Primary Hypersomnia

Updated: Mar 01, 2024
  • Author: Adrian Preda, MD, DFAPA; Chief Editor: Ana Hategan, MD, FRCPC  more...
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Overview

Practice Essentials

Primary hypersomnia, idiopathic hypersomnia (ICSD-3-TR), [1]  and hypersomnolence disorder (DSM-5-TR) [2] refer to a central disorder of hypersomnia. The diagnostic criteria have changed over time and specifics differ depending on the classification. However, all these diagnoses include daily periods of irresistible, excessive sleep or daytime lapses into sleep in the absence of cataplexy, and require that the hypersomnolence is not due to insufficient sleep or another sleep disorder. Sleepiness is frequently associated with difficulties awakening, a phenomenon known as sleep inertia or sleep drunkeness.

Signs and symptoms

Clinical manifestations of hypersomnia include:

  • Daily periods of irresistible need to sleep or daytime lapses into sleep for more than 3 months

  • Absence of cataplexy

  • Multiple Sleep Latency Test (MSLT) showing < 2 sleep-onset REM periods (SOREMPs) or no SOREMPs if the REM sleep latency preceding polysomnogram is 15 minutes or less

The polysymptomatic form of primary hypersomnia is the most common and is characterized by the following:

  • Excessive daytime sleepiness leading to prolonged naps that are not refreshing

  • Sleep drunkenness

These patients do not feel refreshed following naps and, therefore, fight sleepiness as long as they are able. Patients are difficult to awaken from sleep or naps.

Some patients complain of headaches, fainting episodes, orthostatic hypotension, and peripheral vascular complaints of Raynaud phenomenon.

Diagnosis

Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR)

The specific DSM-5-TR criteria [2]  for hypersomnolence disorder are as follows:

  • Clinical presentation: Subjective sense of excessive sleepiness (hypersomnolence) following a main sleep period of at least 7 hours, associated with at least one of the following symptoms:

    • Repeated periods of sleep or lapses into sleep within the same day

    • A daily occurring, nonrestorative prolonged main sleep episode lasting longer than 9 hours

    • Not being fully awake after sudden awakening

  • Duration and course: Hypersomnolence episodes frequency is at least three times per week for at least three months.

  • Functional impairment: There is significant distress or impairment in cognitive, social, occupational, or other important areas of functioning due to hypersomnolence.

  • Differential diagnosis and rule-outs:

    • Other sleeping disorders: The increased sleep is not better accounted by and does not occur only during another sleep disorder (eg, narcolepsy, breathing-related sleep disorder, circadian rhythm sleep-wake disorder, or a parasomnia). 

    • Substance misuse disorders: The hypersomnolence is not explained due to the physiological effects of a substance.

    • Other medical or mental disorders: The hypersomnolence is not attributable to a coexisting mental disorder or medical condition.

International Classification of Sleep Disorders, Third Edition, Text Revision (ICSD-3-TR)

The ICSD-3-TR has redefined the criteria of idiopathic hypersomnia (IH) 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. [1]   

ICSD-3-TR classifies “Central disorders of hypersomnolence” into "primary" and "secondary," with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and Kleine-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, due to insufficient sleep syndrome (ISS). [1]

Management

According to the American Academy of Sleep Medicine (AASM) 2021 guidelines, successful treatment of hypersomnia of central origin requires an accurate diagnosis, individual tailoring of therapy to produce maximum possible return of function, and regular follow-up to monitor response to therapy.

Modafinil, armodafinil, methylphenidate, amphetamines, and sodium oxybate are effective treatments for excessive sleepiness associated with narcolepsy and, by extension, are also used for primary hypersomnias. [3]

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Background

Primary hypersomnia, idiopathic hypersomnia (ICSD-3-TR), [1]  and hypersomnolence disorder (DSM-5-TR) [2] refer to a central disorder of hypersomnia. The diagnostic criteria have changed over time and specifics differ depending on the classification. However, all these diagnoses include daily periods of irresistible, excessive sleep or daytime lapses into sleep in the absence of cataplexy, and require that the hypersomnolence is not due to insufficient sleep or another sleep disorder. Sleepiness is frequently associated with difficulties awakening, a phenomenon known as sleep inertia or sleep drunkeness. In comparison, narcolepsy is characterized by well-defined clinical, polysomnographic, and immunogenetic features. [4, 5] The abrupt sleep attacks seen in classic narcolepsy are not present in idiopathic hypersomnia.

Classification

In the literature, three possible subgroups of idiopathic CNS hypersomnia are described.

Subgroup I

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

Subgroup II

This group includes patients who had a viral infection 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 these patients are initially fatigued, they subsequently have difficulty differentiating fatigue from sleepiness. To fight tiredness, these patients nap and eventually present with excessive daytime sleepiness. Analysis of cerebral spinal fluid (CSF) 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; for this subgroup, the cause of the disorder truly is idiopathic.

Diagnostic criteria (DSM-5-TR and ICSD-3-TR)

The specific DSM-5-TR criteria [2] for hypersomnolence disorder are as follows:

  • Clinical presentation: Subjective sense of excessive sleepiness (hypersomnolence) following a main sleep period of at least 7 hours, associated with at least one of the following symptoms: (1) Repeated periods of sleep or lapses into sleep within the same day; (2) A daily occurring, nonrestorative prolonged main sleep episode lasting longer than 9 hours; (3) Not being fully awake after sudden awakening.

  • Duration and course: Hypersomnolence episodes frequency is at least three times per week for at least three months.

  • Functional impairment: There is significant distress or impairment in cognitive, social, occupational, or other important areas of functioning due to hypersomnolence.

  • Differential diagnosis and rule-outs:

    • Other sleeping disorders: The increased sleep is not better accounted by and does not occur only during another sleep disorder (eg, narcolepsy, breathing-related sleep disorder, circadian rhythm sleep-wake disorder, or a parasomnia). 

    • Substance misuse disorders: The hypersomnolence is not explained due to the physiological effects of a substance.

    • Other medical or mental disorders: The hypersomnolence is not attributable to a coexisting mental disorder or medical condition.

In addition, hypersomnolence disorder is specified by duration: acute (less than 1 month), subacute (1–3 months), persistent (more than 3 months); and by 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, Text Revision (ICSD-3-TR) has redefined the criteria of idiopathic hypersomnia (IH) 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. [1]   

ICSD-3-TR classifies “Central disorders of hypersomnolence” into "primary" and "secondary," with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), idiopathic hypersomnia (IH), and Kleine-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, due to insufficient sleep syndrome (ISS). [1]

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

Primary Secondary

Narcolepsy type 1 (NT1)

Narcolepsy type 2 (NT2)

Hypersomnia due to a medical condition

Hypersomnia due to a psychiatric condition

Idiopathic hypersomnia (IH) Hypersomnia due to a drug or substance
Kleine-Levin syndrome (KLS) Insufficient sleep syndrome (ISS)

Recurrent primary hypersomnia

Kleine-Levin syndrome (KLS) is a rare disorder that starts during adolescence and has a male gender preference. Patients have recurrent episodes of hypersomnia, often associated with compulsive overeating and hypersexuality. [6] 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 confusion, depression, impulsive behavior, irritability, hallucinations, and depersonalization. KLS etiology is unknown but genetic factors are believed to contribute, with 2% to 5% of cases being of multiplex family origin. [7, 8, 9, 10, 11, 12] Autoimmune, inflammatory, and metabolic etiologies are suspected, though not confirmed. [13, 14, 15]

KLS 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). [16, 17, 18, 19]

ISCD-3-TR diagnostic criteria for KLS are as follows: [1]

  1. There are at least two episodes of excessive sleepiness of 2 days to 5 weeks duration.

  2. Episodes recur usually more than once a year and at least once every 18 months.

  3. The patient exhibits normal alertness, cognitive function, behavior, and mood between episodes.

  4. During episodes, the patient must demonstrate at least one of the following: altered perception, cognitive dysfunction, disinhibited behavior (such as hypersexuality), or eating disorder (anorexia or hyperphagia).

  5. The hypersomnia and related symptoms are not better explained by the other sleep disorders, other medical, neurologic, or psychiatric disorders, or use of drugs or medications.

Characteristic symptoms of KLS include the following: [14, 17, 20, 21, 22, 7, 23, 24, 8, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41]

Sleep symptoms:

  • Hypersomnia

  • Intense dreaming

  • Frequent hypnogogic hallucinations

Cognitive changes:

  • Anterograde amnesia

  • Bradyphrenia - frequently present during an episode

  • Derealization - almost all patients

  • Disinhibited behavior - hyperphagia (57%) and hypersexuality (43%–53%)

Neuropsychiatric symptoms:

  • Eating disturbances - 80%

  • Depressed mood - 48%

  • Hallucinations/illusions - 33%

  • Mild psychotic symptoms (delusions, grandiosity, hyperreligiosity, paranoia) - lasting hours to days

  • Anxiety

Common symptoms:

  • Headache

  • Orthostasis

  • Phonophobia

  • Photophobia

Less common symptoms:

  • Ataxia

  • Bradycardia/tachycardia

  • Hypertension

  • Tachypnea

Clinical subtypes

KLS may be mild, moderate, or severe. KLS “menstrual/menstruation-related hypersomnia” is an extremely rare KLS subtype characterized by excessive daytime sleepiness occurring on a periodic basis over a few days preceding menstruation; to date, 18 known cases have been reported worldwide. [22, 42, 43, 44, 45, 46]  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-TR classifies KLS as a recurrent hypersomnia. DSM-5-TR refers to the recurrent hypersomnia as seen in KLS as an “other specified hypersomnolence disorder, brief-duration hypersomnolence." [1, 2]

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Etiology

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. [5]  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. [47]

Genetic contributors

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 have been reported. As a result, HLA typing does not currently play a role in diagnosis of idiopathic hypersomnia. [48, 49, 50, 51, 52, 16] Of note, the majority of patients diagnosed with idiopathic hypersomnia have neither a positive family history nor a past medical history of viral illnesses.

A study in which 10 patients with idiopathic hypersomnia were compared to healthy controls highlighted expression dynamics. The researchers found that the rhythmically expressed circadian clock genes BMAL1, PER1, and PER2 were expressed less in the dermal fibroblasts from idiopathic hypersomnia patients over two circadian periods, and that the overall BMAL1 expression was reduced significantly. [53, 16]

Monoamine neurotransmitters

In experimental animal studies, destruction of the noradrenergic neurons of the rostral third of the locus ceruleus complex resulted in hypersomnia. In a case series, trauma has been associated with excessive daytime sleepiness; however, 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. [54] 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. [55]  Decreased dopamine and indoleacetic acid levels have been found in both narcolepsy and idiopathic hypersomnia patients. [56, 16]

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. [57, 16]

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. [58]

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. [59, 60] 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, [61] hypocretin deficiency may result in excessive daytime sleepiness via decreased histaminergic function. [58]

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Epidemiology

Frequency

While the rates of excessive daytime sleepiness complaints in the general US population are between 0.5% and 5% of adults (in surveys without a specific consideration of causes/diagnoses), idiopathic hypersomnia (IH) is diagnosed in about 5%–10% of individuals who are self-referred to a sleep clinic with a chief complaint of daytime sleepiness. [62] A precise estimation of idiopathic hypersomnia prevalence is complicated by a lack of clear biologic markers or unambiguous diagnostic criteria. As a result, the reported prevalence rates of IH vary broadly.

A 2012 study by Ohayon et al suggested that excessive sleepiness is more prevalent than previously estimated. The study found that 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%. [63]  

A 2023 study reported a much lower prevalence rate, estimating the rate of IH in US adults to be 32.12 per 100,000 persons in 2019, 35.71 per 100,000 persons in 2020, and 37.03 per 100,000 persons in 2021. [64]

A 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. [65, 16]

Sex-, age- and family-related demographics

IH prevalence varies between males and females. In the Wisconsin Sleep Cohort, the estimate prevalence of IH was 3.8% among both males and females, although female predominance was found in some studies. [66, 67, 49, 65, 68]  Approximately 33%–66% of idiopathic hypersomnia cases appear to be familial. [16]

As with narcolepsy and Kleine-Levin syndrome (KLS), onset of hypersomnolence is most common during adolescence and rare in people older than 30 years. The diagnosis of IH is complicated by the fact that differentiating between excessive versus long sleep or normal versus abnormal wakefulness is often difficult, especially during adolescence.

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Prognosis

Typically starting between the ages of 15 and 30 years, hypersomnolence, when untreated, presents a chronic course. Idiopathic hypersomnia (IH) is a lifelong disorder, although a few studies have reported up to 25% of patients with IH demonstrate spontaneous improvement in excessive daytime somnolence; however, most patients show no tendency toward spontaneous remission. Such seemingly conflicting data findings raises the question of diagnostic accuracy. 

Hypersomnia consequences are mostly social and professional in nature, with a psychosocial burden similar to narcolepsy. [69, 70, 71, 16]    

Daytime sleepiness can lead to depression. Of note, in children, daytime sleepiness can present as hyperactivity. [62]

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Patient Education

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

Because hypersomnia can result in a range of social impairments, ranging from social isolation 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 hypersomnia is often misinterpreted as being indicative of professional incompetence or sloth. Education of relatives, friends, and colleagues can help patients 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 a comprehensive patient resource on idiopathic/primary hypersomnia.

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