Myasthenia gravis is a chronic, neuromuscular autoimmune condition that causes muscle weakness. Although there’s no cure, treatments can help people with myasthenia gravis better manage symptoms.
In a WebMD Reddit AMA about living with myasthenia gravis, neurologist Ryan Donaghy, MD, discussed a variety of topics, from new treatments to thymus gland removal and educating providers about MG.
Donaghy, an assistant professor at Northwestern University Feinberg School of Medicine in Chicago, researches and treats myasthenia gravis and other neuromuscular conditions.
Here are Donaghy’s answers to some of the questions asked during the Reddit AMA. The answers have been lightly edited for length and clarity.
For people recently diagnosed with myasthenia gravis, where’s the best place to start discussing treatment?
Donaghy: The best place to start discussing effective medications for myasthenia would be with a neurologist or neuromuscular specialist (neuromuscular neurologist). If you don’t have a neurologist, your primary care doctor may be able to help point you in the right direction. A neurologist who has additional training in neuromuscular diseases can guide you through the early decisions about medications and general knowledge about myasthenia. There are now so many options to help treat the symptoms of this disease.
What can be done to educate practitioners on symptom recognition across multiple fields?
Donaghy: One of the most critical things in my opinion is more exposure to neuromuscular diseases during medical school and residency training. While many of these diseases are uncommon, they often share clinical features that careful observation and history taking can uncover and raise concern for a neuromuscular disease.
Neurology residency programs are already working on this by increasing the amount of time that resident neurologists spend in outpatient clinical settings, which I think will help. Diagnostic delay is so important to improve — we want patients to be diagnosed early, treated with highly effective medication early, and ultimately to achieve symptom improvement as soon as possible in this disease.
What novel treatments are currently promising for severe cases?
Donaghy: The exciting thing about myasthenia gravis care is that there have been rapid advances in novel treatments. Biologic treatments are now coming to the forefront of care.
The three major classes of novel agents are FcRn receptor antagonists (increase recycling of IgG antibodies), B cell depletors (like inebilizumab and rituximab), and complement inhibitors. Complement inhibitors have significant evidence of benefit in being used in more moderate-severe cases. There is also emerging evidence for use of novel FcRn medications early on in severe disease after initial stabilization.
How do you diagnose myasthenia gravis?
Donaghy: Generally, myasthenia gravis can be diagnosed when a person experiences clinical symptoms of the syndrome — fatigable weakness of the eye movements, eyelids, swallowing, speech, and limbs — along with supportive testing, including auto-antibody positivity. (These antibodies include acetylcholine receptor blocking/modulating/binding antibodies, muscle-specific kinase antibody, and LRP4 antibody). Or they lack these antibodies but have electrodiagnostic studies supporting a neuromuscular junction disorder. There are some more nuanced additions to that diagnostic approach, but that’s the general clinical evaluation for myasthenia, which can be a helpful starting point in any patient’s evaluation.
Does dysphagia (trouble swallowing) have a link to myasthenia gravis?
Donaghy: It certainly can, especially if there’s significant fatigability with swallowing. Many patients with myasthenia will experience worsening of swallowing function toward the end of meals, for instance. This is something we pay close attention to in myasthenia patients and can improve with effective treatment.
Is there any science around the interaction of myasthenia gravis and COVID or with COVID’s side effects?
Donaghy: No specific interaction that I’m aware of, but there’s a lot to be said about the importance of trying to reduce infection risk for myasthenia patients. As people with myasthenia often are taking immunosuppressive medications, they have increased risks of upper respiratory infection. Attention to hand hygiene, masks in clinical environments, and caution around others with infectious symptoms are all reasonable steps to avoid infection.
The challenging thing for patients on immunosuppressive medications is that it can take longer to clear the infection and sometimes an infectious trigger can lead to a myasthenia flare, which needs urgent evaluation and treatment.
What’s the connection between myasthenia gravis and removal of the thymus gland?
Donaghy: There’s a well-known correlation between myasthenia patients and thymoma, a slow growing cancer of the thymic gland tissue. In these patients, a thymectomy (removal of the tissue) is performed and can improve the symptom burden from myasthenia long term. There was also a clinical trial that looked at certain patients with “non-thymomatous” generalized myasthenia gravis associated with positive acetylcholine receptor antibodies in the 18- to 65-year-old age range that showed benefit in symptom improvement and reducing the amount of steroids needed in these select myasthenia patients. This procedure is still regularly done for myasthenia patients and is another helpful contribution to successfully managing symptoms in the right patient.
What’s the No. 1 thing you wished more people living with myasthenia gravis knew?
Donaghy: It’s important to know that treating myasthenia gravis is such a collaborative effort by both the patient and the treating provider. Close communication between the patient and doctor through medical record portals in between visits helps me help my patients adjust medications and address symptoms. It can sometimes take a few different medication trials to find the right fit for a patient. The goal is to reduce symptoms as much as possible.
What treatment is available if you’ve been diagnosed with MG?
Donaghy: Every patient with myasthenia has unique clinical characteristics, comorbidities, and preferences that I tailor my treatment recommendations to. Most people with myasthenia gravis are started on a medicine called pyridostigmine (Mestinon). This medicine helps increase the amount of acetylcholine (the neurotransmitter important for neuromuscular signaling) at the “neuromuscular junction,” which helps improve myasthenia symptoms but doesn’t address the underlying autoimmune disease mechanism. Patients with myasthenia tend to get a small boost in motor function shortly after taking this medicine, but it wears off quickly, so many patients are taking this multiple times a day.
Some people do well just on the pyridostigmine. However, there’s more emerging evidence that starting an immunomodulating treatment early in myasthenia can have long-term benefits in reducing risk of generalization if the patient just has ocular (eye-related) symptoms and in reducing flare risk long-term in the generalized population.
Many patients will start with oral steroids to help reduce the autoimmune attack of the neuromuscular junction. Steroids are very effective, but they do have side effects including hyperglycemia, weight gain, hypertension, skin changes. If the steroids are effective but side effects develop, we often think of using a “steroid sparing” immunosuppressant to help reduce the steroid dose while continuing to manage the myasthenia symptoms. These can be anything from oral medicines including mycophenolate (CellCept, Myfortic, and others) and azathioprine (Azasan, Imuran) to novel medicines (e.g., FcRn antagonists, B cell depletion, complement inhibitors). Depending on the severity of symptoms, some of these novel agents can also be considered to be used earlier on in the disease course.
All patients undergo screening for abnormal growth of the thymus gland, which is situated in the front part of the chest. If there is a thymoma — a slow growing cancer of that gland — it should be taken out by a skilled surgeon. There’s also supportive evidence to perform thymus tissue removal in selected generalized myasthenia patients with positive acetylcholine receptor antibodies who do not have a thymoma.
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SOURCES:
Ryan Donaghy, MD, neurologist, assistant professor, Northwestern University Feinberg School of Medicine, Chicago.
National Institute of Neurological Disorders and Stroke: “Myasthenia Gravis.”
