive disorder with fatigue and sleepiness: a double-blind, placebo-controlled study. J Clin Psychopharmacol 2007;27:614-9.
181DeBattista C, Doghramji K, Menza MA, Rosenthal MH, Fieve RR; Modafinil in Depression Study Group. Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry 2003;64:1057-64.
182Schweitzer P. Drugs that disturb sleep and wakefolness. In: Kryger MH, Roth T, Dement WC (eds). Princıpta I and Practice of Sleep Medicine, 3rd ed. Philadelphia,:WB Saunders, 2000;1176-96.
183Roehrs T, Bonahoom A, Pedrosi B, Zorick F, Roth T. Nighttime versus daytime hypnotic self-administmon. Psychopharmacology (Berl) 2002;161:137-42.
184Sateia MJ, Doghramji K, Hauri PJ, Morin CM. Evaluation of chronic insomnia. An Amerrican Academy of Sleep Medicine review. Sleep 2000;23:243-308.
185Roehrs T, Roth T. Insomnia pharmacotherapy. Neurotherapeutics 2012;9:728-38.
186Brower KJ, Perron BE. Sleep disturbance as a universal risk factor for relapse in addictions to psychoactive substances. Med Hypotheses 2010;74:928-33.
187Brower KJ, Hoffmann R, Conroy DA, Arnedt JT, Armitage R. Sleep homeostasis in alcohol-dependent, depressed and healthy control men. Eur Arch Psych Clin Neurosci 2011;261:559-66.
188Sharma R, Sahota P, Thakkar MM. Role of adenosine and the orexinergic perifornical hypothalamus in sleep-promoting effects of ethanol. Sleep 2014;37:525-33.
189Thakkar MM, Sharma R, Sahota P. Alcohol disrupts sleep homeostasis. Alcohol 2014;49:299-310.
190Armitage R, Hoffmann R, Conroy DA, Arnedt JT, Brower KJ. Effects of a 3-hour sleep delay on sleep homeostasis in alcohol dependent adults. Sleep 2012;35:273-8.
191Gurubhagavatula I, Sullivan S, Meoli A, Patil S, Olson R, Berneking M, Watson NF. Management of obstructive sleep apnea in commercial motor vehicle operators: recommendations of the AASM Sleep and Transportation Safety Awareness Task Force. J Clin Sleep Med 2017;13:745-58.
192Conroy DA, Arnedt JT. Sleep and substance use disorders: an update. Curr Psychiatry Rep 2014;16:487.
193Young-McCaughan S, Miaskowski C. Measurement of opioid-induced sedation. Pain Manag Nurs 2001;2:132-49.
194Van Dongen HP, Maislin G, Mullington JM, Dinges DF. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep 2003;26:117-26.
195Pagel JF. Sleep disorders in primary care: evidence-based clinical practice. In: Pagel JF, Pandi-Perumal SR (eds). Primary Care Sleep Medicine: A Practical Guide. Totowa, N.J, Humana Press, 2007;1-14.
196Lauderdale DS, Knutson KL, Yan LL, Liu K, Rathouz PJ. Self-reported and measured sleep duration: how similar are they? Epidemiology 2008;19:838-45.
197Young TJ, Silber MH. Hypersomnias of Central origin. Chest 2006;130:913-20.
198Figueiro MG, Wood B, Plitnick B, Rea MS. The impact of light from computer monitors on melatonin levels in college students. Neuro Endocrinol Lett 2011;32:158-63.
199Carney CE, Lajos LE, Waters WF. Wrist actigraph versus self-report in normal sleepers: sleep schedule adherence and self-report validity. Behav Sleep Med 2004;2:134-43.