Narcolepsy

For other uses, see Narcolepsy (disambiguation).

Narcolepsy
Specialty	Neurology

Narcolepsy is chronic sleep disorder, or dyssomnia. The condition is characterized by excessive daytime sleepiness (EDS) in which a person experiences extreme fatigue and possibly falls asleep at inappropriate times, such as whilst at work or at school. A narcoleptic will most probably experience disturbed nocturnal sleep and also abnormal daytime sleep pattern, which is often confused with insomnia. When a person with narcolepsy falls asleep or goes to bed they will generally experience the 4th stage of sleep REM (rapid eye movement/dreaming state), within 10 minutes; whereas for most people, this shouldn't occur until generally 30 minutes of slumber.

Cataplexy, a sudden muscular weakness brought on by strong emotions (in most cases, there are many people who will experience cataplexy without having a emotional trigger), is known to be one of the other problems that some narcoleptics will experience. Often manifesting as muscular weaknesses ranging from a barely perceptible slackening of the facial muscles to the dropping of the jaw or head, weakness at the knees, or a total collapse. Usually only speech is slurred, vision is impaired (double vision, inability to focus), but hearing and awareness remain normal. In some rare cases, an individual's body becomes paralyzed and muscles will become stiff.

The term narcolepsy derives from the French word narcolepsie created by the French physician Jean-Baptiste-Édouard Gélineau by combining the Greek narke numbness, stupor and lepsis attack, seizure.

Symptoms

The main characteristic of narcolepsy is excessive daytime sleepiness (EDS), even after adequate night time sleep. A person with narcolepsy is likely to become drowsy or fall asleep, often at inappropriate times and places. Daytime naps may occur with little warning and may be physically irresistible. These naps can occur several times a day. They are typically refreshing, but only for a few hours. Drowsiness may persist for prolonged periods of time. In addition, night time sleep may be fragmented with frequent awakenings.

Four other classic symptoms of the disorder, often referred to as the "tetrad of narcolepsy," are cataplexy, sleep paralysis, hypnagogic hallucinations, and automatic behavior.. These symptoms may not occur in all patients. Cataplexy is an episodic condition featuring loss of muscle function, ranging from slight weakness (such as limpness at the neck or knees, sagging facial muscles, or inability to speak clearly) to complete body collapse. Episodes may be triggered by sudden emotional reactions such as laughter, anger, surprise, or fear, and may last from a few seconds to several minutes. The person remains conscious throughout the episode. In some cases, cataplexy may resemble epileptic seizures. Sleep paralysis is the temporary inability to talk or move when waking (or less often, falling asleep). It may last a few seconds to minutes. This is often frightening but is not dangerous. Hypnagogic hallucinations are vivid, often frightening, dreamlike experiences that occur while dozing, falling asleep and/or while awakening.

Automatic behavior means that a person continues to function (talking, putting things away, etc.) during sleep episodes, but awakens with no memory of performing such activities. It is estimated that up to 40 percent of people with narcolepsy experience automatic behavior during sleep episodes. Sleep paralysis and hypnagogic hallucinations also occur in people who do not have narcolepsy, but more frequently in people who are suffering from extreme lack of sleep. Cataplexy is generally considered to be unique to narcolepsy and is analogous to sleep paralysis in that the usually protective paralysis mechanism occurring during sleep is inappropriately activated. The opposite of this situation (failure to activate this protective paralysis) occurs in rapid eye movement behavior disorder.

In most cases, the first symptom of narcolepsy to appear is excessive and overwhelming daytime sleepiness. The other symptoms may begin alone or in combination months or years after the onset of the daytime naps. There are wide variations in the development, severity, and order of appearance of cataplexy, sleep paralysis, and hypnagogic hallucinations in individuals. Only about 20 to 25 percent of people with narcolepsy experience all four symptoms. The excessive daytime sleepiness generally persists throughout life, but sleep paralysis and hypnagogic hallucinations may not.

Although these are the common symptoms of narcolepsy, many people with narcolepsy also suffer from insomnia for extended periods of time. The symptoms of narcolepsy, especially the excessive daytime sleepiness and cataplexy, often become severe enough to cause serious problems in a person's social, personal, and professional life. Normally, when an individual is awake, brain waves show a regular rhythm. When a person first falls asleep, the brain waves become slower and less regular. This sleep state is called non-rapid eye movement (NREM) sleep. After about an hour and a half of NREM sleep, the brain waves begin to show a more active pattern again. This sleep state, called REM sleep (rapid eye movement sleep), is when most remembered dreaming occurs. Associated with the EEG-observed waves during REM sleep, muscle atonia is present (called REM atonia).

In narcolepsy, the order and length of NREM and REM sleep periods are disturbed, with REM sleep occurring at sleep onset instead of after a period of NREM sleep. Thus, narcolepsy is a disorder in which REM sleep appears at an abnormal time. Also, some of the aspects of REM sleep that normally occur only during sleep — lack of muscular control, sleep paralysis, and vivid dreams — occur at other times in people with narcolepsy. For example, the lack of muscular control can occur during wakefulness in a cataplexy episode; it is said that there is intrusion of REM atonia during wakefulness. Sleep paralysis and vivid dreams can occur while falling asleep or waking up. Simply put, the brain does not pass through the normal stages of dozing and deep sleep but goes directly into (and out of) rapid eye movement (REM) sleep.

This has several consequences. Night time sleep does not include as much deep sleep, so the brain tries to "catch up" during the day, hence EDS. People with narcolepsy may visibly fall asleep at unpredicted moments (such motions as head bobbing are common). People with narcolepsy fall quickly into what appears to be very deep sleep, and they wake up suddenly and can be disoriented when they do (dizziness is a common occurrence). They have very vivid dreams, which they often remember in great detail. People with narcolepsy may dream even when they only fall asleep for a few seconds.

Causes

Although the cause of narcolepsy was not determined for many years after its discovery, scientists had discovered conditions that seemed to be associated with an increase in an individual's risk of having the disorder. Specifically, there appeared to be a strong link between narcoleptic individuals and certain genetic conditions. One factor that seemed to predispose an individual to narcolepsy involved an area of Chromosome 6 known as the HLA complex. There appeared to be a correlation between narcoleptic individuals and certain variations in HLA genes, although it was not required for the condition to occur. Certain variations in the HLA complex were thought to increase the risk of an auto-immune response to protein-producing neurons in the brain. The protein produced, called hypocretin or orexin, is responsible for controlling appetite and sleep patterns. Individuals with narcolepsy often have reduced numbers of these protein-producing neurons in their brains. In 2009 the autoimmune hypothesis was supported by research carried out at Stanford University School of Medicine.

The neural control of normal sleep states and the relationship to narcolepsy are only partially understood. In humans, narcoleptic sleep is characterized by a tendency to go abruptly from a waking state to REM sleep with little or no intervening non-REM sleep. The changes in the motor and proprioceptive systems during REM sleep have been studied in both human and animal models. During normal REM sleep, spinal and brainstem alpha motor neuron depolarization produces almost complete atonia of skeletal muscles via an inhibitory descending reticulospinal pathway. Acetylcholine may be one of the neurotransmitters involved in this pathway. In narcolepsy, the reflex inhibition of the motor system seen in cataplexy is believed identical to that seen in normal REM sleep.

In 2004 researchers in Australia induced narcolepsy-like symptoms in mice by injecting them with antibodies from narcoleptic humans. The research has been published in the Lancet providing strong evidence suggesting that some cases of narcolepsy might be caused by autoimmune disease. Narcolepsy is strongly associated with HLA-DQB1*0602 genotype. There is also an association with HLA-DR2 and HLA-DQ1. This may represent linkage disequilibrium. Despite the experimental evidence in human narcolepsy that there may be an inherited basis for at least some forms of narcolepsy, the mode of inheritance remains unknown. Some cases are associated with genetic diseases such as Niemann-Pick disease or Prader-Willi syndrome.

Epidemiology

It is estimated that as many as 3 million people worldwide are affected by narcolepsy. In the United States, it is estimated that this condition afflicts as many as 200,000 Americans, but fewer than 50,000 are diagnosed. It is as widespread as Parkinson's disease or multiple sclerosis and more prevalent than cystic fibrosis, but it is less well known. Narcolepsy is often mistaken for depression, epilepsy, or the side effects of medications. It can also be mistaken for poor sleeping habits, recreational drug use, or laziness. Narcolepsy can occur in both men and women at any age, although its symptoms are usually first noticed in teenagers or young adults. There is strong evidence that narcolepsy may run in families; 8 to 12 percent of people with narcolepsy have a close relative with this neurologic disorder.

Narcolepsy has its typical onset in adolescence and young adulthood. There is an average 15-year delay between onset and correct diagnosis which may contribute substantially to the disabling features of the disorder. Cognitive, educational, occupational, and psychosocial problems associated with the excessive daytime sleepiness of narcolepsy have been documented. For these to occur in the crucial teen years when education, development of self-image, and development of occupational choice are taking place is especially damaging. While cognitive impairment does occur, it may only be a reflection of the excessive daytime somnolence.

The prevalence of narcolepsy is about 1 per 2,000 persons. It is a reason for patient visits to sleep disorder centers, and with its onset in adolescence, it is also a major cause of learning difficulty and absenteeism from school. Normal teenagers often already experience excessive daytime sleepiness because of a maturational increase in physiological sleep tendency accentuated by multiple educational and social pressures; this may be disabling with the addition of narcolepsy symptoms in susceptible teenagers. In clinical practice, the differentiation between narcolepsy and other conditions characterized by excessive somnolence may be difficult. Treatment options are currently limited. There is a paucity in the literature of controlled double-blind studies of possible effective drugs or other forms of therapy. Mechanisms of action of some of the few available therapeutic agents have been explored but detailed studies of mechanisms of action are needed before new classes of therapeutic agents can be developed. Narcolepsy is an underdiagnosed condition in the general population. This is partly because its severity varies from obvious to barely noticeable. Some people with narcolepsy do not suffer from loss of muscle control. Others may only feel sleepy in the evenings.

Diagnosis

Diagnosis is relatively easy when all the symptoms of narcolepsy are present, but if the sleep attacks are isolated and cataplexy is mild or absent, diagnosis is more difficult. It is also possible for cataplexy to occur in isolation. Two tests that are commonly used in diagnosing narcolepsy are the polysomnogram and the multiple sleep latency test (MSLT). These tests are usually performed by a sleep specialist. The polysomnogram involves continuous recording of sleep brain waves and a number of nerve and muscle functions during nighttime sleep. When tested, people with narcolepsy fall asleep rapidly, enter REM sleep early, and may awaken often during the night. The polysomnogram also helps to detect other possible sleep disorders that could cause daytime sleepiness.

For the multiple sleep latency test, a person is given a chance to sleep every 2 hours during normal wake times. Observations are made of the time taken to reach various stages of sleep (sleep onset latency). This test measures the degree of daytime sleepiness and also detects how soon REM sleep begins. Again, people with narcolepsy fall asleep rapidly and enter REM sleep early.

Treatment

Treatment is tailored to the individual, based on symptoms and therapeutic response. The time required to achieve optimal control of symptoms is highly variable, and may take several months or longer. Medication adjustments are also frequently necessary, and complete control of symptoms is seldom possible. While oral medications are the mainstay of formal narcolepsy treatment, lifestyle changes are also important.

The main treatment of excessive daytime sleepiness in narcolepsy is with a group of drugs called central nervous system stimulants such as methylphenidate, racemic - amphetamine, dextroamphetamine, and methamphetamine, or modafinil, a new stimulant with a different pharmacologic mechanism. In Fall 2007 an alert for severe adverse skin reactions to modafinil was issued by the FDA. Other medications used are codeine and selegiline. Another drug that is used is atomoxetine (Strattera), a non-stimulant and Norepinephrine reuptake inhibitor (NRI), that has little or no abuse potential. In many cases, planned regular short naps can reduce the need for pharmacological treatment of the EDS to a low or non-existent level.

Cataplexy and other REM-sleep symptoms are frequently treated with tricyclic antidepressants such as clomipramine, imipramine, or protriptyline, as well as other drugs that suppress REM sleep. Venlafaxine, a newer antidepressant which blocks the reuptake of serotonin and norepinephrine, has shown usefulness in managing symptoms of cataplexy. Gamma-hydroxybutyrate (GHB), a medication recently approved by the FDA, is the only medication specifically indicated for cataplexy. Gamma-hydroxybutyrate has also been shown to reduce symptoms of EDS associated with narcolepsy. While the exact mechanism of action is unknown, GHB is thought to improve the quality of nocturnal sleep.

In addition to drug therapy, an important part of treatment is scheduling short naps (10 to 15 minutes) two to three times per day to help control excessive daytime sleepiness and help the person stay as alert as possible. Daytime naps are not a replacement for nighttime sleep. Ongoing communication between the health care provider, patient, and the patient's family members is important for optimal management of narcolepsy. Finally, a recent study reported that transplantation of hypocretin neurons into the pontine reticular formation in rats is feasible, indicating the development of alternative therapeutic strategies in addition to pharmacological interventions.

Learning as much about narcolepsy as possible and developing a support system or finding a support group may help patients and families deal with the practical and emotional effects of the disorder, possible occupational limitations, and situations that might cause injury. Individuals with narcolepsy should avoid jobs that require driving long distances or handling hazardous equipment or that require alertness for lengthy periods. They may find it helps to take a nap before driving if possible or have a scheduled nap break during a long driving trip.

The National Sleep Foundation, University at Buffalo, and Mayo Clinic suggest it may help sufferers if they alert their employers, co-workers and friends in the hope that others will accommodate their condition and help when needed. The foundation say it may help if the sufferer breaks up larger tasks into small pieces and focuses on one small thing at a time, and if they carry a tape recorder, if possible, to record important conversations and meetings. The clinics say taking several short walks during the day may help sufferers.

Popular culture references

Depictions of the disorder in fiction and pop culture can range greatly in the accuracy of how they depict the symptoms. Narcolepsy is often depicted in an exaggerated fashion in comedy films or TV shows. In his book How to Talk Dirty and Influence People, comedian Lenny Bruce claimed to have struggled with the condition. In Thomas E Sniegoski's "The Sleeper Conspiracy" book series, a teen named Tom Lovett has narcolepsy. In the alien-invasion-themed video game Destroy All Humans!, the scientist Sleepy Ernst has narcolepsy. "The Little Sleep", a detective novel by Paul Tremblay, was released Spring of 2009. The main charater, Mark G. has narcolepsy. In relating Mark's thoughts and experiences the author captures many esoteric nuances of the experience of narcolepsy. As narcolepsy is an “invisible” disease, most people don’t really understand how pervasive the symptoms are-how the symptoms alter your perception of events, time and may at times blur the boundaries between what is experienced when awake, and what was experienced in sleep. The character deals with daily, even hourly frustrations due to the general cognitive fog, not being able to trust his own memory and even not being able to drive. Many of these situtions are presented as humorous, but the reader is always laughing with Mark, rather than at him. Mark shares the frustration felt by many with narcolepsy, that his disease isn’t taken seriously and that he is “the punch line in a joke”. A sequel to this book is planned for release next year.

Films and television

The French movie Narco portrays the disease.

The character 'Muki' in Nimród Antal's surrealistic film about Budapest Metro's Ticket Control Agents, Kontroll suffers from narcolepsy.

The lead character in Gus Van Sant's film about young gay hustlers, My Own Private Idaho, played by River Phoenix, has narcolepsy. A dictionary definition of the condition is presented in the opening sequence. The acceptance and support he receives through these episodes by Keanu Reeves' character illustrates their humanity and counterpoints their dehumanizing work.

In the movie Rat Race, one of the main characters (Enrico Pollini, played by Rowan Atkinson) has narcolepsy and is very eccentric. This portrayal has been criticized for its inaccuracy and insensitivity to the disorder.

In the movie Moulin Rouge!, the Argentine has narcolepsy and falls through Christian's roof. This is how he is introduced to the Bohemians that will later take him to the Moulin Rouge.

In the movie Death Race 2000, the navigator Joe Seasly was later diagnosed with narcolepsy at age 29

In the movie Deuce Bigalow: Male Gigolo, a woman with narcolepsy was shown as the cause of several slap-stick accidents.

In the animated children's film Shrek the Third, Sleeping Beauty has narcolepsy, hence her name.

In the episode "Best Man for the GOB" of the quirky comedy Arrested Development, George Sr. hires a narcoleptic stripper in order to convince his accountant Ira Gilligan that he has killed the stripper in order to get him to leave town. A recurring guest character on the HBO crime drama The Sopranos was Aaron Arkaway, a devout fundamentalist Christian who has narcolepsy. He was dating Janice Soprano, who explained to her bemused family (when Aaron fell asleep at the dinner table) that "narcolepsy is an AMA-recognized dyssomnia."

In Ruby Gloom, Misery's cousin Malaise from the episode "Misery Loves Company" suffers from narcolepsy, causing her to fall asleep in the most untimely situations throughout the episode. In the novel Swindle, Character Ben admits to having Narcolepsy.

In the film Austin Powers: International Man of Mystery, Dr. Evil describes his father as having "low grade narcolepsy and a penchant for buggery".

In the animated series Galactic Football gatekeeper Ahito has narcolepsy - he often falls asleep in the field during matches.

In the American sitcom Frasier, Frasier Crane's brother Niles develops narcolepsy brought about by the stress of speaking to his ex-wife Maris's lawyers.

Cesare, the main character from The Cabinet of Doctor Caligari, a sonambulist, suffers from Narcolepsy, as told by Dr. Caligari in one dialogue in the movie.

In one episode of the American series Scrubs, J.D., Turk, Carla, Elliot, and Laverne go to "laugh at the narcoleptic guy", who passes out upon becoming sexually aroused. This most likely isn't a legitimate portrayal of the disorder.

Music

In the song "Girls, Girls, Girls", Jay-Z mentions "Mami's a narcolyptic, always sleepin on Hov".

Singer and pianist Ben Folds wrote and performed a song called "Narcolepsy". The song was a metaphor for people's tendency to be emotionally numb during large life events.

The band Placebo wrote a song called "Narcoleptic", on their album Black Market Music.

The band Third Eye Blind wrote a song called "Narcolepsy", describing the narcoleptic narrator's uncontrollable nightmares and sleep paralysis.

The Westchester punk band Plow United's third and final full length album was entitled Narcolepsy. The name of Australian band The Sleepy Jackson was inspired by a former drummer who has narcolepsy.

In the group, The Wiggles, the character Jeff possibly has narcolepsy as he sleeps far too much causing the others to constantly use the phrase, "Wake up, Jeff!"

The band 7 Car Pile-Up has a song called Narcoleptic Mime.

Canadian musician Dan Mangan has a song called Journal Of A Narcoleptic.

See also

• Cataplexy
• Dyssomnia
• Orexin
• Microsleep
• List of people with narcolepsy
• Sleep medicine

Sources

• Mitler, M M (1991). "Relative Efficacy of Drugs for the treatment of Sleepiness in Narcolepsy". Sleep. 14 (3): 218. PMID 1680245. {{cite journal}}: Unknown parameter |month= ignored (help)
• Mayer, G (1995). "Selegiline Treatment in Narcolepsy". Clinical Neuropharmacology. 18 (4): 306. PMID 8665543. {{cite journal}}: Unknown parameter |month= ignored (help)
• Chabas, D (2003). "The Genetics of Narcolepsy". Annual Review of Genomics & Human Genetics. 4: 459. doi:10.1146/annurev.genom.4.070802.110432. PMID 14527309. {{cite journal}}: Unknown parameter |month= ignored (help)
• Smith AJ, Jackson MW, Neufing P, McEvoy RD, Gordon TP (2004). "A functional autoantibody in narcolepsy". Lancet. 364 (9451): 2122–4. doi:10.1016/S0140-6736(04)17553-3. PMID 15589310.{{cite journal}}: CS1 maint: multiple names: authors list (link)

External links

• Stanford University: Center for Narcolepsy
• Narcolepsy Network Organization
• Narcolepsy Fact Sheet: National Institute of Neurological Disorders and Stroke
• http://www.narcolepsy.org.uk/index_html
• Read about Narcolepsy in the Sleeptionary
• What is Narcolepsy
• Narcolepsy: Symptoms, Causes, Diagnosis and Treatment
• Narcolepsy & Cataplexy videos and case study
• Transplantation of hypocretin neurons into the pontine reticular formation: preliminary results
• Living With Narcolepsy
• Narcolepsy Linked to Immune System Problem
• Video explaining that narcolepsy is an autoimmune disorder.