Primary Hypersomnia

Primary Hypersomnia

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In 1966, William Dement proposed that patients with excessive daytime sleepiness, but without cataplexy, sleep paralysis, or sleep-onset rapid eye movement (REM), should not be considered narcoleptic. [3] In 1972, Roth et al described a type of hypersomnia with sleep drunkenness that consists of difficulty coming to complete wakefulness, confusion, disorientation, poor motor coordination, and slowness, accompanied by deep and prolonged sleep. [4] The abrupt sleep attacks seen in classic narcolepsy are not present in this disorder.

Primary hypersomnia, idiopathic hypersomnia (ICSD-3), and hypersomnolence disorder (DSM-5) refer to a central disorder of hypersomnia. The diagnostic criteria have changed over time and specifics differ depending on the organization. Similarities from all, however, include daily periods of irresistible sleep or daytime lapses into sleep, absence of cataplexy, and that the hypersomnolence is not better accounted for by either insufficient sleep or by another sleep disorder. In comparison, narcolepsy is characterized by well-defined clinical, polysomnographic, and immunogenetic features. [5, 6]

In the literature, 3 possible subgroups of idiopathic CNS hypersomnia have been suggested.

Subgroup I

These patients have a positive family history, and associated clinical symptoms suggest dysfunction of the autonomic nervous system. These symptoms include headache, syncope, orthostatic hypotension, and peripheral vasoconstriction (cold hands and feet).

Subgroup II

This group includes patients who had a viral infection associated with neurologic symptoms, such as Guillain-Barré syndrome, infectious mononucleosis, or atypical viral pneumonia. Even after their infectious disease resolves, these patients continue to require significantly more nocturnal sleep and continue to feel very tired.

Although initially these patients are fatigued, they subsequently have difficulty differentiating fatigue from sleepiness. To fight tiredness, these patients nap and eventually present with complaints of excessive daytime sleepiness. Analysis of cerebral spinal fluid demonstrates moderate lymphocytosis (30-50 cells/µL with mild to moderate elevation in protein).

Subgroup III

These patients do not have a positive family or viral infection history, and the cause of the disorder truly is idiopathic.

The specific DSM-5 criteria for hypersomnolence disorder are as follows:

Self-reported excessive sleepiness (hypersomnolence) despite a main sleep period of at least 7 hours, with at least one of the following symptoms: 1) Recurrent periods of sleep or lapses into sleep within the same day; 2) A prolonged main sleep episode of more than 9 hours per day that is nonrestorative; 3) Difficulty being fully awake after abrupt awakening.

The hypersomnolence occurs at least three times per week for at least 3 months.

The hypersomnolence is accompanied by significant distress or impairment in cognitive, social, occupational, or other important areas of functioning.

The hypersomnolence is not better explained by and does not occur exclusively during the course of another sleep disorder (eg, narcolepsy, breathing-related sleep disorder, circadian rhythm sleep-wake disorder, or a parasomnia). 

The hypersomnolence is not attributable to the physiological effects of a substance.

A coexisting mental disorder or medical condition does not adequately explain the hypersomnolence.

In addition, hypersomnolence disorder is specified by duration: acute (less than 1 month), subacute (1–3 months), persistent (more than 3 months); and by the severity based on degree of difficulty maintaining daytime alertness: mild (1–2 days a week), moderate (3–4 days a week), severe (5–7 days a week).

The American Sleep Disorders Association’s International Classification of Sleep Disorders, Third Edition (ICSD-3) has redefined the criteria of idiopathic hypersomnia to include varied presentations under the same diagnosis as opposed to distinguishing two separate forms (with and without long sleep time) that were characteristic of the ICSD-2 definition.  

ICSD-3 classifies “Central disorders of hypersomolence” into ‘primary’ and ‘secondary’ groupings, with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and Kline-Levin syndrome (KLS) making up the primary disorders. The secondary disorders include hypersomnia due to a medical or psychiatric disorder, due to a drug or substance, and lastly, insufficient sleep syndrome (ISS).

ISCD-3 Central Disorders of Hypersomnolence (Open Table in a new window)

Narcolepsy type 1 (NT1)

Narcolepsy type 2 (NT2)

Hypersomnia due to a medical condition

Hypersomnia due to a psychiatric condition

Kleine-Levin syndrome (KLS) is a rare disorder that starts during adolescence and has a male gender preference. The patients have recurrent episodes of hypersomnia, which are often associated with compulsive overeating and hypersexuality. [9] The periods of hypersomnia occur for days to weeks at a time and recur several times a year. In between the symptomatic periods, the patients have normal sleep requirements and do not have excessive daytime sleepiness. Some patients may develop symptoms of irritability, impulsive behavior, depersonalization, hallucinations, depression, and confusion. The etiology of this disorder is not known, but genetic factors are believed to contribute, citing 2% to 5% of cases are of multiplex family origin. [70, 73, 95, 96, 97, 98] Metabolic, inflammatory, and autoimmune etiologies are suspected, though not yet confirmed. [10, 11, 62]

The disorder mainly affects males (68%). The median age of onset is 15 years (range, 4–82 years; 81% during the second decade), and the syndrome may last up to 8 years. The episodes recur every 3–4 months and may last up to 10 days, but they may last longer in women. (See Epidemiology.)

KLS may be precipitated by infections (72%), alcohol consumption (23%), sleep deprivation (22%), unusual stress (20%), physical exertion (19%), traveling (10%), head trauma (9%), and marijuana use (6%).  Symptoms of infection-triggered KLS generally occur shortly after onset of fever (3 to 5 days). [63, 64, 65, 66]

ISCD-3 diagnostic criteria for KLS are as follows: [2]

Characteristic symptoms of KLS include the following: [11, 64, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92]

Sleep symptoms:

Cognitive changes:

Neuropsychiatric symptoms:

Common symptoms:

Less common symptoms:

KLS may be mild, moderate, or severe. When episodes consistently occur with a temporal relation to menstruation, it is referred to as subtype “menstrual/menstruation-related hypersomnia” and is extremely rare (18 known cases worldwide). [69, 93, 94, 99, 100, 101]   Menstrual-related hypersomnia is diagnosed when excessive daytime sleepiness occurs on a periodic basis over a few days preceding menstruation. [12] It is assumed that the symptoms follow hormonal changes, but the etiology of the syndrome, as well as its prevalence and course, are virtually unknown.

The ICSD-3 classifies KLS as a recurrent hypersomnia. DSM-5 refers to the recurrent hypersomnia as seen in KLS as an “other specified hypersomnolence disorder, brief-duration hypersomnolence.” [60, 61]

Hypersomnolence is an idiopathic disorder. Although head injury or viral infections can cause a disorder resembling primary hypersomnia, the true causes for most cases remain unknown. No genetic, environmental, or other predisposition has been identified. [6]  Rye et al postulated that there is a naturally occurring “somnogen” in the CSF of those with hypersomnolence that potentiated the inhibitory effects of GABAA in an in vitro setting. [48]

Excessive daytime sleepiness has been described in a subset of patients following viral illnesses such as Guillain-Barré syndrome, hepatitis, mononucleosis, and atypical viral pneumonia. Familial cases associated with HLA-Cw2, -Cw3, -DR5, -DR11, -DQ1, and –DQ3 genotypes have also been reported, and it is known that there are overlapping features found in both idiopathic hypersomnia and narcolepsy, though no consistent findings are agreed upon. HLA typing does not currently play a role in diagnosis of idiopathic hypersomnia. [13, 36, 40, 41, 42, 63] However, the majority of patients diagnosed with idiopathic hypersomnia have neither a positive family history nor a past medical history of viral illnesses.

A recent study highlighted expression dynamics of circadian clock genes in dermal fibroblasts, in which 10 patients with idiopathic hypersomnia were compared to healthy controls. They found the rhythmically expressed BMAL1, PER1, and PER2 were expressed less in cells from idiopathic hypersomnia patients over two circadian periods, and that the overall BMAL1 expression was reduced significantly. [43, 63]

In experimental animal studies, destruction of the nonadrenergic neurons of the rostral third of the locus ceruleus complex has produced hypersomnia. While trauma has been associated with excessive daytime sleepiness in a case series, cerebrospinal fluid (CSF) analysis for specific neurotransmitter metabolites did not differentiate patients with posttraumatic excessive daytime sleepiness from patients with narcolepsy or other patients with excessive daytime sleepiness. [14] Injury to the adrenergic neurons at the bundle of isthmus has led to hypersomnia associated with a proportional increase of both NREM and REM sleep. [15]

Montplaisir et al found decreased dopamine and indoleacetic acid in both narcolepsy and idiopathic hypersomnia patients. [44, 63]

Faull et al discovered dopaminergic dysregulation in narcolepsy and noradrenergic dysregulation in idiopathic hypersomnia. [21]  

This evidence suggests the possibility of aminergic arousal system dysfunction in idiopathic hypersomnia. Feline studies have shown hypersomnia and monoamine dysregulation can be induced reproducibly via lesioning of the ascending noradrenergic pathways. [45, 63]

Evidence suggests that a dopamine system dysfunction may occur in narcolepsy, while a similar malfunction of the norepinephrine system may occur in idiopathic hypersomnia. Decreased CSF histamine levels have been reported in primary hypersomnia, as well as in narcolepsy, but not in non-CNS hypersomnias, suggesting that histamine may be an indicator of a central (versus a peripheral) origin for hypersomnias. [16]

A major advance in the understanding of the pathology of narcolepsy, a disorder closely related to primary hypersomnia, was made after the discovery of narcolepsy-associated genes in animals; ie, genes involved in the pathology of the hypocretin/orexin ligand and its receptor. [17, 18] Low CSF concentrations of hypocretin-1 and hypocretin-2 in HLA DQB1*0602 were also found in primary hypersomnia, and a generalized defect in hcrt-2 transmission may be present in this disorder. As hypocretin peptides excite the histaminergic system by the hypocretin receptor 2, [19] hypocretin deficiency may result in excessive daytime sleepiness via decreased histaminergic function. [16]

While the rates of excessive daytime sleepiness complaints in the general population are between 0.5-5% of adults (in surveys without a specific consideration of causes/diagnoses), idiopathic hypersomnia is diagnosed in about 5-10% of individuals who are self referred to a sleep clinic with a chief complaint of daytime sleepiness. [1] A precise estimation of idiopathic hypersomnia prevalence is complicated by a lack of clear biologic markers or unambiguous diagnostic criteria.

A study by Ohayon et al suggested that excessive sleepiness is more prevalent than previously estimated. The study found that with 27.8% of 15,929 individuals from 15 US states reported excessive sleepiness. Even when using restrictive criteria of frequency at least 3 times per week for at least 3 months despite normal sleep duration, the prevalence was 4.7%. [20]

A recent large series found that idiopathic hypersomnia represented about 1% of 6000 patients seen in sleep centers—given that idiopathic hypersomnia is believed to be 60% as prevalent as narcolepsy, this raises the question of diagnostic accuracy. [37, 63]

Gender ratio for hypersomnolence is unknown, though female predominance was found in some but not all of these studies. [35, 36, 37, 38]   Approximately 33%–66% of idiopathic hypersomnia cases appear to be familial. [63]

 

As with narcolepsy and Klein-Levin syndrome, onset of hypersomnolence is most common during adolescence and rare in people older than 30 years. The diagnosis of idiopathic hypersomnia is complicated by the fact that differentiating between excessive versus long sleep or normal versus abnormal wakefulness is often difficult in this population.

After a typical onset between the ages of 15 and 30 years, untreated hypersomnolence presents a chronic but stable course. Idiopathic hypersomnia is a lifelong disorder, believed to have no tendency to remit spontaneously, though a few studies have reported up to 25% of patients that carry the idiopathic hypersomnia diagnosis demonstrate spontaneous improvement in excessive daytime somnolence. This seemingly conflicting data again raises the question of diagnostic accuracy. 

Consequences of this disease are mostly social and professional in nature, sharing a psychosocial burden that is similar to narcolepsy. [57, 58, 59, 63]    

Daytime sleepiness can lead to depression. Of note, in children, daytime sleepiness can present as hyperactivity. [1]

 

While treating patients with hypersomnolence, the patient’s close family should be involved in the overall education and decision-making process.

Because these disorders may lead to marriage breakdown, extensive counseling for the patient’s partners, educating them about the symptomatology and treatment options, must be part of a comprehensive management plan.

Patients often need significant support because they are at risk of being misunderstood as being incompetent or slothful. Therefore, education of relatives, friends, and colleagues helps the patient to function much better with this incurable disease.

For patient education information, see the Sleep Disorders Center, as well as Disorders That Disrupt Sleep (Parasomnias), the Hypersomnia Foundation, and Narcolepsy.

Medline Plus/National Institutes of Health (NIH) provides concise and to-the-point summaries of the diagnosis and recommendations for patients and families dealing with primary hypersomnia and Kleine-Levine syndrome.

The Mayo clinic offers an additional, more comprehensive patient resource on idiopathic/primary hypersomnia.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th edition. Washington, DC: American Psychiatric Association;

American Academy of Sleep Medicine. International Classification of Sleep Disorders. Third Edition (ICSD-3). Westchester, IL: American Academy of Sleep Medicine; 2014.

Dement W, Rechtschaffen A, Gulevich G. The nature of the narcoleptic sleep attack. Neurology. 1966 Jan. 16(1):18-33. [Medline].

Roth B, Nevsimalova S, Rechtschaffen A. Hypersomnia with “sleep drunkenness”. Arch Gen Psychiatry. 1972 May. 26(5):456-62. [Medline].

Roehrs T, Zorick F, Sicklesteel J. Excessive daytime sleepiness associated with insufficient sleep. Sleep. 1983. 6(4):319-25. [Medline].

Billiard M. Diagnosis of narcolepsy and idiopathic hypersomnia. An update based on the International classification of sleep disorders, 2nd edition. Sleep Med Rev. 2007 Oct. 11(5):377-88. [Medline].

Bassetti C, Pelayo R, Guilleminault C. Idiopathic Hypersomnia. Kryger MH, Roth T, Dement WC. Principles and Practices of Sleep Medicine. 4th Edition. Philadelphia, PA: Elsevier; 2005. 791-800.

Roth T. Introduction: narcolepsy and excessive daytime sleepiness: from the bench to the bedside. J Clin Psychiatry. 2007. 68 Suppl 13:4. [Medline].

Guilleminault C. Disorders of excessive sleepiness. Ann Clin Res. 1985. 17(5):209-19. [Medline].

Roth B. Narcolepsy and hypersomnia: review and classification of 642 personally observed cases. Schweiz Arch Neurol Neurochir Psychiatr. 1976. 119(1):31-41. [Medline].

Arnulf I, Zeitzer JM, File J, et al. Kleine-Levin syndrome: a systematic review of 186 cases in the literature. Brain. 2005 Dec. 128(Pt 12):2763-76. [Medline].

Billiard M, Guilleminault C, Dement WC. A menstruation-linked periodic hypersomnia: Kleine-Levin syndrome or new clinical entity?. Neurology. 1975. 25:436-443. [Medline].

Montplaisir J, Poirier G. HLA in disorders of excessive sleepiness without cataplexy in Canada. Honda Y, Juti T. HLA in Narcolepsy. Berlin, Germany: Springer-Verlag; 1988. 186-190.

Guilleminault C, Faull KF, Miles L. Posttraumatic excessive daytime sleepiness: a review of 20 patients. Neurology. 1983 Dec. 33(12):1584-9. [Medline].

Montplaisir J, de Champlain J, Young SN. Narcolepsy and idiopathic hypersomnia: biogenic amines and related compounds in CSF. Neurology. 1982 Nov. 32(11):1299-302. [Medline].

Kanbayashi T, Kodama T, Kondo H, Satoh S, Inoue Y, Chiba S, et al. CSF histamine contents in narcolepsy, idiopathic hypersomnia and obstructive sleep apnea syndrome. Sleep. 2009 Feb 1. 32(2):181-7. [Medline]. [Full Text].

Nishino S, Okuro M, Kotorii N, Anegawa E, Ishimaru Y, Matsumura M, et al. Hypocretin/orexin and narcolepsy: new basic and clinical insights. Acta Physiol (Oxf). 2009 Jun 25. [Medline]. [Full Text].

Nishino S, Kanbayashi T. Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system. Sleep Med Rev. 2005 Aug. 9(4):269-310. [Medline].

Yamanaka A, Tsujino N, Funahashi H, Honda K, Guan JL, Wang QP, et al. Orexins activate histaminergic neurons via the orexin 2 receptor. Biochem Biophys Res Commun. 2002. 290:1237-45. [Medline]. [Full Text].

Ohayon MM, Dauvilliers Y, Reynolds CF 3rd. Operational Definitions and Algorithms for Excessive Sleepiness in the General Population: Implications for DSM-5 Nosology. Arch Gen Psychiatry. 2012 Jan. 69(1):71-9. [Medline].

Guilleminault C, Faull KF. Sleepiness in nonnarcoleptic, non-sleep apneic EDS patients: the idiopathic CNS hypersomnolence. Sleep. 1982. 5 Suppl 2:S175-81. [Medline].

Bassetti C, Gugger M, Bischof M. The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexin A). Sleep Med. 2003 Jan. 4(1):7-12. [Medline].

Ohayon MM. From wakefulness to excessive sleepiness: what we know and still need to know. Sleep Med Rev. 2008 Apr. 12(2):129-41. [Medline].

Sangal RB; Mitler MM; Sangal JM. Subjective sleepiness ratings (Epworth sleepiness scale) do not reflect the same parameter of sleepiness as objective sleepiness (maintenance of wakefulness test) in patients with narcolepsy. Clin Neurophysiol. Dec 1999. (110)12:2131-5. [Medline].

Sangal RB, Sangal JM, Belisle C. Subjective and objective indices of sleepiness (ESS and MWT) are not equally useful in patients with sleep apnea. Clin Electroencephalogr. 1999 Apr. 30(2):73-5. [Medline].

Rechtschaffen A, Roth B. Nocturnal sleep of hypersomniacs. Act Nerv Super (Praha). 1969. 11(3):229-33. [Medline].

Anderson KN, Pilsworth S, Sharples LD, Smith IE, Shneerson JM. Idiopathic hypersomnia: a study of 77 cases. Sleep. 2007 Oct 1. 30(10):1274-81. [Medline].

[Guideline] Morgenthaler TI, Kapur VK, Brown T, Swick TJ, Alessi C, Aurora RN, et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007 Dec 1. 30(12):1705-11. [Medline].

Ballon JS, Feifel D. A systematic review of modafinil: Potential clinical uses and mechanisms of action. J Clin Psychiatry. 2006 Apr. 67(4):554-66. [Medline].

Valentino RM, Foldvary-Schaefer N. Modafinil in the treatment of excessive daytime sleepiness. Cleve Clin J Med. 2007 Aug. 74(8):561-6, 568-71. [Medline].

Schwartz JR. Modafinil: new indications for wake promotion. Expert Opin Pharmacother. 2005 Jan. 6(1):115-29. [Medline].

Poppe M, Friebel D, Reuner U, Todt H, Koch R, Heubner G. The Kleine-Levin syndrome – effects of treatment with lithium. Neuropediatrics. 2003. 34:113-9. [Medline].

Roth B, Nevsimalova S, Rechtschaffen A. Hypersomnia with “sleep drunkenness”. Arch Gen Psychiatry. 1972 May. 26 (5):456-62. [Medline].

Billiard M, Dauvilliers Y. Idiopathic Hypersomnia. Sleep Med Rev. 2001 Oct. 5 (5):349-358. [Medline].

Vernet C, Arnulf I. Idiopathic hypersomnia with and without long sleep time: a controlled series of 75 patients. Sleep. 2009 Jun. 32 (6):753-9. [Medline].

Bassetti C, Aldrich MS. Idiopathic hypersomnia. A series of 42 patients. Brain. 1997 Aug. 120 ( Pt 8):1423-35. [Medline].

Anderson KN, Pilsworth S, Sharples LD, Smith IE, Shneerson JM. Idiopathic hypersomnia: a study of 77 cases. Sleep. 2007 Oct. 30 (10):1274-81. [Medline].

Bruck D, Parkes JD. A comparison of idiopathic hypersomnia and narcolepsy-cataplexy using self report measures and sleep diary data. J Neurol Neurosurg Psychiatry. 1996 May. 60 (5):576-8. [Medline].

Bassetti C, Gugger M, Bischof M, Mathis J, Sturzenegger C, Werth E, et al. The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexin A). Sleep Med. 2003 Jan. 4 (1):7-12. [Medline].

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):153-8. [Medline].

Billiard M. Idiopathic hypersomnia. Neurol Clin. 1996 Aug. 14 (3):573-82. [Medline].

Honda Y, Honda M. [Idiopathic hypersomnia–review of literatures and clinical experiences on 16 Japanese cases]. Nihon Rinsho. 1998 Feb. 56 (2):371-5. [Medline].

Lippert J, Halfter H, Heidbreder A, Röhr D, Gess B, Boentert M, et al. Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia. PLoS One. 2014. 9 (1):e85255. [Medline].

Montplaisir J, de Champlain J, Young SN, Missala K, Sourkes TL, Walsh J, et al. Narcolepsy and idiopthic hypersomnia: biogenic amines and related compounds in CSF. Neurology. 1982 Nov. 32 (11):1299-302. [Medline].

Petitjean F, Jouvet M. [Hypersomnia and increase of cerebral 5-hydroxyindoleacetic acid due to isthmic lesions in the cat]. C R Seances Soc Biol Fil. 1970. 164 (11):2288-93. [Medline].

Mignot E, Lammers GJ, Ripley B, Okun M, Nevsimalova S, Overeem S, et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol. 2002 Oct. 59 (10):1553-62. [Medline].

Dauvilliers Y, Baumann CR, Carlander B, Bischof M, Blatter T, Lecendreux M, et al. CSF hypocretin-1 levels in narcolepsy, Kleine-Levin syndrome, and other hypersomnias and neurological conditions. J Neurol Neurosurg Psychiatry. 2003 Dec. 74 (12):1667-73. [Medline].

Rye DB, Bliwise DL, Parker K, Trotti LM, Saini P, Fairley J, et al. Modulation of vigilance in the primary hypersomnias by endogenous enhancement of GABAA receptors. Sci Transl Med. 2012 Nov 21. 4 (161):161ra151. [Medline].

Bové A, Culebras A, Moore JT, Westlake RE. Relationship between sleep spindles and hypersomnia. Sleep. 1994 Aug. 17 (5):449-55. [Medline].

Baker TL, Guilleminault C, Nino-Murcia G, Dement WC. Comparative polysomnographic study of narcolepsy and idiopathic central nervous system hypersomnia. Sleep. 1986. 9 (1 Pt 2):232-42. [Medline].

Nicolas A, Lespérance P, Montplaisir J. Is excessive daytime sleepiness with periodic leg movements during sleep a specific diagnostic category?. Eur Neurol. 1998 Jul. 40 (1):22-6. [Medline].

Montplaisir J, Fantini L. Idiopathic hypersomnia: a diagnostic dilemma. A commentary of “Idiopathic hypersomnia” (M. Billiard and Y. Dauvilliers). Sleep Med Rev. 2001 Oct. 5 (5):361-362. [Medline].

Guilleminault C, Stoohs R, Clerk A, Cetel M, Maistros P. A cause of excessive daytime sleepiness. The upper airway resistance syndrome. Chest. 1993 Sep. 104 (3):781-7. [Medline].

Roehrs T, Zorick F, Sicklesteel J, Wittig R, Roth T. Excessive daytime sleepiness associated with insufficient sleep. Sleep. 1983. 6 (4):319-25. [Medline].

Roehrs TA, Roth T. Chronic insufficient sleep and its recovery. Sleep Med. 2003 Jan. 4 (1):5-6. [Medline].

Trotti LM, Saini P, Freeman AA, Bliwise DL, García PS, Jenkins A, et al. Improvement in daytime sleepiness with clarithromycin in patients with GABA-related hypersomnia: Clinical experience. J Psychopharmacol. 2014 Jul. 28 (7):697-702. [Medline].

Broughton R et al. The socio-economic effects of idiopathic hypersomnia-comparison with controls and with compound narcoleptics. Sleep. 1978. 229-33.

Dauvilliers Y, Paquereau J, Bastuji H, Drouot X, Weil JS, Viot-Blanc V. Psychological health in central hypersomnias: the French Harmony study. J Neurol Neurosurg Psychiatry. 2009 Jun. 80 (6):636-41. [Medline].

Vernet C, Leu-Semenescu S, Buzare MA, Arnulf I. Subjective symptoms in idiopathic hypersomnia: beyond excessive sleepiness. J Sleep Res. 2010 Dec. 19 (4):525-34. [Medline].

American Academy of Sleep Medicine. International classification of Sleep Disorders. 3rd edition. Darien, IL: American Academy of Sleep Medicine.;

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth edition. Arlington, VA: American Psychiatric Association; 2013.

Arnulf I, Rico TJ, Mignot E. Diagnosis, disease course, and management of patients with Kleine-Levin syndrome. Lancet Neurol. 2012 Oct. 11 (10):918-28. [Medline].

Kryger MH, Roth T, Dement WC. Principles and Practice of Sleep Medicine. 6th edition. Philadelphia, PA: Elsevier; 2017.

Arnulf I, Lin L, Gadoth N, File J, Lecendreux M, Franco P, et al. Kleine-Levin syndrome: a systematic study of 108 patients. Ann Neurol. 2008 Apr. 63 (4):482-93. [Medline].

Salter MS, White PD. A variant of the Kleine-Levin syndrome precipitated by both Epstein-Barr and varicella-zoster virus infections. Biol Psychiatry. 1993 Mar 1. 33 (5):388-90. [Medline].

GALLINEK A. The Kleine-Levin syndrome: hypersomnia, bulimia, and abnormal mental states. World Neurol. 1962 Mar. 3:235-43. [Medline].

Kas A, Lavault S, Habert MO, Arnulf I. Feeling unreal: a functional imaging study in patients with Kleine-Levin syndrome. Brain. 2014 Jul. 137 (Pt 7):2077-87. [Medline].

A Brierre de Boismont. Des Hallucinations: Ou Histoire Raisonnée des Apparitions, des Visions, des Songes, de l’Extase, des Rêves, du Magnetisme Et du Somnambulisme. Paris: Germer Baillière; 1862.

Billiard M, Jaussent I, Dauvilliers Y, Besset A. Recurrent hypersomnia: a review of 339 cases. Sleep Med Rev. 2011 Aug. 15 (4):247-57. [Medline].

Arnulf I, Lin L, Gadoth N, File J, Lecendreux M, Franco P, et al. Kleine-Levin syndrome: a systematic study of 108 patients. Ann Neurol. 2008 Apr. 63 (4):482-93. [Medline].

Gadoth N, Kesler A, Vainstein G, Peled R, Lavie P. Clinical and polysomnographic characteristics of 34 patients with Kleine-Levin syndrome. J Sleep Res. 2001 Dec. 10 (4):337-41. [Medline].

Huang YS, Guilleminault C, Lin KL, Hwang FM, Liu FY, Kung YP. Relationship between Kleine-Levin syndrome and upper respiratory infection in Taiwan. Sleep. 2012 Jan 1. 35 (1):123-9. [Medline].

Lavault S, Golmard JL, Groos E, Brion A, Dauvilliers Y, Lecendreux M, et al. Kleine-Levin syndrome in 120 patients: differential diagnosis and long episodes. Ann Neurol. 2015 Mar. 77 (3):529-40. [Medline].

Arnulf I, Zeitzer JM, File J, Farber N, Mignot E. Kleine-Levin syndrome: a systematic review of 186 cases in the literature. Brain. 2005 Dec. 128 (Pt 12):2763-76. [Medline].

GALLINEK A. The Kleine-Levin syndrome: hypersomnia, bulimia, and abnormal mental states. World Neurol. 1962 Mar. 3:235-43. [Medline].

Shukla GD, Bajpai HS, Mishra DN. Kleine-levin syndrome: a case report from India. Br J Psychiatry. 1982 Jul. 141:97-8. [Medline].

Landtblom AM, Dige N, Schwerdt K, Säfström P, Granérus G. Short-term memory dysfunction in Kleine-Levin syndrome. Acta Neurol Scand. 2003 Nov. 108 (5):363-7. [Medline].

CRITCHLEY M. Periodic hypersomnia and megaphagia in adolescent males. Brain. 1962 Dec. 85:627-56. [Medline].

American Sleep Disorders Association. The international classification of sleep disorders: Diagnosis and coding manual. Chicago, IL: American Academy of Sleep Medicine; 1990.

American Academy of Sleep Medicine. The international classification of sleep disorders—revised. Chicago, IL: American Academy of Sleep Medicine; 2005.

Rosenow F, Kotagal P, Cohen BH, Green C, Wyllie E. Multiple sleep latency test and polysomnography in diagnosing Kleine-Levin syndrome and periodic hypersomnia. J Clin Neurophysiol. 2000 Sep. 17 (5):519-22. [Medline].

Katz JD, Ropper AH. Familial Kleine-Levin syndrome: two siblings with unusually long hypersomnic spells. Arch Neurol. 2002 Dec. 59 (12):1959-61. [Medline].

Portilla P, Durand E, Chalvon A, Habert M, Navelet Y, Prigent A, et al. [SPECT-identified hypoperfusion of the left temporomesial structures in a Kleine-Levin syndrome]. Rev Neurol (Paris). 2002 May. 158 (5 Pt 1):593-5. [Medline].

Arnulf I, Lecendreux M, Franco P, Dauvilliers Y. [Kleine-Levin syndrome: state of the art]. Rev Neurol (Paris). 2008 Aug-Sep. 164 (8-9):658-68. [Medline].

Schenck CH, Arnulf I, Mahowald MW. Sleep and sex: what can go wrong? A review of the literature on sleep related disorders and abnormal sexual behaviors and experiences. Sleep. 2007 Jun. 30 (6):683-702. [Medline].

Malhotra S, Das MK, Gupta N, Muralidharan R. A clinical study of Kleine-Levin syndrome with evidence for hypothalamic-pituitary axis dysfunction. Biol Psychiatry. 1997 Aug 15. 42 (4):299-301. [Medline].

VLACH V. [Periodic somnolence, bulimia and mental disorder (Kleine-Levin syndrome)]. Cesk Neurol. 1962 Nov. 25:401-5. [Medline].

Domzał-Stryga A, Emeryk-Szajewska B, Kowalski J. [A case of hypersomnia resembling Kleine-Levin syndrome]. Neurol Neurochir Pol. 1986 Mar-Apr. 20 (2):158-60. [Medline].

Manni R, Martinetti M, Ratti MT, Tartara A. Electrophysiological and immunogenetic findings in recurrent monosymptomatic-type hypersomnia: a study of two unrelated Italian cases. Acta Neurol Scand. 1993 Oct. 88 (4):293-5. [Medline].

Hegarty A, Merriam AE. Autonomic events in Kleine-Levin syndrome. Am J Psychiatry. 1990 Jul. 147 (7):951-2. [Medline].

Koerber RK, Torkelson R, Haven G, Donaldson J, Cohen SM, Case M. Increased cerebrospinal fluid 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in Kleine-Levin syndrome. Neurology. 1984 Dec. 34 (12):1597-600. [Medline].

Fukunishi I, Hosokawa K. A female case with the Kleine-Levin syndrome and its physiopathologic aspects. Jpn J Psychiatry Neurol. 1989 Mar. 43 (1):45-9. [Medline].

Kleine W. Periodische schlafsucht. Monatsschr Psychiatr Neurol. 1925. 285-320.

Smolík P, Roth B. Kleine-Levin syndrome ethiopathogenesis and treatment. Acta Univ Carol Med Monogr. 1988. 128:5-94. [Medline].

Abe K. Lithium prophylaxis of periodic hypersomnia. Br J Psychiatry. 1977 Mar. 130:312-3. [Medline].

Itokawa K, Fukui M, Ninomiya M, Yamamoto T, Imabayashi E, Tamura N, et al. Gabapentin for Kleine-Levin syndrome. Intern Med. 2009. 48 (13):1183-5. [Medline].

Peraita-Adrados R, Vicario JL, Tafti M, García de León M, Billiard M. Monozygotic twins affected with Kleine-Levin syndrome. Sleep. 2012 May 1. 35 (5):595-6. [Medline].

Ueno T, Fukuhara A, Ikegami A, Ohishi F, Kume K. Monozygotic twins concordant for Kleine-Levin syndrome. BMC Neurol. 2012 May 30. 12:31. [Medline].

Billiard M, Guilleminault C, Dement WC. A menstruation-linked periodic hypersomnia. Kleine-Levin syndrome or new clinical entity?. Neurology. 1975 May. 25 (5):436-43. [Medline].

Rocamora R, Gil-Nagel A, Franch O, Vela-Bueno A. Familial recurrent hypersomnia: two siblings with Kleine-Levin syndrome and menstrual-related hypersomnia. J Child Neurol. 2010 Nov. 25 (11):1408-10. [Medline].

Sachs C, Persson HE, Hagenfeldt K. Menstruation-related periodic hypersomnia: a case study with successful treatment. Neurology. 1982 Dec. 32 (12):1376-9. [Medline].

Narcolepsy type 1 (NT1)

Narcolepsy type 2 (NT2)

Hypersomnia due to a medical condition

Hypersomnia due to a psychiatric condition

Adrian Preda, MD Professor of Clinical Psychiatry and Human Behavior, University of California, Irvine, School of Medicine

Adrian Preda, MD is a member of the following medical societies: American Association for the Advancement of Science, American Psychiatric Association, International College of Neuropsychopharmacology, International Congress of Schizophrenia Research, Schizophrenia International Research Society, Society of Biological Psychiatry

Disclosure: Nothing to disclose.

David R Bowman, MD Psychiatrist, Deputy Chief, Joint Behavioral Health Clinic, Multi-Disciplinary Outpatient Clinic, Medical Review Officer, Clinical Practice Guidelines Champion, External Behavioral Health Consultant, Department of Behavioral Health, Moncrief Army Health Clinic

David R Bowman, MD is a member of the following medical societies: American Psychiatric Association, American Society for Adolescent Psychiatry, American Society of Addiction Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ana Hategan, MD, FRCPC Associate Clinical Professor, Department of Psychiatry and Behavioral Neurosciences, Division of Geriatric Psychiatry, McMaster University School of Medicine; Geriatric Psychiatrist, St Joseph’s Health Care Hamilton, Canada

Ana Hategan, MD, FRCPC is a member of the following medical societies: Canadian Academy of Geriatric Psychiatry, Canadian Coalition for Seniors’ Mental Health, Canadian Psychiatric Association, International Psychogeriatric Association, Ontario Medical Association, Royal College of Physicians and Surgeons of Canada

Disclosure: Book royalties and/or honoraria for articles from American Psychiatric Publishing, Springer, and Current Psychiatry.

Jennifer S Morse, MD Associate Medical Director, Optum Health

Jennifer S Morse, MD is a member of the following medical societies: Academy of Psychosomatic Medicine, Aerospace Medical Association, and American Psychiatric Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Primary Hypersomnia

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