Primary Hypersomnia 

The International Classification of Sleep Disorders (ICSD) describes primary hypersomnia as an idiopathic disorder of presumed central nervous system (CNS) cause that is associated with excessive sleepiness (ie, prolonged episodes of non–rapid eye movement [NREM] sleep). (See Etiology and Presentation.)^[1]

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) defines primary (idiopathic) hypersomnia as excessive daytime sleepiness without narcolepsy or the associated features of other sleep disorders.^[2]

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.

In comparison with narcolepsy, which is characterized by well-defined clinical, polysomnographic, and immunogenetic features, primary hypersomnia is not well characterized.^{[5, 6]} Moreover, while the DSM-IV-TR and the ICSD each define 2 types of idiopathic/primary hypersomnia based on the sleep time duration (ie, with or without long sleep), the presentation is often heterogeneous. (See Presentation, DDX, and Workup.)^[7]

Please note that while the ICSD prefers the diagnostic label of idiopathic hypersomnia, the DSM prefers the diagnostic label of primary hypersomnia. As the terms are interchangeable, this article will refer to them alternately.

Classification

Primary hypersomnia can be classified as monosymptomatic or polysymptomatic. Isolated excessive daytime sleepiness that is not due to abnormal nocturnal awakenings characterizes the monosymptomatic form. The polysymptomatic form consists of abnormally long nocturnal sleep and signs of sleep drunkenness upon awakening.^[8]

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.

Recurrent primary hypersomnia

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.^{[10, 11]}

The disorder mainly affects males (68%). The median age of onset is 15 years (range, 4-82y; 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 (38.2%), head trauma (9%), or alcohol consumption (5.4%). Characteristic symptoms include the following^[11] :

• Hypersomnia - 100%
• Cognitive changes - 96%, including a specific feeling of derealization
• Eating disturbances - 80%
• Hypersexuality - 43%
• Compulsions - 29%
• Depressed mood - 48%

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 recurrent hypersomnia is classified separately to describe the recurrent form of primary hypersomnia according to the DSM-IV-TR.

Primary hypersomnia 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]

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 and HLA-DR11 genotypes have also been reported.^[13] However, the majority of the patients diagnosed with idiopathic hypersomnia have neither a positive family history nor a past medical history of viral illnesses.

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]

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]

Occurrence in the United States

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]

Sex- and age-related demographics

Gender ratio for idiopathic hypersomnia is unknown. Kleine-Levin syndrome affects males approximately 3 times more often than females.^[1]

As with narcolepsy and Klein-Levin syndrome, onset of primary hypersomnia 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 15-30 years, untreated primary hypersomnia presents a chronic, but stable, course. Idiopathic hypersomnia is a lifelong disorder with no tendency to remit spontaneously. Consequences of this disease are mostly social and professional in nature.

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

While treating patients with primary hypersomnia, 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 with primary hypersomnia 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) 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.