Narcolepsy

Synonyms

6

Overview

Narcolepsy is a chronic brain disorder that involves poor control of sleep-wake cycles. People with narcolepsy have episodes of extreme daytime sleepiness and sudden, irresistible bouts of sleep (called "sleep attacks") that can occur at any time, and may last from seconds or minutes. Other signs and symptoms may include cataplexy (a sudden loss of muscle tone that makes a person go limp or unable to move); vivid dream-like images or hallucinations; and/or total paralysis just before falling asleep or after waking-up. Narcolepsy may have several causes, the most common being low levels of the neurotransmitter hypocretin (for various possible reasons). The disorder is usually sporadic but some cases are familial. There is no cure, but some symptoms can be managed with medicines and lifestyle changes.

Symptoms

The symptoms of narcolepsy most commonly begin between the ages of 10 and 25. They may worsen for the first few years, and then continue for life. They may include:

  • Hallucinations
  • Memory impairment
  • Muscle weakness
  • Reduced consciousness/confusion
  • Sleep disturbance
  • Abnormality of eye movement
  • Neurological speech impairment
  • Obesity
  • Sudden cardiac death
  • Abnormal rapid eye movement sleep
  • Autosomal dominant inheritance
  • Cataplexy
  • Excessive daytime sleepiness
  • Heterogeneous
  • Hypnagogic hallucinations
  • Hypnopompic hallucinations
  • Narcolepsy
  • Paroxysmal drowsiness

Causes

The exact cause of narcolepsy is unknown. There may be many causes. Most people with narcolepsy have low levels of the chemical hypocretin (hi-poe-KREE-tin). Hypocretin is an important neurochemical in your brain that helps regulate wakefulness and REM sleep.
Hypocretin levels are particularly low in those who experience cataplexy. Exactly what causes the loss of hypocretin-producing cells in the brain isn't known, but experts suspect it's due to an autoimmune reaction.

Research indicates a possible association with exposure to the H1N1 virus (swine flu) and a certain form of H1N1 vaccine that's currently administered in Europe. It's not yet known if the virus directly triggers narcolepsy or whether exposure to the virus increases the likelihood that someone will have narcolepsy.

In some cases, genetics may play a role.

Normal sleep pattern vs. narcolepsy:
The normal process of falling asleep begins with a phase called non-rapid eye movement (NREM) sleep. During this phase, your brain waves slow considerably. After an hour or so of NREM sleep, your brain activity changes, and REM sleep begins. Most dreaming occurs during REM sleep.

In narcolepsy, however, you may suddenly enter into REM sleep without first experiencing NREM sleep, both at night and during the day. Some of the characteristics of REM sleep, such as cataplexy, sleep paralysis and hallucinations, occur during wakefulness or drowsiness in people with narcolepsy.

Narcolepsy probably results from a combination of genetic and environmental factors, some of which have been identified, but many of which remain unknown.

In most cases of narcolepsy with cataplexy, and in some cases without cataplexy, sleep abnormalities result from a loss of particular brain cells (neurons) in a part of the brain called the hypothalamus. These cells normally produce chemicals called hypocretins (also known as orexins), which have many important functions in the body. In particular, hypocretins regulate the daily sleep-wake cycle. It is unclear what triggers the death of hypocretin-producing neurons in people with narcolepsy, although evidence increasingly points to an abnormality of the immune system.

Researchers have identified changes in several genes that influence the risk of developingnarcolepsy. The most well-studied of these genes is HLA-DQB1, which provides instructions for making part of a protein that plays an important role in the immune system. The HLA-DQB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-DQB1 gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. A variation of the HLA-DQB1 gene called HLA-DQB1*06:02 has been strongly associated with narcolepsy, particularly in people who also have cataplexy and a loss of hypocretins. Most people withnarcolepsy have the HLA-DQB1*06:02 variation, and many also have specific versions of other, closely related HLA genes. It is unclear how these genetic changes influence the risk of developing the condition.

Variations in several additional genes have also been associated with narcolepsy. Many of these genes are thought to play roles in immune system function. However, variations in these genes probably make only a small contribution to the overall risk of developing narcolepsy. Other genetic and environmental factors are also likely to influence a person's chances of developing this disorder. For example, studies suggest that bacterial or viral infections such as strep throat (streptococcus), colds, and influenza may be involved in triggering narcolepsy in people who are at risk.

Prevention

There is no known way to prevent narcolepsy. Treatment may reduce the number of attacks. Avoid situations that aggravate the condition if you are prone to attacks of narcolepsy.

Diagnosis

Narcolepsy is often diagnosed in adolescence and young adulthood, when falling asleep suddenly in school brings the problem to attention. However, for many people with narcolepsy, the disorder is not diagnosed for up to 10-15 years after symptoms first begin. The disorder may be misdiagnosed as various other conditions or psychological problems. While it is most easily recognized if all the major symptoms are reported, making the diagnosis based solely on symptoms is difficult. People often seek medical help for single symptoms that could be associated with other disorders, particularly epilepsy. In come cases, symptoms are not dramatically apparent for years.

Sleep studies are an essential part of the evaluation of people with possible narcolepsy. The combination of an overnight polysomnogram (PSG) followed by a multiple sleep latency test (MSLT) can provide strongly suggestive evidence of narcolepsy, while excluding other sleep disorders. Measurement of hypocretin levels in the cerebrospinal fluid (CSF) may further help to establish the diagnosis. People with narcolepsy often have extremely low levels of hypocretin in their CSF. In some cases, human leukocyte antigen (HLA) typing may be helpful.

Prognosis

Narcolepsy is lifelong (chronic) condition. It is not deadly, but it may be dangerous if episodes occur during driving, operating machinery, or similar activities. Narcolepsy can usually be controlled with treatment. Treating other underlying sleep disorders can improve symptoms of narcolepsy.

Treatment

There is currently no cure for narcolepsy, but some of the symptoms can be managed with medications and lifestyle changes.

Most affected people improve if they maintain a regular sleep schedule, usually 7.5 to 8 hours of sleep per night. Scheduled naps during the day also may help. Other measures that may help include participating in an exercise program; receiving emotional support and career or vocational counseling; and avoiding high-risk behaviors such as alcohol and drug use, which may make symptoms worse.[Common-sense measures should be taken to enhance sleep quality (such as avoiding heavy meals before bed time).

Treatment with medications involves the use of central nervous system (CNS) stimulants. These medications help reduce daytime sleepiness and improve this symptom in 65-85% of affected people. Two types of antidepressant drugs (tricyclics, and selective serotonin and noradrenergic reuptake inhibitors) are effective in controlling cataplexy in many people. Sodium oxybate (a strong sedative taken during the night) may also be used to treat narcolepsy.
Approved therapies:

  • Modafinil (Provigil) - FDA-approved indication: Improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy. 
  • Oxybate (Xyrem) - FDA-approved indication: Treatment of cataplexy associated with narcolepsy. 

Resources

Refer to Research Publications.