Myasthenia gravis is a chronic autoimmune neuromuscular disease
characterized by varying degrees of weakness of the skeletal (voluntary)
muscles of the body. The name myasthenia gravis, which is Latin and Greek
in origin, literally means "grave muscle weakness." With current
therapies, however, most cases of myasthenia gravis are not as "grave" as
the name implies. In fact, for the majority of individuals with myasthenia
gravis, life expectancy is not lessened by the disorder.
The hallmark of myasthenia gravis is muscle weakness that increases
during periods of activity and improves after periods of rest. Certain
muscles such as those that control eye and eyelid movement, facial
expression, chewing, talking, and swallowing are often, but not always,
involved in the disorder. The muscles that control breathing and neck and
limb movements may also be affected.
Myasthenia gravis is caused by a defect in the transmission of nerve
impulses to muscles. It occurs when normal communication between the nerve
and muscle is interrupted at the neuromuscular junction - the place where
nerve cells connect with the muscles they control. Normally when impulses
travel down the nerve, the nerve endings release a neurotransmitter
substance called acetylcholine. Acetylcholine travels through the
neuromuscular junction and binds to acetylcholine receptors which are
activated and generate a muscle contraction.
In myasthenia gravis, antibodies block, alter, or destroy the receptors
for acetylcholine at the neuromuscular junction which prevents the muscle
contraction from occurring. These antibodies are produced by the body's
own immune system. Thus, myasthenia gravis is an autoimmune disease
because the immune system - which normally protects the body from foreign
organisms - mistakenly attacks itself.
The thymus gland, which lies in the upper chest area beneath the
breastbone, plays an important role in the development of the immune
system in early life. Its cells form a part of the body's normal immune
system. The gland is somewhat large in infants, grows gradually until
puberty, and then gets smaller and is replaced by fat with age. In adults
with myasthenia gravis, the thymus gland is abnormal. It contains certain
clusters of immune cells indicative of lymphoid hyperplasia - a condition
usually found only in the spleen and lymph nodes during an active immune
response. Some individuals with myasthenia gravis develop thymomas or
tumors on the thymus gland. Generally thymomas are benign, but they can
become malignant.
The relationship between the thymus gland and myasthenia gravis is not
yet fully understood. Scientists believe the thymus gland may give
incorrect instructions about the production of the acetylcholine receptor
antibodies, thereby setting the stage for the attack on neuromuscular
transmission.
Although myasthenia gravis may affect any voluntary muscle, muscles
that control eye and eyelid movement, facial expression, and swallowing
are most frequently affected. The onset of the disorder may be sudden.
Symptoms often are not immediately recognized as myasthenia gravis.
In most cases, the first noticeable symptom is weakness of the eye
muscles. In others, difficulty in swallowing and slurred speech may be the
first signs. The degree of muscle weakness involved in myasthenia gravis
varies greatly among patients, ranging from a localized form, limited to
eye muscles (ocular myasthenia), to a severe or generalized form in which
many muscles - sometimes including those that control breathing - are
affected. Symptoms, which vary in type and severity, may include a
drooping of one or both eyelids (ptosis), blurred or double vision
(diplopia) due to weakness of the muscles that control eye movements,
unstable or waddling gait, weakness in arms, hands, fingers, legs, and
neck, a change in facial expression, difficulty in swallowing and
shortness of breath, and impaired speech (dysarthria).
Myasthenia gravis occurs in all ethnic groups and both genders. It most
commonly affects young adult women (under 40) and older men (over 60), but
it can occur at any age.
In neonatal myasthenia, the fetus may acquire immune proteins
(antibodies) from a mother affected with myasthenia gravis. Generally,
cases of neonatal myasthenia gravis are transient (temporary) and the
child's symptoms usually disappear within few weeks after birth. Other
children develop myasthenia gravis indistinguishable from adults.
Myasthenia gravis in juveniles is common.
Myasthenia gravis is not directly inherited nor is it contagious.
Occasionally, the disease may occur in more than one member of the same
family.
Rarely, children may show signs of congenital myasthenia or congenital
myasthenic syndrome. These are not autoimmune disorders, but are caused by
defective genes that control proteins in the acetylcholine receptor or in
acetylcholineterase.
Unfortunately, a delay in diagnosis of one or two years is not unusual
in cases of myasthenia gravis. Because weakness is a common symptom of
many other disorders, the diagnosis is often missed in people who
experience mild weakness or in those individuals whose weakness is
restricted to only a few muscles.
The first steps of diagnosing myasthenia gravis include a review of the
individual's medical history, and physical and neurological examinations.
The signs a physician must look for are impairment of eye movements or
muscle weakness without any changes in the individual's ability to feel
things. If the doctor suspects myasthenia gravis, several tests are
available to confirm the diagnosis.
A special blood test can detect the presence of immune molecules or
acetylcholine receptor antibodies. Most patients with myasthenia gravis
have abnormally elevated levels of these antibodies. However, antibodies
may not be detected in patients with only ocular forms of the disease.
Another test is called the edrophonium test. This approach requires the
intravenous administration of edrophonium chloride or Tensilon(r), a drug
that blocks the degradation (breakdown) of acetylcholine and temporarily
increases the levels of acetylcholine at the neuromuscular junction. In
people with myasthenia gravis involving the eye muscles, edrophonium
chloride will briefly relieve weakness. Other methods to confirm the
diagnosis include a version of nerve conduction study which tests for
specific muscle fatigue by repetitive nerve stimulation. This test records
weakening muscle responses when the nerves are repetitively stimulated,
and helps to differentiate nerve disorders from muscle disorders.
Repetitive stimulation of a nerve during a nerve conduction study may
demonstrate decrements of the muscle action potential due to impaired
nerve-to-muscle transmission.
A different test called single fiber electromyography (EMG), in which
single muscle fibers are stimulated by electrical impulses, can also
detect impaired nerve-to-muscle transmission. EMG measures the electrical
potential of muscle cells. Muscle fibers in myasthenia gravis, as well as
other neuromuscular disorders, do not respond as well to repeated
electrical stimulation compared to muscles from normal individuals.
Computed tomography (CT) or magnetic resonance imaging (MRI) may be
used to identify an abnormal thymus gland or the presence of a thymoma.
A special examination called pulmonary function testing - which
measures breathing strength - helps to predict whether respiration may
fail and lead to a myasthenic crisis.
Today, myasthenia gravis can be controlled. There are several therapies
available to help reduce and improve muscle weakness. Medications used to
treat the disorder include anticholinesterase agents such as neostigmine
and pyridostigmine, which help improve neuromuscular transmission and
increase muscle strength. Immunosuppressive drugs such as prednisone,
cyclosporine, and azathioprine may also be used. These medications improve
muscle strength by suppressing the production of abnormal antibodies. They
must be used with careful medical followup because they may cause major
side effects.
Thymectomy, the surgical removal of the thymus gland (which is abnormal
in myasthenia gravis patients), improves symptoms in more than 50 percent
of patients without thymoma. Other therapies used to treat myasthenia
gravis include plasmapheresis, a procedure in which abnormal antibodies
are removed from the blood, and high-dose intravenous immune globulin,
which temporarily modifies the immune system and provides the body with
normal antibodies from donated blood. These therapies may be used to help
individuals during especially difficult periods of weakness. A
neurologist, along with the primary care physician, will determine which
treatment option is best for each individual depending on the severity of
the weakness, which muscles are affected, and the individual's age and
other associated medical problems.
A myasthenic crisis occurs when weakness affects the muscles that
control breathing, creating a medical emergency and requiring a respirator
for assisted ventilation. In patients whose respiratory muscles are weak,
crises - which generally call for immediate medical attention - may be
triggered by infection, fever, an adverse reaction to medication, or
emotional stress.
With treatment, the outlook for most patients with myasthenia gravis is
bright: they will have significant improvement of their muscle weakness
and they can expect to lead normal or nearly normal lives. Some cases of
myasthenia gravis may go into remission temporarily and muscle weakness
may disappear completely so that medications can be discontinued. Stable,
long-lasting complete remissions are the goal of thymectomy. In a few
cases, the severe weakness of myasthenia gravis may cause a crisis
(respiratory failure), which requires immediate emergency medical care.
(see above)
Much has been learned about myasthenia gravis in recent years.
Technological advances have led to more timely and accurate diagnosis, and
new and enhanced therapies have improved management of the disorder. Much
knowledge has been gained about the structure and function of the
neuromuscular junction, the fundamental aspects of the thymus gland and of
autoimmunity, and the disorder itself. Despite these advances, however,
there is still much to learn. The ultimate goal of myasthenia gravis
research is to increase scientific understanding of the disorder.
Researchers are seeking to learn what causes the autoimmune response in
myasthenia gravis, and to better define the relationship between the
thymus gland and myasthenia gravis.
Today's myasthenia gravis research includes a broad spectrum of studies
conducted and supported by NINDS. NINDS scientists are evaluating new and
improving current treatments for the disorder. One such study is testing
the efficacy of intravenous immune globlin in patients with myasthenia
gravis. The goal of the study is to determine whether this treatment
safely improves muscle strength. Another study seeks to understand the
molecular basis of synaptic transmission in the nervous system. The
objective of this study is to expand current knowledge of the function of
receptors and to apply this knowledge to the treatment of myasthenia
gravis.
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For more information on myasthenia gravis, you may wish to contact:
Myasthenia Gravis Foundation of America
5841 Cedar Lake
Road
Suite 204
Minneapolis, Minnesota 55416
(800)
541-5454
(952) 545-9438
http://www.myasthenia.org/
For more information on research on myasthenia gravis or other
neurological disorders, you may wish to contact:
NIH Neurological Institute
P.O. Box 5801
Bethesda, Maryland
20824
(301) 496-5751
(800) 352-9424
http://www.ninds.nih.gov/
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