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Narcolepsy

 

What is Narcolepsy?

Narcolepsy is a chronic neurological disorder caused by the brain's inability to regulate sleep-wake cycles normally. At various times throughout the day, people with narcolepsy experience fleeting urges to sleep. If the urge becomes overwhelming, patients fall asleep for periods lasting from a few seconds to several minutes. In rare cases, some people may remain asleep for an hour or longer.

Narcoleptic sleep episodes can occur at any time, and thus frequently prove profoundly disabling. People may involuntarily fall asleep while at work or at school, when having a conversation, playing a game, eating a meal, or, most dangerously, when driving an automobile or operating other types of potentially hazardous machinery. In addition to daytime sleepiness, three other major symptoms frequently characterize narcolepsy: cataplexy, or the sudden loss of voluntary muscle tone; vivid hallucinations during sleep onset or upon awakening; and brief episodes of total paralysis at the beginning or end of sleep.

Contrary to common beliefs, people with narcolepsy do not spend a substantially greater proportion of their time asleep during a 24-hour period than do normal sleepers. In addition to daytime drowsiness and involuntary sleep episodes, most patients also experience frequent awakenings during nighttime sleep. For these reasons, narcolepsy is considered to be a disorder of the normal boundaries between the sleeping and waking states.

For most adults, a normal night's sleep lasts about 8 hours and is composed of four to six separate sleep cycles. A sleep cycle is defined by a segment of non-rapid eye movement (NREM) sleep followed by a period of rapid eye movement (REM) sleep. The NREM segment can be further divided into stages according to the size and frequency of brain waves. REM sleep, in contrast, is accompanied by bursts of rapid eye movement (hence the acronym REM sleep) along with sharply heightened brain activity and temporary paralysis of the muscles that control posture and body movement. When subjects are awakened from sleep, they report that they were "having a dream" more often if they had been in REM sleep than if they had been in NREM sleep. Transitions from NREM to REM sleep are governed by interactions among groups of neurons (nerve cells) in certain parts of the brain.

Scientists now believe that narcolepsy results from disease processes affecting brain mechanisms that regulate REM sleep. For normal sleepers a typical sleep cycle is about 100 - 110 minutes long, beginning with NREM sleep and transitioning to REM sleep after 80 - 100 minutes. But, people with narcolepsy frequently enter REM sleep within a few minutes of falling asleep.

Who Gets Narcolepsy?

Narcolepsy is not rare, but it is an under-recognized and under-diagnosed condition. The disorder is estimated to affect about one in every 2,000 Americans. But the exact prevalence rate remains uncertain, and the disorder may affect a larger segment of the population.

Narcolepsy appears throughout the world in every racial and ethnic group, affecting males and females equally. But prevalence rates vary among populations. Compared to the U.S. population, for example, the prevalence rate is substantially lower in Israel (about one per 500,000) and considerably higher in Japan (about one per 600).

Most cases of narcolepsy are sporadic-that is, the disorder occurs independently in individuals without strong evidence of being inherited. But familial clusters are known to occur. Up to 10 percent of patients diagnosed with narcolepsy with cataplexy report having a close relative with the same symptoms. Genetic factors alone are not sufficient to cause narcolepsy. Other factors-such as infection, immune-system dysfunction, trauma, hormonal changes, stress-may also be present before the disease develops. Thus, while close relatives of people with narcolepsy have a statistically higher risk of developing the disorder than do members of the general population, that risk remains low in comparison to diseases that are purely genetic in origin.

* Obstructive sleep apnea is a temporary cessation of breathing that occurs repeatedly during sleep and is caused by a narrowing of the airway. Restless legs syndrome is a neurological disorder characterized by unpleasant sensations-burning, creeping, tugging-in the legs and an uncontrollable urge to move when at rest

What are the Symptoms?

People with narcolepsy experience highly individualized patterns of REM sleep disturbances that tend to begin subtly and may change dramatically over time. The most common major symptom, other than excessive daytime sleepiness (EDS), is cataplexy, which occurs in about 70 percent of all patients. Sleep paralysis and hallucinations are somewhat less common. Only 10 to 25 percent of patients, however, display all four of these major symptoms during the course of their illness.

Excessive daytime sleepiness

EDS, the symptom most consistently experienced by almost all patients, is usually the first to become clinically apparent. Generally, EDS interferes with normal activities on a daily basis, whether or not patients have sufficient sleep at night. People with EDS describe it as a persistent sense of mental cloudiness, a lack of energy, a depressed mood, or extreme exhaustion. Many find that they have great difficulty maintaining their concentration while at school or work. Some experience memory lapses. Many find it nearly impossible to stay alert in passive situations, as when listening to lectures or watching television. People tend to awaken from such unavoidable sleeps feeling refreshed and finding that their feelings of drowsiness and fatigue subside for an hour or two.

Involuntary sleep episodes are sometimes very brief, lasting no more than seconds at a time. As many as 40 percent of all people with narcolepsy are prone to automatic behavior during such "microsleeps." They fall asleep for a few seconds while performing a task but continue carrying it through to completion without any apparent interruption. During these episodes, people are usually engaged in habitual, essentially "second nature" activities such as taking notes in class, typing, or driving. They cannot recall their actions, and their performance is almost always impaired during a microsleep. Their handwriting may, for example, degenerate into an illegible scrawl, or they may store items in bizarre locations and then forget where they placed them. If an episode occurs while driving, patients may get lost or have an accident.

Cataplexy

Cataplexy is a sudden loss of muscle tone that leads to feelings of weakness and a loss of voluntary muscle control. Attacks can occur at any time during the waking period, with patients usually experiencing their first episodes several weeks or months after the onset of EDS. But in about 10 percent of all cases, cataplexy is the first symptom to appear and can be misdiagnosed as a manifestation of a seizure disorder. Cataplectic attacks vary in duration and severity. The loss of muscle tone can be barely perceptible, involving no more than a momentary sense of slight weakness in a limited number of muscles, such as mild drooping of the eyelids. The most severe attacks result in a complete loss of tone in all voluntary muscles, leading to total physical collapse in which patients are unable to move, speak, or keep their eyes open. But even during the most severe episodes, people remain fully conscious, a characteristic that distinguishes cataplexy from seizure disorders. Although cataplexy can occur spontaneously, it is more often triggered by sudden, strong emotions such as fear, anger, stress, excitement, or humor. Laughter is reportedly the most frequent trigger.

The loss of muscle tone during a cataplectic episode resembles the interruption of muscle activity that naturally occurs during REM sleep. A group of neurons in the brainstem ceases activity during REM sleep, inhibiting muscle movement. Using an animal model, scientists have recently learned that this same group of neurons becomes inactive during cataplectic attacks, a discovery that provides a clue to at least one of the neurological abnormalities contributing to human narcoleptic symptoms.

Sleep paralysis

The temporary inability to move or speak while falling asleep or waking up also parallels REM-induced inhibitions of voluntary muscle activity. This natural inhibition usually goes unnoticed by people who experience normal sleep because it occurs only when they are fully asleep and entering the REM stage at the appropriate time in the sleep cycle. Experiencing sleep paralysis resembles undergoing a cataplectic attack affecting the entire body. As with cataplexy, people remain fully conscious. Cataplexy and sleep paralysis are frightening events, especially when first experienced. Shocked by suddenly being unable to move, many patients fear that they may be permanently paralyzed or even dying. However, even when severe, cataplexy and sleep paralysis do not result in permanent dysfunction. After episodes end, people rapidly recover their full capacity to move and speak.

Hallucinations

Hallucinations can accompany sleep paralysis or can occur in isolation when people are falling asleep or waking up. Referred to as hypnagogic hallucinations when accompanying sleep onset and as hypnopompic hallucinations when occurring during awakening, these delusional experiences are unusually vivid and frequently frightening. Most often, the content is primarily visual, but any of the other senses can be involved. These hallucinations represent another intrusion of an element of REM sleep-dreaming-into the wakeful state.

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.

On July 17, 2002, the FDA approved Xyrem (sodium oxybate or gamma hydroxybutyrate, also known as GHB) for treating people with narcolepsy who experience episodes of cataplexy.  Due to safety concerns associated with the use of this drug, the distribution of Xyrem is tightly restricted.

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.

More Information

Narcolepsy Network, Inc.
79 Main Street
North Kingstown, RI 02852
Telephone: (401) 667-2523 
Website: www.narcolepsynetwork.org*  

 

Source: Marketdata Enterprises, Inc. research, Wikipedia

*page last updated  05/10/2008

 

 

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