Myasthenia gravis

What is myasthenia gravis?

Myasthenia gravis is a chronic (long-lasting) and rare disease that affects the way muscles respond to signals from nerves, leading to muscle weakness. The disease can occur at any age, but it mainly affects women between ages 20 and 40. After age 50, men are more likely to get the disease.

Normal muscle movement relies on chemical signals from the nerves. Nerve signals cause the nerve endings to release a chemical called acetylcholine into the small space between the nerve and the muscle. This chemical binds to special acetylcholine receptors on the muscle cells and causes the muscle to contract.

Myasthenia gravis is an autoimmune disease, which means the body's defense mechanism, the immune system, begins to attack the body's own tissues instead of foreign invaders, such as viruses. In myasthenia gravis, the immune system attacks the acetylcholine receptors with specific antibodies. Some of the receptors are destroyed or blocked, which means that the chemical message cannot be received. Therefore, muscles do not contract properly and become weak. It has been estimated that up to 80% of a person's acetylcholine receptors can be damaged due to this disease.

Normally, the amount of acetylcholine available to be released to muscle cells diminishes with repeated, prolonged or strenuous activity. In a person with myasthenia gravis, that normal decrease combined with fewer working receptors causes increasing weakness, or myasthenic fatigue. Muscles that may seem normal at first become weak with continued use. This is why a person with myasthenia gravis will feel strongest immediately after waking up or resting and weakest at the end of the day when muscles have been in continual use.

Myasthenia gravis typically strikes muscles in the face first. Muscles that control the eyelids and eye movements usually are affected early in the disease. Later, facial weakness can make smiling, chewing, swallowing and talking difficult.

In most people, the disease eventually spreads to other areas and can affect the muscles of the arms and legs. Sometimes, the disease affects the muscles that control breathing. In some situations, such as during a respiratory infection, this weakness becomes severe. The person may need a breathing tube and a ventilator. It's known as a myasthenic crisis.

No one knows what causes the body to attack its own cells. The thymus, a gland located in the chest just above the heart, is involved in immunity early in life. The thymus gland is thought to be the site of abnormal antibody production in myasthenia gravis, although its precise role is not yet understood. The thymus is abnormal in about 80% of people with myasthenia gravis; enlargement is the most common abnormality but about 10% to 15% of people with the disease have a benign (noncancerous) tumor of the thymus.

Although myasthenia gravis is not believed to be inherited or contagious, babies born to mothers who have myasthenia gravis have an increased risk of having the disease at birth. This probably is because the baby acquires the antibodies that attack the body's cells from the mother during gestation. Usually, the baby's symptoms go away within a few weeks after birth.

Symptoms of myasthenia gravis

The primary symptoms of myasthenia gravis are that muscles are weak and tire quickly. These symptoms can take many forms, and the symptoms may be more or less severe for different people. Symptoms may include some or all of the following:

• muscles that become progressively weaker with prolonged use
• muscle weakness that seems better in the morning or after resting and worse after activity or at the end of the day
• drooping eyelids
• blurred or double vision
• a change in facial expressions, such as a smile that looks more like a grimace
• jaw muscles that tire easily, such as when chewing gum or meat
• difficulty swallowing
• slurred or impaired speech
• weakness in arms, legs, fingers, hands or neck
• shortness of breath.

Sudden, severe weakness (myasthenic crisis) may develop without warning, sometimes triggered by an infection or other stress, causing breathing and swallowing problems. Ocular myasthenia gravis is limited to the eye while generalized myasthenia gravis may affect muscles throughout the body.

Diagnosing myasthenia gravis

Your doctor will ask detailed questions about your symptoms and will examine you. He or she will test your muscle strength and reflexes, eyelid strength and eye movements.  If you are experiencing drooping eyelids as part of your weakness, your doctor may apply a bag of ice to your eyelids to see if the drooping improves (because weakness tends to improve with direct cooling of the weak muscles).  If the results suggest myasthenia gravis, some specific tests may be done to confirm the diagnosis. These include:

• Blood tests. The test will check for the presence of the specific antibodies associated with myasthenia gravis, including the acetylcholine receptor antibodies that cause myasthenia gravis. High levels of these antibodies will be present in up to 90% of people with the generalized disease but only about half of those with disease limited to the eye. Of the 10% of people with generalized myasthenia gravis who lack acetylcholine receptor antibodies, other antibodies (called MuSK and LRP4) may be present in the blood. The finding of these other antibodies can be helpful when the diagnosis is suspected despite the absence of antibodies to the acetylcholine receptor.  Other blood tests are recommended to identify other explanations for weakness or other associated conditions. For example, thyroid function testing is important because thyroid disease can mimic some features of myasthenia gravis and because many people with myasthenia gravis also have thyroid disease.
• Electrodiagnostic testing. Also called electromyogram (EMG), nerve conduction studies (NCS) and/or repetitive nerve stimulation (RNS), this testing is done by the insertions of tiny needles into muscles or near nerves. Then, the muscle and nerve are stimulated to analyze their function. Repeated stimulation will rapidly weaken the muscle response in people with myasthenia gravis.
• Tensilon test, also called the edrophonium test. Edrophonium (brand name Tensilon) is a drug that temporarily increases the amount of acetylcholine in the neuromuscular junction. That means that more of the chemical signal is available to activate the muscle. In people with myasthenia gravis, this can improve strength temporarily. This test is not perfect: some people with myasthenia gravis have no response to edrophonium, and some people who seem to get stronger during this test turn out to have a different neuromuscular problem. This test is not commonly performed any longer because the drug is no longer available in the US and because of difficulties in interpreting the results.

In addition, magnetic resonance imaging (MRI) scans or computed tomography (CT) scans may be done to look for abnormalities of the thymus. Pulmonary function tests, which measure breathing strength, also may be recommended, because they can alert doctors to any potential breathing problems. Additional testing, including blood tests or other imaging tests, often is suggested to exclude other possible explanations for a person's symptoms.

Expected duration of myasthenia gravis

Myasthenia gravis is a chronic (long-lasting) disease that usually worsens slowly over time. Although symptoms may fluctuate in severity over the years, the disease rarely goes away on its own. It is likely to return even after periods when the disease has not been active.

Preventing myasthenia gravis

Because the cause of myasthenia gravis is unknown, there is no way to prevent it. However, once the disease has developed, there may be ways to prevent episodes of worsening symptoms or flare-ups:

• Give yourself plenty of rest.
• Avoid strenuous, exhausting activities.
• Avoid excessive heat and cold.
• Avoid emotional stress.
• Whenever possible, avoid exposure to any kind of infection, including colds and influenza (flu). You should be vaccinated against common infections, such as influenza, RSV and COVID-19.
• Work with your doctor to monitor your reactions to prescription medications. Some drugs commonly prescribed for other problems, such as infections, heart disease or hypertension, may make myasthenia gravis worse. You may need to choose alternative therapies or avoid some medications entirely.

Treating myasthenia gravis

There are many possible treatments for myasthenia gravis. You and your doctor should work together to determine the best treatment for you.

• Medications that improve symptoms of myasthenia gravis work by allowing more acetylcholine to accumulate in the neuromuscular junction. This increases the chances that receptors will be activated, so that the nerves and the muscles will communicate better and the muscles won't weaken as quickly. Pyridostigmine (Mestinon) is the most commonly prescribed medication for this condition.  Drugs that suppress the immune system, such as corticosteroids and azathioprine (Imuran), mycophenolate mofetil (Cellcept) or cyclosporine (Neoral, Sandimmune, Gengraf), work for some people, probably by reducing the amount of receptor antibodies in the body. Newer medications for this disease include efgartigimod alfa, ravulizumab, rozanolixizumab and zilucoplan; they are also aimed at reducing levels of receptor antibodies.
• Surgical removal of the thymus (thymectomy) improves symptoms in some people with myasthenia gravis, although experts disagree about who should have the surgery and when it should be done. This procedure is recommended routinely for people who have a tumor. It is thought that removing the thymus may somehow re-balance the immune system. Occasionally, radiation of the thymus is offered when the thymus cannot be removed completely. For example, sometimes the gland extends around blood vessels that make complete removal particularly dangerous or technically impossible. Because it can take many years to see a benefit from thymectomy, some experts recommend not removing the thymus in elderly people with myasthenia gravis.
• Plasmapheresis (or plasma exchange) is a process in which plasma is separated from the blood, cleaned of abnormal antibodies, and then replaced. Plasmapheresis can increase muscle strength for many people with myasthenia gravis, perhaps because it lowers the amount of abnormal antibodies. The technique is used mainly in severe cases that may be life threatening or when other treatments fail. One advantage of this treatment is that it tends to work quickly, although its benefits may not last long.
• Some people have been helped with intravenous immunoglobulin therapy, which involves infusions of certain antibodies into a vein to alter the immune system temporarily.
• Experimental therapies often are offered as part of a research study or if conventional treatments have not been effective.

When to call a professional

See your doctor if you experience any unexplained muscle weakness or fatigue.

If you have been diagnosed with myasthenia gravis, it is critically important to be prepared to seek help in case of a myasthenic crisis. If the muscles that control your breathing are affected, call your doctor if you develop a respiratory infection or even a small breathing difficulty. Seek immediate help if you have significant difficulty with breathing or swallowing.

Prognosis

Myasthenia gravis is a chronic disease, although there may be periods of remission, when symptoms disappear. Current treatments, however, can allow most people with myasthenia gravis to live normal or near-normal lives. People with ocular myasthenia gravis (without progression over several years) have a better prognosis than those with generalized disease.

Other autoimmune disorders, such as systemic lupus erythematosus (SLE or lupus) or rheumatoid arthritis, may be associated with myasthenia gravis and may develop either before or after the weakness is noticed.

Additional info

National Institute of Neurological Disorders and Stroke
https://www.ninds.nih.gov/

Myasthenia Gravis Foundation of America
https://www.myasthenia.org/