What is narcolepsy?

Causes and Symptoms

Narcolepsy (narco meaning “numbness” and lepsy meaning “seizure”) consists primarily of attacks of irresistible sleepiness in the daytime. The sleepiness is extreme; it has been described as the feeling that most people would experience if they tried to add columns of numbers in the middle of the night after forty-eight hours without sleep
.

The narcoleptic’s day is broken up by a series of brief and repetitive sleep attacks, perhaps even two hundred attacks in a single day. These transient, overpowering attacks of sleepiness may last from a few seconds to thirty minutes, with an average spell lasting two minutes. It is excruciatingly difficult, and frequently impossible, to ignore the urge to sleep, no matter how inconvenient or inappropriate. Narcoleptics typically fall asleep suddenly, on the job, in conversation, standing up, and even while eating, driving, or making love.

These sleep attacks result from an abrupt failure in resisting sleep, as opposed to a sudden surge in sleepiness, because narcoleptics are actually sleepy all day. The misconception that their daytime sleepiness is caused by insufficient nighttime sleep prompts undiagnosed patients to spend inordinately long hours in bed. Narcoleptics will be sleepy during the day regardless of how much sleep they get at night.

One of the most prominent and troubling features of narcolepsy is cataplexy, a sudden loss of muscle tone that causes the person to collapse. Cataplexy, the second most common symptom of narcolepsy, is experienced by approximately 70 percent of those diagnosed with the disorder. It occurs during the daytime while the person is awake. It may involve all the muscles at once or only a select few, so the severity may range from total collapse to the ground to partial collapse of a limb or the jaw. The cataplectic sometimes remains conscious, able to think, hear, and see, although vision may be blurred. At other times, there is a brief loss of consciousness, associated with an experience of dreaming. Although most attacks of cataplexy last less than a minute, occasionally they go on for several minutes or more. Cataplexy is often triggered by enjoyable feelings, laughter, or excitement during which the person suddenly crumples into a heap. For other patients, a strong negative emotion, such as fear or anger, precipitates an attack.

Many narcoleptics notice the symptom of excessive daytime sleepiness (EDS) for as much as a year before the onset of cataplexy. After many years of experiencing cataplexy, some patients find that less emotional stimulus is required to induce the muscle collapse and that increasingly more muscles are involved. Others find that this symptom diminishes, possibly because they have become adept at anticipating and avoiding the situations that trigger attacks. It has been noted that other hypersomnias—that is, other diseases of excessive sleepiness—do not include cataplexy; only narcoleptics suffer from this embarrassing and troubling symptom of muscle collapse.

Many narcoleptics also experience hypnogogic hallucinations, dreams that intrude into the waking state. In normal sleep, dreaming generally occurs approximately ninety minutes after falling asleep; narcoleptics begin their sleeping episodes with vivid dreams. These hallucinations are extremely realistic and often violent. The patient sees someone else in the room or hears someone calling his or her name, for the hallucinations are nearly always visual and are usually auditory. The vivid sights, sounds, and feelings characteristic of hypnogogic hallucinations are thought to occur while the person is awake, both during the day and just at the edges of nighttime sleep. Since narcoleptics typically fall asleep dozens if not hundreds of times a day, they can experience these disturbing hallucinations with great frequency.

Narcoleptics may suffer from another frightening symptom: sleep paralysis. This condition occurs at the beginning or end of sleep and renders immobile virtually every voluntary muscle, except those around the eyes. During sleep paralysis, the mind is awake and one is aware of the external surroundings, but the muscles refuse to move. The paralysis usually lasts only a few seconds, but it may continue for as long as twenty minutes. Sleep researchers find that almost everyone has an episode of sleep paralysis that lasts a few seconds some time during his or her lifetime. When the paralysis continues for more than a few seconds, however, it is usually a sign of narcolepsy. Although either sleep paralysis or hypnogogic hallucinations alone are distressing enough, they may happen simultaneously. However, it is estimated that only 10 to 25 percent of narcoleptics experience all four major symptoms of this sleep disorder.

Because of their frequent, irresistible sleep attacks, narcoleptics often wobble back and forth between sleep and wakefulness in a state that has been likened to sleepwalking and is termed automatic behavior. When in this state, the person seems to behave normally but later does not remember extended periods of time. For example, narcoleptics might find themselves in a different building or several exits farther down a highway than they last remembered. Obviously, automatic behavior is very anxiety-producing; it is very troubling to narcoleptics to be unable to remember what they have done in the minutes or hours that have just passed.

In addition to these memory difficulties, some narcoleptics experience constant eye fatigue, difficulty focusing, and double vision. They also have a higher incidence of the heart abnormality called mitral valve prolapse, which affects blood flow to the left ventricle.

Although narcolepsy is an illness of excessive daytime sleepiness, the nighttime sleep of those afflicted is far from normal as well. It is often troubled by restlessness and frequent awakenings, which are brief or may last for hours. Patients also experience many nightmares. Many narcoleptics talk, cry out, or thrash about periodically during the night.

One narcoleptic in ten has the added complication of suffering from sleep
apnea. This sleep disorder consists of recurrent interruptions in breathing during sleep. This further disturbance of nighttime sleep aggravates the narcoleptic’s tendency to excessive daytime sleepiness.

Narcolepsy was once thought to be extremely rare. By the late twentieth century, however, it became one of the most diagnosed sleep disorders, behind insomnia, obstructive sleep apnea, and restless legs syndrome. Nevertheless, many medical officials consider narcolepsy to be an underdiagnosed condition.

Males and females are equally affected by narcolepsy. Although the disorder has been diagnosed in a five-year-old, its symptoms most frequently appear for the first time during adolescence. In about 75 percent of cases, the attacks begin between the ages of fifteen and twenty-five; only 5 percent of cases begin before the age of ten. Onset is rare after the age of forty; if narcolepsy seems to appear in an older person, it has probably existed undiagnosed for years. Sleep researchers believe that the extra need for sleep characteristic of adolescence may make this stage of development particularly vulnerable for the onset of narcolepsy. Thus, this disorder may typically begin in adolescence because it is somehow triggered by the brain changes associated with sexual maturation.

While many members of the general population have scattered episodes of excessive daytime sleepiness, they are not considered narcoleptics. It is not until a person has one to several attacks each day that narcolepsy is suspected.

Treatment and Therapy

Narcolepsy is a disease of the nervous system. Although incurable, it can be successfully treated with various medications once it has been diagnosed. The diagnosis of narcolepsy, however, is often slow to occur. The average interval between the first appearance of symptoms and diagnosis is often as long as thirteen years. Because early symptoms are usually mild, narcoleptics typically spend years wondering whether they are sick or whether they merely lack initiative. They are often called lazy because they repeatedly nap during the day and are lethargic even when awake. Diagnosis is made more difficult by the wide range of severity of symptoms. For example, excessive daytime sleepiness may trouble a person for ten or twenty years before cataplexy appears. Patients may even occasionally experience a temporary or partial remission in their condition. Narcoleptics often fight off their sleep attacks by ingesting large amounts of caffeine and never realize that they have an actual disease until years later.

If narcolepsy is suspected, a polysomnographic study is done at a sleep disorders center to confirm the diagnosis. The most reliable confirmation of narcolepsy can be obtained by what is called the multiple sleep latency test (MSLT). The MSLT is easy, convenient, inexpensive, and very informative. The person is given four or five opportunities to lie down and fall asleep during the daytime. Normal individuals take fifteen to thirty minutes to fall asleep. In the MSLT, falling asleep in less than five minutes is considered abnormal. Those afflicted with narcolepsy always fall asleep in less than five minutes and often within a minute. The maintenance of wakefulness test (MOWT) is also used in the confirmation of narcolepsy. In the MOWT, the person is kept all day in a comfortable reclining position. Polysomnography is used to measure the patient’s ability to stay awake and how many times he or she falls asleep.

Along with the MSLT and the MOWT, a thorough physical examination is needed to discover if the person has some other disorder that can mimic narcolepsy; an underactive thyroid gland, diabetes, chronic low blood sugar, anemia, and a malfunctioning liver can each cause excessive daytime sleepiness. Similarly, drug use, poor nutrition, emotional frustration, dissatisfaction, or poor motivation can also result in the type of sleepiness that a narcoleptic experiences.

When the diagnosis of narcolepsy is confirmed, treatment usually consists of stimulant medications such as dextroamphetamine, pemoline, or methylphenidate (Ritalin) during the daytime. These stimulant drugs can increase alertness and cut down the number of sleep attacks from perhaps several per day to several per month. Unfortunately, patients can quickly develop tolerance to these medications.

Even on low doses, some patients become irritable, aggressive, or nervous, or they may develop obesity and sexual problems. It is very important, therefore, to monitor a narcoleptic carefully, determining the lowest effective dose and the best times of day to take it. It may be months before the positive effects of drug therapy are fully experienced. The MSLT will often be given on a day that one takes the medication and on another when it is not taken, in order to evaluate the success of a given treatment.

Because specific drug and dosage schedules may have to be altered frequently, patients may repeatedly have to face drug withdrawal symptoms such as intensified sleepiness and disturbing dreams. To prevent adverse reactions, narcoleptics must often avoid certain foods and common medications. Their use of stimulant drugs may even be viewed as morally wrong, in these days of widespread drug abuse, by neighbors or coworkers who do not comprehend that narcolepsy is a disabling disease.

If cataplexy is present, medications other than amphetamines or Ritalin are required and useful. The class of drugs called tricyclic antidepressants, including protriptyline and imipramine, or the class of drugs called monoamine oxidase inhibitors may alleviate cataplexy. These medicines can often reduce attacks—for example, from three a day to three a month. In addition, effective treatment for cataplexy usually also relieves sleep paralysis and hypnogogic hallucinations.

Since the development of tolerance is common and these drugs can aggravate the symptom of sleepiness, determining the best timing and dose is critical. Another side effect of cataplexy drugs is impaired sexual function in males. Some men even discontinue these medications periodically for a day or two in order to sustain sexual relations. In addition, none of the drugs used for any symptoms of narcolepsy are safe to take during pregnancy.

In some cases, narcoleptics can be treated without medication if they carefully space naps during the day to relieve excessive sleepiness. Patients keep nap diaries to rate their alertness at regular intervals during the day. They then schedule short, strategically timed naps during those daytime periods when their sleep attacks are most likely to occur.

Naps are particularly valuable in treating children with narcolepsy because the consequences of a lifetime of medication on their development or on the course of their illness is unknown. Some children who show hyperactive behavior actually have narcolepsy; they are working frantically to overcome their persistent sleepiness and to keep themselves awake. Children with narcolepsy may also justifiably fear falling asleep, day or night, because of hallucinations and sleep paralysis.

It is evident that supportive counseling must be a strong component of treatment, whatever the patient’s age. Sensitive medical monitoring can offer narcoleptics a measure of satisfactory daily living, but the use of stimulants to improve alertness may also make them more aware of their limitations and, therefore, more frustrated. Depression is not the cause of narcolepsy but may result primarily from the disruption in their lives and the feeling that they are denied the right to a “normal” life. Their constant sleepiness engenders feelings of inferiority and inadequacy. Narcoleptics usually refrain from mentioning their hallucinations and try to hide their automatic behavior for fear of being labeled insane. Loss of work, broken marriages, and social isolation are often witnesses to the crippling effects of narcolepsy.

Of all the people with narcolepsy seen at major sleep disorders centers, more than one-half have been completely disabled with respect to regular employment by the age of forty. With part-time, homebound, or self-employment, however, most narcoleptics can gain self-respect and help support themselves through work that is safe and tailored to their needs. They must be given tasks that can be divided into parts performed in relatively short time periods.

Drug and nap therapy can do little for narcoleptics without education of their families, friends, acquaintances, employers, and coworkers about the reality of this neurological disease. Most people find it hard to accept the notion that sleepiness cannot be controlled and insist that narcoleptics could be more alert if they tried harder. Narcoleptics are often stigmatized as slackers or incompetents, or assumed to be drug abusers or closet drinkers. It is most important that patients and all the people in their lives comprehend that excessive daytime sleepiness is not the patients’ “fault.”

Further help for narcoleptics seems to lie in animal studies, which may fill in many important pieces of the narcolepsy puzzle. The effects of the disease on behavior, the way in which it is inherited, and the benefits and risks of specific drugs continue to be evaluated in narcoleptic dogs.

Perspective and Prospects

Once viewed as “all in the mind,” narcolepsy is now recognized as a neurological disorder. Its origin is unknown, but research has already discovered evidence of possible causes. An understanding of narcolepsy both depended on and advanced the understanding of normal sleep and of other sleep disorders. Scientists define sleep as a reduction in awareness of and interaction with the environment, lowered movement and muscle activity, and partial or complete suspension of voluntary behavior and consciousness.

Although narcolepsy was named and described in 1880, it could not be genuinely studied until the 1930s, when the electroencephalograph (EEG) was developed to record brain activity during the various stages of sleep. By the 1940s, this advancement led to a description of the narcoleptic tetrad, the four usual symptoms of narcolepsy: excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnogogic hallucinations.

In the 1950s, narcolepsy still only rated a paragraph in one neurology textbook, which mistakenly called it a rare variety of epilepsy. A major discovery occurred in 1960: Narcoleptics bypass the normal stages of light and deep sleep and fall directly into rapid eye movement (REM) sleep. Thus, sudden-onset REM period (or SOREMP) became the major distinguishing feature of this brain disorder.

It was soon noted that relatives of narcoleptics are sixty times more likely to have the disease than members of the general population. Clearly, there is a hereditary factor involved, and geneticists have joined the hunt for narcolepsy’s cause. The hereditary aspects of the disease are particularly important to counselors because parents with narcolepsy may feel guilty if their child develops it. (Indeed, some patients abandon plans to have children.) Geneticists have found a gene that may be responsible for narcolepsy. Since the gene produces an antigen called DR2 on patients’ white blood cells, which is not found in nonnarcoleptics, immunologists have also begun to search for the origins of narcolepsy.

Rapid advances have been made in the last few years in determining the cause of narcolepsy. The disease is thought to arise from a biochemical imbalance in the brain that disturbs the mechanism that activates the on/off cycle of sleep. Biochemists are studying the possible relationship of various brain chemicals called neurotransmitters to narcolepsy. A defect in the way in which the body produces or uses dopamine, acetylcholine, or some other neurotransmitter is suspected to precipitate narcolepsy, which never spontaneously disappears once it is developed. The newest discovery has been the finding of abnormalities in the structure and function of a particular group of nerve cells, called hypocretin neurons, in the brains of patients with narcolepsy. The molecules implicated in narcolepsy are neuropeptides known as orexins (originally described as hypocretins). Researchers discovered that changes in the hypocretin
receptor 2 and preprohypocretin genes are able to produce narcolepsy in animals. In one study involving nine human subjects, hypocretin could not be
detected in seven of the subjects. Other studies have produced hypocretin knockout mice, which have symptoms that are quite similar to those found in human narcoleptics. Hypocretins have been found to occur normally in the regions of the central nervous system that appear to be involved in the regulation of sleep. An autosomal recessive mutation has been discovered in narcoleptic dogs that alters the hypocretin receptor 2 gene. In humans, a similar disruption or deficiency in hypocretin is associated with most cases of narcolepsy, although it is still unclear as to what underlies the exact genetic predisposition to the disease. Scientists speculate that they one day may cure narcolepsy or reduce its effects with drugs mimicking secretions of the missing nerve cells or even with brain-cell transplants.

Two interesting discoveries may help in the diagnosis of narcolepsy even before the classical clinical symptoms develop. There is some evidence that REM sleep is entered with abnormal rapidity years before the disorder develops. The drug physostigmine salicylate has no effect on normal dogs but elicits cataplexy in puppies with narcolepsy. Both these discoveries may be useful in screening the children of narcoleptics.

Because narcolepsy involves the fundamental processes of sleep, the combined efforts of neuroscientists, geneticists, biochemists, immunologists, and other scientists to unravel its mysteries will continue to yield important information about the basic mechanism of sleep—that state in which humans spend almost one-third of their lives.

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