Narcolepsy

Narcolepsy is characterized by abnormal daytime sleepiness, often combined with episodes of sudden loss of muscle tone (cataplexy), sleep paralysis and hypnagogic phenomena.

Diagnosis is based on polysomnography and multiple sleep latency testing. Treatment includes modafinil and various stimulants.

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Causes of Narcolepsy

The cause of narcolepsy is unknown. Narcolepsy is strongly associated with certain HLA haplotypes, and children with narcolepsy have a 40-fold increased risk of developing the disease, suggesting a genetic cause. However, the concordance rate in twins is low (25%), suggesting an important role for environmental factors. Animals and most humans with narcolepsy have a deficiency of the neuropeptide hypocretin-1 in the CSF, suggesting an HLA-associated autoimmune destruction of hypocretin-containing neurons in the lateral hypothalamus as the cause. Narcolepsy affects men and women equally.

Narcolepsy is characterized by dysregulation of the periodicity and control of the REM sleep phase, i.e. a change in sleep structure. The REM sleep phase "invades" both periods of wakefulness and periods of transition from wakefulness to sleep. Many symptoms of narcolepsy are manifested by a sharp loss of muscle tone and vivid dreams that characterize REM sleep.

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Symptoms of Narcolepsy

The main symptoms are abnormal daytime sleepiness (ADS), cataplexy, hypnagogic hallucinations, and insomnia; approximately 10% of patients have all four symptoms. Nighttime sleep disturbances are also common. Symptoms usually begin in adolescents or young adults, usually without any previous illness, although the onset of narcolepsy is sometimes associated with illness, stress, or a period of sleep deprivation. Once onset occurs, narcolepsy becomes a lifelong disorder, without affecting life expectancy.

Pathological daytime sleepiness can develop at any time. The number of attacks during the day can vary significantly; attacks can be rare or numerous, their duration ranges from several minutes to several hours. The patient's ability to resist falling asleep is very limited, although waking him up during a narcoleptic attack is no more difficult than during normal sleep. Attacks most often occur in a monotonous environment (e.g., reading, watching TV, at a meeting), which promotes sleep in a healthy person, but in contrast to this, the patient can fall asleep in an environment that requires increased attention (e.g., while driving a car, talking, writing, eating). Sleep attacks are possible - sudden repeated attacks of sleep. The patient may feel alert after waking up, but after a few minutes he can fall asleep again. Night sleep is fragmented, often interrupted by vivid, frightening dreams, and does not bring satisfaction. The consequences are low performance and productivity, disruption of interpersonal relationships, poor concentration, lack of motivation, depression, a significant reduction in quality of life and an increased risk of injury (especially due to road traffic accidents).

Cataplexy is characterized by sudden muscle weakness or paralysis without loss of consciousness, caused by sudden, unexpected emotional reactions such as anger, fear, joy, or surprise. The weakness may be limited to one limb (for example, the patient suddenly drops the fishing rod when a fish is caught) or generalized, such as the patient suddenly falling over in anger or laughing heartily. The loss of muscle tone in such episodes resembles the phenomenon observed in the rapid eye movement (REM) phase of sleep. Cataplexy occurs in approximately three-quarters of patients.

Sleep paralysis - brief episodes of muscle weakness that sometimes occur at the moment of falling asleep or waking up, during which the patient is unable to make any voluntary movement. At this moment, the patient may be overcome by fear. Such episodes resemble the suppression of motor activity during the REM phase of sleep. Sleep paralysis occurs in approximately 1/4 of patients, and sometimes in healthy children and adults.

Hypnagogic phenomena are unusually vivid auditory or visual illusions or hallucinations that occur when falling asleep or, less commonly, when waking up. They are somewhat reminiscent of vivid dreams that occur during rapid eye movement (REM) sleep. Hypnagogic phenomena occur in approximately one-third of patients, are common among healthy young children, and occasionally occur in healthy adults.

Diagnosis of narcolepsy

The diagnosis is made on average 10 years after the onset of the disease. In patients with pathological daytime sleepiness, the presence of cataplexy suggests narcolepsy. The results of nocturnal polysomnography and the multiple sleep latency test (MSLT) are of diagnostic significance. The diagnostic criteria for narcolepsy are registration of the sleep phase in at least 2 of 5 episodes of daytime sleep and shortening of the latency time of sleep onset to 5 minutes in the absence of other disorders according to the results of nocturnal polysomnography. The results of the wakefulness maintenance test have no diagnostic significance, but help to evaluate the effectiveness of treatment.

Other potential causes of chronic hypersomnia may be suggested by the history and physical examination; CT or MRI of the brain and clinical blood and urine tests may help confirm the diagnosis. Causes of chronic hypersomnia include tumors of the hypothalamus or upper brainstem, increased intracranial pressure, some types of encephalitis, as well as hypothyroidism, hyperglycemia, hypoglycemia, anemia, uremia, hypercapnia, hypercalcemia, liver failure, seizures, and multiple sclerosis. Acute, relatively short-term hypersomnia usually accompanies acute systemic illnesses such as influenza.

Kleine-Levin syndrome is a very rare disorder affecting adolescents, characterized by episodic hypersomnia and polyphagia. The etiology is unclear, but may involve an autoimmune response to infection.

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Treatment of narcolepsy

Single episodes of sleep paralysis or hypnagogic phenomena with moderate pathological daytime sleepiness do not require special treatment. In other cases, stimulants are prescribed. Strict sleep hygiene is recommended, with sufficiently long nighttime and short daytime sleep (less than 30 min, usually after lunch) at the same time every day.

For mild to moderate drowsiness, modafinil, a long-acting drug, is effective. The mechanism of action is unclear, but the drug is not a stimulant. Modafinil is typically prescribed at 100-200 mg orally in the morning. According to indications, the dose can be increased to 400 mg, but in some cases a significantly higher dose is required. If the effect of the drug does not last until the evening, a second small dose (100 mg) can be taken at 12:00-13:00, keeping in mind the potential risk of disruption to nighttime sleep. Side effects of modafinil include nausea and headache, which can be smoothed out if you start with low doses and gradually increase them to the desired values.

If modafinil is ineffective, amphetamine derivatives are prescribed instead of or together with modafinil. Methylphenidate may be more effective in doses from 5 mg 2 times a day to 20 mg 3 times a day orally, differing from modafinil in a more rapid onset of therapeutic action. Methamphetamine is prescribed at 5-20 mg 2 times a day orally, dextroamphetamine at 5-20 mg 2-3 times a day orally; as long-acting drugs, in most cases they are effective when taken once a day. Possible side effects include agitation, arterial hypertension, tachycardia, and mood changes (manic reactions). All stimulants have an increased risk of addiction. Pemoline, with a lower potential for addiction compared to amphetamines, is rarely used due to hepatotoxicity and the need for regular monitoring of liver function. According to indications, the anorectic drug mazindol is prescribed (2-8 mg orally once a day).

Tricyclic antidepressants (especially imipramine, clomipramine, and protriptyline) and MAO inhibitors are effective in treating cataplexy, sleep paralysis, and hypnagogic phenomena. Clomipramine 25-150 mg (orally once a day in the morning) is the most effective anticataplectic drug. The new anticataplectic drug Na oxybate (list A, due to the risk of developing dependence and drug addiction) is prescribed at 2.75-4.5 g orally twice a night.