(See also Approach to the Patient With a Sleep or Wakefulness Disorder.)
The cause of narcolepsy is unknown. In Europe, Japan, and the US, incidence is 0.2 to 1.6/1000. Narcolepsy is equally common in both sexes.
Narcolepsy is strongly associated with specific human leukocyte antigen (HLA) haplotypes, but the cause is not thought to be genetic. Concordance in twins is low (25%), suggesting a prominent role for environmental factors, which often trigger the disorder. The neuropeptide hypocretin-1 is deficient in cerebrospinal fluid (CSF) of narcoleptic animals and most human patients, suggesting that the cause may be HLA–associated autoimmune destruction of hypocretin-containing neurons in the lateral hypothalamus.
Narcolepsy features dysregulation of the timing and control of rapid eye movement (REM) sleep. Therefore, REM sleep intrudes into wakefulness and into the transition from wakefulness to sleep. Many symptoms of narcolepsy result from postural muscle paralysis and vivid dreaming, which characterize REM.
There are 2 types:
Type 1: Narcolepsy due to hypocretin deficiency and accompanied by cataplexy (momentary muscular weakness or paralysis evoked by sudden emotional reactions)
Type 2: Narcolepsy with normal hypocretin levels and without cataplexy
The Kleine-Levin syndrome, a very rare disorder in adolescent boys, resembles narcolepsy. The Kleine-Levin syndrome causes episodic hypersomnia (excessive daytime sleepiness) and hyperphagia. Etiology is unclear but may be an autoimmune response to an infection.
Symptoms and Signs of Narcolepsy
The main symptoms of narcolepsy are
Excessive daytime sleepiness (EDS)
Cataplexy
Hypnagogic and hypnopompic hallucinations
Sleep paralysis
Disturbed nocturnal sleep (due to increased arousals)
About 10% of patients have all 5 of these symptoms.
Symptoms usually begin in adolescents or young adults without prior illness, although onset can be precipitated by an illness, a stressor, or a period of sleep deprivation. Once established, narcolepsy persists throughout life; life span is unaffected.
Excessive daytime sleepiness
EDS is the primary symptom and can occur anytime. Sleep episodes vary from few to many per day, and each may last minutes or hours. Patients can resist the desire to sleep only temporarily but can be roused as readily as from normal sleep. Sleep tends to occur during monotonous conditions (eg, reading, watching television, attending meetings) but may also occur during complex tasks (eg, driving, speaking, writing, eating).
Patients may also experience sleep attacks—episodes of sleep that strike without warning. Patients may feel refreshed when they awaken yet fall asleep again in a few minutes.
Nighttime sleep may be unsatisfying with frequent arousals and interrupted by vivid, frightening dreams.
Consequences include low productivity, breaches in interpersonal relationships, poor concentration, low motivation, depression, a dramatic reduction in quality of life, and potential for physical injury (particularly due to motor vehicle collisions).
Cataplexy
Momentary episodes of muscular weakness or paralysis occur without loss of consciousness and usually last < 2 minutes;they are evoked by sudden emotional reactions, such as laughter, anger, fear, joy, or, often, surprise.
Weakness may be confined to the limbs (eg, patients may drop the rod when a fish strikes their line) or may cause a limp fall during hearty laughter (as in “weak with laughter”) or sudden anger. Cataplexy can also affect other muscles: The jaw may droop, facial muscles may flicker, eyes may close, the head may nod, and speech may be slurred. Vision may be blurred. These attacks resemble the loss of muscle tone that occurs during REM sleep.
Clinically significant cataplexy occurs in about 20% of patients.
Sleep paralysis
Patients are momentarily unable to move as they are just falling asleep or immediately after they awaken. These episodes may be very frightening. They resemble the motor inhibition that accompanies REM sleep.
Sleep paralysis occurs in about 25% of patients but also in some healthy children and, less commonly, in healthy adults.
Hypnagogic or hypnopompic hallucinations
Particularly vivid auditory or visual illusions or hallucinations may occur when just falling asleep (hypnagogic) or, less often, immediately after awakening (hypnopompic). They are difficult to distinguish from intense reverie and are somewhat similar to vivid dreams, which are normal in REM sleep.
Hypnagogic hallucinations occur in about 30% of patients, are common among healthy young children, and occasionally occur in healthy adults.
Disturbed nocturnal sleep
Sleep is often also disturbed by increased arousals in patients with narcolepsy, potentially worsening EDS.
Diagnosis of Narcolepsy
Polysomnography
Multiple sleep latency testing
A delay of 10 years from onset of symptoms to diagnosis of narcolepsy is common.
A history of cataplexy strongly suggests narcolepsy in patients with EDS.
In patients with EDS, nocturnal polysomnography, followed by multiple sleep latency testing (MSLT), can confirm a diagnosis of narcolepsy when the findings include the following:
Sleep-onset REM episodes during at least 2 of 5 daytime nap opportunities or one during daytime nap opportunities plus one during the preceding nocturnal polysomnogram
Average sleep latency (time to fall asleep) of ≤ 8 minutes
No other diagnostic abnormalities on nocturnal polysomnography
Narcolepsy type 1 is diagnosed if patients also have cataplexy; type 2 is diagnosed if patients do not have cataplexy. EDS occurs in patients with narcolepsy type 1 or type 2.
The maintenance of wakefulness test does not help with diagnosis but does help monitor treatment efficacy.
Other disorders that can cause chronic EDS are usually suggested by the history and physical examination; brain imaging and blood and urine tests can confirm the diagnosis. These disorders include space-occupying lesions affecting the hypothalamus or upper brain stem, increased intracranial pressure, and certain forms of encephalitis. Hypothyroidism, hyperglycemia, hypoglycemia, anemia, uremia, hypercapnia, hypercalcemia, hepatic failure, and seizure disorders can also cause EDS with or without hypersomnia. Acute, relatively brief EDS and hypersomnia commonly accompany acute systemic disorders such as influenza. Hypersomnia also occurs in patients with meningoencephalitis due to African trypanosomiasis (sleeping sickness), which is transmitted by the tsetse fly.
Treatment of Narcolepsy
Oxybates
Narcolepsy may not require treatment if patients have occasional episodes of sleep paralysis or hypnagogic and hypnopompic hallucinations, infrequent and partial cataplexy, and mild EDS. For others, wake-promoting drugs and anticataplectic drugs are used. Patients should also get enough sleep at night and take brief naps (< 30 minutes) at the same time every day (typically afternoon). Patients with cataplexy should avoid precipitating factors (eg, laughter, anger, fear).
For type 1 narcolepsy,
For type 2 narcolepsy,
pm may be used, although this dose sometimes interferes with nocturnal sleep.
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Tricyclic antidepressantsSSRIs
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Key Points
Narcolepsy may be caused by autoimmune destruction of hypocretin-containing neurons in the lateral hypothalamus.
The main symptoms are excessive daytime sleepiness (EDS), cataplexy, hypnagogic and hypnopompic hallucinations, sleep paralysis, and disturbed nocturnal sleep.
Confirm the diagnosis by polysomnography and multiple sleep latency testing.
