Myasthenia Gravis (MG) is an autoimmune disease. It targets the communication point between the nerve and muscle (called the “neuromuscular junction.”) In MG, antibodies block, alter, or destroy the neurotransmitter receptors on muscle tissue. Since the muscles can’t receive the signal to contract, people with myasthenia become weak. MG causes weakness in voluntary muscles that worsens with activity and improves with rest.
MG’s primary symptoms fluctuate, vary in severity and occur in many combinations. Symptoms may include droopy eyelids; double or blurred vision; weak arms, hands, neck, face or legs; and excessive fatigue. When severe, MG can result in difficulty chewing, smiling, swallowing, talking or breathing.
The name myasthenia gravis comes from Greek and Latin words meaning “grave muscle weakness.” This reflects the situation for patients with MG before the discovery of available treatments. Today, with appropriate therapy, most people with MG can expect to live normal or nearly normal lives.
What Causes MG?
MG is caused by a defect in the way nerves transmit signals to muscles. Movement is initiated by impulses travelling down a nerve and reaching the nerve ending, where a neurotransmitter called acetylcholine is released. Acetylcholine binds or attaches to receptors on the muscle and makes the muscle contract. The strength of the contraction depends on how much acetylcholine the muscles receive.
In MG, your immune system abnormally produces antibodies that block or damage some of the receptor sites for acetylcholine on muscles. Because there are fewer receptor sites, the affected muscles get fewer nerve signals and are unable to sustain a full contraction. These muscles weaken easily with sustained effort, leading to worsening of myasthenic symptoms with activity.
In another form of MG, your immune system produces antibodies to MuSK (muscle specific tyrosine kinase), a protein that helps organize ACh receptors on the muscle cell surface. This also interferes with the nerve-to-muscle communication and causes muscle weakness.
Recently a new antibody has been identified that causes MG muscle weakness. This is an antibody to low-density lipoprotein receptor-related protein 4 (LRP4). This antibody disrupts the function of LRP4, which is needed for activating MuSK, organizing ACh receptors, and forming the neuromuscular junction.
Although not fully understood, doctors believe the thymus gland likely plays a role in MG. This gland lies in the chest area beneath the breastbone, and plays an important role in the development of the immune system in early life. Its cells form a part of the body’s normal immune system. The gland is somewhat large in infants, grows gradually until puberty, and then gets smaller and is replaced by fat as a person ages. In some adults with MG, the thymus gland remains large and is abnormal, containing clusters of immune cells (called lymphoid hyperplasia) usually found only during an active immune response. The thymus gland may give incorrect instructions to developing immune cells, setting the stage for an attack of the acetylcholine receptors.
Some people with MG develop “thymomas” or tumors of the thymus gland. Generally thymomas are benign, but in rare cases they can become malignant. When a thymoma is discovered, surgery to remove it should be performed.
What triggers the onset of MG? Scientists suspect there may be a combination of factors. For example, if you have an abnormal thymus gland or genetic predisposition, then an illness or other event that stimulates the immune system could trigger myasthenia.
Who Gets MG?
It is difficult to determine how many people actually have MG because the disease is often undiagnosed or misdiagnosed. However, it’s estimated that there are two to seven people in every 10,000 that have MG (Muscular Dystrophy Association, “Facts About Myasthenia Gravis,” 2011). MG occurs in all ethnic groups throughout the world, and in both genders. According to the National Institute of Neurological Disorders and Stroke, it most commonly affects women under age 40, and men over age 60, but it can occur at any age.
MG is not thought to be directly inherited. It is not contagious. MG is more common in families with other autoimmune diseases. According to the MDA’s Facts About Myasthenia Gravis (2011), “it’s estimated that 5 to 10 percent of people with MG have another autoimmune disease,” most commonly autoimmune thyroid disease, pernicious anemia, rheumatoid arthritis, diabetes and systemic lupus. Sometimes the disease may occur in more than one member of the same family.
If a woman with MG becomes pregnant, there is a 10-20% chance that the newborn baby will acquire antibodies from the mother. Generally, cases of neonatal MG are temporary and the child’s symptoms usually disappear within 2-3 months after birth. Click to read about Pregnancy and MG (from the September 2016 issue of Conquer by Kourosh Rezania, MD, University of Chicago).
Other children develop MG indistinguishable from adults, although MG in juveniles is uncommon. Click to read about Juvenile MG (from the March 2014 issue of Conquer by Kourosh Rezania, MD, University of Chicago).
In rare cases, a form of myasthenia can be caused by a defective gene and appears in infants born to non-myasthenic mothers. This form of myasthenia is called congenital myasthenic syndrome; it involves abnormal development of the neuromuscular junction, and is not caused by an abnormal immune system.
With treatment, most individuals with MG can significantly improve their muscle weakness and lead normal or nearly normal lives. Some cases of myasthenia may go into remission – either temporarily or permanently – and muscle weakness may disappear completely so that medications can be discontinued in 10-15% of patients. Stable, long-lasting remissions and control of symptoms are the goals of treatment. The course of MG is often unpredictable, and in some cases, the rapid development of severe weakness results in a myasthenic crisis which may include respiratory failure requiring emergency medical care.
Generally, those who are quickly diagnosed and receive effective treatment have the best outcomes. The first two or three years of illness are often when the full extent of MG symptoms emerge, and so can be the most difficult. During this time you may need to try a number of different therapies, to see which you tolerate best and which is most effective. Finding the best treatment can be an extended process, and one that balances your MG progress with the severity of medication side effects.
MG generally doesn’t worsen with aging, and for many, symptoms diminish over time.
This information was abstracted from these sources:
The Myasthenia Gravis Fact Sheet published by the National Institute of Neurological Disorders
(updated February 19, 2016) and retrieved April 27, 2016.
“Facts about Myasthenia Gravis,” published in 2011 by the Muscular Dystrophy Association.
“Diagnosis and management of myasthenia gravis” by Sivakumar Sathasivam, Progress in Neurology and Psychiatry, Volume 18, Issue 1, January/February 2014.
Additional medical references were used as well.
Reviewed by the Conquer MG Medical Advisory Board, April 2016.
Unless otherwise stated, the information provided here is of a general nature, composed by non-medical personnel. It is meant to be accurate and helpful advice for MG patients. It is not intended to be medical opinion, nor is it a substitute for personal professional medical care.