Narcolepsy pp 167-178 | Cite as

Hypersomnias Other than Narcolepsy: Differential Diagnosis

  • Michel Billiard


Although narcolepsy can be viewed as a key hypersomnia in relation to its severity and the light it sheds on the whole field of sleep due to its special clinical, polysomnographic, pharmacological and neurochemical, immunogenetic and hypocretinergic features, it is not by far the most frequent hypersomnia. Diagnosing other hypersomnias is a matter of clinical reasoning leading to a clinical impression, sufficient by itself or orienting towards various laboratory tests. This review will cover five different groups of hypersomnia: hypersomnia as a direct consequence of a behaviour or of the use of a drug or substance, hypersomnia as a consequence of a sleep-related breathing disorder, hypersomnia of central origin other than narcolepsy, hypersomnia associated with various medical disorders and hypersomnia not due to substance or known physiological condition (psychiatric hypersomnia). For all these conditions clinical and laboratory tests will be reviewed, as well as the present state of knowledge in terms of pathophysiology. In addition, the issue of periodic limb movements in sleep and excessive daytime sleepiness will be discussed.


Behaviorally induced insufficient sleep syndrome Hypersomnia due to drug or substance Idiopathic hypersomnia Recurrent hypersomnia Hypersomnia due to medical condition Hypersomnia not due to substance or known physiological condition 


  1. 1.
    Johns MW. (1994) Sleepiness in different situations measured by the Epworth Sleepiness Scale. Sleep 17, 703–710PubMedGoogle Scholar
  2. 2.
    Littner M, Kushida C, Wise M, Davila DG, Morgenthaler T, Lee-Chiong T, Hirshkowitz M, Loube DL, Bailey D, Berry RB, Kapen S, Kramer M. (2005) Practice parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test. Sleep 28, 113–121PubMedGoogle Scholar
  3. 3.
    Carskadon MA, Dement WC, Mitler MM, Roth T, Westbrook PR, Keenan S. (1986) Guidelines for the multiple sleep latency test (MSLT) a standard measure of sleepiness. Sleep 9, 519–524PubMedGoogle Scholar
  4. 4.
    Silber MH, Krahn LE, Morgenthaler TI. (2004) Sleep medicine in clinical practice. Taylor and Francis, LondonGoogle Scholar
  5. 5.
    American Academy of Sleep Medicine. (2005) International classification of sleep disorders, 2nd ed.: Diagnostic and coding manual. American Academy of Sleep Medicine, Westchester, ILGoogle Scholar
  6. 6.
    Komada Y, Inoue Y, Hayashida K, Nakajima T, Honda M, Takahshi K. (2008) Clinical significance and correlates of behaviorally induced insufficient sleep syndrome. Sleep Med 2008:9:851–6Google Scholar
  7. 7.
    Ohayon MM. (2008) From wakefulness to excessive sleepiness: what we know and still need to know. Sleep Med Rev 12, 129–141CrossRefPubMedGoogle Scholar
  8. 8.
    Cunningham LA, Borison RL, Carman JS, Chouinard G, Crowder JE, Diamond BI, Fischer DE, Hearst E. (1994) A comparison of venlafaxine, trazodone, and placebo in major depression. J Clin Psychopharmacol 14, 99–106CrossRefPubMedGoogle Scholar
  9. 9.
    Goldberg TE, Weinberger DR. (1996) Effects of neuroleptic medications on the cognition of patients with schizophrenia: a review of recent studies. J Clin Psychiatry 57(Suppl 9), 62–65PubMedGoogle Scholar
  10. 10.
    Gerlach J, Peacock L. (1995) New antipsychotics: the present status. Int Clin Psychopharmacol 10(Suppl 3), 39–48PubMedGoogle Scholar
  11. 11.
    Paykel ES, Fleminger R, Watson JP. (1982) Psychiatric side effects of anti-hypertensive drugs other than reserpine. J Clin Psychopharmacol 2, 14–39CrossRefPubMedGoogle Scholar
  12. 12.
    Ghorayeb I, Loundou A, Auquier P, Dauvilliers Y, Bioulac B, Tison E. (2007) A nationwide survey of excessive daytime sleepiness in Parkinson’s disease in France. Mov Disord 22, 1567–1572CrossRefPubMedGoogle Scholar
  13. 13.
    Högl B, Seppi K, Brandauer E, Glatzl S, Frauscher B, Niedermüller U, Wenning G, Poewe W. (2003) Increased daytime sleepiness in Parkinson’s disease: a questionnaire survey. Mov Disord 18, 668–672CrossRefGoogle Scholar
  14. 14.
    Stevens S, Comella CL, Stepanski EJ. (2004) Daytime sleepiness and alertness in patients with Parkinson disease. Sleep 27, 967–972PubMedGoogle Scholar
  15. 15.
    Paus S, Brecht HM, Köster J, Seeger G, Klockgether T, Wüllner U. (2003) Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson’s disease. Mov Disord 18, 659–667CrossRefPubMedGoogle Scholar
  16. 16.
    Körner Y, Meindorfner C, Möller JC, Stiasny-Kolster K, Haja D, Cassel W, Oertel WH, Krüger HP.(2004) Predictors of sudden onset of sleep in Parkinson’s disease. Mov Disord 19, 1298–1305CrossRefPubMedGoogle Scholar
  17. 17.
    Chung S, Wang N, Hank N. (2007) Comparative retention rates and long-term tolerability of new antiepileptic drugs. Seizure 16, 296–304CrossRefPubMedGoogle Scholar
  18. 18.
    Guilleminault C, Tilkian A, Dement WC. (1976) The sleep apnea syndromes. Ann Rev Med 27, 465–484CrossRefPubMedGoogle Scholar
  19. 19.
    Young T, Palza M, Dempsey J, Skatrud J, Weber S, Badr S. (1993) The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328, 1230–1235CrossRefPubMedGoogle Scholar
  20. 20.
    Guilleminault C, Stoohs R, Clerk A, Cetel M, Maistros P. (1993) A cause of excessive daytime sleepiness. The upper airway resistance syndrome. Chest 104, 781–787CrossRefPubMedGoogle Scholar
  21. 21.
    Lattimore JDL, Celermajer DS, Wilcox I. (2003) Obstructive sleep apnea and cardiovascular disease. J Am Coll Cardiol 41, 429–437CrossRefGoogle Scholar
  22. 22.
    Guilleminault C, Motta J (1978) Sleep apnea syndrome as a long-term sequela of poliomyelitis. In: Guilleminault C, Dement WC (eds). Sleep apnea syndromes. Liss, New York, NY, 309–315Google Scholar
  23. 23.
    Friberg D, Gazelius B, Hokfelt T, Nordlander B (1997) Abnormal afferent nerve endings in the soft palate mucosa of sleep apnoics and habitual snorers. Regul Pept 71, 29–36CrossRefPubMedGoogle Scholar
  24. 24.
    Xie A, Rutherford R, Rankin F, Wong B, Bradley TD. (1995) Hypocapnia and increased ventilatory responsiveness in patients with idiopathic central sleep apnea. Am J Respir Crit Care Med 152, 1950–1955PubMedGoogle Scholar
  25. 25.
    Roth B. (1957) Narkolepsie a Hypersomnie s Hlediska Fysiologie Spanku, Statni Zdravoniché Nakladatelstvi, PrahaGoogle Scholar
  26. 26.
    Roth B. (1976) Narcolepsy and hypersomnia; review and classification of 642 personally observed cases. Schweiz Arch Neurol Neurochir Psychiat 119, 31–41Google Scholar
  27. 27.
    Bassetti C, Aldrich MS. (1997) Idiopathic hypersomnia. A series of 42 patients. Brain 120, 1423–1435CrossRefPubMedGoogle Scholar
  28. 28.
    Billiard M. (1996) Idiopathic hypersomnia. Neurol Clin 14, 573–582CrossRefPubMedGoogle Scholar
  29. 29.
    Mignot E, Lammers GJ, Ripley B, Okun M, Nevsimalova S, Overeem S, Vankova J, Black J, Harsh J, Bassetti C, Schrader H, Nishino S. (2002) The role of cerebrospinal fluid hypocretin in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 59, 1553–1562CrossRefPubMedGoogle Scholar
  30. 30.
    Kanbayashi T, Inoue Y, Chiba S, Aizawa R, Saito Y, Tsukamoto H, Fujii Y, Nishino S, Shimizu T. (2002) CSF hypocretine-1 (orexine-A) concentrations in narcolepsy with and without cataplexy and idiopathic hypersomnia. J Sleep Res 11, 91–93CrossRefPubMedGoogle Scholar
  31. 31.
    Dauvilliers Y, Baumann CR, Carlander B, Bischof M, Blatter T, Lecendreux M, Maly F, Besset A, Touchon J, Billiard M, Tafti M, Bassetti CL. (2003) CSF hypocretin-1 levels in narcolepsy, Kleine-Levin syndrome, and other hypersomnias and neurological conditions. J Neurol Neurosurg Psychiatry 74, 1667–1673CrossRefPubMedGoogle Scholar
  32. 32.
    Bassetti C, Gugger M, Bischof M, Mathis J, Sturzenegger C, Werth E, Radanov B, Ripley B, Nishino S, Mignot E. (2003) The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexin-A). Sleep Med 4, 7–12CrossRefPubMedGoogle Scholar
  33. 33.
    Billiard M. (2007) Narcolepsy and idiopathic hypersomnia. In: Léger D, Pandi-Perumal SR (eds) Sleep disorders, their impact on public health. Informa Healthcare, Abingdon 225–234Google Scholar
  34. 34.
    Faull KF, Thiemann S, King RJ, Guilleminault C. (1986) Monoamine interactions in narcolepsy and hypersomnia: a preliminary report. Sleep 9, 246–249PubMedGoogle Scholar
  35. 35.
    Kanbayashi T, Kodama T, Kondo H, Satoh S, Miyazaki N, Kuruda K, Abe M, Nishino S, Inoue Y, Shimizu T. (2004) CSF histamine and noradrenaline contents in narcolepsy and other sleep disorders. Sleep 27, A236Google Scholar
  36. 36.
    Nevsimalova-Bruhova S, Roth B. (1972) Heredofamilial aspects of narcolepsy and hypersomnia. Schweiz Arch Neurol Neurochir Psychiat 110, 45–54Google Scholar
  37. 37.
    Kleine W. (1925) Periodische schlafsucht. Mschr Psychiat Neurol 57, 285–320CrossRefGoogle Scholar
  38. 38.
    Levin M. (1929) Narcolepsy (Gelineau’s syndrome) and other varieties of morbid somnolence. Arch Neurol Psychiatr (Chicago) 22, 1172–1200Google Scholar
  39. 39.
    Critchley M, Hoffman HL. (1942) The syndrome of periodic somnolence and morbid hunger (Kleine-Levin syndrome). Br Med J 1, 137–139CrossRefPubMedGoogle Scholar
  40. 40.
    Arnulf I, Zeitzer JM, File J, Farber N, Mignot E. (2005) Kleine-Levin syndrome: a systematic review of 186 cases in the literature. Brain 128, 2763–2776CrossRefPubMedGoogle Scholar
  41. 41.
    Arnulf I, Lin L, Gadoth N, File J, Lecendreux M, Franco P, Zeitzer J, Lo B, Farazo JH, Mignot E. (2008) Kleine-Levin syndrome: a systematic study of 108 patients. Ann Neurol 63, 482–492CrossRefPubMedGoogle Scholar
  42. 42.
    Bonkalo A. (1968) Hypersomnia. A discussion of psychiatric implications based on three cases. Br J Psychiat 114, 69–75CrossRefGoogle Scholar
  43. 43.
    Janicki S, Franco K, Zarko R. (2001) A case report of Kleine-Levin syndrome in an adolescent girl. Psychosomatics 42, 350–352CrossRefPubMedGoogle Scholar
  44. 44.
    Dauvilliers Y, Mayer G, Lecendreux M, Neidhart E, Peraita-Adrados R, Sonka K, Billiard M, Tafti M. (2002) Kleine-Levin syndrome. An autoimmune hypothesis based on clinical and genetic analyses. Neurology 59, 1667–1673Google Scholar
  45. 45.
    Katz JD, Ropper AH. (2002) Familial Kleine-Levin syndrome: two siblings with unusually long hypersomnic spells. Arch Neurol 59, 1959–1961CrossRefPubMedGoogle Scholar
  46. 46.
    Billiard M, Cadilhac J. (1988) Les hypersomnies récurrentes. Rev Neurol (Paris) 144, 249–258Google Scholar
  47. 47.
    Critchley M. (1962) Periodic hypersomnia and megaphagia in adolescent males. Brain 85, 627–656CrossRefPubMedGoogle Scholar
  48. 48.
    Huang YS, Guilleminault C, Kao PF, Liu FY. (2005) SPECT findings in the Kleine-Levin syndrome. Sleep 28, 955–960PubMedGoogle Scholar
  49. 49.
    Hong SB, Joo EY, Tae WS, Lee J, Han SJ, Lee HW. (2006) Episodic diencephalic hypoperfusion in the Kleine-Levin syndrome. Sleep 29, 1091–1093PubMedGoogle Scholar
  50. 50.
    Podesta C, Ferreras M, Mozzi M, Bassetti C, Dauvilliers Y, Billiard M. (2006) Kleine-Levin syndrome in a 14-year-old girl: CSF hypocretin-1 measurements. Sleep Med 7, 649–651CrossRefPubMedGoogle Scholar
  51. 51.
    Billiard M, Guilleminault C, Dement WC. (1975) A menstruation-linked periodic hypersomnia. Kleine-Levin syndrome or new clinical entity? Neurology 25, 436–443PubMedGoogle Scholar
  52. 52.
    Thiebaut F, Rohmer F, Kurtz D. (1967) Les hypersomnies symptomatiques continues. Rev Neurol (Paris) 116, 491–546Google Scholar
  53. 53.
    Castaigne P, Escourolle R. (1967) Etude topographique des lésions anatomiques dans les hypersomnies. Rev Neurol (Paris) 116, 547–584Google Scholar
  54. 54.
    Nishino S, Kanbayashi T. (2005) Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system. Sleep Med Rev 9, 269–310CrossRefPubMedGoogle Scholar
  55. 55.
    Bassetti CL, Valko P. (2006) Poststroke hypersomnia. Sleep Med Clin 1, 139–155CrossRefGoogle Scholar
  56. 56.
    Hobson DE, Lang AE, Martin WR, Razmy A, Rivest J, Fleming J. (2002) Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease. A survey by the Canadian movement disorder group. JAMA 287, 509–511CrossRefGoogle Scholar
  57. 57.
    Arnulf I. (2005) Excessive daytime sleepiness in parkinsonism. Sleep Med Rev 9, 185–200CrossRefPubMedGoogle Scholar
  58. 58.
    Arnulf I, Konofal E, Merino-Andreu M, Houeto JL, Mesnage V, Welter ML, Lacomblez L, Golmard JL, Derenne JP, Agid Y. (2002) Parkinson’s disease and sleepiness an integral part of PD. Neurology 58, 1019–1024PubMedGoogle Scholar
  59. 59.
    Fronczek R, Overeem S, Lee SY, Hegeman IM, van Pelt J, van Duinen SG, Lammers GJ, Swaab DF. (2007) Hypocretin (orexin) loss in Parkinson’s disease. Brain 130, 1577–1585CrossRefPubMedGoogle Scholar
  60. 60.
    Thannickal TC, Lai YY, Siegel JM. (2007) Hypocretin (orexin) cell loss in Parkinson’s disease. Brain 130, 1586–1595CrossRefPubMedGoogle Scholar
  61. 61.
    Ghorayeb I, Yekhlef F, Chrysostome Y, Balestre E, Bioulac B, Tison F. (2002) Sleep disorders and their determinants in multiple system atrophy. J Neurol Neurosurg Psychiatry 72, 798–800CrossRefPubMedGoogle Scholar
  62. 62.
    Bliwise DL (2004) Sleep disorders in Alzheimer’s disease and other dementias. Clin Cornerstone 6 (Suppl IA), S16–S28CrossRefPubMedGoogle Scholar
  63. 63.
    Lee JH, Bliwise DL, Ansari FP, Goldstein FC, Cellar JS, Lah JJ, Levey AI. (2007) Daytime sleepiness and functional impairment in Alzheimer disease. Am J Geriat Psychiatry 15, 620–626CrossRefGoogle Scholar
  64. 64.
    Laberge L, Begin P, Montplaisir J, Mathieu J. (2004) Sleep complaints in patients with myotonic dystrophy. J Sleep Res 13, 95–100CrossRefPubMedGoogle Scholar
  65. 65.
    Gibbs III JW, Ciafaloni E, Radtke RA. (2002) Excessive daytime somnolence and increased rapid eye movement pressure in myotonic dystrophy. Sleep 25, 672–675Google Scholar
  66. 66.
    Ono S, Kanda F, Takahashi K, Fukuoka Y, Jinnai K, Kurisaki H, Mitaki S, Inagaki T, Nagao K. (1995) Neuronal cell loss in the dorsal raphe nucleus and the superior central nucleus in myotonic dystrophy: a clinicopathological correlation. Acta Neuropathol 89, 122–125CrossRefPubMedGoogle Scholar
  67. 67.
    Stanton BR, Barnes F, Silber E. (2006) Sleep and fatigue in multiple sclerosis. Mult Scler 12, 481–486CrossRefPubMedGoogle Scholar
  68. 68.
    Malow B, Bowes R, Lin X. (1997) Predictors of sleepiness in epilepsy patients. Sleep 20, 1105–1110PubMedGoogle Scholar
  69. 69.
    Dauvilliers Y, Stal V, Abril B, Coubes P, Bobin S, Touchon J, Escourrou P, Parker F, Bourgin P. (2007) Chiari malformation and sleep related breathing disorders. J Neurol Neurosurg Psychiatry 12, 1344–1348CrossRefGoogle Scholar
  70. 70.
    Guilleminault C, Mondini S. (1986) Infectious mononucleosis and excessive daytime sleepiness. A long-term follow-up study. Arch Intern Med 146, 1333–1335CrossRefPubMedGoogle Scholar
  71. 71.
    Kanbayashi T, Ishiguro H, Aizawa R, Saito Y, Ogawa Y, Abe M, Hirota K, Nishino S, Shimizu T. (2002) Hypocretin-1 (orexin-A) concentrations in cerebrospinal fluid are low in patients with Guillain-Barre syndrome. Psychiatry Clin Neurosci 56, 273–274CrossRefPubMedGoogle Scholar
  72. 72.
    Darko DF, Mc Cutchan JA, Kripke DF, Gillin JC, Golshan, S. (1992) Fatigue, sleep disturbance, disability and indices of progression of HIV infection. Am J Psychiatry 149, 514–520PubMedGoogle Scholar
  73. 73.
    Buguet A, Bisser S, Josenando T, Chapotot F, Cespuglio R. (2005) Sleep structure: a new diagnostic tool for stage determination in sleeping sickness. Acta Trop 93, 107–117CrossRefPubMedGoogle Scholar
  74. 74.
    Guilleminault C, Faull KF, Miles L, van den Hoed J. (1983) Post-traumatic excessive sleepiness: a review of 20 patients. Neurology 33, 1584–1589PubMedGoogle Scholar
  75. 75.
    Baumann CR, Werth E, Stocker R, Ludwig S, Bassetti CL. (2007) Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study. Brain 130, 1873–1883CrossRefPubMedGoogle Scholar
  76. 76.
    Dolenc C, Besset A, Billiard M. (1996) Hypersomnia in association with dysthymia in comparison with idio­pathic hypersomnia and normal controls. Plfugers Arch 431, R303–R304CrossRefGoogle Scholar
  77. 77.
    Billiard M, Dolenc L, Aldaz C, Ondze B, Besset A. (1994) Hypersomnia associated with mood disorders: a new perspective. J Psychosomat Res 38(Suppl 1), 41–47CrossRefGoogle Scholar
  78. 78.
    Nofzinger EA, Thase M, Reynolds CF, Himmelhoch JM, Mallinger A, Houck P, Kupfer DJ. (1991) Hypersomnia in bipolar depression: a comparison with narcolepsy using the multiple sleep latency test. Am J Psychiatry 148, 1177–1181PubMedGoogle Scholar
  79. 79.
    Allen R. (2006) Periodic leg movements in sleep and restless legs syndrome. Relation to daytime alertness and sleepiness. Sleep Med Clin 1, 157–163CrossRefGoogle Scholar
  80. 80.
    Mendelson WB. (1996) Are periodic leg movements associated with clinical sleep disturbances? Sleep 19, 219–223PubMedGoogle Scholar
  81. 81.
    Nicolas A, Lespérance P, Montplaisir J. (1998) Is excessive daytime sleepiness with periodic leg movements during sleep a specific diagnostic category? Eur Neurol 40, 22–26CrossRefPubMedGoogle Scholar
  82. 82.
    Chervin RD. (2001) Periodic leg movements and sleepiness in patients evaluated for sleep-disordered breathing. Am J Resp Crit Care Med 164, 1454–1458PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of NeurologyGui de Chauliac HospitalMontpellier Cedex 5France

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