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*
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