Narcolepsy

Definition

Narcolepsy is a disorder of the nervous system marked by excessive daytime sleepiness, uncontrollable sleep attacks, and cataplexy (a sudden loss of muscle tone, usually lasting up to half an hour). The American Psychiatric Association (APA) classifies narcolepsy as a sleep disorder in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders , or DSM-IV . The National Institute of Neurological Disorders and Stroke (NINDS) defines narcolepsy as a "disorder caused by the brain's inability to regulate sleep-wake cycles normally." The disorder is sometimes called Gélineau's syndrome because it was first identified in 1880 by the French neurologist Jean-Baptiste Gélineau. The word narcolepsy itself comes from two Greek words that together mean "seized by sleepiness."

Description

Narcolepsy is the second-leading cause of excessive daytime sleepiness (after obstructive sleep apnea). Persistent sleepiness and sleep attacks are the hallmarks of this condition. The sleepiness has been compared to the feeling of trying to stay awake after not sleeping for two or three days. It is not correct, however, to describe people with narcolepsy as sleeping longer or spending more time asleep in a 24-hour period than people without the disorder. Although patients with narcolepsy experience drowsiness and sleep attacks during the daytime, they also wake up frequently during the nighttime hours. For this reason, narcolepsy is more accurately described as a disorder of the normal boundaries between sleep and wakefulness.

People with narcolepsy fall asleep suddenly—anywhere, at any time, maybe even in the middle of a conversation. These sleep attacks can last from a few seconds to more than an hour. Depending on where they occur, they may be mildly inconvenient or even dangerous. Some people continue to function outwardly during the sleep episodes, such as talking or putting things away. But when they wake up, they have no memory of the event.

Narcolepsy is related to the deep, dreaming part of sleep known as rapid eye movement (REM) sleep. Normally when people fall asleep, they experience 80 to 100 minutes of non-REM sleep, which is then followed by about 20 minutes of REM sleep. People with narcolepsy, however, enter REM sleep immediately. In addition, REM sleep occurs inappropriately throughout the day in patients with narcolepsy.

Demographics

There has been considerable debate in the early 2000s over the incidence of narcolepsy. Some researchers think the disorder is underdiagnosed. According to NINDS, the disorder affects one American in every 2000, or about 135,000 people in the general United States population. However, the rates in other countries vary considerably, from one in 600 people in Japan to one in 500,000 in Israel. The reasons for these variations in different ethnic groups are not yet fully understood.

Males and females seem to experience this disorder at about the same rate.

Narcolepsy is a somewhat unusual disorder in terms of age distribution. Although the disorder has been identified in children as young as three years of age, most patients with narcolepsy are diagnosed either between the ages of ten and 25 or between the ages of 40 and 45. It is uncommon for a person to develop the signs of narcolepsy for the first time after age 55.

Causes and symptoms

Causes

In 1999 researchers identified the gene that causes narcolepsy on chromosome 12. The gene allows cells in the hypothalamus (the part of the brain that regulates sleep behavior) to receive messages from other cells. When this gene is abnormal, cells cannot communicate properly, and abnormal sleeping patterns develop. However, not everyone who has the gene develops narcolepsy; between 12 percent and 35 percent of the United States population is thought to carry the gene but only 0.02 percent develop the disorder. Narcolepsy sometimes clusters in families; first-degree relatives of a person diagnosed with the disorder have a 1 percent to 2 percent risk of developing narcolepsy themselves, or about 10 to 40 times the risk of a person in the general population.

In the late 1990s, three independent research groups discovered a neuropeptide system in the hypothalamus, the part of the brain that regulates body temperature and appetite. The newly discovered system, which has been called the hypocretinergic system, regulates sleep and wakefulness. The nerve cells, or neurons, in this part of the hypothalamus secrete substances known as hypocretins or orexins, which regulate the sleep/wake cycle in humans. There are two of these compounds, known as orexin-A and orexin-B, or as hypocretin-1 and hypocretin-2. As of the early 2000s, narcolepsy is thought to be an orexin deficiency syndrome; that is, it develops when a person's hypothalamus does not secrete enough orexins to keep the person from falling asleep at inappropriate times. Samples of cerebrospinal fluid taken from patients with narcolepsy contain little or no orexins. MRI scans of these patients indicate that there is some loss of brain tissue in the hypothalamus itself, suggesting that the neurons responsible for secreting orexins have died.

In a few cases, the first signs of narcolepsy are triggered by traumatic damage to the part of the brain that governs REM sleep or from a rapidly growing tumor that puts pressure on this region of the brain. It is also thought that the hormonal changes of puberty may affect this region of the brain in some people.

Symptoms

Narcolepsy is defined by four major symptoms:

• Excessive daytime sleepiness (EDS).
• Cataplexy, the most dramatic symptom of narcolepsy, affecting 75 percent of people with the disorder. During an attack of cataplexy, the person's knees buckle and the neck muscles go slack. In extreme cases, the person may become paralyzed and fall to the floor. This loss of muscle tone is temporary, lasting from a few seconds to half an hour, but it is frightening to other family members or friends. Attacks of cataplexy can occur at any time but are often triggered by such strong emotions as anger, joy, or surprise.
• Hypnagogic hallucinations, intense and sometimes terrifying experiences that occur as the person is falling asleep. The hallucinations may be either visual or auditory. They are thought to represent an intrusion of REM sleep/dreaming into the wakeful state.
• Sleep paralysis, a frightening inability to move shortly after awakening or dozing off.

When to call the doctor

The symptoms of narcolepsy in children below the age of ten are somewhat different from the classical signs of the disorder in adolescents and adults. They may include the following (in addition to cataplexy and daytime sleepiness):

• unexplained falls or dropping of objects
• night terrors
• moodiness and abrupt episodes of irritability
• restlessness and hyperactivity
• difficulty waking up in the morning

Children between the ages of ten and 12 frequently report falling asleep in school or being unable to pay attention during class. In some cases a sudden drop in the child's academic performance is the first indication of narcolepsy.

Parents who suspect that their child may have narcolepsy should consult a specialist (usually a pediatric neurologist) and have the child tested in a sleep clinic. Children with narcolepsy have often been misdiagnosed as having attention-deficit hyperactivity disorder, while adolescents have sometimes been misdiagnosed as having substance abuse or personality disorders . The sooner narcolepsy is correctly identified, the better the child's chances of maintaining normal academic and social development.

Diagnosis

Narcolepsy is a complex disorder, and it is not always easy to identify. It takes ten years on average for an individual to be correctly diagnosed. The diagnosis of younger patients is additionally complicated by the fact that children with narcolepsy rarely have all four of the classical symptoms of the disorder as described in adults. Most often, the first symptom in children is an overwhelming feeling of fatigue. After several months or years, cataplexy and the other classical symptoms of the disorder may appear.

The child's doctor will not be able to diagnose narcolepsy on the basis of a routine physical examination. If the child has experienced both excessive daytime sleepiness and cataplexy, a tentative diagnosis may be made on the basis of the patient's history. In addition, the doctor may give the child or adolescent a short self-administered list of eight questions known as the Epworth Sleepiness Scale (ESS). First published by an Australian doctor in 1991, the ESS asks the person to rate how likely they are to doze off or fall asleep in eight different situations from everyday life. A score above ten (maximum score is 24) generally indicates that the doctor should consider laboratory testing for narcolepsy.

Imaging studies are not helpful in diagnosing narcolepsy, although in some cases the doctor may order an MRI or CT scan to rule out a brain tumor or other abnormality in brain structure. Laboratory tests used to evaluate a person for narcolepsy include an overnight polysomnogram (a test in which sleep is monitored with electrocardiography, a video camera, and respiratory parameters). A multiple sleep latency test, which measures sleep latency (onset) and how quickly REM sleep occurs, may also be used. People who have narcolepsy usually fall asleep much more rapidly that people without the disorder, often in less than five minutes.

If the diagnosis is still questionable, a genetic blood test can reveal the existence of certain substances in people who have a tendency to develop narcolepsy. Positive test results suggest but do not prove that the person has narcolepsy. As of the early 2000s, the diagnosis of narcolepsy also can be confirmed by taking a sample of the patient's cerebrospinal fluid by a spinal tap and testing it for the presence of hypocretin-1. Patients with narcolepsy have no hypocretin-1 in their spinal fluid.

Treatment

There is no cure for narcolepsy. The disorder is neither progressive nor fatal, but it is chronic. The symptoms, however, can be managed with a combination of medications and lifestyle adjustments. Amphetamine-like stimulant drugs are often prescribed to control drowsiness and sleep attacks. Patients who do not like taking high doses of stimulants may choose to take smaller doses and make adjustments in their lifestyles, such as napping every couple of hours, to relieve daytime sleepiness. Antidepressants are also often effective in treating symptoms of abnormal REM sleep.

Newer nonamphetamine wake-promoting drugs are available to treat narcolepsy. These medications lack the unpleasant side effects of amphetamines, particularly jitteriness and anxiety . Modafinil (Provigil) is the most commonly prescribed of the newer psychostimulants. As of 2004, however, researchers do not know exactly how modafinil prevents the drowsiness associated with narcolepsy. Its most common side effect is headache . A study published in 2003 reported that modafinil appears to be safe for use in children.

With discovery of the gene that causes narcolepsy, researchers are hopeful that therapies can eventually be designed to relieve the symptoms of the disorder.

Alternative treatment

The botanical remedy yohimbe ( Pausinystalia yohimbe ) may be useful in promoting alertness. As with any herbal preparation or medication, however, individuals should check with their healthcare professional before taking the remedy to treat narcolepsy.

Nutritional concerns

Children with narcolepsy sometimes fall asleep while eating, but the disorder itself does not cause or lead to malnutrition . Adolescents should be advised to avoid tobacco, caffeine , and alcoholic beverages, as these substances can increase daytime sleepiness in patients with narcolepsy.

Prognosis

The symptoms of narcolepsy are more severe when they develop in children than when they emerge in adult life. Narcolepsy is not a degenerative disease, however, and patients do not develop other neurologic symptoms. In fact, older patients often report that their symptoms decrease in severity after age 60. Apart from falls or other accidents, narcolepsy does not affect a person's life expectancy. It can, however, severely interfere with a young person's ability to study, play , participate in sports and other social activities, and develop close relationships with others. The sooner it is diagnosed and treated, the better the child's outlook for a happy and productive adult life.

Prevention

There is no way to prevent narcolepsy as of the early 2000s.

Parental concerns

Narcolepsy can affect a family in a number of ways before it is diagnosed. Younger children are at risk of injuring themselves by falling, and adolescents with driving privileges are at high risk of automobile accidents. Poor performance in school and difficulty making friends as a result of irritability or embarrassment over sleep attacks can have a lasting impact on a child's chances of preparation for college or the choice of a challenging and satisfying line of work. In many cases the child is accused of being lazy or stupid, which can have devastating effects on his or her self-esteem . Misdiagnoses can lead to inappropriate treatment and psychological depression for the affected child. In addition, sleep attacks and cataplexy can be frightening to other family members who witness them.

Narcolepsy can be particularly stressful for a family when the affected child reaches adolescence , because of peer pressure to experiment with smoking and recreational drugs, and because of resentment about restrictions on learning to drive or use of the family car. Families with a child diagnosed with narcolepsy should consider joining a support group for people affected by the disorder.

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision. Washington, DC: American Psychiatric Association, 2000.

"Sleep Disorders: Narcolepsy." Section 14, Chapter 173 in The Merck Manual of Diagnosis and Therapy. Edited by Mark H. Beers, and Robert Berkow. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

PERIODICALS

Beuckmann, C. T., and M. Yanagisawa. "Orexins: From Neuropeptides to Energy Homeostasis and Sleep/Wake Regulation." Journal of Molecular Medicine 80 (June 2002): 329–42.

Ivanenko, A., R. Tauman, and D. Gozal. "Modafinil in the Treatment of Excessive Daytime Sleepiness in Children." Sleep Medicine 4 (November 2003): 579–82.

Kotagal, S. "Sleep Disorders in Childhood." Neurologic Clinics 21 (November 2003): 961–81.

Ohayon, M. M., et al. "Prevalence of Narcolepsy Symptomatology and Diagnosis in the European General Population." Neurology 58 (June 25, 2002): 1826–33.

Silvestri, A. J., et al. "The Central Nucleus of the Amygdala and the Wake-Promoting Effects of Modafinil." Brain Research 941 (June 21, 2002): 43–52.

ORGANIZATIONS

American Sleep Disorders Association. 1610 14th St. NW, Suite 300, Rochester, MN 55901. Web site: http://www.sleepapnea.org.

Narcolepsy Network. PO Box 42460, Cincinnati, OH 45242. Web site: http://www.narcolepsynetwork.org.

National Center on Sleep Disorders Research. Two Rockledge Centre, 6701 Rockledge Dr., Bethesda, MD 20892. Web site: http://www.nhlbi.nih.gov/health/public/sleep.

National Institute of Neurological Disorders and Stroke (NINDS). National Institutes of Health. 9000 Rockville Pike, Bethesda, MD 20892. Web site: http://www.ninds.nih.gov .

National Sleep Foundation. 1522 K St., NW, Suite 500, Washington, DC 20005. Web site: http://www.sleepfoundation.org.

Stanford Center for Narcolepsy. 1201 Welch Rd-Rm P-112, Stanford, CA 94305. Web site: http://blackdogstudieos.com/portfolio/Web/narcolepsy.

University of Illinois Center for Narcolepsy Research. 845S. Damen Ave., Chicago, IL 60612. Web site: http://www.uic.edu/depts./cnr/

WEB SITES

Baker, Matthew J., and Selim R. Benbadis. "Narcolepsy." eMedicine , October 4, 2004. Available online at http://www.emedicine.com/neuro/topic522.htm (accessed January 14, 2005).

OTHER

National Institute of Neurological Disorders and Stroke (NINDS). Narcolepsy Fact Sheet . Bethesda, MD: NINDS, 2003.

Michelle Lee Brandt