Understanding Narcolepsy, Part 2

How is Narcolepsy Diagnosed?

Narcolepsy is not definitively diagnosed in most patients until 10 to 15 years after the first symptoms appear. This unusually long lag-time is due to several factors, including the disorder's subtle onset and the variability of symptoms. As important, however, is the fact that the public is largely unfamiliar with the disorder, as are many health professionals. When symptoms initially develop, people often do not recognize that they are experiencing the onset of a distinct neurological disorder and thus fail to seek medical treatment.

A clinical examination and exhaustive medical history are essential for diagnosis and treatment. However, none of the major symptoms is exclusive to narcolepsy. EDS-the most common of all narcoleptic symptoms-can result from a wide range of medical conditions, including other sleep disorders such as sleep apnea, various viral or bacterial infections, mood disorders such as depression, and painful chronic illnesses such as congestive heart failure and rheumatoid arthritis that disrupt normal sleep patterns. Various medications can also lead to EDS, as can consumption of caffeine, alcohol, and nicotine. Finally, sleep deprivation has become one of the most common causes of EDS among Americans.

This lack of specificity greatly increases the difficulty of arriving at an accurate diagnosis based on a consideration of symptoms alone. Thus, a battery of specialized tests, which can be performed in a sleep disorders clinic, is usually required before a diagnosis can be established.

Two tests in particular are considered essential in confirming a diagnosis of narcolepsy: the polysomnogram (PSG) and the multiple sleep latency test (MSLT). The PSG is an overnight test that takes continuous multiple measurements while a patient is asleep to document abnormalities in the sleep cycle. It records heart and respiratory rates, electrical activity in the brain through electroencephalography (EEG), and nerve activity in muscles through electromyography (EMG). A PSG can help reveal whether REM sleep occurs at abnormal times in the sleep cycle and can eliminate the possibility that an individual's symptoms result from another condition.

The MSLT is performed during the day to measure a person's tendency to fall asleep and to determine whether isolated elements of REM sleep intrude at inappropriate times during the waking hours. As part of the test, an individual is asked to take four or five short naps usually scheduled 2 hours apart over the course of a day. As the name suggests, the sleep latency test measures the amount of time it takes for a person to fall asleep. Because sleep latency periods are normally 10 minutes or longer, a latency period of 5 minutes or less is considered suggestive of narcolepsy. The MSLT also measures heart and respiratory rates, records nerve activity in muscles, and pinpoints the occurrence of abnormally timed REM episodes through EEG recordings. If a person enters REM sleep either at the beginning or within a few minutes of sleep onset during at least two of the scheduled naps, this is also considered a positive indication of narcolepsy.

What Treatments are Available?

Narcolepsy cannot yet be cured. But EDS and cataplexy, the most disabling symptoms of the disorder, can be controlled in most patients with drug treatment. Often the treatment regimen is modified as symptoms change.

For decades, doctors have used central nervous system stimulants-amphetamines such as methylphenidate, dextroamphetamine, methamphetamine, and pemoline-to alleviate EDS and reduce the incidence of sleep attacks. For most patients these medications are generally quite effective at reducing daytime drowsiness and improving levels of alertness. However, they are associated with a wide array of undesirable side effects so their use must be carefully monitored. Common side effects include irritability and nervousness, shakiness, disturbances in heart rhythm, stomach upset, nighttime sleep disruption, and anorexia. Patients may also develop tolerance with long-term use, leading to the need for increased dosages to maintain effectiveness. In addition, doctors should be careful when prescribing these drugs and patients should be careful using them because the potential for abuse is high with any amphetamine.

In 1999, the FDA approved a new non-amphetamine wake-promoting drug called modafinil for the treatment of EDS. In clinical trials, modafinil proved to be effective in alleviating EDS while producing fewer, less serious side effects that do ampehtmines. Headache is the most commonly reported adverse effect. Long-term use of modafinil does not appear to lead to tolerance.

Two classes of antidepressant drugs have proved effective in controlling cataplexy in many patients: tricyclics (including imipramine, desipramine, clomipramine, and protriptyline) and selective serotonin reuptake inhibitors (including fluoxetine and sertraline). In general, antidepressants produce fewer adverse effects than do amphetamines. But troublesome side effects still occur in some patients, including impotence, high blood pressure, and heart rhythm irregularities.

What Behavioral Strategies Help People Cope With Symptoms?

None of the currently available medications enables people with narcolepsy to consistently maintain a fully normal state of alertness. Thus, drug therapy should be supplemented by various behavioral strategies according to the needs of the individual patient.

To gain greater control over their symptoms, many patients take short, regularly scheduled naps at times when they tend to feel sleepiest. Adults can often negotiate with employers to modify their work schedules so they can take naps when necessary and perform their most demanding tasks when they are most alert. The Americans with Disabilities Act requires employers to provide reasonable accommodations for all employees with disabilities. Children and adolescents with narcolepsy can be similarly accommodated through modifying class schedules and informing school personnel of special needs, including medication requirements during the school day.

Improving the quality of nighttime sleep can combat EDS and help relieve persistent feelings of fatigue. Among the most important common-sense measures patients can take to enhance sleep quality are: (1) maintaining a regular sleep schedule; (2) avoiding alcohol and caffeine-containing beverages for several hours before bedtime; (3) avoiding smoking, especially at night; (4) maintaining a comfortable, adequately warmed bedroom environment; and (5) engaging in relaxing activities such as a warm bath before bedtime. Exercising for at least 20 minutes per day at least 4 or 5 hours before bedtime also improves sleep quality and can help people with narcolepsy avoid gaining excess weight.

Safety precautions, particularly when driving, are of paramount importance for all persons with narcolepsy. Although the disorder, in itself, is not fatal, EDS and cataplexy can lead to serious injury or death if left uncontrolled. Suddenly falling asleep or losing muscle control can transform actions that are ordinarily safe, such as walking down a long flight of stairs, into hazards. People with untreated narcoleptic symptoms are involved in automobile accidents roughly 10 times more frequently than the general population. However, accident rates are normal among patients who have received appropriate medication.

Finally, patient support groups frequently prove extremely beneficial because people with narcolepsy may become socially isolated due to embarrassment about their symptoms. Many patients also attempt to avoid experiencing strong emotions, since humor, excitement, and other intense feelings can trigger cataplectic attacks. Moreover, because of the widespread lack of public knowledge about the disorder, people with narcolepsy are too often unfairly judged to be lazy, unintelligent, undisciplined, or unmotivated. Such stigmatization often increases the tendency toward self-imposed isolation. The empathy and understanding that support groups offer people can be crucial to their overall sense of well-being and provide them with a network of social contacts who can offer practical help and emotional support.

What Research is Being Done?

Within the Federal government, the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH), has primary responsibility for sponsoring research on neurological disorders. As part of its mission, the NINDS supports research on narcolepsy and other sleep disorders with a neurological basis through grants to major medical institutions across the country.

Within the National Heart, Lung, and Blood Institute, also a component of the NIH, the National Center on Sleep Disorders Research (NCSDR) coordinates Federal government sleep research activities and shares information with private and nonprofit groups. NCSDR staff also promote doctoral and postdoctoral training programs, and educates the public and health care professional about sleep disorders. For more information, go to the NCSDR website at http://www.nhlbi.nih.gov/about/ncsdr/index.htm.

NINDS-sponsored researchers are conducting studies devoted to further clarifying the wide range of genetic factors-both HLA genes and non-HLA genes-that may cause narcolepsy. Other scientists are conducting investigations using animal models to identify neurotransmitters other than the hypocretins that may contribute to disease development. A greater understanding of the complex genetic and biochemical bases of narcolepsy will eventually lead to the formulation of new therapies to control symptoms and may lead to a cure. Researchers are also investigating the modes of action of wake-promoting compounds to widen the range of available therapeutic options.

Scientists have long suspected that abnormal immunological processes may be an important element in the cause of narcolepsy, but until recently clear evidence supporting this suspicion has been lacking. NINDS-sponsored scientists have recently uncovered evidence demonstrating the presence of unusual, possibly pathological, forms of immunological activity in narcoleptic dogs. These researchers are now investigating whether drugs that suppress immunological processes may interrupt the development of narcolepsy in this animal model.

Recently there has been a growing awareness that narcolepsy can develop during childhood and may contribute to the development of behavior disorders. A group of NINDS-sponsored scientists is now conducting a large epidemiological study to determine the prevalence of narcolepsy in children aged 2 to 14 years who have been diagnosed with attention-deficit hyperactivity disorder.

Finally, the NINDS continues to support investigations into the basic biology of sleep, including the brain mechanisms involved in generating and regulating REM sleep. Scientists are now examining physiological processes occurring in a portion of the hindbrain called the amygdala in order to uncover novel biochemical processes underlying REM sleep. A more comprehensive understanding of the complex biology of sleep will undoubtedly further clarify the pathological processes that underlie narcolepsy and other sleep disorders.

How Can I Help Research?

The NINDS contributes to the support of the Human Brain and Spinal Fluid Resource Center in Los Angeles. This bank supplies investigators around the world with tissue from patients with neurological and other disorders. Tissue from individuals with narcolepsy is needed to enable scientists to study this disorder more intensely. Prospective donors may contact:

Human Brain and Spinal Fluid Resource Center
Neurology Research (127A)
W. Los Angeles Healthcare Center
11301 Wilshire Blvd. Bldg. 212
Los Angeles, CA 90073
310-268-3536
24-hour pager: 310-636-5199
Email: RMNbbank@ucla.edu
http://www.loni.ucla.edu/~nnrsb/NNRSB

Where can I get more information?

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov

Information also is available from the following organizations:

Narcolepsy Network, Inc.
631B Ten Rod Road
North Kingstown, RI   02852
narnet@narcolepsynetwork.org
http://www.narcolepsynetwork.org
Tel: 888-292-6522 401-667-2523
Fax: 401-633-6567

National Sleep Foundation
1522 K Street NW
Suite 500
Washington, DC   20005
nsf@sleepfoundation.org
http://www.sleepfoundation.org
Tel: 202-347-3471 (no public calls please)
Fax: 202-347-3472

National Heart, Lung, and Blood Institute (NHBLI)
National Institutes of Health, DHHS
31 Center Drive, Rm. 4A21 MSC 2480
Bethesda, MD   20892-2480
http://www.nhlbi.nih.gov
Tel: 301-592-8573/240-629-3255 (TTY) Recorded Info: 800-575-WELL (-9355)

This document appears courtesty of the National Institute of Neurological Disorders and Stroke.