Myasthenia Gravis

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What is myasthenia gravis?

Myasthenia gravis (my-us-THEE-nee-uh GRAY-vis) is a chronic autoimmune, neuromuscular disease that causes muscles to become weak and quickly fatigued. Myasthenia gravis (MG) affects muscles that control the eyes, mouth, throat, arms and legs. It can cause problems with swallowing and breathing. These symptoms occur because of the breakdown in normal communication between muscles and nerves. 

MG can affect men and women of all racial and ethnic groups, and of all ages. Early diagnosis and treatment can help control symptoms, improve quality of life, and provide a normal life expectancy. MG diagnosis is often missed or delayed because other conditions have similar symptoms.

Relatively rare, an estimated 20 people in 100,000 will develop MG. However, that number is probably much higher because MG is underdiagnosed. More women used to be affected, compared to men, but that is changing. As the United States population ages, the average age at onset continues to increase. Men are now more likely to develop MG than women.

Causes

What causes myasthenia gravis?

The cause of MG is unknown. It is not contagious or inherited, but is an acquired immunological abnormality. There is no specific gene that causes MG. However, there are specific genes that regulate the immune system. 

MG can occur when your body’s immune system produces antibodies that block or destroy receptor sites on muscles. As electrical impulses travel down a nerve, the nerve releases a neurotransmitter called acetylcholine that binds to receptor sites on the muscle. Neurotransmitters are chemicals that brain cells use to communicate with your muscles.  Normally, the acetylcholine activates the muscle and causes a muscle contraction. But MG blocks, alters, or destroys the muscle’s receptors and prevents muscle contractions. With fewer receptor sites available, your muscles receive fewer signals from nerves, resulting in muscle weakness. 

Another type of MG, called seronegative myasthenia gravis or antibody-negative myasthenia gravis, is not caused by specific antibodies blocking receptor sites. However, it’s possible that it’s also caused by a faulty autoimmune function.

About 3% of patients had a close relative with MG, suggesting a small direct genetic influence to developing MG. Additionally, there’s a temporary form of MG (neonatal myasthenia) that can develop in the fetus when the mother with MG passes antibodies to the fetus. With treatment, it resolves in a couple of months after birth.

The thymus gland, part of the immune system, may trigger or maintain the production of the antibodies that block the muscles’ receptor sites. Some people with MG have an abnormally large thymus gland, or have tumors on their thymus (thymomas). Thymomas are usually harmless, but occasionally become cancerous. The thymus gland may send incorrect instructions to developing immune cells, causing the immune system to attack its own cells, and produce acetylcholine receptor antibodies. 

Although rare, children can develop congenital myasthenia. This is not an autoimmune disease but is caused by defective genes that can cause symptoms similar to MG.

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Symptoms

What are the symptoms of myasthenia gravis? 

MG symptoms can begin suddenly, and tend to get worse over the next few years after the disease begins. Symptoms can go through periods of flare-ups and remissions (easing of symptoms). Remissions are rarely permanent or complete. The level of muscle weakness varies a great deal among patients. 

The chief symptom of MG is muscle weakness that gets worse after periods of activity, improving after a rest period. Other muscle-related symptoms can vary but may include: 

  • Weakness of eye muscles (ocular myasthenia)   
  • Double or blurry vision occur in more than half of MG patients (often the first symptom)
  • Drooping eyelids
  • Speech difficulties
  • Problems with chewing and swallowing; may include weight loss
  • Shortness of breath
  • Change in facial expression or mask-like appearance
  • Weakness in the fingers, hands, arms, neck and legs; making it hard to walk or hold your head up
  • Myasthenic crisis is a medical emergency that can occur when the breathing muscles are so weak that the patient requires a ventilator to breathe. About 20% of MG patients have at least one myasthenic crisis. It can be triggered by an infection, stress, surgery, medication reaction, or unknown cause.

What makes myasthenia gravis better?

Making good lifestyle choices can help prevent or minimize MG symptoms, especially a myasthenic crisis. These include:

  • Balance periods of activity with periods of rest
  • Eat a healthy diet to maintain muscle strength and a healthy weight
  • Use stress-reducing techniques every day because stress worsens symptoms
  • Take anticholinesterase medications exactly as prescribed to help maintain the strength of breathing muscles; taken 30-45 minutes before meals, they can reduce the risk of aspirating food into your lungs
  • Avoid crowds and people with respiratory infections (cold or flu)
  • Whenever you’re prescribed a medication, be sure the prescriber knows you have MG because some medications interfere with MG

What makes myasthenia gravis worse?

Factors that may worsen MG symptoms include:

  • Fatigue
  • Emotional upset, stress, and anxiety
  • Illness, especially viral infections affecting your lungs
  • Hypothyroidism or hyperthyroidism
  • Pregnancy
  • Menstrual periods
  • Surgery
  • Increase in body temperature
  • Having certain autoimmune conditions (lupus or rheumatoid arthritis)
  • Taking medications that affect neuromuscular transmission (beta blockers, quinidine gluconate, quinidine sulfate, quinine, phenytoin, some anesthetics and some antibiotics)

Almost always progressive, MG symptoms get worse with time. From the onset of the disease, it can progress in these ways:

  • Up to 40% of patients have weakness only in their eye muscles. 
  • Spontaneous improvement is possible, usually early in the course of the disease. 
  • Weakness gets worse during the first two years, usually affecting arm, leg and throat muscles.
  • In 60% of patients, the maximum weakness occurs during the first year. The active stage of MG is when symptoms are at their worst. 
  • Inactive stage follows the active stage, which can include occasional changes in strength due to fatigue, or other specific factors.
  • Weakness often becomes fixed after 15 to 20 years. The most damaged muscles are usually burned out and shrunken.

Diagnosis

How is myasthenia gravis diagnosed?

To confirm a MG diagnosis, your doctor will listen to your symptoms, and do physical and neurological exams to test reflexes, muscle strength, coordination and balance. 

Other tests may include:

  • Measuring your response to anticholinesterase medication. MG is confirmed if muscle weakness dramatically improves when taking it.
  • Edrophonium test is done if you have eye problems, to test for eye-muscle weakness. 
  • Blood test checks for antibodies that block muscle receptor sites.
  • Single fiber electromyography (EMG), the most sensitive test for MG, measures electrical activity of a muscle to detect faulty nerve-to-muscle transmission. 
  • Nerve conduction studies provide repetitive nerve stimulation.
  • Imaging tests such as CT scan or an MRI check for thyroid tumors. 
  • Pulmonary function test measures breathing strength to help predict the likelihood of a myasthenic crisis. 
  • Genetic tests can check for inherited conditions.

Treatment

How is myasthenia gravis treated?

While there is no cure for MG, symptoms can be controlled. The goal of treatment is to increase, or at least stabilize, your muscles’ ability to function normally, and prevent swallowing and breathing problems. By improving muscle strength, most patients can lead normal lives. Severe cases may require help with breathing and eating.

Treatment for this lifelong condition will depend on your age, gender, overall health, medical history, the extent of your MG, and if you can tolerate specific medications. 

Therapies to improve muscle strength include:

  • Thymectomy removes an abnormal thymus gland. Although results can be unpredictable, this surgery can rebalance the immune system, reduce muscle weakness, reduce the need for immunosuppressive medications, and even cure some patients, especially younger ones. It’s also performed on patients without thyroid tumors.
  • Monoclonal antibodies target the process that damages or destroys muscle function.
  • Anticholinesterase medications treat MG by slowing the breakdown of nerve-to-muscle transmission and increasing muscle strength.
  • Corticosteroids provide improvement, or a complete relief of symptoms, in more than 75% of patients. It can cause side effects. If patients don’t do well on prednisone, azathioprine may be used instead, or with prednisone. 
  • Immunosuppressive medications suppress abnormal antibodies. They can cause major side effects and must be monitored carefully.
  • Plasmapheresis removes harmful antibodies from your blood plasma and replaces them with normal plasma. Intravenous immunoglobulin gives you a highly concentrated dose of antibodies to temporarily change how the immune system works. Only used in severe cases of MG, this therapy lasts a few weeks to months. 

Self-care can help with symptoms, such as:

  • Eat when you have good muscle strength and chew food slowly. Soft foods and smaller meals can also help.
  • Make your home safe to avoid falls. Consider installing grab bars or railings where you need support. Remove slippery area rugs, and keep walkways clear inside and outside.
  • Conserve your energy by using electric appliances such as electric toothbrush. and can opener.
  • If you have double vision, wear an eye patch; alternate which eye you cover. 
  • For essential activities or chores, do them when you have the most energy, usually early in the day.

References

Johns Hopkins Medicine. (N.d.) Myasthenia Gravis. Retrieved 2-4-22, {https://www.hopkinsmedicine.org/health/conditions-and-diseases/myasthenia-gravis#:~:text=Myasthenia%20gravis%20(MG)%20is%20a,%2C%20mouth%2C%20throat%20and%20limbs.}
Myasthenia Gravis Foundation of America. (2015, June) Clinical Review of MG. Retrieved 2-4-22, {https://myasthenia.org/Professionals/Clinical-Overview-of-MG}
Mayo Clinic. (2021, June). Myasthenia gravis. Retrieved 2-4-22, {https://www.mayoclinic.org/diseases-conditions/myasthenia-gravis/symptoms-causes/syc-20352036}
Mayo Clinic. (2021, June). Myasthenia gravis Diagnosis and Treatment. Retrieved 2-4-22, {https://www.mayoclinic.org/diseases-conditions/myasthenia-gravis/diagnosis-treatment/drc-20352040}
National Institute of Neurological Disorders and Stroke. (2021, Nov) Myasthenia Gravis Fact Sheet. Retrieved 2-4-22, {https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Myasthenia-Gravis-Fact-Sheet}

Information

Medically reviewed by:

Dr. Desiree Levyim

Dr. Desiree Levyim is a board eligible neurologist in practice since 2020. She joins TeleMed2U in our mission to provide increased access to healthcare.

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