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Melanie Cole (Host): Welcome to Back To Health, your source for the latest in health, wellness, and medical care. Keeping you informed, so you can make informed healthcare choices for yourself and your whole family. Back to Health features conversations about trending health topics and medical breakthroughs from our team of world-renowned physicians at Weill Cornell Medicine.

I'm Melanie Cole. And joining me today is Dr. Mary Vo. She's an Assistant Professor of Neurology at Well Cornell Medicine. And she's here with me to highlight the condition called myasthenia gravis. Dr. Vo, it's a pleasure to have you join us today. Let's start by giving a working definition for people that have never heard of this condition. What is myasthenia gravis? How common is it?

Dr Mary Vo: Hi, Melanie. Thank you for having me again. And I'm excited to educate our crowd about myasthenia gravis. So what this is, it's a relatively rare neuromuscular disorder and it results in fluctuating weakness affecting voluntary muscle groups, including muscles of breathing. When I say rare, it affects probably 20 people per 100,000 in the population. So how that works out is there are probably between 36,000 and 60,000 people in the United States living with myasthenia as we speak. That being said, it's a condition that's really felt to be underdiagnosed. So it's probably more common than our statistics are indicating.

In this condition, just to back up a little, the voluntary muscles of the entire body are controlled by nerve impulses that arise in the brain. These impulses travel all the way down the nerves to the place where the nerves and muscles meet. So there's a small gap there that we call the neuromuscular junction. And where that becomes important is that in myathenia, this is an autoimmune condition that destroys the receptors that live along the surface of the muscle. So the signal from the nerve endings is not correctly making their way to the muscle and not stimulating it appropriately. And so what this translates into is weakness.

For someone with myasthenia, there can be as much as an 80% reduction in the number of these receptor sites of what that ultimately results in is progressive weakness. And this can affect different muscles of the body. Most commonly, people with myasthenia might report that double vision, lid drooping, weakness with swallowing and chewing muscles, as well as extremity weakness that we'll get into in a little bit.

Melanie Cole (Host): Wow. It's a pretty comprehensive definition you just gave us. So are there any risk factors you can point to? Do we know the causes of this as far as any lifestyle, genetics, anything that you can point to for us?

Dr Mary Vo: It's interesting that you mentioned some of these. There's no clear cut risk factor. We know that this is a condition, it's autoimmune and it manifests in adulthood. In fact, there are two peaks that we always talk about with myasthenia. It's women in their 20s and 30s who get diagnosed. And again, we see another peak in men around their 60s, 70s, 80s. However, as the population ages, we're noticing that more men are affected than women. There are no clear risk factors as far as lifestyle changes that one does that would predispose you to this condition.

By and large, it's not really felt to be a genetic condition. It is in an acquired autoimmune condition. The only caveat is that there are some genetic variants that might modulate the immune response predisposing one to myasthenia, but there's no myasthenia gravis gene per se.

Melanie Cole (Host): Thank you for clarifying that. So let's talk about the symptoms, the most common presentation, because some of the symptoms as I was researching really sound like a stroke, Dr. Vo. And how can you tell the difference? I mean, we've learned about stroke. It's so emergent and time-sensitive. Can you tell us the symptoms that someone would notice that would send them to see a neurologist in the first place, and if there's any differentiation between that? I mean, you mentioned eye drooping and some of the things that do sound like a stroke.

Dr Mary Vo: Yes, actually. And the main difference is that myasthenia is much more gradual than stroke. In stroke, you would expect that the weakness or the neurological deficit is there right at onset. Everything can happen very emergently in an instant, whereas myasthenia is a repetitive pattern of perhaps more subtle weakness that is better in the morning and gradually gets worse over the course of the day, and it's reproducible. It can affect different areas of the body. And, as I had indicated earlier, the most common manifestation, especially when the disease presents, is eye drooping and double vision, particularly at the end of the day or after a very fatiguing activity. Over time, other muscles can also be involved including muscles of swallowing. And in 10% of cases, one can develop weakness in the arms or legs as part of the clinical onset.

Melanie Cole (Host): So, how do you diagnose it? How do we know?

Dr Mary Vo: Well, this repetitive pattern of weakness, not generalized weakness, but weakness of specific muscles that is brought out by activity. So people will often say their best time is in the morning, but as the day goes on, sometimes they can barely keep their eyes open in the second half of the day. It's often relieved by rest, so brief periods of rest or even a nap can allow someone to reset, so to speak, in terms of their muscle weakness. And importantly, there are no sensory symptoms that are associated with myasthenia. It's a pure neuromuscular condition and weakness is the key feature. So that is one historical part that leads the physician and the patient down this path of trying to diagnose myasthenia. One is best served by seeing a neuromuscular specialist. Well, we see this condition relatively commonly. There are certain physical exam abnormalities that we can do to provoke weakness. We can fatigue muscle and see a predictable pattern of weakness. There are also tests that we can do, including blood tests, looking for specific antibodies implicated in myasthenia that can confirm the diagnosis.

And lastly, there's a role for electrodiagnostic testing, including a test called repetitive nerve stimulation. It's exactly what it sounds like. We stimulate a nerve at a fixed frequency of three Hertz, and we look to see how the muscle responds over time. In conditions like myasthenia, we actually can fatigue the muscle and can see a predictable rate of detrimental response, an abnormal weakness that's brought out by this type of testing. And in some instances, if the diagnosis between all of these testing cannot be confirmed, we can do things like a specialized single fiber EMG to study the activity of muscle, the instability of muscle firing and make the diagnosis that way.

Melanie Cole (Host): So once you do figure out that that's what's going on, what are some of the treatment options that are available? Tell us a little bit about what you might do for a patient. And what is life like with someone who is living with myasthenia gravis?

Dr Mary Vo: So treatment for a myasthenic is two-pronged. First and foremost, there is a very good symptomatic treatment that everybody uses for myasthenia. And this is a medication called pyridostigmine or the trade name is Mestinon. And what it does, it blocks the body's enzyme, acetylcholinesterase enzyme, from breaking down this much needed neurotransmitter, and makes it last a little bit longer in the neuromuscular junction and thereby allowing it to work better to stimulating muscle. So that's a good symptomatic quick fix, but it doesn't change the underlying cause of the disease, which is the body's immune system destroying these receptors that was on a muscle.

So that brings me to the important second prong of this approach, which is immunosuppression. There are a number of different long-term treatments that we can do to suppress the immune system and to quiet down this destructive process and allow the muscles to function more normally. And the tried and true options are steroids, including prednisone as they quickly and effectively suppress the immune system. And most patients actually feel better within a few weeks after starting steroids for this condition.

That being said, while steroids are very effective, long-term steroids carry with them a lot of undesired side effects, which I don't know if we have enough time to really go into them all. But for that reason, there are a number of steroid-sparing medications. So immunosuppressants that don't have the same profile and the same side effect profile as steroids that can be used long-term to keep the immune system at bay. So some of them are oral, including medications that have been around for quite some time. One is azathioprine and another is mycophenolate.

Outside of several oral medications that are taken daily to suppress disease, there are a couple of intravenous medications that are felt to be more potent for patients who have disease that might otherwise be difficult to bring under control.

One exciting development for us, or rather two exciting developments for us, in the field is that there are approvals for two very specific medications that have a very narrow activity and selectively suppress the small arms of the immune system. So meaning that they're specific enough to have an impact on myasthenia gravis, but it spares you side effects of much broader immunosuppression. So the two that I'm talking about, one is called efgartigimod, the brand name is Vyvgart. And this is a new in class neonatal receptors. And what it's ultimately thought to do is to bring down the antibodies that are specific to myasthenia. And we have a new long-acting complement inhibitor, which blocks the complement arm of the immune system and ultimately does the same thing to bring myasthenia activity under control.

Melanie Cole (Host): Wow, what an interesting topic this is. And since it can happen at these two different points in life, that is such an interesting thing for people to hear. So wrap it up for us, Dr. Vo. What would you like listeners to take away from this about myasthenia gravis and your best advice for patients that may be living with it?

Dr Mary Vo: Well, certainly, for patients who are developing new symptoms, including repetitive weakness, certainly one that gets worse at the end of the day, I would encourage them to go see a neuromuscular specialist, sooner rather than later, to obtain a diagnosis, because there really are a lot of well-tolerated and effective treatments to keep this at bay.

And two, for patients who are already diagnosed with myasthenia, this is actually a very fortunate time in the sense that there are so many new treatments that are available to us, that we didn't have even two years ago. And there are a number of new treatments in the pipeline that are certainly more potent and have less side effects than traditional agents. So I think that we are looking at more streamlined and tailored approaches for myasthenia control.

Melanie Cole (Host): Thank you so much, Dr. Vo, for joining us again. What a great guest you are. So informative and educational. Thank you again for being with us. And Weill Cornell Medicine continues to see our patients in person, as well as through video visits, and you can be confident of the safety of your appointments at Weill Cornell Medicine.

That concludes today's episode of Back To Health. We'd like to invite our audience to download, subscribe, rate, and review Back To Health on Apple Podcasts, Spotify and Google Podcasts. And for more health tips, go to weillcornell.org and search podcasts. So parents, don't forget to check out our Kids Health Cast. I'm Melanie Cole. 

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