Myasthenia gravis is a neuromuscular disorder characterized by
variable weakness of voluntary muscles, which often improves with rest and worsens with
activity. The condition is caused by an abnormal immune response.
Myasthenia gravis affects the neuromuscular junction, interrupting the communication
between nerve and muscle, and thereby causing weakness. A person with MG may have
difficulty moving their eyes, walking, speaking clearly, swallowing, and even breathing,
depending on the severity and distribution of weakness. Increased weakness with exertion,
and improvement with rest, is a characteristic feature of MG.
About 30,000 people in the United States are affected by MG. It can occur at any age,
but is most common in women who are in their late teens and early twenties, and in men in
their sixties and seventies.
Causes of Myasthenia Gravis
In myasthenia gravis, weakness occurs when the nerve impulse to
initiate or sustain movement does not adequately reach the muscle cells. This is caused
when immune cells target and attack the body's own cells (an autoimmune response). This
immune response produces antibodies that attach to affected areas, preventing muscle cells
from receiving chemical messages (neurotransmitters) from the nerve cell.
The cause of autoimmune disorders such as myasthenia gravis is unknown. In some cases,
myasthenia gravis may be associated with tumors of the thymus (an organ of the immune
system). Patients with myasthenia gavis have a higher risk of having other autoimmune
disorders like thyrotoxicosis, rheumatoid arthritis, and systemic lupus erythematosus.
Myasthenia gravis affects about 3 of every 10,000 people and can affect people at any age.
It is most common in young women and older men.
Why the immune system creates these self-reactive "autoantibodies" is
unknown, although there are several hypotheses:
- During fetal development, the immune system generates many B cells that can make
autoantibodies, but B cells that could harm the body's own tissues are screened out and
destroyed before birth. It is possible that the stage is set for MG when some of these
cells escape detection.
- Genes controlling other parts of the immune system, called MHC genes, appear to
influence how susceptible a person is to developing autoimmune disease.
- Infection may trigger some cases of MG. When activated, the immune system may mistake
portions of the acetylcholine receptor for portions of an invading virus, though no
candidate virus has yet been identified conclusively.
- About 10% of those with MG also have thymomas, or benign tumors of the thymus gland. The
thymus is a principal organ of the immune system, and researchers speculate that thymic
irregularities are involved in the progression of MG.
Some or all of these factors (developmental, genetic, infectious, and thymic) may
interact to create the autoimmune reaction.
The earliest symptoms of MG often result from weakness of the extraocular muscles,
which control eye movements. Symptoms involving the eye (ocular symptoms) include double
vision (diplopia), especially when not gazing straight ahead, and difficulty raising the
eyelids (ptosis). A person with ptosis may need to tilt their head back to see.
Eye-related symptoms remain the only symptoms for about 15% of MG patients. Another common
early symptom is difficulty chewing and swallowing, due to weakness in the bulbar muscles,
which are in the mouth and throat. Choking becomes more likely, especially with food that
requires extensive chewing.
Weakness usually becomes more widespread within several months of the first symptoms,
reaching their maximum within a year in two-thirds of patients. Weakness may involve
muscles of the arms, legs, neck, trunk, and face, and affect the ability to lift objects,
walk, hold the head up, and speak.
Symptoms of MG become worse upon exertion, and better with rest. Heat, including heat
from the sun, hot showers, and hot drinks, may increase weakness. Infection and stress may
worsen symptoms. Symptoms may vary from day to day and month to month, with intervals of
no weakness interspersed with a progressive decline in strength.
"Myasthenic crisis" may occur, in which the breathing muscles become too weak
to provide adequate respiration. Symptoms include weak and shallow breathing, shortness of
breath, pale or bluish skin color, and a racing heart. Myasthenic crisis is an emergency
condition requiring immediate treatment. In patients treated with anticholinesterase
agents, myasthenic crisis must be differentiated from cholinergic crisis related to
Pregnancy worsens MG in about one third of women, has no effect in one third, and
improves symptoms in another third. About 12% of infants born to women with MG have
"neonatal myasthenia," a temporary but potentially life-threatening condition.
It is caused by the transfer of maternal antibodies into the fetal circulation just before
birth. Symptoms include weakness, floppiness, feeble cry, and difficulty feeding. The
infant may have difficulty breathing, requiring the use of a ventilator. Neonatal
myasthenia usually clears up within a month.
Diagnosis of Myasthenia Gravis
Myasthenia gravis is often diagnosed accurately by a careful medical history and a
neuromuscular exam, but several tests are used to confirm the diagnosis. Other conditions
causing worsening of bulbar and skeletal muscles must be considered, including
drug-induced myasthenia, thyroid disease, Lambert-Eaton myasthenic syndrome, botulism, and
inherited muscular dystrophies.
MG causes characteristic changes in the electrical responses of muscles that may be
observed with an electromyogram, which measures muscular response to electrical
stimulation. Repetitive nerve stimulation leads to reduction in the height of the measured
muscle response, reflecting the muscle's tendency to become fatigued.
Blood tests may confirm the presence of the antibody to the acetylcholine receptor,
though up to a quarter of MG patients will not have detectable levels. A chest x ray or
chest computed tomography scan (CT scan) may be performed to look for thymoma.
Treatment of Myasthenia Gravis
While there is no cure for myasthenia gravis, there are a number of treatments that
effectively control symptoms in most people.
Edrophonium (Tensilon) blocks the action of acetylcholinesterase, prolonging the effect
of acetylcholine and increasing strength. An injection of edrophonium rapidly leads to a
marked improvement in most people with MG. An alternate drug, neostigmine, may also be
Pyridostigmine (Mestinon) is usually the first drug tried. Like edrophonium,
pyridostigmine blocks acetylcholinesterase. It is longer-acting, taken by mouth, and
well-tolerated. Loss of responsiveness and disease progression combine to eventually make
pyridostigmine ineffective in tolerable doses in many patients.
Thymectomy, or removal of the thymus gland, has increasingly become standard treatment
for MG. Up to 85% of people with MG improve after thymectomy, with complete remission
eventually seen in about 30%. The improvement may take months or even several years to
fully develop. Thymectomy is not usually recommended for children with MG, since the
thymus continues to play an important immune role throughout childhood.
Immune-suppressing drugs are used to treat MG if response to pyridostigmine and
thymectomy are not adequate. Drugs include corticosteroids such as prednisone, and the
non-steroids azathioprine (Imuran) and cyclosporine (Sandimmune).
Plasma exchange may be performed to treat myasthenic crisis or to improve very weak
patients before thymectomy. In this procedure, blood plasma is removed and replaced with
purified plasma free of autoantibodies. It can produce a temporary improvement in
symptoms, but is too expensive for long-term treatment. Another blood treatment,
intravenous immunoglobulin therapy, is also used for myasthenic crisis. In this procedure,
large quantities of purified immune proteins (immunoglobulins) are injected. For unknown
reasons, this leads to symptomatic improvement in up to 85% of patients. It is also too
expensive for long-term treatment.
People with weakness of the bulbar muscles may need to eat softer foods that are easier
to chew and swallow. In more severe cases, it may be necessary to obtain nutrition through
a feeding tube placed into the stomach (gastrostomy tube).
Prognosis of Myasthenia Gravis
Most people with MG can be treated successfully enough to prevent their condition from
becoming debilitating. In some cases, however, symptoms may worsen even with vigorous
treatment, leading to generalized weakness and disability. MG rarely causes early death
except from myasthenic crisis.
Prevention of Myasthenia Gravis
There is no known way to prevent myasthenia gravis. Thymectomy improves symptoms
significantly in many patients, and relieves them entirely in some. Avoiding heat can help