Central types of hypersomnolence are primary sleep disorders characterized by profound sleepiness or the excessive need to sleep. Classification of central disorders of hypersomnolence in” the International Classification of Sleep Disorders,
1. Narcolepsy type 1
2. Narcolepsy type 2
3. Idiopathic hypersomnia
4. Kleine-Levin syndrome
5. Hypersomnia associated with a psychiatric disorder
6. Hypersomnia due to a medical disorder
7. Hypersomnia due to a medication or substance
8. Insufficient sleep syndrome
The first four disorders, sleepiness and associated symptoms are manifestations of the hypersomnia disorder itself, not a consequence or comorbidity of another condition.
Hypersomnia associated with a psychiatric disorder is similar, in that excessive daytime sleepiness occurs in the presence of a psychiatric disorder. (the excessive daytime sleepiness is not necessarily caused by the comorbid psychiatric disease – just comorbid with each other).
In the last three conditions, excessive daytime sleepiness is due to a comorbid medical disorder, a substance, or chronically short sleep durations.
Excessive daytime sleepiness (EDS)
Daytime sleepiness is defined to be excessive when if causes a subjective complaint or interferences with function.
Excessive daytime sleepiness (EDS) is defined as the inability to maintain wakefulness and alertness during the major waking hours of the day, with sleep occurring unintentionally or at inappropriate times almost daily for at least 3 months.
It is important to distinguish EDS from fatigue.
Fatigue presents with a lack of energy without unintended or excessive sleep, sleepiness implies an increased propensity to sleep.
It is used interchangeably with hypersomnia and hypersomnolence.
According to ICD-4, hypersomnolence is excessive sleepiness when wakefulness is expected, and hypersomnia is a disorder characterised by hypersomnolence.
The Epworth Sleepiness Scale can be quickly administered and is commonly used to identify sleepiness and assess the severity of daytime sleepiness.
Fig 1. Epworth Sleepiness Scale
Common causes of excessive daytime sleepiness are insufficient amounts of habitual sleep, other sleep disorders (e.g., obstructive sleep apnea, insomnia, circadian rhythm sleep-wake disorders), and the adverse effects of medications.
Sleep evaluation
1.Sleep logs
- For at least 2-week duration.
- It tend to overestimate the amount of sleep.
2.Actigraphy
- A surrogate marker of sleep and wakefulness.
- It helps to identify insufficient sleep and circadian rhythm sleep-wake disorders.
- A device worn on the nondominant wrist that detects motion.
- Lack of motion is suggestive of sleep periods, whereas motion is consistent with wakefulness and movement.
Fig 2. Actigraphy
The screening tools such as the STOP-BANG are helpful for inquiring about clinical suspicion for obstructive sleep apnea (by scoring for snoring, gasping, choking, and pauses in breathing during sleep).
Fig 3: STOP-Bang Questionnaire
3.Polysomnogram
The overnight polysomnogram helps to exclude other factors that contribute to daytime sleepiness such as sleep apnea or acute sleep deprivation (a minimum of 6 hours of sleep is required on overnight polysomnography to proceed with the MSLT) and to record rapid eye movement (REM) sleep latency.
4. The Multiple Sleep Latency Test (MSLT)
MSLT consists of five 20-minute nap opportunities every 2 hours throughout the day and measures sleep latency and sleep-onset REM periods. A mean sleep-onset latency of less than or equal to 8 minutes indicates hypersomnolence.
Optimally, medications that impact sleep propensity and sleep architecture should be tapered and discontinued at least 2weeks prior to the multiple sleep latency test.
Primary Chronic Central Nervous System Disorders of Hypersomnolence
Central disorders of hypersomnolence are characterized by excessive daytime sleepiness that impacts daily functions.
Narcolepsy, idiopathic hypersomnia, and hypersomnia disorders associated with other medical or neurologic diseases are defined by chronic symptoms of sleepiness, while Kleine-Levin syndrome is characterized by episodic hypersomnolence.
Narcolepsy
Narcolepsy is a rare chronic neurologic disorder.
People with narcolepsy typically present with severe or overwhelming urges to sleep during desired waking periods and, less commonly, sleep attacks.
Many patients also experience symptoms of REM sleep intruding into waking periods, including cataplexy, hypnagogic or hypnopompic hallucinations, and sleep paralysis.
There are two types of narcolepsy.
Type-1: Associated with cataplexy with low level of CSF orexin (hypocretin)
Type-2: NOT associated with cataplexy with normal level of CSF orexin.
Table 1: Summary table for narcolepsy type 1
Table 2: Summary table for narcolepsy type 2
Secondary narcolepsy
Nonspecific damage to the orexin (hypocretin) neurons or their pathways by trauma, malignancy, inflammation, or infection can cause secondary narcolepsy with or without cataplexy in both adults and children.
People with cataplexy who have focal neurologic deficits or encephalopathy merit further evaluation with brain MRI to evaluate for secondary narcolepsy.
Associated features of narcolepsy
Narcolepsy type 1 can be distinguished from narcolepsy type 2 by the presence of cataplexy or low orexin (hypocretin) levels in CSF (less than or equal to 110 pg/mL) in narcolepsy type 1.
People with either narcolepsy type 1 or narcolepsy type 2 may describe (a)episodic sleep paralysis and (b)sleep-related hallucinations. (more common in narcolepsy type 1 than narcolepsy type 2).
Sleep paralysis and sleep-related hallucinations can occur in otherwise healthy people when provoked by sleep deprivation or circadian rhythm misalignment.
The narcolepsy tetrad of sleepiness, cataplexy, sleep paralysis, and sleep-related hallucinations is present in approximately 45% of people with narcolepsy type 1.
All four features are rarely present at the time of the initial clinical evaluation.
(a)Sleep paralysis
It is characterized by the inability to move one’s arms or legs or the feeling that something heavy is pushing down on one’s body, and typically occurs upon waking from sleep.
These events typically last a few minutes; affected patients are awake during these episodes and have full recall after the event.
Sleep paralysis may occur with sleep-related hallucinations.
(b)Sleep-related hallucinations
It is a frightening event.
It is characterized by seeing or hearing things that are not there while falling asleep (hypnagogic) or waking up (hypnopompic)
Those hallucinations may include seeing a person, animal, or shape, and rarely involve auditory and tactile components.
Associated comorbidities of narcolepsy
Patients with narcolepsy often have other sleep symptoms that disturb sleep quality. (disrupted nighttime sleep)
Vivid or lucid dreams (i.e., dreams that a person is consciously aware of dreaming) are frequently reported by people with narcolepsy. (dreams are so realistic, believing false memories or dream-reality confusion)
Either clinical dream enactment behavior or REM sleep without atonia seen on polysomnogram can be present in 20% to 60% of people with narcolepsy.
Other comorbid sleep disorders include obstructive sleep apnea, periodic limb movement disorder, and restless legs syndrome.
People with narcolepsy have an increased risk of medical and psychiatric comorbidities including obesity, hypertension, endocrinopathies, headaches, chronic pain, and diabetes.
Depression has been reported in over 30% of patients with narcolepsy at time of diagnosis, with rates increasing to 50% over time.
Idiopathic hypersomnia (IH)
It is characterized by excessive daytime sleepiness, severe difficulty waking from sleep (sleep inertia), and daytime brain fog or cognitive cloudiness.
Descriptions of EDS are variable, including severe urges to sleep during the day, generalized low energy or fatigue, or prolonged nocturnal sleep duration.
Patients with idiopathic hypersomnia can have prolonged sleep duration with more than 10 to 11 hours of nocturnal sleep plus long daytime naps.
Severe sleep inertia, or difficulty rising from sleep in the morning (prolonged and pronounced) is notable features. Sleep inertia is
- Also known as sleep drunkenness, due to cognitive dysfunction and clumsiness of movement.
Table 3: Summary table for idiopathic hypersomnia
Cataplexy
The generalized or partial loss of muscle tone, typically triggered by strong positive emotions, including laughter or anticipation.
Anger is a less common trigger, other emotional triggers include surprise embarrassment, or fear.
These triggers can change or become less frequent with age.
Cataplexy can also occur during intercourse or be related to orgasm, which can impact personal relationships.
Each episode usually lasts for second to minutes and patient is fully conscious and able to recall the full event.
Cataplexy can also occur during intercourse or be related to orgasm, which can impact personal relationships.
Fig 3. Cataplexy is transient weakness of the face, neck, or limbs (partial) or the whole body (generalized), triggered by emotion.
Typically, daytime sleepiness precedes or co-occurs with the first episode of cataplexy, but cataplexy can occur years or even decades after the onset of daytime sleepiness.
Cataplexy is commonly misdiagnosed as syncope, seizures, or psychogenic events and video recordings of events can be helpful for diagnosis.
Management of Narcolepsy and Idiopathic Hypersomnia
Basic principles
Existing therapies for chronic central disorders of hypersomnolence target symptom control. They are lifelong.
There is no disease-modifying therapies that exist for these disorders.
The therapeutic goal is to improve excessive daytime sleepiness and other burdensome symptoms to optimize academic, social, family, and workplace function.
Pharmacologic and behavioral approaches can lessen daytime sleepiness severity.
Medications should be selected considering possible short-term and long-term adverse effects, cost, and risk-benefit to the patient.
Non-pharmacologic management
1. Education about these disorders and lifestyle adjustments.
2. Consistent nighttime schedule
3. Schedules naps
4. Treat comorbid sleep disorders and metabolic (obesity) and psychiatric disorders
5. Psychological support
6. Medications to avoid
- Benzodiazepines
- Opioids
- Alcohol
- Antipsychotic drugs
- Alpha-1 antagonists
Treatment recommendations for EDS in narcolepsy
Strong recommendations for treatment in adults
- Modafinil (dopamine reuptake blocker through binding to the dopamine transporter)
- Pitolisant (histamine H3 receptor inverse agonist)
- Sodium oxybate (MOA is unclear, but it is believed to activate the GABA-B receptor)
- Solriamfetol (a selective dopamine and norepinephrine reuptake inhibitor)
Conditional recommendations for treatment in adults
- Armodafinil
- Dextroamphetamine (modulator of the catecholamines, norepinephrine and dopamine)
- Methylphenidate (amphetamine-like drugs)
Fig. 4 Clinical pathway for management of narcolepsy in adults
Fig 5. Clinical pathway for management of narcolepsy in children
For pregnancy and lactation
- Discontinue all medications for narcolepsy during pregnancy and lactation
- Benefit vs. risk to fetus in selected cases
- Modafinil/Armodafinil three% risk of major malformations
Table 4: Summary table for Kleine- Levin Syndrome
For diagnosis, patients must have two separate attacks, returning to a normal baseline in between; these episodes last 2 days to 5 weeks and occur at least once every 18 months.
Unlike narcolepsy and IH, symptoms of Kleine-Levin syndrome often lessen or resolve over time, typically after about 8 years.
It can be debilitating due to limitations on academic and occupational functioning during recurrent episodes.
The etiology of Kleine-Levin syndrome is unknown.
It is typically sporadic; a minority of cases can be familial.
Lithium may decrease the frequency, severity, and duration of episodes in Kleine-Levin syndrome.
Summary
Central disorders of hypersomnolence have a significant impact on daily function and optimal participation in school, work, social, and family interactions.
Make the correct diagnosis and these disorders can be differentiated by obtaining a detailed clinical sleep history and by a thoughtful interpretation of sleep diagnostic testing.
Maximize non-pharmacological approach first.
Consider pharmacologic options (if needed).
Modifying treatment approaches to meet the needs of individuals.
Rationalize the medical and psychiatric comorbidities (if necessary).
Tailoring treatment approach is the best way to meet the needs of individuals and account for medical and psychiatric comorbidities to improve disease burden, daytime function, and quality of life.
References
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4. Laura Pérez-Carbonell, Emmanuel Mignot, et al. Understanding and approaching excessive daytime sleepiness, The Lancet, Volume 400, Issue 10357, 2022, Pages 1033-1046, doi:10.1016/S0140-6736(22)01018-2.
5. Margaret Blattner; Kiran Maski. Central Disorders of Hypersomnolence Sleep Neurology, Continuum (Minneap Minn). p. 1045-1070 August 2023, Vol.29, No.4 doi: 10.1212/CON.0000000000001265
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Author Information
Thar Thar Oo
M.B; B.S., MD, MPH, FAAN
Senior Consultant Neurologist
