You may have heard of Lou Gehrig’s Disease,  Multiple Sclerosis and Muscular Dystrophy, but you might not have heard about another neuromuscular disease: Myasthenia Gravis, or MG. It’s a breakdown in the normal communication between your nerves and voluntary muscles that will cause weakness, fatigue, and a loss of function. For many patients, it can make it hard to work or drive or raise a family and carry out other normal activities. In some cases it can even lead to hospitalizations.

There’s no cure for Myasthenia Gravis, but various treatments may help relieve symptoms. Listen to an interview with Michael Hehir, MD, a neurologist and assistant professor at the Larner College of Medicine at UVM. He’s also Chief of the Division of Neuromuscular Medicine.

Let’s start with the basics and add to that very brief description.

Michael Hehir: Sure. Myasthenia Gravis is a disease of the immune system and of muscle. It’s a disorder where the immune system becomes confused and instead of fighting off infections or other foreign bodies instead it is reacting to patient’s muscle at a very specific place called the neuromuscular junction, which is the portion of muscle where a nerve is trying to communicate with the muscle and tell it what to do.

Because of this immune system reaction to muscle, it becomes difficult for patients to use their muscles and they develop the symptom of weakness. Myasthenia is a condition that affects very specific regions of the body. It tends to have a predilection for the muscles that move the eyes, the muscles that open your eyelids, muscles that affect chewing and swallowing, breathing, and arm and leg function.

The most common symptom experienced by patients with myasthenia is double vision, because they have difficulty as this immune reaction is taking place moving their eyes together and having the eyes focus on an image in the same place. This can be a harrowing and very disabling symptom for people because it affects your everyday function. Things like reading, driving, watching television or a movie become difficult.

Other areas of weakness can also become quite difficult. Some patients develop difficulty with chewing and swallowing. Some patients develop difficulty with communication, or other everyday functions such as lifting objects in your house, getting up and down from a chair, walking can become difficult in this disease.

So this is really pretty devastating for folks potentially?

Michael Hehir: Yeah, it is a potentially devastating disease. The name “Gravis” refers to how bad this disease used to be. Before we had treatments, many patients would die from Myasthenia because of the weakness in their breathing muscles. Fortunately, in 2016 we have many good treatments for this condition, so for many patients they can have a pretty good outcome with Myasthenia.

Is the breathing the most dangerous piece of this?

Michael Hehir: Yeah. Patients with Myasthenia can be hospitalized primarily if they develop difficulty with breathing function or they develop severe difficulty with swallowing function. When those things happen, they need to be admitted to the hospital for both supportive care to help support breathing and swallowing function, but also to give immune based therapies that can turn the process around for patients.

Any idea of what causes this involving the immune system, but specifically what makes this process start happening?

Michael Hehir: Unfortunately, like many other autoimmune diseases we don’t know the ultimate source of what brings on that confusion in the immune system. One thing we do know about autoimmune diseases is they do tend to cluster in families and cluster in specific patients. A patient who develops Myasthenia may have a first degree relative that has some other autoimmune disease like hypothyroidism or lupus or rheumatoid arthritis. These conditions that affect the immune system tend to cluster in families and some patients who develop autoimmune diseases will develop multiple diseases. Many patients with myasthenia also develop thyroid disease. We understand that part of it, but the ultimate trigger is not well understood.

Are there any ways to prevent it from developing?

Michael Hehir: No.

You did mention that there are some pretty effective treatments.

Michael Hehir: Yeah. There’s sort of two treatment strategies for myasthenia. We have a way to try and improve communication between nerve and muscle. It’s a little trick that we have that keeps the chemical that sends the signal from the nerve to your muscle around longer so it’s more likely to be able to get the muscle to contract and do its job. That can be a good strategy for patients who have mild symptoms from myasthenia.

For patients who have moderate or more severe symptoms with myasthenia, they often need a medicine to quiet down or suppress the immune system in some way, and there are varied strategies to do that. Some of the therapies are oral medicines that can be taken at home. Other medicines that are needed for myasthenia are infusion-based medicines that need to be administered at a hospital or with a nurse in your home.

With both of those, what are the side effects like?

Michael Hehir: Side effects of the medicines can be varied. With symptomatic therapy it’s a medicine called pyridostigmine. The most common side effect is gastrointestinal upset, which can sometimes limit our ability to use that medicine.

The side effects of the immune-based therapies are varied. The common side effects to those medicines is that patients on them have an increased risk of developing infection because we’re suppressing the immune system which would be fighting off infections. The medicines do have unique side effect profiles. Among them, the most commonly used medicine in myasthenia is prednisone, which is a corticosteroid, which is considered by many physicians and patients to be a medicine that carries many bad side effects.

The other medicines can do things such as over-suppress your immune system or affect liver function, so they’re varied and sometimes it’s hard to compare to medicines from different classes that treat the same disease, which is actually my area of research interest right now.

I think with myasthenia and with other conditions that have multiple potential therapies we’re sometimes left trying to figure out which therapy is the best therapy for a particular patient on a particular day. Many things go into making a decision about which therapy to choose. We think about how likely a medicine is to relieve the symptoms of the disease. In the case of myasthenia, how likely is a medicine to improve muscle strength and get back function for patients.

We also think about cost of medicines. Is it going to be $100 a month or is it going to be $10,000 a month for a particular therapy? We think about quality of life. How are these things going to impact patients on a day-to-day basis? We also think about side effects. As a doctor or as a patient myself, that’s one of the first things that comes to mind, is what are the side effects of the medicine, and certainly one of the first questions my patients ask me when we start talking about treatment.

For conditions like myasthenia, we’re very good at measuring strength and function and there are many validated tools to do these things in the clinic and in research. We’re pretty good at measuring how much something costs in terms of dollars. We’re also pretty good at measuring quality of life. There are many instruments that can be used for myasthenia, but we’re not so good at measuring side effects. We certainly ask patients about common side effects that are associated with medicines, or if you’re doing a clinical trial you list the percentage of patients who’ve developed this side effect or that one, but we don’t really have a way to compare medicines based on their side effect profile alone.

What we’re working on is developing a unit to do that. We’re calling it the Adverse Effect Unit. It’s a way where we’re weighting side effects of all medicines really and having physicians rate the severity of certain categories of side effects, and then we’re also having patients do the same thing. We’re putting that data together to create almost a currency that you could use to compare two different medicines from two different classes that have very different side effect profiles.

You might have a patient on a medicine like prednisone and you may have another patient on a medicine like Cellcept, which is another immune-based therapy that we use for myasthenia, and we could see how likely the two are to make you stronger, how much the two medicines cost, and they may be about equivalent. Then we could measure side effects with this weighted scale, and if one of them seems to have a very high rate of side effects, well then that probably wouldn’t be the medicine you’d want to choose as a first line therapy.

Alternatively, if we had this unit and you were following a patient in clinic, you could sort of administer it at each of their clinic visits and if you found that the side effect scale seemed to be rising with the more rigorous way of measuring it, that might prompt you to change therapy for a patient. We’re not very good at doing that. As physicians we certainly ask people if they’re having side effects, but I think that if we did it in a more rigorous fashion it would improve care.

This does seem like a tool that could be used across many other disease types, right?

Michael Hehir: Yeah. We’re piloting this and developing it in myasthenia, and one of the reasons to do that is because there are very nice things that it could be compared to in myasthenia. We have very good ways to administer metrics of strength, very good ways to administer measures of quality of life that have all been validated, and we have a very good idea of how much medicines cost, so we can take this unit and apply it to this community and compare it against these other metrics to see how it performs and see if it gives us novel information.

It seems to be useful for comparing medicines, but the ultimate goal is to expand this to other subspecialties in neurology, other diseases, and could even expand outside of neurology. As part of this award, I was at a meeting in the spring and I got to present some of my ideas and preliminary research at the American Academy of Neurology meeting, and I was approached by many other neurologists outside of neuromuscular medicine about somehow applying this in their subspecialty, either in the MS population or the epilepsy population, so I think it’s something that I’d like to move out into other aspects of medicine in the future.


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