Published: Oct. 17, 2006
Updated: Mar. 21, 2011
The symptoms are troubling, yet subtle.
You might notice, for example, occasional double vision, drooping eyelids, or the occasional difficulty to chew or swallow food. You may become hoarse or talk through your nose. It may be hard to smile, and people may tell you that you look depressed, even though you feel fine.
If any of these symptoms sound familiar, you may have myasthenia gravis (MG), an autoimmune disease that affects the transmission of signals from nerves to muscles.
Although it often involves muscles that control eye and eyelid movement, facial expression, chewing, talking, and swallowing, MG can also affect muscles in the neck, limbs, and even those that control breathing. Typically, symptoms come and go, with muscle weakness increasing during activity and improving after periods of rest.
MG most typically appears in adult women under 40 and men over 60, but it can occur at any time, even in children. It is rare enough (affecting between 50,000 and 60,000 Americans) that most patients have never heard of it -- and most doctors are not attuned to look for it. But early diagnosis is important because myasthenia gravis is one of the best-understood autoimmune diseases. A wide array of new treatments allow most people with MG to live normal, productive, symptom-free lives.
The name myasthenia gravis comes from the Greek and Latin words meaning “grave muscle weakness.” That’s because one-third of the people who contracted MG died from it before medical advances in the past few decades unlocked many of the disease’s mysteries.
“Before we had good treatments, I can remember how severe MG was and how frequently fatal it was,” says Duke neurologist Donald B. Sanders, MD, an internationally recognized expert on MG who has written more than 100 papers on the condition. “It's been very gratifying to be part of the process of developing new treatments.”
MG is caused by a defect in the transmission of nerve impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction -- the place where nerve cells connect with the muscles they control. In MG, the body produces antibodies that block, alter, or destroy neurotransmitters (biochemical substances within the muscle) that allow muscle contraction.
In many cases, a blood test can confirm a diagnosis of MG. Another diagnostic strategy uses electromyography (EMG) to test the muscle response to nerve activation. Sanders, director of the MG Clinic at Duke, says that people who may have MG should go to a major care center with state-of-the-art diagnostic tools and clinical expertise.
“There are a relatively small number of experts in MG nationwide, based at probably fewer than a dozen specialized clinics,” Sanders says. “We all know each other and work together.”
According to Sanders, Duke has one of the largest MG clinics in the country. Sanders and colleagues Janice Massey, MD, and Vern Juel, MD, follow 300 to 350 MG patients at any given time. Most are from the Southeast, but some come from distant parts of the country and the world for treatment.
Current treatments for MG involve the use of drugs and surgery, either alone or in combination. Many MG drugs are immunosuppressants that were first used in organ transplantation, where they help to suppress the body’s rejection of new organs. When used to treat MG, these medications suppress the destructive antibodies, allowing muscle strength to increase.
Corticosteroids such as prednisone were the first immunosuppressants used to fight MG. But prednisone has serious side effects of its own. Sanders says that immunosuppressant treatment typically starts out with a combination of prednisone and another drug, such as azathioprine, mycophenolate mofetil (CellCept™), or cyclosporine. The goal is to discontinue the prednisone after the symptoms have abated to control the condition with as few medications as possible.
Another class of frontline drugs used to treat MG includes neostigmine and pyridostigmine, which help improve neuromuscular transmission to increase muscle strength. The problem with this class of drugs is that, although they begin working within minutes, they wear off after a few hours, so they must be taken throughout the day. And they often don’t completely alleviate symptoms.
If the disease is severe when the patient first arrives for treatment, doctors may use plasmapheresis to help quickly alleviate weakness. In this blood purification treatment similar to kidney dialysis, the blood is processed through a machine and the harmful antibodies are removed before the blood is returned to the body. High doses of gamma globulin may also be used to produce rapid improvement.
Another common treatment is thymectomy, the removal of the thymus gland. Located in the chest, the thymus is part of the body’s normal immune system in childhood, then shrinks to a barely existent size in adulthood. In MG patients, however, thymic abnormalities are common. Many have enlarged thymus glands. Ten to 15 percent have tumors called thymomas, which are usually benign.
Although the connection between the thymus and MG is not fully understood, removal of the gland (thymectomy) often improves the disease and may even be followed by complete remission for some patients.
“Thymectomy is the closest thing to what you would consider a cure for MG,” says Sanders. “When it works, it works really well. At least half the people who have it done will receive some benefit.”
In the MG Clinic, Massey is currently leading Duke's participation in a clinical trial designed to further investigate and document the connection between thymectomy and MG.
Although new treatments offer promise for MG sufferers, one of the biggest challenges remains in beginning treatment promptly after a proper diagnosis.
According to the federal government’s National Institute of Neurological Disorders and Stroke, it is not unusual for a diagnosis of MG to be delayed one to two years. Weakness is a common symptom of many disorders, and MG is rare enough that it doesn’t jump onto the radar of many doctors -- even neurologists.
But Sanders says that early diagnosis is critical, and not only because it saves patients unnecessary anxiety and expense. There is compelling evidence that the earlier treatment starts, the more effective it is. That’s why Sanders recommends diagnostic testing at a facility, such as Duke, that is recognized for its expertise in the field.
Because so much is known about MG, doctors and researchers hope to apply some of their knowledge about this autoimmune disease to other conditions.
“In MG, we know what the antibodies are," says Sanders. "We know what areas of the body they target and how they produce weakness. That level of knowledge makes MG an ideal disease on which we can model the study of autoimmune diseases in general.”
But one major mystery remains with MG: no one knows yet what sparks the disease or triggers the autoimmune process that causes the body to make the destructive antibodies.
“The ultimate challenge is to find the cause,” says Sanders.
And that could well lead to the cure.
To make an appointment to visit Duke’s Myasthenia Gravis Clinic, call 888-ASK-DUKE (888-275-3853).