Narcolepsy

Narcolepsy is a sleep disorder that consists of overwhelming, severe daytime sleepiness; sometimes the sleep attacks happen anywhere without warning.

Narcolepsy is a sleep disorder that causes overwhelming and severe daytime sleepiness. Pathologic sleepiness is characterized by the fact that it occurs at inappropriate times and places. The daytime sleep attacks may occur with or without warning and can occur repeatedly in a single day. Persons with narcolepsy often have fragmented nighttime sleep with frequent brief awakenings.

The following are some little known facts about narcolepsy:

• Frequently, narcolepsy is unrecognized for many years. There could be a delay of 10 years between the onset of the condition and the diagnosis.
• Approximately half of adults with narcolepsy retrospectively report symptoms beginning in their teenage years. For most patients, narcolepsy begins between the ages of 15 and 30 years. It less frequently occurs in children younger than age 10 years of age.
• Narcolepsy may lead to impairment of social and academic performance in otherwise intellectually normal children.
• Narcolepsy is a treatable condition. A multi-modal approach is most effective (medications, a regular nighttime sleep schedule, and scheduled naps during the day)is required for the most favorable outcome.

Excessive daytime sleepiness and inability to stay awake are hallmarks of the sleep disorder called narcolepsy.

Narcolepsy is typically characterized by the following four symptoms with varying frequencies:

1. Excessive daytime sleepiness
2. Cataplexy (sudden and temporary loss of muscle tone often triggered by emotions such as laughter)
3. Hallucinations (vivid dreamlike experiences that occur while falling asleep or upon awakening)
4. Sleep paralysis (paralysis that occurs most often upon falling asleep or waking up; the person is unable to move for a few minutes)

Less frequently persons have all four symptoms.

Narcolepsy is believed to result from a genetic predisposition and abnormal neurotransmitter (hypocretin, also known as orexin) functioning and sensitivity.

Genetic predisposition

Understanding of narcolepsy stems primarily from research involving narcoleptic dogs (for example, special laboratory-bred Dobermans and Labradors). In these animal models, the disorder is transmitted in an autosomal recessive fashion and is characterized mainly by cataplexy. A small percentage of human cases are inherited and, unlike the canine form, are transmitted in an autosomal dominant manner.

Neurotransmitter

The neurotransmitter hypocretin was identified in the last few years and is strongly associated with narcolepsy in dogs with a genetic predisposition. Hypocretin levels in human subjects with narcolepsy have been found to be undetectable or low in several recent studies of patients with narcolepsy. Hypocretin appears to modulate activity in the hypothalamus (the part of the brain associated with sleep). The deficiency of hypocretin might produce sleep attacks. The drug modafinil (Provigil) is useful in the treatment of narcolepsy is believed to activate hypocretin-containing nerve cells.

Epworth Sleepiness Scale

Questionnaires are used to measure excessive sleepiness. The most commonly used questionnaire is the 8-question Epworth Sleepiness Scale (1991).

• Response to each question on a scale from 0 (not at all likely to fall asleep) to 3 (very likely to fall asleep) is obtained.
• The resulting total score is between 0 and 24.
• Although what score constitutes abnormal sleepiness is controversial, total scores above 10 generally warrant investigation.
• You can take the Epworth Sleepiness Scale Test.

Polysomnography

For this exam, one needs to come to a sleep laboratory about two hours before bedtime without making any changes in the daily habits. Then, the whole night's sleep is monitored and recorded. The following parameters are monitored:

• Electrical activity of the brain (electroencephalogram)
• Electrical activity of the heart (electrocardiogram)
• Movements of the muscles (electromyogram)
• Eye movements (electrooculogram)
• Respirations (oral thermistor or nasal pressure transducer)

These parameters are monitored as one passes through the various sleep stages (see Sleep: Understanding the Basics).

If a person has narcolepsy, the polysomnograph shows short sleep latency of usually less than five minutes and an abnormally short latency before the first sleep onset REM sleep (SOREMPs). During a daytime sleep study or nap study called a Multiple Sleep Latency Test (MSLT), more than two SOREMPs and a mean sleep latency of fewer than five minutes strongly suggest narcolepsy.

Multiple Sleep Latency Test

In this test, the time taken by a person to fall asleep (sleep latency) during the day while lying in a quiet room is measured. This test is performed the morning after the overnight polysomnogram. The person takes four or five scheduled naps every two hours. The first nap starts two hours after awakening that morning. People with normal sleep and alertness take about 10-20minutes to fall asleep. Persons with narcolepsy (and other causes of abnormal sleepiness) take a much shorter time (less than five minutes) to go from wakefulness into sleep.

This test is not routinely done in isolation, but maybe part of a full evaluation of a patient for hypersomnia. Two weeks before these tests, the patient is asked to keep a sleep diary that records bedtime, wake-up times, and nap times. Their physician will inform them to gradually eliminate medications that could affect the sleep tests.

CSF (cerebrospinal fluid) hypocretin test

This has not yet become part of the routine diagnostic tools for narcolepsy but is being used more frequently. For this test, a sample of cerebrospinal fluid is removed by lumbar puncture and sent to the laboratory for analysis. The specificity and sensitivity of the CSF hypocretin test are high enough that it should have clinical usefulness for diagnosis. Thus, defining the precise criteria for the diagnosis of narcolepsy and other sleep disorders is an evolving process.

Treatment for narcolepsy ranges from

• proper sleep routines,
• exercise, and
• other measures sufferers may institute on their own, to drugs like antidepressants and stimulants administered by doctors.

• Sleep hygiene is very important. For example, many people have an improvement in their symptoms if they maintain a regular sleep schedule, usually seven to eight hours of sleep per night.
• Scheduled naps during the day also help. One study suggested that the optimal sleep pattern is a combination of scheduled nighttime sleep (such as from 11:00 pm to 7:30 am) and two 15-minute naps.
• Patients with narcolepsy should also avoid heavy meals and alcohol (as it can interfere with sleep).
• Driving should be restricted when the patient feels sleepy.
• Children should be encouraged to participate in after-school activities and sports. A well-designed exercise program can be beneficial and stimulating.
• Parents should request school personnel to excuse the child from activities if he or she appears drowsy.

The main focus of medical treatment is symptomatic relief of excessive daytime sleepiness and cataplexy with stimulants of the central nervous system and antidepressants. Stimulants increase wakefulness, vigilance, and performance, while antidepressants reduce cataplectic attacks.

Drugs that act as stimulants are standard treatments for narcolepsy. They include the following:

• methylphenidate (Ritalin)
• modafinil (Provigil), or
• armodafinil (Nuvigil).

Methylphenidate (Ritalin)

• Methylphenidate helps reduce excessive daytime sleepiness, improving the symptoms of narcolepsy in 65%-85% of patients. Methylphenidate, the most frequently used stimulant, improves alertness in a dose-related fashion.
• Unfortunately, these medications have undesirable side effects including headache, irritability, nervousness, and gastrointestinal complaints. Nocturnal sleep may be impaired, thus decreasing sleep time.
• There are theoretical concerns that these drugs may become ineffective if used continuously for long periods. Therefore, some healthcare providers advise people with narcolepsy to abstain from medication one day each week (typically on a weekend; known as a "drug holiday"). During that day, the person should not engage in activities that require being awake, such as driving.

Modafinil (Provigil) or Armodafinil (Nuvigil)

• Modafinil (Provigil) was discovered as a novel drug that promotes long-lasting wakefulness. Armodafinil (Nuvigil) has a similar chemical structure and effect.
• It has been shown in several trials to reduce excessive daytime sleepiness. People treated with modafinil experienced both subjective improvement and objective improvement in sleepiness.
• The most common side effect is headache.
• Its safety in children has not been established.

Anticataplectic agents

Cataplectic attacks are usually treated by clomipramine, imipramine, fluoxetine, or sodium oxybate.

• Clomipramine (Anafranil) and imipramine (Tofranil) belong to the family of tricyclic antidepressants. They reduce the frequency of cataplexy in people with narcolepsy.
• Fluoxetine (Prozac) is a selective serotonin reuptake inhibitor that is useful in the treatment of cataplexy. It has fewer side effects than tricyclic antidepressants.

For both excessive daytime sleepiness and cataplexy:

• Sodium oxybate (Xyrem), commonly called gamma hydroxybutyrate, is a central nervous system depressant initially approved for a small subset of people with narcolepsy and cataplexy that does not respond to the other anticataplectic medications. The precise mechanism by which it produces an effect on cataplexy is unknown. It has a history of abuse as a recreational drug; therefore, the FDA approved it as a Schedule III Controlled Substance. After its initial approval for cataplexy, it has become approved for excessive daytime sleepiness in narcolepsy.

Problems in children with narcolepsy include poor school performance, social impairment, ridicule from peers, and dysfunction in other activities of normal childhood development.

Adults often perceive narcoleptic symptoms as embarrassing, and social isolation may result.

• They may encounter interpersonal stress in relationships, sexual dysfunction, and difficulty working because of the condition itself or its treatment.
• They may experience job impairment from sleep attacks, memory problems, cataplexy, interpersonal problems, and personality changes. These symptoms may lead coworkers to perceive them as "lazy."
• Persons with narcolepsy are sometimes falsely suspected of illegal drug use.
• Persons who are taking stimulant medications should inform their employers, because they may test positive for amphetamines on screening drug tests.
• Persons with narcolepsy are at an increased risk for automobile accidents.
• Left untreated, narcolepsy may be psychosocially devastating. However, with proper management and treatment, persons with narcolepsy usually lead meaningful and productive personal and professional lives.

If a person is diagnosed with narcolepsy, he or she can join a support group. By becoming a member of a support group, one gets emotional support from people who are having similar problems. It will alleviate isolation and the feeling that he or she is the only one with the condition.

The Narcolepsy Network can help locate a support group in one's area.

Narcolepsy Network Inc.
National Office
10921 Reed Hartman Hwy
Cincinnati, OH 45242
Tel: (513) 891-3522
Fax: (513) 891-3836
Email: [email protected]