Narcolepsy is a
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 while at work or at school. A
narcoleptic will most likely 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 REM stage of sleep (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 (though many people 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 or just be
very tired throughout the day, 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
A depiction of the neuropeptide
Orexin A.
People with narcolepsy often have a reduced number of neurons
that produce this protein.
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, and more recently,
armodafinil. 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.
Portrayal of narcolepsy in popular culture
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 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.
"The Little Sleep", a detective novel by
Paul Tremblay, portrayed the main
character, Mark G. as having 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".
In the series, "Sleeper", The main character,Tom Lovett experiences
attcks of this sort but soon realizes that it was caused by a
neurological brainchip being activated to turn him into an
assassin.
See also
References
- Entry Narcolepsy. in the Online
Etymology Dictionary. Douglas Harper, Historian. 18 Sep
2007.
-
http://www.taumed.com/content/adam/browse.jsp?pid=10&cid=000098
- Modafinil (marketed as Provigil): Serious Skin
Reactions; FDA Drug Safety Newsletter
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