Basic Facts About Narcolepsy

Narcolepsy is a potentially disabling, lifelong neurological condition estimated to afflict about 1 in every 2000 people in the United States. Although it is not rare, narcolepsy is often misdiagnosed, or diagnosed years after the symptoms first appear. This disorder is best characterized as an inability of the nervous system to maintain the boundaries between wakefulness and sleep. During usual waking hours, people experience periods when sleep involuntarily encroaches into wakefulness. Most people with this disorder also experience awakenings and restlessness during their usual nighttime sleeping hours. There is no evidence that narcolepsy is a mental disorder or has a psychological basis.

Symptoms

The two primary symptoms of narcolepsy are excessive daytime sleepiness and cataplexy. People with narcolepsy are unable to resist falling asleep and do so regardless of the number of hours slept the previous night. The excessive daytime sleepiness experienced by people with narcolepsy has been described as being like trying to stay awake after going 72 hours without sleep. Frequently, people with narcolepsy fall asleep at inappropriate times, for example while eating or in the middle of a conversation.

Cataplexy is the sudden loss of strength in voluntary muscles triggered by emotions such as laughter, excitement, or anger, and occurs when the normal bodily processes that usually occur during rapid eye movement (REM) sleep intrude into wakefulness. The cataplectic attack, which can last from several seconds to several minutes, can range from partial muscle weakness, often in the face or neck, to a complete loss of muscle control in the arms and legs.

Several other symptoms commonly occur with narcolepsy:

• Sleep attacks are defined as short, irresistible episodes of sleep during the day. People with narcolepsy may experience short 10-20 minutes of sleep from which they awaken feeling refreshed, but the intense feelings of sleepiness return within 1-2 hours.
• Sleep paralysis is the inability to move while going to sleep or waking up.
• Hypnagogic/hynopompic hallucinations (when falling asleep or waking up, respectively) are intense visual or auditory experiences at the beginning or end of a sleep period that are hard to distinguish from reality, and are sometimes terrifying. Both sleep paralysis and hypnagogic/hypnopompic hallucinations are also associated with the intrusion of REM sleep physiology into wakefulness.
• Disturbed nighttime sleep is manifested as tossing and turning in bed, leg jerking, nightmares, and frequent awakenings.

The symptoms of narcolepsy are usually first noticed during the teenage or young adult years although it can strike at any age. Most often the initial symptom to appear is excessive daytime sleepiness. Later, after several months or even years, cataplexy or one or more of the other symptoms frequently develops. Different individuals experience wide variations in the development, number, and severity of their symptoms. Family, friends, educators, employers, and even those with narcolepsy often have a hard time understanding the problem and just what is happening.

Pathophysiology of Narcolepsy

While the exact cause of narcolepsy is not clearly understood, recent findings indicate that it may be associated with a deficit in the production of the hypocretins, hypocretin-1 and hypcretin-2 (also known as orexins, or orexin-a and orexin-b). The hypocretins are peptides that are produced by genes located in the lateral hypothalamus of the human brain. Originally, the hypocretins were thought to regulate appetite, and now are thought also to be major sleep moderating substances.

Hypocretin-producing cells have been found to be reduced or absent in the brains of people with narcolepsy. Additionally, when the cerebrospinal fluid was examined by a spinal tap by Dr. Mignot and his colleagues at Stanford, hypocretin-1 was found at levels that were low to undetectable in over 90% the people with narcolepsy who also experienced cataplexy compared to normal controls. (At present, the hypocretins cannot be measured in blood or other peripheral body tissue.) However, low hypocretin-1 spinal fluid levels have also been found in people with other neurological disorders so whether or not this is a specific cause of narcolepsy remains unclear. At present, hypocretin-1 levels in people who have narcolepsy and do not experience cataplexy need to be investigated.

Genetics of Narcolepsy

A predisposition for narcolepsy to run in families is low since most people with this disorder have no other family members with narcolepsy. People who do have a first-degree relative with this disorder (mother, sister, etc.) only have a 1-2% chance of developing narcolepsy. Furthermore, the way the predisposition might be inherited remains unknown and, while it is low when a first degree relative does have narcolepsy, the predisposition to develop the disorder is still 20-40 times higher than in the general population.

Human narcolepsy has been found to be strongly associated with the presence of a Human Leukocyte Antigen (HLA), molecules produced by HLA genes. The HLA antigens are found on the surface of white blood cells; they are responsible for coordinating and regulating the immune system. Over 90% of people with narcolepsy-cataplexy have been found to have HLA-DQB1*0602, a specific subtype of the HLA-DQ molecule. HOWEVER, the presence of this antigen cannot be used to diagnose narcolepsy because over 20% of the general population is also positive for this antigen.

Many autoimmune diseases, disorders where the immune system turns on its own body, have been found to be associated with a specific HLA subtype. The HLA-DQ subtype associated with narcolepsy, and the absence of hypocretin-producing cells in the brains of people with this disorder suggest that narcolepsy may be an autoimmune disorder. However, the environmental factor(s) or event(s) responsible for an autoimmune attack on the hypocretin-producing cells of the hypothalamus has yet to be identified.

Diagnosis of Narcolepsy

The 1997 edition of the International Classification of Sleep Disorders - Revised lists certain criteria that need to be present in order for the diagnosis of narcolepsy to be made. These criteria are as follows:

1. A complaint of excessive sleepiness or sudden muscle weakness.
2. Recurrent daytime naps (lapses into sleep) that have occurred almost daily for the past 3 months.
3. Sudden bilateral loss of postural muscle tone that occurs with intense emotion (cataplexy).
4. Associated features:
   1. Sleep paralysis
   2. Hypnagogic hallucinations
   3. Automatic behaviors – periods of inappropriate behavior (for example, the person puts salt in the refrigerator) for which the person has no memory
   4. Disrupted nighttime sleep
5. Polysomnography [sleep and nap (Mulitple Sleep Latency Test, MSLT) studies show one or more of the following:
   1. Sleep latency less than 10 minutes
   2. REM (rapid eye movement) sleep latency less than 20 minutes
   3. The MSLT demonstrates a mean sleep latency (time to falling asleep during 4-5 nap opportunities) of less than 5 minutes and 2 or more sleep-onset REM periods (REM sleep occurs within 15 minutes of falling asleep)
6. HLA typing demonstrates the person is positive for DQB1*0602 or DR2.
7. No other medical or mental disorder can account for the symptoms.
8. Another sleep disorder (if present) is not the primary cause of the symptoms.

MINIMUM CRITERIA: B plus C, or A plus D plus E plus G.

Excessive daytime sleepiness is a non-specific symptom that can be present in a wide variety of situations or conditions so the presence of this symptom is not diagnostic of narcolepsy. Some sleep professionals believe that cataplexy must be present for the diagnosis of narcolepsy to be made. Cataplexy is a symptom that may not be recognized by the person experiencing it, and is difficult to elicit clinically by a sleep professional. Additionally, the diagnostic criteria have been criticized for not being specific. Currently, the diagnostic criteria are under review by the American Academy of Sleep Medicine and may be published in revised form in the near future.

Treatment

There is no known cure for narcolepsy. Narcolepsy symptoms can be treated with varying degrees of success with medications and adjustments of lifestyle. Because of differences in the symptoms experienced and how the person with narcolepsy responds to medication, adjustments in lifestyle may be necessary.

For detailed information on you may wish to consult a statement from the American Academy of Sleep Medicine entitled, "Practice Parameters for the Treatment of Narcolepsy: An Update for 2000". To obtain the full text, click here. The obtain a summary statement from the National Guideline Clearinghouse, click here.

Funds for research are needed to advance knowledge about narcolepsy, and to test the effectiveness of methods of treatment and management.