Myasthenia Gravis — The Dana Guide

by Daniel B. Drachman

March, 2007

sections include: the mechanism behind myastheniadiagnosis and treatment 

Myasthenia gravis means “serious muscle weakness,” which indicates this condition’s essential symptoms: weakness of the voluntary muscles and muscular fatigue. In this case, fatigue does not mean a feeling of tiredness but rather that a person’s muscles become progressively weaker during activity. Often this weakness appears in characteristic patterns. The most common pattern affects the muscles of the eyelids and eyes. One or both lids may droop, or the person may experience double vision or blurriness with both eyes open. Early on, these symptoms may come and go at variable levels, but later they may become constant and more severe.

In about 80 percent of people with myasthenia, the initial eye symptoms become more severe and spread to additional muscle groups. These individuals may also develop difficulty in swallowing, trouble chewing (especially tough foods), slurred (dysarthric) speech, difficulty keeping their head erect, and weakness in their limbs.

An important characteristic of myasthenia is the variability of its symptoms from time to time. Characteristically, people suffering from the condition are somewhat better after waking up in the morning or after rest, and worse later in the day or after physical exertion.

Usually the visual symptoms and weakness cause a person with myasthenia to seek medical care. Because the early symptoms are so often variable, however, they can be easily confused with psychiatric disorders. Also, because many of the early symptoms affect the eyes, physicians often suspect some intrinsic eye problem. Double vision, for example, can also result from disorders of the eyes or orbits, aneurysms or tumors affecting the nerves to the eye muscles, and occasionally thyroid disorders. The symptom of weakness is also common to a wide variety of problems affecting the brain, spinal cord, peripheral nerves, and muscles. The most important step in diagnosing myasthenia gravis may therefore be to suspect it in the first place. Since it is relatively uncommon, many physicians have either never seen a case or do not think of it. There is often a long period between the onset of symptoms and the diagnosis.

The Mechanism Behind Myasthenia

Myasthenia gravis is an autoimmune disease, meaning that it develops from within the body’s own defense system. In fact, due to remarkable advances over the past 25 years, it is the best understood of all the autoimmune diseases. In this type of condition, a person’s immune system, which normally fights germs and other invaders, produces antibodies that attack his or her own cells. Myasthenia gravis results when the body’s defenses mistakenly produce antibodies that attack the acetylcholine receptors on skeletal (voluntary) muscles.

To understand how myasthenia causes problems, we must start with how nerves and muscles interact. To move any muscle—to breathe, swallow, speak, smile, or look in any direction—your nerves must transmit a signal to that muscle. An electrical impulse traveling down the motor nerve releases the neurotransmitter acetylcholine. The muscle receives this chemical signal in a specialized area, below the nerve, that is tightly packed with acetylcholine receptors. When the acetylcholine released from the nerve combines with the receptor on the muscle, a new electrical impulse is initiated within the muscle, which causes the muscle to contract.

If something interferes with the signal’s transmission from nerve to muscle, the result is weakness and fatigue. In myasthenia, the problem is that antibodies attack the acetylcholine receptors, leaving too few of them available to receive the signal. The brain itself is not involved in myasthenia gravis, and the body’s mechanisms for initiating movement at the level of the brain and spinal cord are intact. Even the peripheral nerves remain healthy. Only the acetylcholine receptors on the skeletal muscles are abnormal.

As we have learned more about myasthenia gravis, we have come to recognize it in more people. About 1 in every 7,000 individuals has the condition, and the rate may even be three times that. Females often develop it in their teens and twenties, while in men it usually appears in the fifth to eighth decades. However, myasthenia can occur at any age.

Why some people’s immune systems erroneously attack their acetylcholine receptors is not clear. The answer in many cases seems to be related to the thymus gland, a lymph gland located under the breastbone that serves its main function during early development. About three quarters of all people with myasthenia have abnormalities of the thymus gland. Eighty-five percent of these show evidence of overactivity (hyperplasia) of the gland, and the other 15 percent have tumors there. We therefore suspect that the immune system’s error may originate in the thymus gland.

Myasthenia may also occur in association with other autoimmune diseases, such as thyroiditis, lupus, and certain blood diseases. This suggests a more generalized error by the immune system in distinguishing between “self,” which should not be attacked, and “nonself,” which could represent a threat.

It is rare for myasthenia to be inherited. However, similar disorders of nerve-to-muscle transmission do have a genetic component. These are termed congenital myasthenic syndromes, and they are extremely rare.

Diagnosis and Treatment

Early diagnosis and treatment of myasthenia gravis are helpful because recovery is generally quicker the earlier a person begins treatment. The condition is diagnosed by the following methods:

  1. Typical clinical features, such as the symptoms described earlier.
  2. A blood test measuring antibodies to acetylcholine receptors; 80 percent to 90 percent of myasthenic people show these antibodies in their blood. (Surprisingly, only about half of people with weakness limited to the eye muscles seem to have positive results for this antibody test.)
  3. Electrical tests with nerve stimulation and recording from muscles, to check how strongly signals are getting through.
  4. Injection of edrophonium, which temporarily increases acetylcholine in the body by blocking the enzyme that usually breaks it down. If the body’s response to this drug is better neuromuscular transmission for a short time, that is a useful clue to the problem.

 It is also important to exclude other possible diagnoses. 

One of the common myths about myasthenia is that it is severe, chronic, disabling, and untreatable. In fact, well over 90 percent of people who develop the condition can return to fully productive lives with proper treatment. Neurologists who specialize in neuromuscular disorders or immunological disorders have the most experience in treating myasthenia gravis successfully. Treatments fall into several categories.

Thymectomy. This is the surgical removal of the thymus gland; it provides long-term benefit for most patients. About 30 percent eventually achieve remission or resolution of their symptoms. About another 50 percent benefit partially. The surgery does not have an immediate benefit, however; improvement takes months to many years. As mentioned above, about 10 percent of people with myasthenia have tumors of the thymus gland. These tumors must be removed because they may spread locally and damage the important structures in the chest. Thymectomy should never be done as an urgent or emergency procedure, however. A person’s overall condition, particularly his or her breathing, should be optimized before the surgery in order to assure a smooth and safe recovery. A thymectomy should only be done at a hospital where surgeons commonly perform the operation for myasthenia.

Anticholinesterase medications. The neurotransmitter acetylcholine acts very quickly on its receptor and is then rapidly broken down by an enzyme, as mentioned above. That enzyme is acetylcholinesterase. Drugs that cut back on the acetylcholinesterase in a person’s body allow the existing acetylcholine to interact repeatedly with the receptors. In other words, the muscle receives multiple signals from a single neurotransmitter molecule. This partially improves muscle strength and function but is only a temporary measure.

Immunotherapy. The goal of immunotherapy is to modify the body’s autoimmune attack against the acetylcholine receptors. Some treatments act more quickly or last longer than others. For relatively fast, short-term improvement, usually to get a person over a difficult period or to prepare him or her for surgery, doctors may carry out one of two procedures. Plasmapheresis uses a machine that separates the liquid portion of blood, which contains the troublesome antibodies, from the blood cells, and then returns only the cells to the person’s veins. For most people this produces improvement within a week or so, but the effect is only temporary since their immune cells continue to produce antibodies. On average, the benefit lasts four to nine weeks. Infusing large amounts of immunoglobulin into a person’s blood also produces benefits in a short time, benefits that last for weeks or a month or two. The immunoglobulin is available commercially, prepared from the blood serum of many individuals. Like plasmapheresis, this treatment is used to get a person with myasthenia over a difficult period.

There are several drugs that help suppress the immune system, thereby decreasing the autoimmune disease process. Adrenal corticosteroids (such as prednisone) and cyclosporin A are the most common. These drugs have many side effects, so they must be used with care. Working with skilled and experienced doctors, a person can usually avoid the medications’ problems. Both types of drug work in a time frame of one to three months and often provide excellent benefit. Often these drugs are used in conjunction with other medications that work over the long term. This allows a person to take moderate doses of each drug, thereby minimizing the side effects while optimizing the therapeutic benefit. Two drugs that are prescribed for long-term benefit are azathioprine and mycophenolate. It is worth emphasizing that physicians with experience in managing myasthenia and prescribing these drugs should be in charge.

People with myasthenia gravis should learn as much as possible about their condition, any warning signs that it might get worse, and the side effects of their drugs. It is particularly important for people with myasthenia gravis to seek prompt attention in the event of an infection. Infection can make myasthenia worse because it prompts the body’s immune system to work harder. At the same time, the immunosuppressive medications useful in treating myasthenia may increase a person’s susceptibility to infections.

The goal of research is to devise new methods that will cure myasthenia gravis specifically. Current treatments require some suppression of the immune system as a whole, and, of course, a working defense system is important for a healthy body. An ideal treatment would suppress only the abnormal immune response affecting acetylcholine receptors. Research is now under way to target and eliminate the specific cells of the immune system that are responsible for the disorder. In the meantime, new immunosuppressive agents with fewer side effects are greatly improving the treatments available to people with myasthenia.

As noted above, most people with myasthenia can already expect to live virtually normal lives if they are properly treated. Their life expectancy and the variety of activities they can enjoy should be well within the ordinary range. Without treatment, however, the prognosis for myasthenia is serious. That makes early diagnosis all the more important.  

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