Myasthenia Gravis

(Muscle Weakness)

In this factsheet:
• The Facts on Myasthenia Gravis
• Causes of Myasthenia Gravis
• Symptoms and Complications of Myasthenia Gravis
• Diagnosing Myasthenia Gravis
• Treating and Preventing Myasthenia Gravis
The Facts on Myasthenia Gravis

Myasthenia gravis is an autoimmune disease of the neuromuscular junction, the contact point
between nerves and muscles. For some unknown reason, the body's immune system, which normally
helps fight infections, attacks the acetylcholine receptors found on muscles. These receptors normally
receive a chemical called acetylcholine, which is released by the nerves at the neuromuscular
junction (the point of contact between nerve and muscle) and signals the muscles to contract. Once these
receptors are damaged, the muscles cannot respond to the nerve signals and the muscles become weak.

Myasthenia gravis is almost twice as common in women as in men. It is most commonly found in women
under 40 and men over 60. However, it can occur at any age. Children are very unlikely to suffer from this
disease. People from all continents are equally susceptible. A closely related disease called congenital
myasthenic syndrome is genetically inherited. Myasthenia gravis itself probably has a genetic component,
but the children of people with this condition are only slightly more likely than average to suffer from
autoimmune disease.

Myasthenia gravis is a serious condition, but not usually a life-threatening one. However, in severe cases,
the chest muscles can become so weak that patients have trouble breathing on their own and may
require a ventilator for a few days to a few weeks.

Causes of Myasthenia Gravis

The cause of Myasthenia gravis and other autoimmune diseases such as rheumatoid arthritis and
lupus is not known. One theory is that the disease may be triggered by a virus or other infection which
has a similar structure to a part of the acetylcholine receptor (which is found in the neuromuscular junction
and is needed for it to function normally). The antibodies that the immune system produces to fight the
virus then also mistakenly attack the receptors.

What we do know is that certain antibodies have been found in the blood of people with myasthenia
gravis that are built to attack acetylcholine receptors. Sometimes women with myasthenia gravis who give
birth transmit these particular antibodies to their babies causing muscle weakness in the infant. This is
called neonatal myasthenia. It is different from congenital myasthenia because the infant gets better in a
few weeks as the antibody blood levels go down.

The other abnormality that often shows up in people with myasthenia gravis is an overactive,
overlarge, or otherwise malfunctioning thymus. Thethymus is a gland located where the neck joins
the chest. It is important for the normal development of the immune system. Normally, tht thymus is larger
in childhood than in adulthood, and becomes inactive around puberty. In people with myasthenia gravis,
however, it often keeps going into adulthood.

Some people with myasthenia gravis turn out to have a thymoma (a tumour in the thymus). This is a type
of cancer, and obviously it's frightening, but in fact very few people die of thymomas (see"Treatment and
Prevention").

Symptoms and Complications of Myasthenia Gravis

The most common symptoms of myasthenia gravis are double vision (diplopia), drooping eyelids
(ptosis), and muscle weakness that usually gets worse after exercise or at the end of the day and
improves with rest.

The muscles around the eyes are particularly likely to be affected by myasthenia gravis, and eye
problems are the first sign of the disease in about 40% of cases. Eventually, almost everyone with
myasthenia gravis will experience eye symptoms. Some people experience symptoms only around the
eyes and nowhere else - this is called ocular myasthenia gravis.

Other common symptoms of this disease include:

• blurred vision
• difficulty blow-drying hair
• difficulty chewing or swallowing
• difficulty looking around without moving the head
• difficulty reaching for objects above the head (e.g., in cupboards)
• inability to stand up without using hands
• unstable or unusual gait
• weakness in the arms, legs, hands, and fingers
• weakness in the muscles of facial expression
Many people find that their symptoms rise and fall in intensity many times in the course of a
single day. Often, they follow a similar pattern each day, with muscle fatigue at its worst in the evening.

People who find it temporarily impossible to eat may have to be admitted to hospital and be fed
intravenously. Of more immediate danger is when the disease causes difficulty in breathing. This is called
a myasthenic crisis, and it's responsible for most of the small number of deaths due to myasthenia gravis.
People with breathing problems must go to a hospital immediately.

Diagnosing Myasthenia Gravis

There's a quick and simple test for myasthenia gravis.Anticholinesterase medications are used to
control symptoms in this disease. One such medication, edrophonium,* has a very short duration of action
(its effects don't last very long), and is used for diagnosis. A tiny bit is injected to start with. If there are no
problems, the rest is injected. In people with myasthenia gravis, this will produce a sudden major
improvement in muscle strength and control, lasting about five minutes.

The test is also valuable in people with diagnosed myasthenia because it distinguishes symptoms due to
the disease from similar symptoms that are sometimes caused by the medications. The drugs given for
myasthenia gravis can trigger a cholinergic crisis, which is characterized by increasing muscle weakness.
Edrophonium will relieve symptoms of myasthenic crisis, but may temporarily worsen a cholinergic crisis.

Another important diagnostic test is called electromyography (EMG) and single-fiber EMG. These tests
are used to determine whether the nerve-to-muscle contact is working properly.

Blood tests can be done to detect the anti-acetylcholine antibodies.

A chest X-ray or CAT scan of the chest may be done to look for a thymoma.

Treating and Preventing Myasthenia Gravis

There are four treatments used in myasthenia gravis, and most sufferers receive more than one of
them. They are:
• medications - Anticholinesterase medications like pyridostigmine and neostigmine control symptoms.
Corticosteroids (e.g., prednisone) and immunosuppressants (e.g., azathioprine) can slow or stop the
disease process. Although these drugs don't cure it, they are the mainstay of long-term management.
• plasmapheresis - Large amounts of blood are removed, then put in a centrifuge to separate the red
and white cells from the serum, the liquid that contains the immune antibodies which are doing the
damage. The red and white cells are then replaced, along with donated or synthetic serum.
• immunoglobulin - The fact that this treatment works suggests that a weakened immune system is
part of the cause of myasthenia gravis. Immunoglobulin therapy involves injections of blood serum
from a person without autoimmune disease. It lowers the numbers of tissue-attacking antibodies in the
bloodstream of the person with myasthenia gravis. A course of injections lasting a few months can
provide permanent relief from symptoms.
• thymectomy - The thymus isn't essential in adults and it can be surgically removed without negative
effects. This cures about two-thirds of people with myasthenia gravis, whether they have evidence of
an abnormal thymus or not. In fact, the cure rate in myasthenia gravis patients with thymomas
(tumours of the thymus) is about the same as in people with an apparently healthy thymus or a
malfunctioning but non-cancerous thymus. Of the one-third of patients who aren't cured by this
operation, many can reduce their drug dosage afterwards.
Some people diagnosed with myasthenia gravis are diagnosed with thymoma at the same
time. Fortunately, thymomas are slow-growing tumours, and while they're not actually benign (non-
cancerous), they have a low chance of spreading in any given year. Most thymomas are found while
they're still localized in the thymus, and removing that organ usually provides a complete and lasting cure
for both the myasthenia and the cancer. In fact, myasthenia gravis is often a lifesaver, because it alerts
doctors to a tumour while there's still plenty of time to do something about it.

Nothing can prevent this disease, since we don't know what causes it. However, serious complications
can be prevented if people with myasthenia gravis go to the hospital if they ever have difficulty breathing.
About one in ten people with this disease will face a myasthenic crisis at some point.