Most people have experienced muscle weakness after exercise, heavy exertion, or illness, but extreme fatigue and loss of motor control can be signs of a neurological disorder called myasthenia gravis (MG). Pronounced “my-as-theen-ee-a grav-us,” the condition affects between 14 to 40 Americans per 100,000.

Patients with MG have overactive immune systems that disrupt the body’s normal communication between nerve cells and muscle cells. 

Clinicians at the Yale Medicine Myasthenia Gravis Clinic specialize in rare neuromuscular diseases; their patients have access to high-tech diagnostics, newly approved medications, and advanced surgery.

Patients with MG might first notice drooping eyelids, trouble chewing and swallowing, or slurred speech. MG can also cause muscle weakness in the legs or arms; it can even cause breathing problems. Typically, motor control becomes worse during periods of exertion and gets better with rest.

Sometimes periods of muscle weakness come on so suddenly that a person may have trouble breathing and will require medical assistance. This type of acute episode, called a myasthenic crisis does not occur in most cases. However, these episodes can be exacerbated by a number of factors, including pregnancy, infection, surgery, or some other trauma.

Some patients will experience symptoms involving their eyes only, which is referred to as ocular MG. 

Unfortunately, because the symptoms of MG are often subtle, they can be easily dismissed. It can take up to a year for some patients to receive a proper diagnosis. If muscle weakness continues with no other diagnosis, a doctor might begin to suspect MG. Next a patient is usually referred to a specialist.

Once MG is suspected, blood tests can often definitively diagnose the condition. Those tests measure the levels of antibodies in the blood—the same antibodies that are activated by an overactive immune system.

A small percentage of patients will not have those antibodies detected in their blood and their ailment will have to be diagnosed with electrical testing. Yale’s Myasthenia Gravis Clinic offers an advanced diagnostic technique called electromyography (EMG). A “repetitive nerve stimulation” test will determine how well the nerve cells are communicating with the the main criteria of MG, being muscle cells.

There are three tests that are used specifically for diagnosing MG: anti-AChR antibody titers, the Tensilon test, and electromyography, including both the Jolly test and single fiber EMG. Used together, these three studies provide an accurate diagnoses for MG.

• Anti-AChR antibody titers are positive in a majority of patients with systemic MG, and somewhat fewer in ocular MG. When positive, however, this is the most specific test for MG. There are rare false positives in the elderly population and those with other autoimmune disorders. The titers do not correlate with severity of disease between patients, but will rise and fall with activity of disease in a single patient. 
• The Tensilon test is both less specific and less sensitive than antibody titers. A test dose of 2mg of edrophonium, followed by 4-8 mg, is given to the patient and should result in an improvement in the clinical marker within 30-60 seconds in myasthenics. Improvement should subside within 4-5 minutes. There is some risk to these tests and they should only be performed in an appropriate clinical setting.
• The Jolly test refers to a sequence of repetitive nerve stimulation studies specifically designed to look for neuromuscular junction disease. 

Myasthenia gravis is an autoimmune disease, which means that a patient’s immune system overreacts, causing damage to organs or tissues in the body. In the case of MG, the immune system releases proteins (autoantibodies) that interfere with the normal communication between muscle and nerve cells and in turn, results in weakness.

Plus, like many autoimmune diseases, MG’s exact cause is unclear—it may have to do with genetic factors, environmental factors, or a combination of both. Although the condition occurs spontaneously in most patients, it could also be caused because of a thymoma, or noncancerous tumor on the thymus gland.

As is the case with other autoimmune diseases, MG has risk factors that are not well understood. 

MG is considered a “sporadic disease,” meaning it can strike anyone, at any time. It can occur in people of all ethnic backgrounds and ages, but tends to be more common among women younger than 40, and men older than 60.

There is no one approach to treating MG. It sometimes takes several months to find the best course of treatment. Patients will receive a personalized treatment regimen that may involve the following.

• Steroids: A class of drugs commonly used to treat autoimmune disease. (Prednisone is considered to be the gold standard of care for MG, as the drug effectively alleviates the symptoms of MG.) But steroids are not necessarily a good long-term option. When taken for years, steroids can lead to other health problems, such as elevated blood pressure and increased risk of infection.
• Pyridostigmine: A synthetic drug that boosts the connection between muscle cells and nerve cells, leading to improved muscle strength and contraction. This drug is not considered a cure because if a patient stops taking it, muscle weakness will return.
• Immunosuppressants: A class of drugs that can suppress the body’s immune system, which helps lessen the symptoms of MG. 
• Intravenous Immunoglobulin (IVig): A blood product that contains purified antibodies that have been isolated from donated blood.
• Plasmapheresis: A process during which a patient’s blood is filtered to remove the antibodies that interfere with the communication between nerve and muscle cells. When combined with oral medication, it can benefit patients with MG.
• Surgery: Patients who have a thymoma, or a noncancerous tumor on the thymus gland, will need to have the tumor surgically removed in a procedure called a thymectomy.

Clinicians at Yale Medicine are determined to find the right treatment for each individual. The Myasthenia Gravis Clinic emphasizes “precision medicine,” or customized treatment determined by each patient’s specific symptoms and medical history. The risks and benefits of each therapeutic option is carefully considered and discussed with each patient. The clinic is also designated by the Myasthenia Gravis Foundation of America (MGFA) as a national "Partner in MG Care" site.

Patients at the clinic have the option of enrolling in clinical trials of new, not-yet-approved therapies and other advanced diagnostics.