Narcolepsy: what is it, symptoms, treatment, causes, prognosis

What is Narcolepsy?

Narcolepsy Is a neurological sleep disorder characterized by chronic, excessive sleepiness during the day, sometimes called excessive daytime sleepiness (NPD). Drowsiness attacks can last only a few seconds or a few minutes. These episodes range in frequency from one episode to several in a single day. Sleep at night can also be disrupted.

Narcolepsy is often associated with three additional symptoms - sudden extreme muscle weakness (cataplexy), a specific type hallucinations that occur just before falling asleep or after waking up, and brief episodes of paralysis during awakening. Narcolepsy can also be associated with "automatic behavior", ie. with automatic execution of something without saving in memory after waking up.

The incidence of narcolepsy is approximately 1 in 2000, and most researchers believe that the disease remains undiagnosed or misdiagnosed in many sick. There is growing evidence that narcolepsy is an autoimmune disorder.

Autoimmune diseases occur when the body's immune system mistakenly attacks healthy tissue or cells. In narcolepsy, the immune system destroys certain brain cells that produce a peptide called hypocretin (orexin). Hypocretin affects many brain functions, but the details of its action are not yet clear. Why the immune system attacks healthy cells in narcolepsy is unknown; environmental and genetic factors may play a role in the development of the disorder.

Signs and symptoms

The development and severity of symptoms associated with narcolepsy varies greatly from person to person. The first symptoms appear one at a time; the onset of new symptoms can take years, with cataplexy usually preceding drowsiness. Narcolepsy usually begins in an adolescent whose initial symptoms are mild but worsen with age. Sometimes the symptoms do not change for months, and sometimes the symptoms can change very quickly. Depending on the severity of the illness, narcolepsy can dramatically affect a person's daily routine, disrupting every aspect of their life.

Excessive daytime sleepiness (NPD) is usually the first sign of narcolepsy. People with narcolepsy typically experience periods of sleepiness, fatigue, lack of energy, an overwhelming desire to sleep (“sleep attacks”), and / or an inability to resist sleep. This predisposition to endless sleepiness and / or falling asleep can occur every day, but its severity varies from day to day and during each day. These episodes are more likely to occur during monotonous, boring activities such as watching TV. However, seizures can occur at any time, even when a person is walking, talking, eating, or driving. Consequently, narcolepsy can seriously disrupt a person's life. Patients can fall asleep for short periods ranging from a few seconds to several minutes.

Narcolepsy can also interfere with sleep patterns at night. People who are sick may wake up frequently during the night and may be awake for significant periods of the night. Despite disturbed sleep patterns, the total sleep time for people with narcolepsy every 24 hours is generally normal, as they sleep multiple times during short periods of the day and night.

Many people with narcolepsy experience weakness and sudden loss of muscle tone (cataplexy). This often occurs during intense emotions such as laughter, anger, elation, and / or surprise. Episodes of cataplexy can occur as short periods of partial muscle weakness and can vary in duration and severity. In some cases, a cataplectic attack may be subtle. Patients may have very short, mild episodes, as a result of which the knees buckle, the jaw becomes plump, the eyelids or the head droop. Sometimes, in severe cases, there can be an almost complete loss of muscle control, which lasts for several minutes. During a severe cataplectic attack, speech and movement may become difficult or impossible, although loss of consciousness does not occur. Cataplexy can improve as sick people get older.

Some people with narcolepsy do not have cataplexy and are not required to diagnose narcolepsy. Cataplexy usually develops about a few weeks or months after the onset of excessive daytime sleepiness. In rare cases, cataplexy may precede the development of difficulty maintaining vigilance.

Some people with narcolepsy may experience hallucinations that may occur at the beginning or end of their sleep period. They are often bright and intimidating. Examples of hallucinations can include the ringing of a phone or a person walking nearby, seeing people or animals that are not there, or an out-of-body experience. When hallucinations occur upon awakening, they are called hypnopompic hallucinations; when they occur on falling asleep, they are called hypnagogic hallucinations. Hallucinations often occur in conjunction with sleep paralysis.

People with narcolepsy may experience temporary "sleep paralysis». They may be unable to move their limbs or head or speak for a short time. Sleep paralysis episodes are very short and usually coincide with falling asleep or waking up. After these short episodes, all movement in the affected people is restored.

Some sufferers may also experience additional symptoms, including fatigue, depression, difficulty concentrating and memory problems. Periodic limb movement syndrome and sleep apnea in people with narcolepsy.

Causes and risk factors

Cataplexic narcolepsy (type 1) is associated with low levels of a specific brain chemical called hypocretin (also known as orexin). This chemical plays an important role in regulating sleep and other functions. Hypocretin also acts as a neurotransmitter, a chemical that modifies, enhances or transmits nerve impulses from one nerve cell (neuron) to another, allowing nerve cells communicate. The researchers found that the number of neurons that produce hypocretin is significantly reduced in people with narcolepsy. The neurons that produce hypocretin are found in the hypothalamus, an area of ​​the brain that regulates many functions, including sleep, appetite, and body temperature. In some people, up to 80-90 percent of the hypothalamic neurons that produce hypocretin are lost.

In 2009, researchers discovered that people with narcolepsy have changes in a gene known as the T cell receptor gene. (T cells are specialized immune cells that play a role in all responses of the immune system.) This variant of the T-cell receptor gives people a genetic predisposition to develop narcolepsy. Genetic predisposition means that a person carries the gene or genes for the disease, but the disorder may not manifest unless other additional factors are present. The genetic factors associated with narcolepsy are not sufficient to cause the disease on their own.

Many cases of narcolepsy are closely related to a group of genes known as the human leukocyte antigen (HLA) complex, located on human chromosome 6. These genes play a role in regulating the proper function of the immune system. Patients often have variants of some of these genes. The exact role and significance of these HLAs in narcolepsy are not fully understood. Most disorders associated with the HLA complex have an immunological component of the disorder, either due to autoimmunity or an inappropriate response of the immune system to a foreign substance. The researchers believe that HLA and a variant of T lymphocytes found in people with narcolepsy interact in ways that cause the destruction of brain cells that produce hypocretin.

The exact cause of narcolepsy without cataplexy (type 2) is unknown.

Affected populations

The exact number of people with narcolepsy in Russia is unknown. One estimate is that the prevalence is between 0.03 and 0.16 percent of the total population in various ethnic groups around the world. One American study found that the incidence of new cases of narcolepsy is 0.74 per 100,000 person-years in the general US population. An estimated 1 in 2,000 people in the general population suffer from this disorder. However, because narcolepsy is often misunderstood or misdiagnosed, it is difficult to determine its true incidence in the general population.

Narcolepsy can develop at any time between the ages of early childhood and 50 years. Two peak periods have been identified; one is about 15 years old and the other about 36 years old. Some researchers believe that narcolepsy is undiagnosed in children. Narcolepsy is usually lifelong. Although the nature and severity of the patient's symptoms may change over time, the disease does not progress.

Narcolepsy was first described in the medical literature in 1880 by Zhelino and in 1887 by Westphalus.

Symptomatic disorders

Symptoms of the following conditions may be similar to those of narcolepsy. Comparisons can be useful for differential diagnosis:

• Idiopathic hypersomnia Is a rare condition characterized by episodes of extreme sleepiness that occur for no known cause (idiopathic). Episodes can be chronic or persistent. The disorder differs from narcolepsy in that patients do not have sudden sleep episodes and do not develop cataplexy. In addition, those affected do not feel rested after sleeping. Some people with idiopathic hypersomnia sleep for long periods of time (eg, more than 10 hours); others sleep for shorter periods (eg, less than 10 hours). Idiopathic hypersomnia can disrupt many aspects of life. Behavior changes and certain medications are used to treat the disorder.
• Sleep apnea- a common sleep disorder characterized by temporary, repetitive interruptions in breathing during sleep. Symptoms of the disorder include frequent breaks from sleep at night, excessive sleepiness in during the day, loud snoring, irritability, poor concentration and / or cognitive impairment abilities. Sleep apnea is commonly associated with obesity, including obesity in the neck and the presence of a narrowing of the airways in the neck. In obstructive sleep apnea syndrome, the most common form of sleep apnea, difficulty breathing is interrupted by a collapsed airway. Then a partial awakening can occur and the person can breathe. Sleep resumes when breathing begins again. Untreated sleep apnea may be associated with high blood pressure (arterial hypertension), irregular heartbeat and increased risk heart attack, heart failure, stroke and diabetes.
• Kleine syndrome–Levin (Sleeping Beauty Syndrome) - a rare disease characterized by the need for excessive sleep (hypersomnia) (i.e. up to 20 hours a day); excessive food intake (compulsive hyperphagia); and behavioral changes such as abnormally uninhibited sex drive. While awake, patients may exhibit irritability, lack of energy (lethargy), and / or lack of emotion (apathy). They may also appear confused (disoriented) and experience hallucinations. The symptoms of Kleine-Levin syndrome are cyclical. The victim may not experience symptoms for weeks or months. If present, symptoms may persist for days to weeks. In some cases, the symptoms associated with Kleine-Lewin syndrome disappear over time with age. However, episodes may recur later in life. The exact cause of Kleine-Levin syndrome is not known.

Symptoms similar to those of narcolepsy can also occur after brain tumors (intracranial), trauma scalp, hardening of the arteries in the brain (cerebral arteriosclerosis), psychosis, and / or excessive amounts of protein in the blood due to renal failure. Hypothyroidism, delayed sleep phase syndrome, disorder of periodic limb movements, depression, hypoglycemia and other conditions can also cause excessive daytime sleepiness.

Diagnostics

Narcolepsy is diagnosed on the basis of a thorough clinical examination;

• a thorough history of the patient and family;
• objective examination of characteristic symptoms (eg, excessive daytime sleepiness, potentially associated with cataplexy, hypnagogic hallucinations and / or sleep paralysis);
• specialized sleep research.

The two main tests used to diagnose narcolepsy are nocturnal polysomnography (PSG), followed by multiple sleep latency test (MTLS). PSG is a sleep test that continuously measures various parameters, including changes in brain waves, heart rate, eye movements, limb movements, muscle tone and breath. PSG is usually followed by MTLS, which measures how quickly someone falls asleep every two hours during the day (4 or 5 times). People with narcolepsy fall asleep more easily during the day than people without narcolepsy. In addition, they will enter dreaming (rapid eye movement sleep) even during a short nap, which a healthy, soundly sleeping person cannot do.

People with narcolepsy often have extremely low levels of hypocretin in their cerebrospinal fluid. Analysis of cerebrospinal fluid for hypocretin levels can help diagnose narcolepsy.

Standard treatments

Narcolepsy treatment focuses on the specific symptoms that each person has. Various medications can help relieve certain symptoms associated with narcolepsy.

For people who experience excessive daytime sleepiness and sleep bouts, therapy may include the administration of certain stimulants, such as Modafinil (Provigil). Modafinil was approved by the Food and Drug Administration (FDA) for the treatment of excessive daytime sleepiness in narcolepsy in 1999. Modafinil is currently the most widely prescribed drug for excessive daytime sleepiness. The mechanism of action of the drug is different from other stimulants and does not affect alertness or memory. In addition, evidence suggests that modafinil therapy is not associated with addiction or symptoms. withdrawal and can therefore be an effective alternative to other treatments for excessive daytime sleepiness. Modafinil is usually associated with fewer side effects than previous drugs used to treat this condition.

Previous drugs that have been used to treat excessive daytime sleepiness in narcolepsy include methylphenidate (Ritalin, methylin), methamphetamine, or dextroamphetamine. These drugs stimulate the central nervous system and are still used when modafinil is ineffective. Because these medications can be associated with certain side effects, including nervousness, insomnia, or irritability, requires careful monitoring by physicians to ensure proper dosage and efficacy adjustments such therapy. In addition, if therapy is discontinued, close monitoring and long-term observation by doctors may be required.

Additional stimulants that have been used to treat excessive daytime sleepiness and narcolepsy include manzindole, selegiline, and pemoline.

A variety of medications have been used to treat cataplexy. The orphan drug Xyrem, manufactured by Jazz Pharmaceuticals, has been approved by the FDA for the treatment of cataplexy, sudden loss of muscle control, and weakness associated with narcolepsy. Xyrem is also effective in improving nighttime sleep in people with narcolepsy. Some people with narcolepsy who received high doses of the drug experienced improvements in daytime sleepiness. However, Xyrem is potentially associated with serious side effects. The generic name for Xyrem is sodium hydroxybutyrate and is also known as gamma hydroxybutyric acid (GHB).

People with cataplexy, sleep paralysis, and / or hypnagogic hallucinations can be treated with certain antidepressants. Specifically, doctors often prescribe selective serotonin reuptake inhibitors, which suppress REM sleep, to relieve these symptoms. These drugs include, for example, fluoxetine (Prozac, Serafem, and others), sertraline (Zoloft), atomoxetine (Strattera), and venlafaxine (Effexor). The most common side effects are decreased sex drive and delayed orgasm. Other side effects can include digestive problems, anxiety, headache, and insomnia. Older tricyclic antidepressants such as imipramine, desimipramine, protriptyline, and clomipramine may also be effective in reducing cataplexy, sleep paralysis and / or hallucinations, but many people are concerned about the side effects including dry mouth and constipation.

Beyond drug therapy, many people have benefited from behavior modification. For people with narcolepsy, regular sleep habits are important, including ensuring regular bedtime and avoiding sleep interruptions. If possible, taking regular naps during the day can help control excessive daytime sleepiness. Regular exercise is also recommended. Sufferers should discuss with their physician regarding appropriate sleep patterns.

Forecast

People with narcolepsy have a significantly higher risk of death or serious injury from road traffic accidents or accidents at work, and they must avoid situations in which such accidents may occur cases.