Moving your muscles may seem automatic, but it’s actually the result of a chain reaction taking place between your brain, nerves, muscles and chemicals inside your body.
A quick lesson in neurology: First, your brain releases a chemical called glutamate that activates a motor nerve. The motor nerve passes the message through your nervous system until it reaches your muscle, where it releases another chemical called acetylcholine. Acetylcholine binds to receptors on the muscle and triggers it to move.
Of course, all this happens almost instantaneously—until it doesn’t.
For people with myasthenia gravis, that messaging system is disrupted by their own immune system, which produces abnormal antibodies that block acetylcholine from binding to the muscle. When muscles don’t get those routine messages to move, they become weak, which can cause a range of symptoms.
Myasthenia gravis is rare, affecting about 37 people per 100,000 in the United States. But while there’s no cure for the condition, treatment options have greatly expanded in the past decade.
We talked to UNC Health neurologist Andrea Corse, MD, who directs UNC Health’s Myasthenia Gravis Clinical Center, to learn more.
Myasthenia Gravis Symptoms
Myasthenia gravis can affect any skeletal muscle, which are the muscles that connect to bones and are used in voluntary movements, like walking, chewing and breathing. Some skeletal muscles are more commonly affected than others.
“About 90 percent of people with myasthenia gravis will have their eye muscles affected within the first two years of onset of the disorder,” Dr. Corse says. “This can result in drooping eyelids or double vision.”
For some people, symptoms only affect the eyes. But for the majority of people with myasthenia gravis, the disorder is “generalized,” affecting the muscles used to chew, swallow, speak and breathe, as well as to move the arms and legs. A hallmark of myasthenia gravis is that the weakness is worse with use.
“You might notice that the jaw fatigues quickly when chewing or that you have trouble swallowing,” Dr. Corse says. “There can be intermittent slurred speech or weakness in the arms and legs, so that you feel fatigued working with your arms above your shoulders or rising from a chair or climbing stairs.”
Symptoms tend to worsen later in the day, as repeated attempts to move weakened muscles exacerbate the fatigue, and can be worsened by some medications, such as antibiotics, and other illnesses.
The symptoms also can be unpredictable.
“Often, people can have their worst symptoms in the first few years with the disorder, but then they don’t chronically progress, which is counterintuitive compared to many chronic disorders,” Dr. Corse says. “Symptoms also can be intermittent, and rarely, patients will have a spontaneous remission—their symptoms completely disappear without treatment.”
People with myasthenia gravis have a normal life expectancy, but there is a serious complication to be aware of. A myasthenia crisis affects the respiratory muscles and requires being on a ventilator in the hospital.
“It’s not like an asthma attack which comes on suddenly, though,” Dr. Corse says. “Often there will be worsening symptoms for days, weeks or months, so with patient education and good communication with a care provider, therapies can often be implemented to prevent a crisis.”
Myasthenia Gravis Risk Factors and Diagnosis
Myasthenia gravis can affect all ages, but it’s more common in women younger than 40 years old and men 50 years and older. People who have another autoimmune disorder may be at higher risk, and there appears to be a genetic predisposition.
Myasthenia can sometimes be difficult to recognize because the symptoms can be varied and intermittent, but there are specific blood tests that can confirm it in 90 percent of patients, Dr. Corse says.
These blood tests are looking for the specific antibodies implicated in myasthenia gravis; knowing which one you have will affect treatment. Sometimes, special nerve stimulation and muscle testing is required to make the diagnosis.
If your doctor suspects myasthenia gravis, they will perform a chest CT scan to look at your thymus gland, underneath the breastbone. This gland is important to your immune system and is supposed to get smaller with age; people with myasthenia gravis often have a thymus gland that is larger than normal and may develop tumors called thymomas.
Myasthenia Gravis Treatment Options
If you’re diagnosed with myasthenia gravis, your doctor will determine your treatment after considering the severity of your symptoms and the type of antibody present in your blood.
“Some patients have disease so mild that they don’t require treatment, just monitoring,” Dr. Corse says. “With treatment, it’s a very tailored strategy based on many factors such as how quickly we need to intervene to stop symptoms and the patient’s other health factors and lifestyle, because some current interventions are more cumbersome compared to others.”
Surgery
The removal of a thymoma or of an enlarged thymus in patients younger than 60 can reduce the number of symptom-causing antibodies. While this used to be a major procedure because it required opening the entire chest, it now can be accomplished via minimally invasive robotic surgery.
“It’s not a cure, but it’s fairly well-studied that removal of the thymus means you’ll require less medication in your lifetime to control the disease,” Dr. Corse says.
Medications
Medications known as cholinesterase inhibitors work quickly to treat mild to moderate symptoms, rather than the underlying disease; the most common is pyridostigmine (Mestinon).
“These medications can improve symptoms within 15 to 30 minutes, and the benefits can last for three to four hours,” Dr. Corse says. “They give the person some control, so they might take these before a meal so they can better chew or swallow, or they could take them before a long drive to minimize eye symptoms.”
Other medications work directly on the immune system to reduce the production of abnormal antibodies and to give the acetylcholine a better chance to work as intended. While oral steroids were traditionally used for this purpose, there are now other options that avoid side effects of using those drugs long-term.
One option is the same medication used by people who have just had an organ transplant and need to suppress their immune system so the transplanted organ won’t be rejected.
Another group of medications, known as complement inhibitors, work by reducing activity in a part of the immune system that the symptom-causing antibodies need to work.
“Antibodies need the complement to cause damage,” Dr. Corse says, noting that the first drug in this class, eculizumab (Soliris), was FDA-approved in 2017, following research led by UNC. “Think about an army being summoned—that’s the antibodies—but you don’t give them weapons, so they can’t fire. That’s how I describe what the complement inhibitor can do, and they work within days.”
Another class of drugs called FcRn antagonists was approved for use in myasthenia gravis in recent years. These medications work through the receptors which control the number of circulating antibodies, reducing the total number of antibodies in the body, including the harmful ones that cause symptoms.
Therapies to avert a crisis
Some people presenting with severe symptoms or those in danger of a myasthenia crisis need very rapid removal of antibodies. Plasmapheresis, where a patient’s blood is circulated thru a filter to remove antibodies before being returned to the patient, is one option. This has fast results but the effects are temporary, lasting only a few weeks.
Intravenous immunoglobin, which is an infusion of a blood product with antibodies that reduce abnormal antibody production, also can minimize the risk of myasthenia crisis. While it can be used to manage ongoing symptoms, it requires a lot of time for repeated infusions.
Emerging Treatments and Future Possibilities
Dr. Corse says this is a particularly exciting time for research into new treatments that may provide longer lasting, more durable results and more directly target the abnormal antibodies without suppressing the entire immune system.
Interestingly, many of the advances are coming from cancer treatment. “In oncology, they have learned how to better target certain cells, and we’re translating that into targeting the cells that cause problems in myasthenia,” she says.
CAR T-cell therapy, in which a patient’s own lymphocytes are trained to recognize and fight cancerous cells, is being evaluated in clinical trials for myasthenia. This treatment holds promise for longer lasting benefit than any other existing treatment, Dr. Corse says.
Living with Myasthenia Gravis
Because of the increase in treatments in recent years, people diagnosed with myasthenia have more options than ever—but not all doctors may know about them as the advances are happening quickly.
“I think this explosion in myasthenia gravis clinical trials research shows the importance of a patient having a consultation in a myasthenia-specific clinic or finding a doctor with a lot of experience,” Dr. Corse says. The Myasthenia Gravis Foundation of America maintains a listing of expert providers. “My goals for treatment are to return patients back to their normal functioning.”
If you have myasthenia gravis, it’s important to be in regular contact with your provider and let them know if any symptoms worsen. Dr. Corse encourages patients to connect with the Myasthenia Gravis Foundation of America for resources and to find support groups, locally or online, to learn from the experience of others and to hear about new treatment options.
Emerging research means “it’s a time to be optimistic and encouraged,” Dr. Corse says.
If you’re concerned about new symptoms you’re experiencing, talk to your doctor or find one near you.