Facts About Autoimmune Myasthenia Gravis
Myasthenia Gravis (MG)
Myasthenia Gravis comes from the Greek and Latin words meaning “grave
muscular weakness.” The most common form of MG is a chronic autoimmune neuromuscular disorder that is characterized
by fluctuating weakness of the voluntary muscle groups. The prevalence of MG in the United States is estimated to be about
20/100,000 population. However, MG is probably under diagnosed and the prevalence may be higher.
Clinical Features and Symptoms
MG occurs in all races, both genders and at any age. MG is not directly
inherited nor is it contagious. It does occasionally occur in more than one member of the same family. MG may affect any muscle
that is under voluntary control. Certain muscles are more frequently involved and these include the ones that control eye
movements, eyelids, chewing, swallowing, coughing and facial expression. Muscles that control breathing and movements of the
arms and legs may also be affected. Weakness of the muscles needed for breathing may cause shortness of breath, difficulty
taking a deep breath and coughing.
The muscle weakness of MG increases with continued activity and improves
after periods of rest. The muscles involved may vary greatly from one patient to the next. Weakness may be limited to the
muscles controlling eye movements and the eyelids. This form of myasthenia is referred to as ocular MG. In its severest form,
MG involves many of the voluntary muscles of the body, including those needed for breathing. The degree and distribution of
muscle weakness for many patients falls in between these two extremes. When the weakness is severe and involves breathing,
hospitalization is usually necessary.
There are many disorders that cause weakness. In addition to a complete
medical and neurological evaluation, a number of tests may be used to establish a diagnosis of MG. A blood test for the abnormal
antibodies can be performed to see if they are present. Electromyography (EMG) studies can provide support for the diagnosis
of MG when characteristic patterns are present. The edrophonium chloride (Tensilon®) test is performed by injecting this chemical
into a vein. Improvement of strength immediately after the injection provides strong support for the diagnosis of MG. Sometimes
all of these tests are negative or equivocal in someone whose story and examination still seem to point to a diagnosis of
MG. The positive clinical findings should probably take precedence over negative confirmatory tests.
There is no known cure for MG, but there are effective treatments that
allow many—but not all—people with MG to lead full lives. Common treatments include medications, thymectomy and
plasmapheresis. Spontaneous improvement and even remission may occur without specific therapy.
Medications are most frequently used in treatment. Anticholinesterase
agents (e.g., Mestinon®) allow acetylcholine to remain at the neuromuscular junction longer than usual so that more receptor
sites can be activated. Corticosteroids (e.g., prednisone) and immunosuppressant agents (e.g., Imuran®) may be used to suppress
the abnormal action of the immune system that occurs in MG. Intravenous immunoglobulins (IVIg) are sometimes used to affect
the function or production of the abnormal antibodies also.
Thymectomy (surgical removal of the thymus gland) is another treatment
used in some patients. The thymus gland lies behind the breastbone and is an important part of the immune system. When there
is a tumor of the thymus gland (in 10-15% of patients with MG), it is always removed because of the risk of malignancy. Thymectomy
frequently lessens the severity of the MG weakness after some months. In some people, the weakness may completely disappear.
This is called a remission. The degree to which the thymectomy helps varies with each patient.
Plasmapheresis, or plasma exchange, may be useful in the treatment of
MG also. This procedure removes the abnormal antibodies from the plasma of the blood. The improvement in muscle strength may
be striking, but is usually short-lived, since production of the abnormal antibodies continues. When plasmapheresis is used,
it may require repeated exchanges. Plasma exchange may be especially useful during severe MG weakness or prior to surgery.
Treatment decisions are based on knowledge of the natural history of
MG in each patient and the predicted response to a specific form of therapy. Treatment goals are individualized according
to the severity of the MG weakness, the patient’s age and sex, and the degree of impairment.
The current treatments for MG are sufficiently effective that the outlook
for most patients is bright. Although the treatments will not cure MG, most patients will have significant improvement in
their muscle weakness. In some cases, MG may go into remission for a time, during which no treatment is necessary. There is
much that can be done, but still much to understand. New drugs to improve treatments are needed. Research plays an important
role in finding new answers and treatments for MG.
What Causes Autoimmune MG?
The voluntary muscles of the entire body are controlled by nerve impulses
that arise in the brain. These nerve impulses travel down the nerves to the place where the nerves meet the muscle fibers.
Nerve fibers do not actually connect with muscle fibers. There is a space between the nerve ending and muscle fiber; this
space is called the neuromuscular junction.
When the nerve impulse originating in the brain arrives at the nerve
ending, it releases a chemical called acetylcholine. Acetylcholine travels across the space to the muscle fiber side of the
neuromuscular junction where it attaches to many receptor sites. The muscle contracts when enough of the receptor sites have
been activated by the acetylcholine. In MG, there is as much as an 80% reduction in the number of these receptor sites. The
reduction in the number of receptor sites is caused by an antibody that destroys or blocks the receptor site.
Antibodies are proteins that play an important role in the immune system.
They are normally directed at foreign proteins called antigens that attack the body. Such foreign proteins include bacteria
and viruses. Antibodies help the body to protect itself from these foreign proteins. For reasons not well understood, the
immune system of the person with MG makes antibodies against the receptor sites of the neuromuscular junction. Abnormal antibodies
can be measured in the blood of many people with MG. The antibodies destroy the receptor sites more rapidly than the body
can replace them. Muscle weakness occurs when acetylcholine cannot activate enough receptor sites at the neuromuscular junction.