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Nicholas J. Silvestri, MD: Welcome to Medscape InDiscussion: Myasthenia Gravis (MG). I'm your host, Dr Nick Silvestri. This is episode five of season one, and today we'll zero in on evidence supporting non-pharmacologic therapies for MG. How helpful are exercise and physical rehabilitation medicine in the management of MG? What strategies are improving mobility and functional ability? How is quality of life affected, and what do we know about optimal timing for these interventions? For expert guidance, we've invited Dr Kelly Gwathmey, associate professor of Neurology and chair of the Neuromuscular Division at Virginia Commonwealth University in Richmond, Virginia. Welcome, Kelly.
Kelly G. Gwathmey, MD: Thank you so much for having me, Nick.
Silvestri: Always a pleasure. Kelly, you're known for your research on quality of life metrics as well as your compassionate care and ability to communicate complex information in a way that patients and loved ones understand. Can you tell us what it is that made you want to specialize in neurology and focus on MG? And how do you stay engaged and recharged today?
Gwathmey: Thanks, Nick. I was actually drawn to neurology in parallel with majoring in neuroscience and behavioral biology at my university. When I started shadowing neurologists in college and working with neurologists in medical school, I knew it was my calling. Some of the very first patients I met in college were myasthenic, and their stories and the treatment approach really stuck with me and ultimately influenced me to go into neurology and neuromuscular medicine.
I truly enjoy caring for the myasthenic patients. And as you know so very well, we're in the midst of this therapeutic explosion. Our treatment approach 10 years ago was very different than what we're doing these days, so it's very gratifying to see the progress that we've made, and I've become quite impatient with suboptimal disease control.
Having all these different tools in our toolkit is really fun. And to your question regarding how I stay engaged and recharged, when it comes to MG, it comes back to the patients. In recent years, there's been increasing awareness of the impact of this disease on our patients not just physically but also emotionally and from a social and financial standpoint, too.
We've been working really hard to build out additional support systems at our institution and in our region to take care of the whole patient. Seeing the differences we make not only therapeutically with our patients but also in a more comprehensive, holistic manner is very meaningful, too.
Silvestri: That's great, Kelly. I think one of the important points here is that we're treating the patient, we're not treating the disease. We need to have that holistic approach about our patients — the impact of the disease on our patients, the impact on their lives, and really thinking about them holistically.
That's fantastic. Thanks so much for that lead-in. Our focus today is on the evidence for lifestyle management strategy with MG, including therapeutic exercise, sleep hygiene, symptom management, and stress reduction. They all reasonably fall within a patient's range of control. Kelly, tell us how you talk to your patients about exercise and/or rehabilitation. How do you motivate and monitor patients, and what do you recommend in terms of exercise to your patients with MG?
Gwathmey: I think exercise is a tricky proposition in MG, right? I recall a patient I saw nearly 10 years ago who was a college student with MG who was desperate to get to the gym. She wanted some guidance on what was safe to do and what was not safe to do.
There really wasn't much literature out there a decade ago, and no one really knew how to counsel her. The reason this is tricky is the very nature of the disease. As you know, it's a disease that causes fatigable muscle weakness. So, can you actually have a myasthenic patient participate in exercise safely? Or is it the more they exercise, the weaker they get, which isn't advisable? So, in short, yes, we can train our patients with exercise and improve quality of life, fatigue, and strength in select patients. In patients who have mild to moderate disease under somewhat good control, it's likely safe to prescribe exercise. Now, we certainly wouldn't want to take a very ill, unstable patient and send them to the gym. I think the outcomes there would not be very good. But in patients who have mild to moderate disease, certainly we can consider exercise. Looking at the body of literature, there are different forms of physical training, including aerobic training, strength training, and progressive resistance training, that have all been demonstrated in small studies to improve strength, and usually it's proximal muscle strength.
Exercise improves aerobic capacity and may improve the patient's mobility, balance, fatigue, and quality of life. There's actually even a study that demonstrated that long-term physical activity may reduce the autoimmune response, and there's not a case these days that exercise is actually detrimental to the disease itself.
As you know, a lot of our patients, especially those who've been doing poorly — say, a patient who's been hospitalized for 10 days getting plasma exchange — they get deconditioned. So, there's also a role for rehabilitating these patients and building back up their stamina and endurance.
Now, in patients for whom I think that an exercise regimen would be advisable and beneficial, I don't necessarily tell them to go to the gym and start lifting as many weights as they possibly can. We've all talked to patients who say they go to the gym, they overdo it, and they can't walk back out to their car afterwards. We certainly don't want that to happen. So, if I want a patient to start a new exercise regimen, I personally ask them to work with a physical therapist, especially one who has experience in working with our patients with MG, and they can tailor the exercises to the patient's individual goals and needs.
I'll say as a general thought here, there's also been a study that showed that patients who have higher levels of physical activity — and in this study it was over 150 minutes per week — and lower rates of sedentary activity actually have lower fatigue levels, higher quality of life, less limitation in walking, and improved balance. So, overall, it's absolutely advisable for select patients in a monitored setting to participate in exercise and rehabilitate at times from deconditioning and when they've been quite weak because of their disease being poorly controlled.
Silvestri: I think you bring up a lot of great points there. I think the key is really patient selection, right? And a lot of it is common sense. If you've got a patient who's very severely affected, that approach is a little bit different than a patient who is doing a little bit better in terms of their disease control. But certainly regardless, you can have a mild patient who goes to the gym and overdoes it, and that could set them back a little bit. Those are excellent points. So, let's say you have a patient with MG who gets diagnosed early on and starts exercising. The patient initially feels well but then starts to report fatigue and other symptoms that interfere with their ability to exercise. How do you approach that situation?
Gwathmey: Nick, I'm so happy that you brought up the topic of fatigue. It's very much a hot topic in the field of myasthenia right now. And as you likely know and experience on a daily basis when you see your own patients, fatigue impacts up to 80% of our myasthenic patients, and it is extremely challenging to assess and measure in clinic. I mean, there are some questionnaires here and there, but they really don't capture the fatigue that these patients are experiencing. And if we think about fatigue and the definition of it, it's the subjective perception of lacking either mental or physical energy with difficulty sustaining voluntary activities. So, that's really the key. We have a disease that is characterized by fatigable muscle weakness, but then people can feel fatigue because of depression or anxiety or poor sleep. There are a lot of different things that go into fatigue. And a challenging situation that I encounter on a weekly basis is the patient who comes in with their myasthenia under excellent control, and yet they have severe fatigue. What do you do with those patients? And there's a lot of counseling and back and forth between the provider and the patient about realistic expectations, because the answer is not always escalation of the myasthenia treatment, especially if the myasthenia symptoms are under good control. So, then we need to take a few steps back and look at what could be fueling the fatigue that the patients are experiencing. Fatigue certainly could be fueled by depression. It could be fueled by sleepiness. We think that fatigue and myasthenia have a higher prevalence in our female patients, and it does also correlate with disease severity. There are certainly the patients out there who have their disease not well controlled who have fatigue as well. So, what can we do to address it? There was actually a Dutch study a couple years ago that suggested that strenuous physical activity actually results in less fatigue. So, perhaps exercise can help address the fatigue that these patients experience. There's also some literature out there that supports that in addition to physical therapy, psychological therapy can be quite helpful. So, we often will screen our patients in clinic for depression if they are complaining about fatigue. Then, of course, if they're depressed, we either manage that or advise them to speak with their primary care provider and/or their psychiatrist.
Silvestri: Let's say that our same hypothetical patient starts researching what to do on the internet. We've all seen that happen, right?
Silvestri: And what are the things that you tell them to avoid? Maybe you can prioritize for us, starting with the most important.
Gwathmey: Whenever one of our patients is not doing well, or they're having new symptoms, and we don't think it's just the natural progression of the disease with the typical fluctuations, we want to do a timeout and see what's changed in their lives. The most common thing that I encounter is that the patient's been exposed to a new medication that potentially is exacerbating their symptoms. A lot of times, and we see this in the emergency department or in the hospital, a patient has a new infection. They have the flu or a urinary tract infection, and that's upsetting their very delicate balance with their disease, too. In terms of things that the patients can potentially address, sleep's a major consideration here. If a patient is having sleep deprivation, then that certainly can make their myasthenia worse. A stressful situation, stress at work, and stress within the home can correlate with disease activity and worsening disease control. Right now, we are in August, so heat is another significant contributor to worsening of symptoms. Some of my patients like to go out in the heat and play tennis, and that doesn't usually end very well. So, advising them to stay cool in an air-conditioned room and know what their limits are is very important. And in terms of less common things that we encounter, pregnancy can sometimes make their myasthenia a little bit less controlled as well.
Silvestri: You bring up a lot of great points there that I think are really germane to heat and hydration. I always push the importance of hydration with my patients as well. You mentioned medications. That's a hot topic for patients with myasthenia. Tell us about the medications that patients should absolutely avoid when they have myasthenia.
Gwathmey: If we want to start with the ones that we absolutely avoid, Botox is a no-no. Our myasthenia patients cannot have Botox. The ones that tend to get us in trouble on a daily basis are the antibiotics, so I advise my patients to always do a timeout when they're getting prescribed a new medication and either check the list that I provide them in clinic — there are, of course, lists online that guide our patients to medications that are safe or unsafe — or I advise our patient to call me, and I'll say, "Yes, this is okay," or, "No, it's not okay." Certain antibiotics are not as safe as other ones, so the major classes of antibiotics that we're concerned about are the fluoroquinolones. How many patients have we seen prescribed ciprofloxacin for a urinary tract infection that got them in trouble?
The macrolides, like a Z-Pak (azithromycin), for an upper respiratory infection often can trigger an exacerbation, and then aminoglycosides are also concerns. Prednisone is going to be on every list as a medication that potentially exacerbates MG, but it is the backbone of our immunotherapy for a lot of different patients. It's important to remember there's a theoretical risk that shortly after starting, especially high-dose prednisone, patients can have worsening of their symptoms before they get the immunosuppressant benefit from the drug. And then also very common things come up every single day, such as beta blockers. Some of our patients need to be on propranolol or metoprolol because of their cardiac history, and we talk about how, in theory, they could worsen their MG, but a lot of times we just have to treat around it because it's in the best interest of the patient from a cardiac standpoint. Same is true for statins. There's a theoretical risk that those could make myasthenia worse, but a lot of times we just treat around it, and we talk about it.
Silvestri: Absolutely. There are those categories of medicines that absolutely need to be avoided, and those that are relative, right? And we have to determine on a patient-by-patient basis. Let's go back to our hypothetical patient. Talk to us about how MG tends to affect quality of life. What are coping strategies that your patients employ when they experience depression and anxiety? What else should practitioners know about common psychosocial needs that may need to be addressed?
Gwathmey: To your first question on quality of life: In myasthenia, we often think about health-related quality of life because it's specific to MG. Remember, this is a complicated concept. It's influenced by physical health, psychological status, social relationships, and the person's relationship to their environment — be their job or their home — as a result of their disease.
What do we know about health-related quality of life and myasthenia? It does tend to be a little bit worse in our female patients, and it tends to get better with treatment of the disease. That's probably not surprising. We know that unemployment certainly can correlate with lower quality of life, as can disease exacerbations.
We feel like patients who have physically active lifestyles have better quality of life. We've touched on that before. Then, if a patient has hope and independence in their activities of daily living, that can certainly correlate with improved quality of life and mental health.
Now, moving on to the depression and anxiety concern. I think it's important to understand to the best of our ability, the scope of anxiety and depression in MG. There was a meta-analysis that was published in 2023 that looked at the prevalence of depression and anxiety across the number of studies, and it demonstrated that 36% of our myasthenic patients have depression and 33% have anxiety. So, it's extremely common. It's very important for the providers to remember that when they're assessing their patients in clinic. Looking at some other literature, myasthenic patients who are more frequently hospitalized and have more severe symptoms, as you might imagine, have worse depression, anxiety, and fatigue.
It's all interconnected: the fatigue, the depression, the anxiety, the disease severity, and the relapse rate. There's also some more recent data that increased stress can be associated with higher relapse rates. I feel like we've been seeing that for years, and people haven't published on it.
In stressful home and work situations, patients' symptoms clearly tend to get worse. How do we start to address the anxiety and the depression? It's likely going to be a combination of psychotherapy and pharmacological therapy. In our area, we've started up a myasthenia support group that's been very helpful, especially for some of our patients who've been recently diagnosed. And in terms of your question about coping, we don't have a ton of data on this, but there was an article that was published back in 2016 that found patients with an optimistic coping style tended to do quite well. And if they had positive thinking and used humor, those were helpful strategies to cope with their myasthenia symptoms. So, it's quite intuitive, I would say, but certainly something we would encourage our patients to consider.
Silvestri: Covered a lot of ground there, Kelly. Thanks very much. It's a very comprehensive answer and to speak to your point about stress, I think it's key, right? Patients always come into clinic and talk about how they've not been doing well and trying to figure out how to get to the bottom of it. Talking about things that might be going on in their lives in general and approaching the whole patient [are how we can] really try to help as best as we can. We've covered a lot of ground here, so what is the one thing that you want listeners to do differently after hearing this podcast?
Gwathmey: I know that we have a lot of different types of listeners. We have providers who are neurologists, we have providers who are in primary care. So, to take a slightly different angle that ties together a bunch of the themes that we've been touching on, I think it's important to encourage our patients to take notes on how they're doing at home. We get a snapshot of patients every 3 months or even every 6 months on how they're doing, but I often encourage my patients to take notes on what they feel is causing worsening of their symptoms.
Did they not sleep well the night before? Is something going on at work? I know this is not the topic for today, but most people know I'm a big believer in patient-reported outcome measures. I encourage our patients to self-administer the MG-ADL (the activities of daily living scale) and the MG-QoL15r (the revised quality of life instrument) on a weekly basis.
We trend scores and look at that data together when they come into clinic and really try to unwind this disease. I think we're only as good as the data that we have. So, to encourage the patient to participate in that is extremely important and is also very gratifying.
Silvestri: Absolutely. We've talked about several topics today, but the most important thing is approaching our patients holistically, treating them as a whole patient and not just treating the disease. We talked about fatigue and issues with other medications patients might be taking. We talked about their depression and anxiety. I'm incredibly grateful to you, Kelly, for taking on such a vast but important topic.
Gwathmey: Well, thank you for the very kind invitation, Nick.
Silvestri: Always a pleasure and thanks to you for joining our discussion with Dr Kelly Gwathmey. There's more ahead in the next episode, so be sure to check out the Medscape app and share, save, and subscribe if you enjoyed this episode. I'm Dr Nick Silvestri from Medscape InDiscussion.
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Cite this: Myasthenia Gravis: Exercise and Lifestyle Considerations - Medscape - Sep 21, 2023.