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In the hospital setting, neurologists may be responsible for managing common end-of-life symptoms. Comprehensive end-of-life care integrates knowledge of the biomedical aspects of disease with patients' values and preferences for care; psychosocial, cultural, and spiritual needs; and support for patients and their families. In this episode, Teshamae Monteith, MD, FAAN, speaks with Claudia Z. Chou, MD, author of the article "End-of-Life Care and Hospice" in the Continuum® December 2025 Neuropalliative Care issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Knox is an assistant professor of neurology and a consultant in the Division of Community Internal Medicine, Geriatrics and Palliative Care at Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: End-of-Life Care and Hospice Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @headacheMD Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Monteith: This is Dr Teshamae Monteith. Today I'm interviewing Dr Claudia Chou about her article on end-of-life care and hospice, which is found in the December 2025 Continuum issue on neuropalliative care. Welcome to our podcast. How are you? Dr Chou: I'm doing well. Thank you for having me. This is really exciting to be here. Dr Monteith: Absolutely. So, why don't you introduce yourself to our audience? Dr Chou: Sure. My name is Claudia Chou. I am a full time hospice and palliative medicine physician at Mayo Clinic in Rochester. I'm trained in neurology, movement disorders, and hospice and palliative medicine. I'm also passionate about education, and I'm the program director for the Hospice and Palliative Medicine fellowship here. Dr Monteith: Cool. So just learning about your training, I kind of have an idea of how you got into this work, but why don't you tell me what inspired you to get into this area? Dr Chou: It was chance, actually. And really just good luck, being in the right place at the right time. I was in my residency and felt like I was missing something in my training. I was seeing these patients who were suffering strokes and had acute decline in functional status. We were seeing patients with new diagnosis of glioblastoma and knowing what that future looked like for them. And while I went into neurology because of a love of neuroscience, localizing the lesion, all of those things that we all love about neurology, I still felt like I didn't have the skill set to serve patients where they perhaps needed me the most in those difficult times where they were dealing with serious illness and functional decline. And so, the serendipitous thing was that I saw a grand rounds presentation by someone who works in neurology and palliative care for people with Parkinson's disease. And truly, it's not an exaggeration to say that by the end of that lecture, I said, I need to do palliative care, I need to rotate in this, I need to learn more. I think this is what I've been missing. And I had plans to practice both movement disorders neurology and palliative care, but I finished training in 2020… and that was not a long time ago. We can think of all the things that were going on, all the different global forces that were influencing our day-to-day decisions. And the way things worked out, staying in palliative care was really what my family and I needed. Dr Monteith: Wow, so that's really interesting. Must have been a great lecturer. Dr Chou: Yes, like one of the best. Dr Monteith: So why don't you tell me about the objectives of your article? Dr Chou: The objectives may be to fill in some of the gaps in knowledge that may be present for the general neurologist. We learn so much in neurology training, so much about how to diagnose and treat diseases, and I think I would argue that this really is part and parcel of all we should be doing. We are the experts in these diseases, and just because we're shifting to end-of-life or transitioning to a different type of care doesn't mean that we back out of someone's care entirely or transition over to a hospice or palliative care expert. It is part of our job to be there and guide patients and their care partners through this next phase. You know, I'm not saying we all need to be hospice and palliative care experts, but we need to be able to take those first steps with patients and their care partners. And so, I think objectives are really to focus in on, what are those core pieces of knowledge for end-of-life care and understanding hospice so we can take those first steps with patients and their care partners? Dr Monteith: So, why don't you give us some of those essential points in your article? Dr Chou: Yeah. In one section of the article, I talk about common symptoms that someone might experience at the end of life and how we might manage those. These days, a lot of hospitals have order sets that talk us through those symptoms. We can check things off of a drop-down menu. And yet I think there's a little bit more nuance to that. There may be situations in which we would choose one medication over another. There may be medications that we've never really thought of in terms of symptom management before. Something that I learned in my hospice and palliative medicine fellowship was that haloperidol can be helpful for nausea. I know that's usually not one of our go-tos in neurology for any number of reasons. So, I think that extra knowledge can take us pretty far when we're managing end of life symptoms, particularly in the hospital setting. And then I think the other component is the hospice component. A lot of us may have not had experience talking about hospice, talking about what hospice can provide, and again, knowing how to take those first steps with patients. We may be referring to social work or palliative medicine to start those conversations. But again, I think this is something that's definitely learnable and something that should be part of our skill set in neurology. Dr Monteith: Great. And so, when you speak about symptom management and being more comfortable with the tools that we have, how can we be more efficient and more effective at that? Dr Chou: Think about what the common symptoms are at end of life. We may know this kind of intuitively, but what we commonly see are things like pain, nausea, dyspnea, anxiety, delirium or agitation. And so, I think having a little bit of a checklist in mind can be helpful. You know, how can I systematically think through a differential, almost, for why my patient might be uncomfortable? Why they might be restless? Have I thought through these different symptoms? Can I try a medication from my tool kit? See if that works, and if it does, we can continue on. If not, what's the next thing that I can pivot to? So, I think these are common skills for a little bit of a differential diagnosis, if you will, and how to work through these problems just with the end-of-life lens on it. Dr Monteith: So, are there any, like, validated tools or checklists that are freely available? Dr Chou: I don't think there's been anything particularly validated for end-of-life care in neurologic disease. And so, a lot of our treatments and our approaches are empiric, but I don't think there's been anything validated, per se. Dr Monteith: Great. So, why don't we talk a little bit about the approach to discussions on hospice? We all, as you kind of alluded to, want to be effective neurologists, care for our patients, but we sometimes deal with very debilitating diseases. And so, when we think that or suspect that our patient is kind of terminally ill, how do we approach that to our patients? Of course, our patients come from different backgrounds, different experiences. So, what is your approach? Dr Chou: So, when we talk about hospice and when a patient may be appropriate for hospice, we have to acknowledge that we think that they may be in the last six months of their disease. We as the neurologist are the experts in their disease and the best ones to weigh in on that prognosis. The patient and their care partners then have to accept that the type of care that hospice provides is what makes sense for them. Hospice focuses on comfort and treating a patient's comfort as the primary goal. Hospice is not as interested in treating cancer, say, to prolong life. Hospice is not as interested in life-prolonging measures and treatments that are not focused at comfort and quality of life. And so, when we have that alignment between our understanding of a patient's disease and their prognosis and the patient care partner's goal is to focus on comfort and quality of life above all else, that's when we have a patient who might be appropriate for hospice and ready to hear more about what that actually entails. Dr Monteith: And what are some, maybe, myths that neurologist healthcare professionals may have about hospice that you really want us to kind of have some clarity on? Dr Chou: That's a great question. What we often tell patients is that hospice's goal is to help patients live as well as possible in the time that they have left. Again, our primary objective is not life prolongation, but quality of life. Hospice's goal is also not to speed up or slow down the natural dying process. Sometimes we do get questions about that: can't you make this go faster or we're ready for the end. But really, we are there to help patients along the natural journey that their body is taking them on. And I think hospice care can actually be complex. In the inpatient setting, in particular in neurology, we may be seeing patients who have suffered large strokes and have perhaps only days to a few weeks of life left. But in the outpatient setting and in the home hospice setting, patients can be on hospice for many months, and so they will have new care needs, new urinary tract infections, sometimes new rashes, the need to change their insulin regimens around to avoid extremes of hyperglycemia or hypoglycemia. So, there is a lot of complexity in that care and a lot that can be wrapped up under that quality-of-life and comfort umbrella. Dr Monteith: And to get someone to hospice requires a bit of prognostication, right? Six months of prediction in terms of a terminal illness. I know there's some nuances to that. So how can you make us feel more comfortable about making the recommendations for hospice? Dr Chou: I think this is a big challenge in the field. We're normally guided by Medicare guidelines that say when a patient might be hospice-appropriate. And so, for a neurologic disease, this really only encompasses four conditions: ALS, stroke, coma, and Alzheimer's dementia. And we can think of all the other diseases that are not encompassed in those four. And so, I think we say that we paint the picture of what it means to have a prognosis of six months or less. So, from the neurologic side, that can be, what do you know about this disease and what end-stage might look like? What is the pattern of the patient's functional decline? What are they needing more help with? Are there other factors at play such as heart failure or COPD that may in and of themselves not be a qualifying diagnosis for hospice, but when it's taken together in the whole clinical picture, you have a patient who's very ill and one that you're worried may die in the next six months or less? Dr Monteith: Then you also had some nice charts on kind of disease-specific guidelines. Can you take us a little bit through that? Dr Chou: The article does contain tables about specific criteria that may qualify someone for hospice with these neurologic conditions. And they are pretty dense. I know they're a checklist of a lot of different things. And so, how we practice is by trying to refer patients to hospice based on those guidelines as much as possible and then using our own clinical judgment as well, what we have seen through taking care of patients through the years. So, again, really going back to that decline. What is making you feel uncomfortable about this patient's prognosis? What is making you feel like, gosh, this patient could be well supported by hospice, and they could have six months or less? So, all of that should go into your decision as well. And all of that should go into your discussion with the patient and their care partners. Dr Monteith: Yeah. And reading your article, what stood out was all the services that patients can receive under hospice. So, I think sometimes people think, okay, this is terminal illness, let's get to hospice for whatever reasons, but not necessarily all the lists and lists and lists of benefits of hospice. So, I don't know that everyone's aware of all those benefits. So, can you talk to us a little bit about that? Dr Chou: Yeah, I like that you brought that up because that's also something that I often say to patients and their care partners when we're talking about hospice. When the time is right for a patient to enroll in hospice, they should not feel like they're giving anything up. There should be no more clinical trial that they're hoping to chase down, and so they should just feel like they're gaining all of those good supports: care that comes to their home, a team that knows them well, someone that's available twenty-four hours a day by phone and can actually even come into the home setting if needed to help with symptom management. Hospice comes as well with the psychosocial supports for just coping with what dying looks like. We know that's not easy to be thinking about dying for oneself, or for a family member or care partner to be losing their loved one. So, all of those supports are built into hospice. I did want to make a distinction, too, that hospice does not provide custodial care, which I explain to patients as care of the body, those daily needs for bathing, dressing, eating, etc. Sometimes patients are interested in hospice because they're needing more help at home, and I have to tell them that unfortunately, our healthcare system is not built for that. And if that's the sole reason that someone is interested in hospice, we have to think about a different approach, because that is not part of the hospice benefit. Dr Monteith: Thank you for that. And then I learned about concurrent care. So why don't you tell us a little bit about that? That's a little bit of a nuance, right? Dr Chou: Yeah, that is a little bit of a nuance. And so, typically when patients are enrolling in hospice, they are transitioning from care the way that it's normally conducted in our healthcare system. So, outpatient visits to all of the specialists and to their primary care providers, the chance to go to the ER or the ICU for higher levels of care. And yet there are a subset of patients who can still have all of those cares alongside hospice care. That really applies to two specific populations: veterans who are receiving care through the Veterans Administration, and then younger patients, so twenty six years old and less, can receive that care through, essentially, a pediatric carve out. Dr Monteith: Great. Well, I mean, you gave so much information in your article, so our listeners are going to have to read it. I don't want you to spill everything, but if you can just kind of give me a sense what you want a neurologist to take away from your article, I think that would be helpful. Dr Chou: I think what I want neurologist to take away is that, again, this is something that is part of what we do as neurologists. This is part of our skill set, and this is part of what it means to take good care of patients. I think what we do in this transition period from kind of usual cares, diagnosis, full treatment to end of life, really can have impact on patients and their care partners. It's not uncommon for me to hear from family members who have had another loved one go through hospice about how that experience was positive or negative. And so, we can think about the influence for years to come, even, because of how well we can handle these transitions. That really can be more than the patient in front of us in their journey. That is really important, but it can also have wide-reaching implications beyond that. Dr Monteith: Excellent. And I know we were talking earlier a little bit about your excitement with the field and where it's going. So why don't you share some of that excitement? Dr Chou: Yeah. And so, I think there is a lot still to come in the field of neuropalliative care, particularly from an evidence base. I know we talked a lot about the soft skills, about presence and communication, but we are clinicians at heart, and we need to practice from an evidence base. I know that's been harder in palliative care, but we have some international work groups that really are trying to come together, see what our approaches look like, see where standardization may need to happen or where our differences are actually our strength. I think there can be a lot of variability in what palliative care looks like. So, my hope is that evidence base is coming through these collaborations. I know it's hard to have a conversation these days without talking about artificial intelligence, but that is certainly a hope. When you look at morbidity, when you look at patients with these complicated disease courses, what is pointing you in the direction of, again, a prognosis of six months or less or a patient who may do better with this disease versus not? And so, I think there's a lot to come from the artificial intelligence and big data realm. For the trainees listening out there, there is no better time to be excited about neuropalliative care and to be thinking about neuropalliative care. I said that I stumbled upon this field, and hopefully someone is inspired as well by listening to these podcasts and reading Continuum to know what this field is really about. And so, it's been exponential growth since I joined this field. We have medical students now who want to come into neuropalliative care as a profession. We have clinicians who are directors of neuropalliative care at their institutions. We have an international neuropalliative care society and neuropalliative care at AAN. And I think we are moving closer to that dream for all of us, which is that patients living with serious neurologic illness can be supported throughout that journey. High-quality, evidence-based palliative care. We're not there yet, but I think it is a possibility that we reach that in my lifetime. Dr Monteith: Well, excellent. I look forward to maybe another revision of this article with some of that work incorporated. And it's been wonderful to talk to you and to reflect on how better to approach patients that are towards the end of life and to help them with that decision-making process. Thank you so much. Dr Chou: Yeah, thank you for having me. And we're very excited about this issue. Dr Monteith: Today. I've been interviewing Dr Claudia Chou about her article on end-of-life care and hospice, which is found in the December 2025 Continuum issue on neuropalliative care. Be sure to check out Continuum Audio episodes from this and other issues, and thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Neurologists are privileged to act as guides for patients as they navigate the complex course of serious neurologic illnesses. Because of the impact on quality of life, personhood, and prognosis, neurologists must be able to conduct serious-illness conversations to improve rapport, reduce patient anxiety and depression, and increase the likelihood that treatment choices agree with patient goals and values. In this episode, Teshamae Monteith, MD, FAAN speaks with Jessica M. Besbris, MD, author of the article "The Approach to Serious-Illness Conversations" in the Continuum® December 2025 Neuropalliative Care issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Besbris is an assistant professor of neurology and internal medicine, and the director of the neuropalliative care, at Cedars-Sinai Medical Center in Los Angeles, California. Additional Resources Read the article: The Approach to Serious-Illness Conversations Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @headacheMD Guest: @JessBesbris Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Monteith: Hi, this is Dr Teshamae Monteith. Today I'm interviewing Dr Jessica Besbris about her article on the approach to serious illness conversation, which is found in the December 2025 Continuum issue on neuropalliative care. How are you? Dr Besbris: I'm doing great. Thank you so much for having me here today. Dr Monteith: Well, thank you for being on our podcast. Dr Besbris: My pleasure. Dr Monteith: Why don't we start off with you introducing yourself? Dr Besbris: Sure. So, my name is Jessica Besbris. I am a neurologist with fellowship training in palliative care, and I am currently at Cedars Sinai Medical Center in Los Angeles, where I am the director of our neuropalliative care program. Dr Monteith: Excellent. So, how did you get involved in that? Dr Besbris: Like, I think, many neurologists, I always knew I wanted to be a neurologist---or, I should say, from the moment I decided to be a doctor I knew that that was the type of doctor I wanted to be, a neurologist. So, I went into medical school with the aim of becoming a neurologist. And very quickly, when I started my clinical years, I was exposed to patients who were living with very serious illnesses. And I found myself really drawn to opportunities to help, opportunities to make people feel better, opportunities to improve quality of life in situations that on the face of it seemed really challenging, where maybe it seemed like our usual treatments were not necessarily the answer or were not the only answer. And so, I pretty quickly recognized that taking care of patients with serious illness was going to be a big part of my life as a neurologist and that palliative care was the way I wanted to help these patients and families. Dr Monteith: And you mentioned you're leading the group. So, how many colleagues do you have in the program? Dr Besbris: We have a very large palliative care group, but within neuropalliative care, it's myself and one other physician, a nurse practitioner, and a social worker. Dr Monteith: Okay, well, I know you guys are busy. Dr Besbris: Yes, we are very happy to be busy. Dr Monteith: Yes. So, let's talk about the objectives of your article. Dr Besbris: Sure. So, the goal of this article is to impress upon neurologists that it really is all of our jobs as neurologists to be having these conversations with our patients who are affected with serious illness. And then, in most areas of neurology, these conversations will come up. Whether it's giving a life changing diagnosis, or talking about treatment choices, or treatment not going the way that we had hoped, or even sometimes progression of disease or end-of-life care. These topics will come up for most of us in neurology, and really, we're hoping that this article not only makes the case that neurologists can and should be having these conversations, but that there are skills that we can teach in this article and with other resources to improve the skill level and sense of confidence that neurologists have when they enter into these conversations. Dr Monteith: Great. I read that there are some developments in the field, on organizational levels, about really making these skills part of standard of care in terms of education. So, can you speak to that? Dr Besbris: Yes. So, there have been a couple of really landmark papers and changes in the educational landscape that I think have really brought neuropalliative care in general, and serious illness conversation in particular, to the forefront. So, there were the position statements released by the American Academy of Neurology in 1996 and 2022, both of which really said, hey, all neurologists should be doing this and receive training on how to have these conversations and provide this care. And the ACGME, the Accreditation Council for Graduate Medical Education, also requires neurology residency programs to learn how to communicate with patients and families, assess goals, and talk about end-of-life care. So, there's a real structural imperative now for neurologists to learn early on how to have serious illness conversations with their patients. Dr Monteith: Great. If there's anything for our listeners to get out of this conversation, what are the essential points? Dr Besbris: If you only take away one or two things from this conversation, I hope that they're that this is an awesome responsibility to be in a moment with a patient going through something challenging, to meet them in that moment with thoughtful, honest, empathic conversations about who they are and what's important to them. And that, just like any other procedure, these are skills that can be taught so that you can feel really confident and comfortable being in these moments. Dr Monteith: Excellent. Wow. Okay, I feel your energy and your empathy already. And so, why don't we just talk about skills? What is the best way to deliver tough news? I read this wonderful chart on SPIKES protocol. Dr Besbris: Yeah, the SPIKES protocol is one really well-known way to deliver serious news. And what's nice about SPIKES is it gives a mnemonic. And as neurology learners, we all love a good mnemonic to help you really center yourself when you're entering into these conversations so that you have a structured format to follow, just like with any procedure. So, the SPIKES protocol stands for Setting: so, making sure you have the right environment; Perception, or assessing what your patient or surrogate decision maker knows already so that you know where to begin; receiving an Invitation to deliver serious news. And then K stands for Knowledge, delivering in a clear and concise way the information that you want to make sure the family or patient walk away with. E for exploring Emotion; and S for really Summarizing what's been discussed and Strategizing on next steps. I think that having these kinds of conversations, it's just like being expert in anything. When you first start learning, it's helpful to have a set of very concrete steps you can follow. And you might even think through the mnemonic as you get ready to walk into that room. And as you become more expert, the flow becomes more natural. And maybe what you do before walking in to prepare is just honing what is that headline? What is that concise statement that I'm really going to give? And the rest may start to feel more natural and less protocolized. Dr Monteith: And there are a few other mnemonics. There's the NURSE mnemonic, which I like. You know, there's a balance between saying things and sounding kind of… you know, sometimes they're like, well, how could you understand what I'm going through? Have you been through something like this? And people shy away, and they're afraid to kind of be a part of these conversations. So how do we approach that with this, a NURSE mnemonic in a way that's kind of sincere? Dr Besbris: Absolutely. So, the NURSE mnemonic, unlike SPIKES, is not a step-by-step protocol. So, NURSE is a mnemonic, but you don't go through each letter and sort of give a naming statement and then an understanding statement and then a respecting statement and so on. Nurse is really a toolkit of different types of statements that we can give in response to emotions so that when you find yourself in a situation where a patient or family member is tearful, is scared, is angry, is expressing feelings, you have some phrases ready that feel authentic to you and that you feel are going to meet the moment and allow you to empathically respond to those emotions. Because until we do that, we really can't move further in this conversation with our patients and families feeling heard and respected. So, that NURSE mnemonic, those Naming, Understanding, Respecting, Supporting and Exploring statements, are really examples of statements that we can use to meet that moment with empathy and understanding and without implying that we have walked in their shoes. We want to avoid being presumptuous and really focus on just being present and empathic. Dr Monteith: So, let's just kind of run through, I think it's really important. Let's run through some of these examples. Maybe if someone's crying hysterically, how would we respond to that? Dr Besbris: So, this is an opportunity for Naming. And I made this one, I think, in the chart, a little bit obvious, meaning that we recognize when someone is crying that they are feeling probably very sad. This is an opportunity for us to name and thus normalize that emotion. I just think something as simple as, I think anyone would be really sad hearing this. These responses are not intended to fix this emotion. I'm not trying to get someone to stop crying or to, you know, necessarily not feel sad. It's really just to say, yeah, it's normal that you're feeling sad. It's okay. I'm here with you while you're feeling sad. And I'm going to be with you no matter what you're bringing to the table. Dr Monteith: Yeah. Let's go through just a couple of others. I mean, these are really good. Dr Besbris: Sure. Maybe Respecting. Dr Monteith: Yeah. So, my Dad is a fighter. Only God, not doctors, can know the future. Dr Besbris: Yeah. So, I love giving these examples with our learners because these statements, things like my Dad is a fighter or God will bring me a miracle or you don't know the answer. Only God knows what's going to happen, I think that they give a lot of doctors a feeling of confrontation, a feeling of anxiety. And I think there are a few reasons for that. And I think one of the main ones is that they're statements that imply that we as doctors are not all-powerful and it's our patients or families sort of looking for a different locus of control, whether it's internal fortitude or a higher power. They're looking to something other than us, and maybe that makes us feel a little bit uncomfortable. And I think that sometimes physicians think that these statements imply that someone doesn't even understand what's going on. But maybe they're coming to this from a place of denial. And I would argue that when someone comes to you with a statement like my dad is a fighter or, you know, I'm looking to God to bring me a miracle or to show me the future. I think that what they're really saying is, wow, I'm really hearing that things are serious, so much so that I'm reaching for these other resources to give me strength and hope. I don't think anyone asks for a miracle if they think that a miracle is not needed, if the problem is easy to fix. And so, rather than come to these types of statements from a confrontational place of I'm the doctor and I know best, I think this is a great opportunity to show some respect and give some respecting statements. Your dad is a fighter. I don't think he could have come this far without being a fighter. Or, you know, I am so grateful that you have your faith to lean on during times like these to give you strength. These are also nice opportunities for exploring statements. For example, I'm so grateful to learn more about your dad. Can you tell me what it is that he has been fighting for all of this time? Dr Monteith: I love that. It's like a follow-up, and also validating. Dr Besbris: Yeah, it's validating. And it allows us to learn a little bit more about this person and to learn, well, is he fighting for a life that we can still achieve with our interventions to lead into the next part of a conversation? Or, is God is going to bring me a miracle? Well, tell me what a miracle looks like for you. I can't tell you how many times I thought someone was going to tell me that a miracle would be cure. And sometimes that is what comes up. But other times I hear, a miracle would be, you know, my loved one surviving long enough for the rest of the family to gather. And, you know, that is certainly something we can work towards together. Dr Monteith: So, why don't we talk a little bit about approach to goals of care discussions? They are tough, and let's just put it into perspective to the critical care team. It's time, the person's been in the ICU, the family wants everything thrown at medically. And it's to the point that the assessment is that would be medical futility. Dr Besbris: Lots to unpack there. Dr Monteith: I wanted to make it hard for you. Dr Besbris: No, no, this is good! I mean, this is something- I work in a, you know, almost one thousand-bed hospital with a massive critical care building. And so, these are not unusual circumstances at all. First of all, I would just say that goals of care conversations are not only about end-of-life care. And I make that point a few different times in the article because I think when people imagine goals of care, and one of the reasons that I think clinicians may sometimes shy away from goals of care discussions, is that they think they have to be sad, they have to be scary, they have to be about death and dying. And I would argue that, really, goals of care discussions are about understanding who a person is, how they live their life, what's most important to them. Most of these conversations should be about living. How are we going to together achieve a quality of life that is meaningful for you and treatments that are going to fit your needs and your preferences? But there is a little slice of that pie in the pie chart of goals of care discussions that is in the arena of end-of-life care. For example, ICU care with, really, the highest levels of intensity of care, and having to talk about whether that still is meeting the moment from the perspective of goals as well as the perspective of efficacy. So, from the goals standpoint, I approach these conversations just like any other goals of care conversation. Usually at this point, we're speaking to family members and not our patients because in a neurocritical care unit, if someone is that sick, they probably are incapacitated. And so, it's a moment to really sit down with family and say, please tell me about the human being lying in that bed. They can't introduce themselves. What would they tell me about themselves if they could speak right now? What kinds of things were important to them in the course of their treatment? What kind of a life did they want to live or do they want to live? So that then we can reflect on, well, can our treatment achieve that? And this process is called shared decision making. This is really where we take in data from the family, who are experts in the patient, and then our own expertise in the illness and what our treatments can achieve, and then bring all of that information together to make a recommendation that aligns with what we believe is right for a particular patient. So, in the example that you gave, the extreme circumstance where someone is receiving maximal intensive care and we're starting to reach the point of futility, I think that we need to first really understand, well, what does futility mean for this particular patient? Is it that we as healthcare providers would not value living in the state this person is in? Or is it that the treatments truly cannot physiologically keep them alive or meet their stated goals? If it's the first one, that I wouldn't want to be on machines unconscious, you know, at the end of my life, well, I have to set that aside. It's really about what this patient wants. and if the family is telling you they valued every breath, every moment, and if we have care that can achieve that, we should continue to offer and recommend that care. And as healthcare providers, it is so important that we do explain when treatments are not going to be able to physiologically meet a patient's needs or achieve their goals. And that's where we can say, I'm going to continue to do everything I can, for example, to, you know, keep your loved one here for these meaningful moments. And we are at a point where performing CPR would no longer be able to restart his heart. And I just wanted to let you know that that's not something that we're going to do because I have an obligation not to provide painful medical treatments that will not work. So, my approach to futility is really different than my approach to shared decision-making because in the context of objective futility, it's not about necessarily- it's not about decision-making, it's not about shared decision-making as much as it is explaining why something is simply not going to work. Does that make sense? Dr Monteith: Absolutely. And what I love in your article is that, you know, you go beyond the skills, but also potential communication challenges---for example, patients' neurologic status, their ability to understand complex communication, or even cultural differences. So, can you speak about that briefly? Dr Besbris: Absolutely. In the world of neurological serious illness, it is incredibly common for our patients to face challenges in communication. That might be because they are aphasic, because they have a motor speech deficit, it might be because they're intubated, it might be because their capacity is diminished or absent. And so, there are a lot of challenges to keeping patients in these conversations. And in the article, I summarize what those challenges can look like and some strategies that we can use to continue to engage our patients in these conversations to the greatest extent possible and also turn to their surrogate decision makers where the patients themselves are no longer able to participate or participate fully. In terms of cultural considerations, I mean, there could be an entire article or an entire Continuum just on cultural considerations in neurology and in serious illness communication. And so, the key points that I really tried to focus on were exploring from a place of cultural humility what the beliefs and practices of a particular patient and family are in their cultural context, to ask questions to help you understand how those cultural differences may impact the way you approach these conversations. And being sensitive to folks with limited English proficiency, to ensure that we are using medical interpreters whenever possible. Dr Monteith: Excellent. Well, there's so much in the article. There's already so much that we just discussed, but our listeners are going to have to go to the article to get the rest of this. I do want to ask you to just kind of reflect on, you know, all the different cases and experiences that you have, and just, if you can give us a final remark? Dr Besbris: I can think of a number of cases that I've seen in my work as both an inpatient and outpatient neuropalliative provider where I've seen patients after strokes in the hospital with uncertain prognosis, whose families were struggling with a decision around feeding tubes. And where we have made a determination based on goals; for example, to pursue what's called a time-limited trial, to say let's place a feeding tube, let's meet again in the clinic in a few months after some rehab and let's just see, is this meeting this patient 's goals and expectations? I have been pleasantly surprised by the number of patients who have walked into my office after a period of rehabilitation who have regained the ability to eat, who are living an acceptable quality of life, and who have expressed gratitude for the work that I did in eliciting their goals, helping support their families. And some of whom have even come in and said, now that I'm doing better, I'd really like to do an advance directive to better guide my family in the future. People asking for more goals of care discussions, having seen how successful and helpful these conversations have been. Dr Monteith: Great. That's really life-altering for that patient, the family, so many people. Thank you so much for the work you do and for writing this great article and sharing all of this that we really need to learn more about. Dr Besbris: It's been a privilege. Thank you so much for talking with me today. Dr Monteith: Today I've been interviewing Dr Jessica Besbris about her article on the approach to serious illness conversation, which is found in the December 2025 Continuum issue on neuropalliative care. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Maisha T. Robinson, MD, MSHPM, FAAN, FAAHPM, who served as the guest editor of the December 2025 Neuropalliative Care issue. They provide a preview of the issue, which publishes on December 2, 2025. Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota. Dr. Robinson is the Chair of the Division of Palliative Medicine and an assistant professor of neurology at Mayo Clinic in Jacksonville, Florida. Additional Resources Read the issue: continuum.aan.com Subscribe to Continuum®: shop.lww.com/Continuum Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @LyellJ Guest: @neuropalldoc Full episode transcript available here Dr Jones: Most of us who see patients with chronic progressive neurologic disease are aware of the value of palliative care. The focus on symptom management and quality of life is a key aspect of helping these patients. But how many of us are comfortable starting the conversation about palliative care or care at the end of life? Today we have the opportunity to speak with a leading expert on neuropalliative care, Dr Maisha Robinson, about how we can better integrate neuropalliative care into our practices. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum: Lifelong Learning in Neurology. Today I'm interviewing Dr Maisha Robinson, who is Continuum's Guest Editor for our latest issue of Continuum on neuropalliative care, and our first-ever issue fully dedicated to this topic. Dr Robinson is an assistant professor of neurology at Mayo Clinic in Florida, where she is Chair of the Division of Palliative Medicine, and she also serves on the AAN Board of Directors as Chair of the Member Engagement Committee. Dr Robinson, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners? Dr Robinson: Well, Dr Jones, thank you for having me. Really a pleasure to be here. I'm Maisha Robinson at the Mayo Clinic in Jacksonville, Florida. I spent my time as a neurohospitalist, a general palliative care physician, and a neuropalliative care physician. Dr Jones: So, this is a topic that at Continuum, we have heard about from subscribers for a long time requesting a fully dedicated issue to palliative care. And we've titled this neuropalliative Care. So, we want to respond to our subscribers and bring them content that they're interested in. I also think that palliative medicine is a big education gap in our specialty of neurology and something that we have room to improve on. So, let's start with the basics, Dr Robinson. Palliative medicine has been around for a long time, but this concept of "neuropalliative care" feels relatively new. What is neuropalliative care? Dr Robinson: That's a great question. Generally, what I would say is palliative care, first of all, is really just a specialty that focuses on trying to improve quality of life for people that have a serious or advanced medical condition. And neuropalliative care is really palliative care for people with neurologic conditions. And you'll see a number of neurologists doing neuropalliative care, but also there are internists as well, and people from other specialties, who focus on patients with neurologic disease and really trying to improve their quality of life. Dr Jones: Got it. And so, it's really the principles of palliative medicine in a specialty-specific context, which I think is important for us given the prevalence of chronic disease in our specialty. And I was obviously reading through these articles in this issue, and in the really wonderful articles, there are some themes that came up multiple times in various different articles. And one of them was obviously the importance of communication with patients and families. I think, and I'm speaking a little bit from personal experience here, many physicians feel uncomfortable bringing up the discussion of palliative care. And I'm sure that is something that reflects on your practice, too. How often do you have a patient who shows up to clinic and they ask you, why am I here? Dr Robinson: It happens all the time, because colleagues who are referring patients are nervous to tell them that they're sending them to palliative care. But we try to tell people it's really just to normalize it, to say that the palliative care team is going to see you, they're going to help with some symptoms, they're going to help you think about big picture, and they're going to be sort of an added layer of support to your team. And I think if people approach it from that standpoint, then patients and family members will say, that sounds great, I need a little extra support. Dr Jones: So, I think most neurologists have a threshold at which they would feel more comfortable having specialty support, having a palliative medicine specialist to help them in symptom management with the patient. For the palliative care that they provide themselves---and we want our subscribers to read this issue and feel more comfortable with delivering some palliative care on their own---how would you encourage them to begin that conversation? How should they initiate that conversation with a patient about working more toward palliative management of symptoms? Dr Robinson: So, one of the things we recommend is really introducing an approach to palliative care very early in the disease process. So, discussions about big picture and goals of care, discussions about who might help make medical decisions if the person can't make them for themselves. Those kinds of things can be discussed very early on. And in fact, that's palliative care. And then they can talk to patients more about the fact that as the disease progresses, there may be an additional team that can help walk along alongside the neurologist in helping you prepare for what's to come. You know, I think it's very important for patients and family members who feel like you're not abandoning them, but you're adding additional resources. And so, I like the way that we often will suggest to people to say partner or collaborate or bring in extra resources with the palliative care team. I think patients and family members will respond to that. Dr Jones: Yeah. So, by talking about it early, you kind of, at least, help to avoid that problem of the patient perceiving the introduction of palliative care as the quote-unquote "giving-up problem." Is that right? Dr Robinson: Correct. Because we also don't want to see people who are just being referred to us for end-of-life care. Palliative care is about much more than that. But if patients will Google palliative care, they may see hospice come up. And so, introducing the concept early and discussing some palliative topics early will allow the patient and family members to think that, okay, this isn't because I'm at the end of life. This is just because my clinician wants to make sure that I have all the bases covered. Dr Jones: This was also mentioned in several of the articles, the studies that have shown how frequently palliative care is initiated very near the end of life, which is usually, I think, perceived as a missed opportunity, right? To not wait so long to take advantage of what palliative care has to offer. Dr Robinson: That's correct. And the benefit of palliative care is that oftentimes we work alongside an interdisciplinary team, a team that could be quite helpful to patients and their support systems throughout the course of the disease. So, we have chaplains, we have nurses, we often have other clinicians, advanced practice providers as well, who work with us. We have spiritual advisors as well. And the patients and family members could benefit from some of those resources throughout the course of the disease. Who they might need to meet with may vary depending on what the disease is and how they're doing. But there's definitely some benefit to having a longitudinal relationship with the palliative care team and not just seeking them out at the end of life. Dr Jones: So- that's very helpful. So, it'll obviously vary according to an individual provider's level of comfort, right, where they're comfortable providing certain palliative management care versus when they need to have some assistance from a specialist. Are there types of care or are there certain thresholds that you say, wow, this patient really should go see a specialist in palliative medicine or neuropalliative care? Dr Robinson: So, I think that if there are, for instance, refractory symptoms, where the neurologist has been working with a patient for a while trying to manage certain symptoms and they're having some challenges, that person may benefit from being referred to palliative care. If patients are being hospitalized multiple times and frequently, that may suggest that a good serious-illness conversation may be necessary. If there are concerns about long-term artificial nutrition, hydration, or functional and cognitive decline, then some of those patients have benefited from palliative care. Not only the patient, but also the caregiver, because our team really focuses on trying to make sure that we're walking through the course of disease with these patients to ensure that all of the needs are managed both for the patient and the family member. Dr Jones: Got it. And that's very helpful. And I know that we talk about a lot of these decisions happening in an ideal environment when there's good access to the neurologist and good access to a palliative medicine specialist or even a neuropalliative medicine expert. In your general sense, I- and maybe we'll talk a little bit here in a minute or two about the growing interest in neuropalliative care. But in terms of access, in terms of availability of really, truly neuropalliative expertise, what is your sense of how widely available that is in the US? Dr Robinson: There's a shortfall of palliative care clinicians in the United States. Everybody who needs a palliative care clinician won't have access to one. And I think your point about the primary palliative care is so important. That's really what we encourage all clinicians, neurologists, neurosurgeons, even, physiatrists, the neurology care team members need to be comfortable with at least initiating some of these conversations. Because, to your point, not everyone's going to have access to a palliative care physician. But by reading issues such as this one, attending some courses---for instance at the American Academy of Neurology meetings---, doing some online trainings, those types of things can be helpful to bring any neurology clinician up to speed who certainly may not have access to a palliative care physician. Dr Jones: So, I know---and this is in part from my own conversations with patients in my own practice---there are a number of fears that patients have when they have a chronic disease, something that's progressive or something that we don't have a curative treatment for. But I think one of, if not the most common fear among patients is pain, and pain that can't be managed adequately during the course of chronic illness or at the end of life. One of the interesting concepts that I saw mentioned in a few of the articles in this issue is this concept of total pain. So, not just the somatic pain that I think we tend to think of as clinicians and patients tend to think of as patients, but a more holistic definition of pain. Walk us through that and how that relates to palliative medicine. Dr Robinson: So, Dame Cicely Saunders, the modern-day founder of palliative medicine, really described this biopsychosocial model for pain. And so, you're right, it's not just physical pain, but it's psychological pain, it's spiritual pain. And oftentimes when we are taking care of patients with neurologic disease, they may have some physical pain, but a lot of them are thinking about, for instance, the things that they will miss, which may cause some internal discomfort. Things that they're grieving, the life they thought they were going to have, the person that they used to be, the life they used to have, and what they anticipated their life as being. And some of that can cause people to have not only the spiritual discomfort, but also some psychological discomfort as well. And so, when we're thinking about how to provide rehensive care to these patients, we have to be thinking about all of these aspects. Dr Jones: It's really helpful. And I guess the more you can identify those, the more you can either help yourself or find the right expert to help the patient. I thought that was an interesting expansion of, of my view of how to think about pain. And another observation that came up in several of the articles was a lack of high-quality clinical trial evidence to inform a lot of the interventions in neuropalliative care. Some of them are common-sense, some of them are based on clinical experience or expert advice. In your own practice, if there was one key knowledge gap to close---in other words, if there was one pivotal trial that we could do to answer one question in helping patients with chronic neurologic disease---what would you say is the main gap? Dr Robinson: I think the real gap is, who needs palliative care and when? That seems very simple. We have tried things such as automatic triggers for palliative care, for instance, in patients with ALS, or we've said that maybe all glioblastoma patients should see palliative care. But is that true? Are we utilizing the resources in the best possible way that we can? We're not sure. And so, you'll see these practices doing things all a little bit different because we don't have a best practice and it's not really standardized about when people should see palliative care, or why, for instance, they should see palliative care, or who should see palliative care. And I think if we could help drill that down, we can provide some better guidance to our colleagues about when and why and who should see palliative care. Dr Jones: It's a really kind of a fundamental, foundational, who needs the service to begin with or who needs to care. Okay, that's- that is a big gap. So, one of the interesting concepts that I read- and it was in Benzi Kluger's article on neuropalliative care for patients who have movement disorders. I think it's a concept that is interesting, really, maybe in the management of patients with a lot of different chronic, progressive neurologic diseases. And it's this idea of stealing victories or bringing joy to patients. In other words, not just managing or trying to minimize some of the negative aspects or symptoms of disease, but looking for opportunities to bring something positive to their experience or improving their quality of life. Tell us a little more about that, because I think that's something patients would appreciate, but I think neurologists would appreciate that, too. Dr Robinson: Dr Kluger loves to talk about sustaining and finding joy in patients who have really serious or advanced neurologic conditions. He likes to talk about stealing victories, which can relate to the fact that patients and their loved ones can find even some benefit despite having a serious or advanced neurologic condition. Neurologists and neurology clinicians also can steal victories in their patients when they notice, for instance, that they've gained a new skill, and they've lost a skill that they used to love because of the advancing disease. And this is just an opportunity for not only the patients and family members, but also the care providers to recognize that in the midst of decline, there are positive things to be found. Dr Jones: I think it gives patients a sense of maybe reclaimed autonomy when they can say, well, there's maybe nothing I can do to cure this disease in the conventional sense, but I can maybe go on this trip with my family, which has been something I've always wanted to do. Or, I can do these things, so I can attend certain events that I want to. And I think that autonomy and independence aspect of that, I think that I think that was really meaningful and something that I'm going to bring back to my own practice in my care of patients who have ALS, for example. When you think about neuropalliative care---and you've been a leader in this area, Dr Robinson---what do you think the biggest change in neuropalliative care has been over the last few years? Dr Robinson: I think there's a growing cohort of people who are recognizing that there is some benefit in having dedicated specialists who focus on palliative care for patients with neurologic disease. When I said I was going to do neuropalliative care, somebody asked me, why would a neurologist be interested in palliative care? Over the last decade and a half, we've seen that shift. And not only are our colleagues recognizing the benefit, but also patients and caregivers are. Some are even asking for palliative care. I think people are recognizing that not only having their primary neurologist or neurology clinician taking care of them, they have this extra layer of support, and this extra team really focused on quality-of-life issues can be beneficial. Dr Jones: So, one of the things that I think you and I have both seen, Dr Robinson, is a growing interest among neurology trainees in palliative medicine. And maybe that's anecdotal, but in my own practice, I've seen more and more trainees express an interest in this. For neurology residents who are interested in this as a component of or maybe a focus of their career, what would you recommend to them? How should they go about this? Dr Robinson: Yes, it used to be that every neurology resident interested in palliative care would call me or email me or send me a message, but now there are so many that I can't keep up. We're excited about the growing number of people interested in neuropalliative care. What I would say to those people is that you can really try to hone your skills by, for instance, doing a rotation with the palliative care team at your hospital, if there is one. If there isn't one, you might even ask to spend some time with the local hospice agency, which may be helpful to you. If you're attending some of the national meetings---for instance, the American Academy of Neurology meeting---you may want to go to a course and learn a little bit about palliative care. There are a couple that are offered every year. There is an education opportunity for education in palliative and end-of-life care as well. And so, there are a number of resources that you can find in addition to this issue of Continuum as well. Dr Jones: I find it gratifying that trainees ask about this. And I'm sorry, I think I've probably sent a bunch of trainees your way for advice about this, and you've been incredibly generous with your time and expertise. So, I find it very gratifying that our neurology trainees are interested in this area, because it's an important area of medicine. It's also probably a challenging practice just from the cognitive load and the emotional load of caring for patients who are moving through a progressive illness. What is your thinking about how to have a sustainable career in palliative medicine? What is your approach to that? Is it for everyone? Dr Robinson: Yeah, the issue with palliative care is that we do see some very challenging situations, and frankly some very sad situations. But I actually love what I do because I think that we're helping patients and their family members during very, very difficult times. I feel like this is why I went to medical school, to try to be there for people when they need me the most. The way that I think about it is, the patients and family members will be going through this anyway. We're trying to help improve their quality of life as they're going through it. And what you might find interesting is that these patients are so grateful. And their loved ones, they're so grateful. Even if they're nearing the end of life, just to have someone who's helping them see that, for instance, the pain could be better, or that they have more resources for the loved ones to be able to take care of them. And so, I think that helps sustain us, realizing that we are really having a positive benefit on the patients and also their family members. Dr Jones: Well, I think that's a great point to end on. And these are patients who need help. Even if we don't have a curative therapy, they do need support. And that's an important service and a function and an important facet of our profession. So, Dr Robinson, I want to thank you for joining us, and I want to thank you for such a great discussion of neuropalliative care. I learned a lot from our conversation today. I've learned a lot reading the articles and the experts that you put together. This is an important topic. I'm really grateful to you to having assembled this team of expert authors and put together an issue that I think will be really important for not only our junior readers, but also our more experienced subscribers as well. Dr Robinson: Thank you, Dr Jones, for the opportunity. Dr Jones: Again, we've been speaking with Dr Maisha Robinson, Guest Editor of Continuum's most recent issue and first issue fully dedicated to neuropalliative care. Please check it out, and thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. Thank you for listening to Continuum Audio.

In this engaging discussion, Dr. Divya Jayaraman, an expert in pediatric neuromuscular disorders, delves into dystrophinopathies, genetic muscle disorders stemming from the DMD gene. She highlights the critical role of early diagnosis through creatine kinase checks and explains how timely intervention can lead to better treatment outcomes. Dr. Jayaraman shares tips on recognizing clinical signs and emphasizes the importance of a multidisciplinary care team. She also discusses exciting advancements in gene therapies and future research directions.

Myotonic dystrophies (DM), in addition to muscle weakness and myotonia, are associated with broad and variable multiorgan involvement. Neurologists need to recognize DM to ensure prompt diagnosis, effective symptom management, and prevention of life-threatening events. In this episode, Casey Albin, MD, speaks with Paloma Gonzalez Perez, MD, PhD, author of the article "Myotonic Dystrophy" in the Continuum® October 2025 Muscle and Neuromuscular Junction Disorders issue. Dr. Albin is a Continuum® Audio interviewer, associate editor of media engagement, and an assistant professor of neurology and neurosurgery at Emory University School of Medicine in Atlanta, Georgia. Dr. Gonzalez Perez is an assistant professor at Harvard Medical School in Boston, Massachusetts. Additional Resources Read the article: Myotonic Dystrophy Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @caseyalbin Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Albin: Hello everyone, this is Dr Casey Albin. Today I'm interviewing Dr Paloma Gonzalez-Perez about her article on myotonic dystrophy, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Welcome to the podcast, Dr Gonzalez-Perez. I'd love for you to introduce yourself to our listeners. Dr Gonzalez-Perez: Thank you very much for the invitation. My name is Paloma Gonzalez-Perez. I'm a neuromuscular neurologist at Massachusetts General Hospital in Boston since 2018. And I'm originally from Spain. I did residency there and also here in Iowa City. And then I did the neuromuscular fellowship here at Mass General Brigham, and then I stayed here as a faculty. So, my focus is myopathies, and more specifically muscular dystrophies, and more particularly myotonic dystrophy, which is what we are going to talk today. Dr Albin: Wonderful. And this is a really fantastic tour de force article about myotonic dystrophy. And in reading your article, it really did stand out to me that these myotonic dystrophies are probably under-recognized. And so, I was hoping that, just to start, you could tell us a little bit about, what is a myotonic dystrophy, and how should we sort of situate that within the larger context of all muscular dystrophies? Dr Gonzalez-Perez: Yes, so muscular dystrophies, we have many of them, right? And mostly affecting the skeletal muscle. And basically, the definition of muscular dystrophy is a genetic or inherited muscle disease that causes a progressive muscle weakness. And also, in the muscle biopsies of patients with muscular dystrophies, we see some fractures that are characteristic of this category of muscle diseases, such as, for example, the nuclei of the muscle fibers are in the center---that's what we call internal nuclei---or maybe fat infiltration or increased connective tissue or a variability in the size of the muscle fibers. So, now in the last few years, the genetic testing is more accessible to us. So, we don't need muscle biopsies all the time to diagnose patients with muscular dystrophy. So many times, we go directly to genetic testing. And this is basically the category of muscular dystrophies. Myotonic dystrophy is very fascinating muscular dystrophy in the sense that many times not only affect the skeletal muscle, but other organs can be affected. And it is true that other muscular dystrophies can affect other organs such as, for example, the brain and the heart, which is something that we always have in mind as a clinician to make sure this muscular dystrophy affect the heart or affect the brain, because it is important for patient care. But myotonic dystrophy actually can affect any organ in the body. I think it is one of these muscular dystrophies in which there is a multisystem involvement of the body. So, the immune, immunological system can be affected and the endocrine system can be affected, the GI system can be affected. In addition to, obviously, to the brain, to the heart, to the skeletal muscle. And sometimes that is why it is under-recognized because of course, if there is a very severe phenotype, maybe the patient comes very easily to a neurologist who is very familiar with myotonic dystrophy. But if the phenotype is a little bit milder, and maybe it doesn't affect much the skeletal muscle. So, these patients probably are in the care of other specialists, such as, for example cardiology or GI doctors, and obviously these specialists are not really aware of this muscular dystrophy. So, I think it is a complex disease because it is very variable in phenotype, can affect many organs and can be also mild. Dr Albin: That is fantastic. That is just a wonderful overview of, really, muscular dystrophy. One of the things I was really curious about: the name includes myotonia. Is myotonia, like, always present, or is that a little bit misleading? Dr Gonzalez-Perez: Yeah. I would say that it is a little bit misleading---maybe not too much in myotonic dystrophy type one, because it is true that in adults with myotonic dystrophy type one, many times they have the myotonia, but not many times they complain about the myotonia. This is the thing. So, it is a diagnostic clue that we have at bedside when we ask the patient, for example, to squeeze the hands and then release and we see the myotonia there. And then, obviously, this can actually give you the diagnosis at bedside, but the patients usually don't come to the clinic complaining of this myotonia, which is delaying the relaxation of the muscles. Sometimes they don't- they are not bothered by that. They don't need treatment for that. But it is a very important clue at bedside. I have to say, adults, myotonic dystrophy type one, because the congenital myotonic dystrophy type one you don't see myotonia, clinical myotonia. These babies, right, are born with severe muscle weakness and we don't see myotonia. And then myotonic dystrophy type two, many patients don't have clinical myotonia. And then, you know, the absence of myotonia, the absence of this delay in the muscle relaxation doesn't rule out a myotonic dystrophy, and especially doesn't rule out a myotonic dystrophy type two. Dr Albin: Fantastic. So probably is going to be a feature of the adult-onset type one. May or may not be present in type two. And then the congenital forum where children are presenting as infants, they're not going to tell you that, oh, I have delayed relaxation. That's not going to be part of that. Dr Gonzalez-Perez: Exactly. Dr Albin: This is one of those things that I think, unless you're in neuromuscular clinic, you might not think to ask people about. Maybe the patient isn't actually saying, oh, I have this delayed reaction. How do you get them to give you that history? Like, what are the questions that you ask? Dr Gonzalez-Perez: Sometimes I will say, do your hands get locked? You know, this could be the first question that they noticed something there, and then they can give you maybe the clue. But actually, it's the exam more than the question. I will say it's more do the exam and, you know, intentionally test for myotonia. And you test for spontaneous myotonia and percussion myotonia. So spontaneous myotonia, we tell the patient to squeeze the hands very strongly and then open the hands quickly. And then if they cannot open the hands quickly, this is a delay in muscle relaxation. We call it grip myotonia, spontaneous grip myotonia. Or sometimes close your eyes very, very, very strongly and then open the eyes quickly. And if they have this delay in the eye opening, we call it eyelid myotonia. This eye is spontaneous myotonia, you don't touch the patient and you don't use your hammer yet. And then if we don't find anything, we go to the hammer. We use our reflex hammer, and then we try to test for percussion myotonia. And sometimes we with the reflect hammer, we tap the thinner eminence of the hand, and we can see that you tap, there is a contraction, and then the thumb goes up and then takes a while to go down again. It is a delay in the relaxation of the thinner eminence muscles. Or sometimes in the posterior aspect of the forearm, if we tap the extensor digitorum communis muscle. Again, so, there is a contraction of that muscle, the fingers go up and then take a while to go down. It is also a perfusion myotonia of the extensor digitorum communis muscle. Sometimes people do it even in the tongue. I don't do that because could be very painful. But you can, you know, use a tongue depressor and put it in the tongue, and you tap the tongue depressor and sometimes there is contraction of the tongue, which can be very painful. I don't do it. So- but this is the perfusion myotonia, that can give you also a clue. Dr Albin: That's fantastic. I think this is one of the most memorable things that I saw in pediatric neurology. I remember very distinctly a kid coming in, and then us also examining the mother and having that delayed relaxation. And just one of those really great neurologic exams, those little findings to tuck away to really make a diagnosis, recognizing that not all patients with muscular dystrophy or myotonic dystrophy will have that finding. But so beautiful. And I think that's a really great explanation. And I will also direct our listeners, if you are a Continuum subscriber, she has some really wonderful videos in her article from the EMG sounds of this, which is another layer of being able to appreciate the physical exam finding. One of the things that I was really struck by, and that you've already mentioned, is that there is this really incredible spectrum of disease. That some of the myotonic dystrophy patients may barely have any skeletal involvement, and the ones with congenital myotonic dystrophy may have significant mortality even within the first year of life. Given how many subtypes of this disease there are in that varied presentation, let's just walk through sort of starting with congenital myotonic dystrophy. What are some of the clues to that diagnosis? Dr Gonzalez-Perez: Yes. So, you know, these babies with congenital myotonic dystrophy, actually when they are born, the phenotype is what we call a floppy baby. Floppy baby syndrome right? So, they are very weak. There is generalized weakness, including the swallowing muscles and the respiratory muscles. So sometimes, you know, these patients, these babies have to be intubated---to have a feeling tube, right---to survive. So, that's why the mortality can be so high during the first year of life, because obviously swallowing and breathing is affected because the muscle, those muscles, are also affected. So, one of the clues, actually- you know, sometimes these patients may have, like, a tented mouth, which could be a sign of congenital myotonic dystrophy. The differential diagnosis for a floppy baby syndrome is very broad and can be caused by central nervous system problems or peripheral nervous system problems. So, it's very broad, but maybe the tented mouth can be a clue to suspect the congenital myotonic dystrophy type one. And I will say that also, examine the mom. Because sometimes the mom is not diagnosed with myotonic dystrophy, and as simple as going into the mom who is an adult and can have already the myotonia that we talked about before and maybe, you know, try to do, like, a grip myotonia, eyelid myotonia, or use your reflex hammer and tap a few muscles, and then can give you the diagnosis of potential congenital myotonic dystrophy in the baby. And I have to say that there is no newborn screening for myotonic dystrophy type one yet. Maybe in the future it's going to be, but not at this time. So, I'm pretty sure that pediatricians probably rule out other things before unless there is distinctive mouth or unless the mom is affected. Dr Albin: Great pearls about how to take it to the bedside and try to look for that hereditary nature of this. Let's move up a little bit in sort of the childhood and adolescent onset. What are some of the clues that you're seeing for those children who come to presentation a bit later in life, but still probably more likely to be seen in pediatric clinic? Dr Gonzalez-Perez: Yes. So, the childhood and adolescent onset in myotonic dystrophy type one, it is interesting because the skeletal muscle may not be the organ that is more affected or the organ that impacts the life of the patient and the family of the patient. So, it's- the phenotype is predominantly focused on behavioral and intellectual disabilities. They may develop at some point myotonia, and they may develop also muscle weakness. But for the most part they are ambulatory. They eat by themselves, they breathe okay, and there is not too much problem with the skeletal muscle, but mostly with behavioral problems such as, for example, ADHD or intellectual disability. So, they may need some help in school and things like that. So, it is more, I will say, a central nervous system phenotype at this age. Dr Albin: Yeah, I love that that this is- to me, this was part of the complexity of this was that, while we call it myotonic dystrophy, the muscle part of this disease really may not be the main issue for the patients and their families. And that we're actually looking for something that involves the central nervous system, endocrine system, GI system. And knowing that maybe the muscle is not the main problem here, why is it so important that these patients actually get the correct diagnosis? Dr Gonzalez-Perez: Exactly. So, it is very important. And I always think about the heart. You know, the heart can be affected in the sense like the rhythm of the heart can be abnormal. And sometimes, you know, the patient doesn't have symptoms. But it's important to detect this because, you know, an abnormal rhythm in the heart can cause sudden death. So that's why it's so important. The diagnosis of this muscular dystrophy at this time, and of course in the future when we have a treatment, right, will be very important also to have the diagnosis, the earlier is the better, because probably the treatment is going to be more effective in the earlier stages than in the later stages. But I will say that right now making sure that the heart is in a good shape and the patient has a cardiologist on board if they have myotonic dystrophy. And also, you know, there are consensus-based care recommendations for myotonic dystrophy type one for the pediatric population and the adult population, and also for myotonic dystrophy type two for the adult population, that are published. And I also included in the chapter because they are very important to look for things that maybe the patient it doesn't complain about, but it's important to look for them in the case that we can prevent some future complications. Dr Albin: Absolutely. I really love that. This is a systemic disease that has multiple manifestations, and while the skeletal muscle involvement may or may not be causing problems, we really do have to get the right diagnosis, particularly as it impacts the heart and preventing fatal cardiac arrhythmias. Up to this point, we've mostly been talking about type one myotonic dystrophy. What sets type two apart? Dr Gonzalez-Perez: Yes. So, type two is, I think, even more under-recognized, probably because the phenotype is even more variable than type one and can be much milder in some sense. We are not aware of, you know, like, there are some pediatric cases that have been reported, but for the most part it's an adult muscular dystrophy, type two. So, we diagnose these muscular dystrophies usually in the forties, fifties. The thing is, like, sometimes patients actually may only have muscle pain. And not even muscle weakness. And so… and actually some of these patients may receive a diagnosis of fibromyalgia, for example, just because of the muscle pain. And it is more difficult to obtain myotonia on exam, actually. I think there is a delay in diagnosis in this population, and also the multisystem involvement, which is present but maybe even more variable than that in type one. And we have less patients, so we understand less the phenotype of these patients. But for the most part it is, I think, more under-recognized in the type one. Dr Albin: Fascinating. So again, could have pretty mild skeletal involvement and may just have cramps and muscle pain. So, you have to be really sort of mindful of keeping this on the differential for people with multiple areas of pain in the muscles. When is this suspected? Are you usually sending genetic tests to confirm? How do we get to the diagnosis? Dr Gonzalez-Perez: In the history, in the past medical history, you have probably- sometimes you have the clue. For example, a patient with muscle pain, imagine like for example a forty-eight-year-old male with muscle pain comes to the clinic, and then he tells you that he had cataract surgery at the age of twenty. And then you see a CK that is a little bit more elevated than usual. And then at that time I will go for genetic testing right away, for my myotonic dystrophy type two. Because of the muscle pain is so characteristic of myotonic dystrophy type two, and the multiorgan involvement sometimes includes a very early cataracts, the same as in type one. But the muscle pain is much more typical for type two than for type one. So, that's why I will go, in this specific scenario to type two. If I still think that my alternative dystrophic type two is a possibility, although I'm not totally convinced if it is or not, I usually go for EMG. I mean, if you don't see myotonia at the side, maybe with the EMG and the needle in the muscle, you can see this electrical myotonia that I have some videos in the chapter to see if there is this motorcycle sound of the electrical discharges from the muscle that are consistent with- they can be seen in myotonic dystrophy type two. They are not as specific, but can be seen in myotonic dystrophy type two. So if I have a patient with muscle pain and then I see this electrical myotonia on EMG, so then I will go then next to a genetic testing for myotonic dystrophy type two. Sometimes if there are some family history, it gives you also clues about the possibility of myotonic dystrophy in general, but also myotonic dystrophy type two. Myotonic dystrophy type two, usually the muscle weakness, when it is present, it's more proximal. While in myotonic dystrophy type one it's more distal. So, this also, you know, helps you to differentiate. But specifically in this myotonic dystrophy area, I think the past medical history helps you a lot and the family history helps you too. If you see an autosomal dominant inheritance of muscle or other organ problems, you suspect this type of muscular dystrophy. And I have low threshold to test for this if it is possible because, as we mentioned before, knowing what the patient has helps a lot in their care. Dr Albin: Absolutely. I love that. Spoken like a true neurologist, using the history, the physical, thinking about the family history, using EMG as an extension of our physical to really find and clinch that diagnosis, and then using genetic tests as a confirmation to get to the right answer. I love the mention of early-onset cataract. Are there any other things that pop into your mind or when you're reading the chart and you look at the medical history that, like cataracts, stand out to you as, this really clues me into myotonic dystrophy? Dr Gonzalez-Perez: Yes. So, for example, a pacemaker at early age---in their thirties, in their forties---; a family history of sudden death---for example, having a surgery for whatever reason, having a surgery like for example, surgery for appendicitis and have complications from general anesthesia, like a delay in the awakening from the general anesthesia because patients with melatonin dystrophy are very sensitive to anesthetics and also any sedative medication. So, that gives me a clue that, you know, patients with melatonin dystrophy can have this type of history. I think that those will be the main ones. Sleep apnea is very common, but we know it's also common in the general population. So, maybe sometimes, actually, we may think too much and it is, you know, normal for the general population, more frequent in the general population. But, yeah. And daytime sleepiness that can be caused by the sleep apnea. But sometimes these patients have profound daytime sleepiness. Like, they really complain about that. You know, I need to nap very often during the day because of this. Those features, I think, increase my suspicion for myotonic dystrophy. Dr Albin: Fantastic. So, in the brief time that we have left, I'd love for you to tell us a little bit about what's on the horizon for treatment for these patients. Dr Gonzalez-Perez: Yes, we have exciting preclinical and clinical trials in myotonic dystrophy type one; not yet in myotonic dystrophy type two. And these trials try to target the genetic defect at the level of the DNA or at the level of RNA. So, we have small molecules in clinical trials. We have also some antisense oligonucleotides in clinical trials. We have some small interfering RNAs in clinical trials. And then the CRISPR, which is another new technology, that is trying, you know, to repair this long function that causes myotonic dystrophy type one. And the important thing is, like, once we know what works for myotonic dystrophy type one, we may have good clues also for myotonic dystrophy type two because they share the common pathogenic mechanism. Dr Albin: Fantastic. So, it sounds like there's some genetic therapy in the pipeline. There is some small molecule treatments that are going to be available. So, really an exciting time. There's going to be a lot of changes coming forward to these patients. Again, today I've been interviewing Dr Paloma Gonzalez-Perez about her article on myotonic dystrophy, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Be sure to check out Continuum Audio episodes from this and other issues, and thank you so much to our listeners for joining again today. Dr Gonzalez-Perez: Thank you very much for the invitation. My pleasure. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Dr. Hani Kushlaf, a neurology and pathology professor at the University of Cincinnati, dives into the complex world of muscle channelopathies and rhabdomyolysis. He shares his journey from epilepsy to neuromuscular medicine, revealing the latest updates on genetic causes and treatment hopes. Listeners learn about changing definitions of rhabdomyolysis, the significance of initial workups, and the use of the RABDO acronym for genetic testing. The discussion also covers the clinical impact of genetic disorders and practical examination tips for recognizing muscle dysfunction.

Inflammatory myopathies are a large group of disorders associated with an inflammatory response targeting skeletal muscle. Treatment hinges on the use of evolving immunotherapies and diagnostic tools to quickly identify inflammatory myopathy, initiate appropriate therapy, and exclude underlying malignancy or infection of other organs. In this episode, Katie Grouse, MD, FAAN speaks with Anthony A. Amato, MD, an author of the article "Idiopathic Inflammatory Myopathies" in the Continuum® October 2025 Muscle and Neuromuscular Junction Disorders issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Amato is the Brigham and Women's Hospital Distinguished Chair in Neurology and the director of neuromuscular research at Mass General Brigham, and is a professor of neurology at Harvard Medical School in Boston, Massachusetts. Additional Resources Read the article: Idiopathic Inflammatory Myopathies Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Anthony Amato about his article on idiopathic inflammatory myopathies, which he wrote with Dr Kian Salajegheh. This article appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Welcome to the podcast, and please introduce yourself to our audience. Dr Amato: Thank you. And I am Tony Amato. I'm in Boston at Mass General Brigham. Dr Grouse: It is a distinct pleasure to have you here with us today, and I'm really excited to talk with you about your article. I thought it was a fantastic overview of the subject. And I'd like to start by asking what you hope will be the key takeaway for those who are reading this article. Dr Amato: I think it's kind of basic: how to make a diagnosis, describe about the inflammatory myopathy as approach to, again, diagnosis, and then a little bit on pathogenesis, which… and kind of leading to the treatments, and hopefully we'll have more treatments based on the distinct pathogenesis in the future. Dr Grouse: Can you give a brief overview of the categories of inflammatory myopathies you reviewed in your article? Dr Amato: So, I mean, the major inflammatory myopathies, radiopathic inflammatory myopathies, are dermatomyositis, antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, and polymyositis. Now, that's been a big change, as you know. I mean it used to be, you know, we all started off it was dermato or poly. But I've kind of made a name for myself- a bad name for myself in the early 2000s saying, I'm not sure there's much of a thing called polymyositis. I think it's a hodgepodge and it's not distinct. And that's come to be, now most of those cases are- now we find out having antisynthetase syndrome or necrotizing myositis or IBM. Dr Grouse: Could you walk us through your diagnostic approach with a patient in your clinic presenting with symptoms that are suspicious for inflammatory myopathy? Dr Amato: So, you want to really make sure that they have inflammatory myopathy as opposed to some other kind of myopathy, a muscular dystrophy, for example. Taking family history first is going to be important, clueing in are they really weak or what they're complaining of is fatigue or muscle pain? Are they feel weak but what they really are complaining of is stiffness and rigidity from parkinsonism, or they have a sensory ataxia so they can't modulate? I want to know about other organ system involvement. Do they have a rash? Do they have joint swelling and pain that you might see with arthritis? Do they have shortness of breath that you might see with interstitial lung disease or ventilatory muscle weakness? Or do they have a cardiomyopathy? What kind of weakness do they have? Is it proximal weakness in the arms or legs? Getting out of a chair, climbing stairs. Do they have problems lifting their arms over their head---so, proximal weakness---or do they have more problems with grip, finger flexion, holding a pen, tripping? Do they have swallowing problems? Do they have ocular problems? So that's the big history on the exam. Again, I'm looking for pattern of involvement. So, on my exam, is there atrophy or weakness in muscles---you know, fasciculations---which would take it out of the motor? Is it mainly proximal? Is it distal? Again, is there ocular bulbar involvement? Is it symmetric, particularly in, like, the IBM? Most of the other inflammatory myopathies are going to be mainly and proximal and mainly symmetric. IBM is different, and that the- at least in the hands it's more distal, and it's finger flexors. So, you're looking at flexing the tips of the fingers, you're looking at the forearms, best looked at in a semipronated position to see if it's atrophied. And that leads you to an IBM if you see that. So that's the main things on exam. Dr Grouse: That's a really helpful overview. I was wondering, in earlier training days, the convention was you- once you've suspected myopathy, you get your CK, you get your EMG, then that may give you the information you need for your diagnosis. It seems that things have been turned a little on their head. We're often skipping those things to go straight to the antibody testing. When should we be going for the myositis-specific antibodies before considering other things like EMG or muscle biopsy? Dr Amato: I would always get a CK first. You know, in somebody who's weak. You know, the EMG, I don't need an EMG if the CK is two or three thousand. I mean, EMG is- localize it to, is it muscle, nerve, neuromuscular junction. If it's very elevated CK, it really doesn't help me there. Sometimes if I have myotonic discharges or something that might make me think of a myotonic dystrophy or something else like that. But you can see that with the inflammatory myopathy. So, if I'm pretty sure of a myositis, I don't always do an EMG, or- unless I really need it to help guide what muscle biopsies I do. if I'm suspicious then on my exam and I see the CK---or they come to me already with the CK, which often happens, and it's very elevated---that's when I'll do the myositis-specific antibody panels if I'm really thinking that. And the important thing to know from that is, you have antibodies for dermatomyositis and antisynthetase that are on the panel that are available, and even signal recognition particle, which is a necrotizing myositis. But what's not on the panel is HMGCR antibodies, which is important because that's 70% of the necrotizing myocidites are HMGCR, and then the IBM antibody and T5-C1A is not on that. So, you need to order those separately. If somebody doesn't know, they order a myositis-specific antibody and think that it's all-inclusive, but it doesn't have IBM or the HMGCR antibody. And the other test that I sometimes will do is a skeletal-muscle MRI to help in the evaluation. Sometimes, not all the time, but I'm not sure it's a dystrophy, is it a myositis when I see a lot of STIR signal, which is edema. And you can still see STIR signal in a dystrophy and toxic. But sometimes I'll do it depending on whether I need a biopsy or not. Dr Grouse: What is the benefit of an open biopsy versus a needle biopsy, and when should we be considering using one over the other? Dr Amato: So, it really is not our decision. It's the pass lab. So, it's the technicians and the pathologists who read the biopsies need to be able to process a needle biopsy, which might be much smaller. Needle biopsies show to be fairly accurate in a lot of the hereditary disorders where you might just look for central nuclear core, and they might be- so, mainly in kids, but in the inflammatory myopathies, it's really patchy. So, if I'm thinking of an inflammatory, I like an open biopsy. I think it's hit and miss. And so, I like open biopsies for the adults that I'm thinking of inflammatory. Dr Grouse: Do you have any other tips or tricks in the diagnosis of inflammatory myopathies that you could share with our listeners? Dr Amato: I would say first, in terms of what muscle to biopsy, you're not doing them yourself, but you're referring to a surgeon. You have to tell them what to do with the biopsy. And you want to pick a muscle that's about an MRC grade 4 because if it's a normal muscle, the muscle strength, the biopsy, is likely to be normal. If it's less than a 4, you might just have end-stage muscle. And saying you can't tell end-stage muscle from a bad myositis, from a dystrophy, from a severe end-stage neurogenic. If I don't have a muscle that I would typically biopsy that's an MRC grade 4---for example, somebody with an early weakness and they're only weak, say, in their in their hip girdle. So hip flexors, abductors, extensors, and we're usually not biopsying the iliopsoas or the gluteal muscles. Then what do you pick? That's when I like to do an EMG on one side of the body and look at proximal and distal muscles and select one that's irritable, you know, some fibs and positive sharp waves that I might biopsy. And then maybe consider doing a skeletal muscle MRI to go from muscle that's abnormal, that has a lot of edema in it, to increase the yield. Dr Grouse: That's really helpful. And then, I think, jumping from that, what are pitfalls that you've seen neurologists fall into in this diagnosis or other challenging aspects of the diagnosis that you could review with us? Dr Amato: Some of the things that we see are hard to pick up. It might be hard to pick up a rim vacuole. They're very rare, too. And so, you might miss it, particularly if you don't see a lot. Sometimes, like looking at the dermato and that's the, on the exam question, perifascicular atrophy, but that's a late stage, usually. And so, if you're really attuned and you're a good clinician, you make that diagnosis really quick. You do a biopsy, you might not see that paraphysical atrophy. So, they don't know that in a necrotizing myopathy, the pathologists often think of what they see in a toxic myopathy or a metabolic where there's a lot of necrotic fibers. But in most of the autoimmune necrotizing, it's not. It's actually what you see is more regenerating fibers, a few necrotic fibers. It's because it's usually been smoldering along for a while, and so you have many more regenerating fibers than ones that are actively, and that can fool a lot of people. So, that's a pitfall from that end of things. Some of these myositis specific antibodies aren't specific and at a low titer, particularly if you have more than one antibody being positive, that would be a red flag that it could be false. That's another pitfall. I think a lot of people don't, when they're examining people, really look at the finger flexors and stuff. And again, if I have somebody over the age of fifty, the most common muscle disease is IBM. Number two is IBM, number three is IBM. If you don't- and you have to think about that, and you need to examine the distal finger flexors because it doesn't get better with immunotherapy. You don't want to put people at the risk of immunotherapy when they're not going to get better. I talked a lot about the biopsies, and biopsy, biopsy, biopsy. But you know, sometimes you can make the diagnosis without a biopsy. So, if somebody's like a classic dermato rash and they have a dermato antibody, do they need a biopsy? No. If they have, you know, CKs of ten thousand proximal weakness, they're on a statin and they have HMGCR antibody, do they need us have a biopsy to confirm? Probably not. Dr Grouse: Those are some really great pearls that you've shared with us, and I think will be very helpful to many of our listeners. Now, you mentioned earlier about the diminishing category of polymyositis as other types of myosidites have been discovered and better described. Do you think that is the most controversial aspect of this field currently, or are there other controversial areas or areas of ongoing debate that exist? Dr Amato: It was very controversial twenty years ago, or maybe ten years ago. So, the rheumatology guidelines, they're the ones that are often saying, oh yeah, we were right. Polymyositis, it's just hodgepodge, and it's ever-shrinking. So that's not so controversial anymore. I mean, the controversies that we have, what's the pathogenesis of dermato? It's still a little debated, some- the old theory was that it was a complement-mediated microangiopathy and the damage was caused by ischemia. That's probably not the case. It looks more and more like it's a type 1 interferonopathy, and that's toxic to the vessels in the muscle. There's still a little bit of a debate about that or, you know, you have complement might be on it, but how much that might be damaging, or it's just a secondary phenomenon. I think in the antisynthetase things, I think there's some interesting things also with that these antibodies. We used to think of that they're just diagnostic biomarkers. But there's some recent studies suggesting that these antibodies which are directed against intracellular targets, which is interesting and applies to other autoimmune diseases and that are in the brain too. And we would think that, oh, if it's a intracellular target, it it's secondary. But there's suggestion now that- again, it did demonstrate that the antibodies actually get into muscle fibers. And they bind to these targets. So maybe they're just not epiphenomenon, but they might be binding to a target and causing pathology. And that's what there's some preliminary studies that are impressed, I will say, that have antibodies, anti-HMGCR, that actually go into the cell and they inhibit the enzyme. And that might be causing the pathology. And so that's interesting. And then IBM is a big field. Is this a primary autoimmune disease that has these other kinds of degenerative features like REM vacuoles, or is it a primary degenerative that has secondary inflammation, or is it a combination of both? So, that's probably the biggest controversy these days. It is probably with IBM. What the heck is causing it? Dr Grouse: Sounds like a lot that we still have to understand about these diseases. This does lead me to wonder, though, have some of these new discoveries and ideas led to or will lead to any new breakthroughs, either in diagnostics or in therapeutics? Dr Amato: So, certainly in therapeutics. So, the discovery of dermato being an interferonopathy, probably a beta-interferonopathy, has led to development of monoclonal antibodies that target interferon, and there's trials underway. And in phase 2 studies, I can tell you from talking to colleagues that participate just melted away the rash of dermato. So, I think that's going to be a very, very good drug in the future for dermato. There's others, like JAK. JAK inhibitors work on that interferon pathway too. So, I think we'll be going towards, like, less broad-spectrum steroids, IVIG, to going, let's go to the target. Certainly, in dermato, I mean, IBM, we don't know. There is an inflammatory cell that we see in IBM that has a receptor, KCRRN receptor, and there's a monoclonal antibody that targets that in IBM, and that's a phase 3 trial right now. Hopefully that study should be ending in December, and so early next year we'll have results about that. The fact that these antibodies might be pathogenic of themselves is other ways to get rid of the antibodies. So, getting rid of plasma cells and B cells, and FCRN receptors which have been approved or antagonists that are approved for myasthenia. Now CIDP might work in some of the inflammatory myopathies where we think the antibodies might be pathogenic. So, FCRN receptor antagonist and they're in trial now as well. And there's CAR-T therapies to knock out the antibody-producing lymphocytes and plasma cell. So, I think we're going to move into the field of individualized therapies as we find the distinct pathogenesis of these disorders. Dr Grouse: That's really exciting to hear and I can't wait to see what's coming down the pipeline as more of these discoveries are made and the clinical trials advance. It has been such a pleasure. I've learned so much. So much is packed into the article. So again, I can't stress enough, please take the time to check out this article. I think you'll learn a lot, and it'll really help you fine-tune your diagnostic pathway in relation to myopathies. Dr Amato: Oh, my pleasure. Thank you. Anybody has questions, please feel free to send me an email. Dr Grouse: We may just take you up on that. Again, today I've been interviewing Dr Anthony Amato about his article on idiopathic inflammatory myopathies, which he wrote with Dr Kian Salajegheh. This article appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Be sure to check out Continuum Audio episodes from this and other issues, and thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Dr. Elie Naddaf, a renowned neuromuscular neurologist at Mayo Clinic, dives deep into inclusion body myositis (IBM). He discusses its classic and atypical presentations, highlighting key symptoms like finger flexor and quadriceps weakness, as well as dysphagia and severe facial weakness. Naddaf outlines diagnostic tools, emphasizing the gold standard muscle biopsy and the role of EMG and antibody testing. He also explores why IBM is uniquely resistant to immunosuppression and its underlying mechanisms, providing valuable insights for clinicians.

Limb-girdle muscular dystrophies (LGMDs) encompass a group of genetically heterogeneous skeletal muscle disorders. There has been an explosion of newly identified LGMD subtypes in the past decade, and results from preclinical studies and early-stage clinical trials of genetic therapies are promising for future disease-specific treatments. In this episode, Gordon Smith, MD, FAAN, speaks with Teerin Liewluck, MD, FAAN, FANA, author of the article "Limb-Girdle Muscular Dystrophies" in the Continuum® October 2025 Muscle and Neuromuscular Junction Disorders issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Liewluck is a professor of neurology at the Division of Neuromuscular Medicine and Muscle Pathology Laboratory at Mayo Clinic College of Medicine in Rochester, Minnesota. Additional Resources Read the article: Limb-Girdle Muscular Dystrophies Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Guest: @TLiewluck Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr Gordon Smith with Continuum Audio. Today I'm interviewing Dr Teerin Liewluck, a good friend of mine at the Mayo Clinic, about his article on the limb girdle muscular dystrophies. This article appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders, a topic that is near and dear to my heart. Teerin, welcome to the podcast, and maybe you can introduce yourself to our listeners. Dr Liewluck: Thank you very much, Gordon, and I want to say hi to all the Continuum fans. So, I'm Dr Teerin Liewluck, I'm the professor of neurology at Mayo Clinic in Rochester, Minnesota. So, my practice focus on all aspects of muscle diseases, both acquired and genetic myopathies. Glad to be here. Dr Smith: I just had the great pleasure of seeing you at a seminar in Houston where you talked about this topic. And so, I'm really primed for this conversation, which I'm very excited about. I find this topic a little hard, and I'm hoping I can learn more from you. And I wonder if, as we get started, recognizing many of our listeners are not in practices focused purely on muscle disease, maybe you can provide some context about why this is important for folks doing general neurology or even general neuromuscular medicine? Why do they need to know about this? Dr Liewluck: Yes, certainly. So, I would say limb girdle muscular dystrophy probably the most complex category of subgroup of muscle diseases because, by itself, it includes thirty-four different subtypes, and the number's still expanding. So, each subtype is very rare. But if you group together, it really have significant number of patients, and these patients present with proximal weakness, very high CK, and these are common patients that can show up in the neurology clinic. So, I think it's very important even for general neurologists to pick up what subtle clues that may lead to the diagnosis because if we are able to provide correct diagnosis for the patients, that's very important for patient management. Dr Smith: So, I wonder if maybe we can talk a little bit about the phenotype, Terran. I mean, your article does a great job of going over the great diversity. And you know, I think many of us here, you know, limb girdle muscular dystrophy and we think of limb girdle weakness, but the phenotypic spectrum is bananas, right? Rhabdomyolysis, limb girdle distal myopathy. I mean, when should our listeners suspect LGMD? Dr Liewluck: Yes, I think by the definition to all the LGMD patients will have limb girdle of proximal weakness and very high CK. So, these are common phenotypes among thirty-four different subtypes. But if it did take into details, they have some subtle differences. In the article, what I try to simplify all these different subtypes that we can categorize at least half of them into three main group that each group the underlying defect sharing among those subtypes and also translate into similar muscles and extra muscular manifestations. You will learn that some of the limb girdle muscular dystrophy may present with rhabdomyolysis. And we typically think of this as metabolic myopathies. But if you have a rhabdomyolysis patient, the CK remain elevated even after the acute episode, that's the key that we need to think this could be LGMD. That's for an example. Dr Smith: So, I wonder if maybe we can start there. I was going to go in a different direction, but this is a good transition. It's easy to see the opportunity to get confused between LGMD or, in that case, a metabolic myopathy or other acquired myopathies. And I think particularly adult neurologists are more accustomed to seeing acquired muscle disease. Are there particular clues that, or pearls that adult neurologists seeing patients with muscle disease can use to recognize when they should be thinking about LGMD given the diverse phenotype? Dr Liewluck: Yes. What I always tell the patient is that there are more than a hundred different types of muscle diseases, but we can easily divide into groups: acquired and genetic or hereditary. So, the acquired disease is when you encounter the patients who present with acute or subacute cause of the weakness, relatively rapidly progressive. But on the opposite, if you encounter the patient who present with a much more slowly progressive cause of weakness over several months or years, you may need to think about genetic disease of the muscle with also including limb-girdle muscular dystrophy. The detailed exam to be able to distinguish between each type of muscular dystrophy. For example, if proximal weakness, certainly limb girdle muscular dystrophy. If a patient has facial weakness, scapular winking, so you would think about facial scapular hematoma dystrophy. So, the slowly progressive cause of weakness, proximal pattern of weakness, CK elevation, should be the point when you think about LGMD. Dr Smith: So, I have a question about diagnostic evaluation. I had a meeting with one of my colleagues, Qihua Fan, who's a great peripheral nerve expert, who also does neuromuscular pathology. And we were talking about how the pathology field has changed so much over the last ten years, and we're doing obviously fewer muscle biopsies. Our way of diagnosing them has changed a lot with the evolution of genetic testing. What's your diagnostic approach? Do you go right to genetic testing? Do you do targeted testing based on phenotype? What words of wisdom do you have there? Dr Liewluck: Yes, so, I mean, being a muscle pathologist myself, it is fair to say that the utility of muscle biopsies when you encounter a patient with suspects that limb girdle muscular dystrophy have reduced over the year. For example, we used to have like fifteen, seventeen hundred muscle biopsies a year; now we do only thirteen hundred biopsies a year. Yes, as you pointed out, the first step in my practice if I suspect LGMD is to go with genetic testing. And I would prefer the last gene panel that not only include the LGMD, but also include all other genetic muscle disease as well as the conjunctive myopic syndrome, because the phenotype can be somehow difficult to distinguish in certain patients. Dr Smith: So, do you ever get a muscle biopsy, Teerin? I mean you obviously do; only thirteen hundred. Holy cow, that's a lot. So, let me reframe my question. When do you get a muscle biopsy in these patients? Dr Liewluck: Muscle biopsy still is present in LGMD patients, it's just we don't use it at the first-tier diagnostic test anymore. So, we typically do it in selected cases after the genetic testing in those that came back inconclusive. As you know, you may run into the variant of unknown significance. You may use the muscle biopsy to see, is there any histopathology or abnormal protein Western blot that may further support the heterogenicity of the VUS. So, we still do it, but it typically comes after genetic testing and only in the selected cases that have inconclusive results or negative genetic testing. Dr Smith: I'd like to ask a question regarding serologic testing for autoantibodies. I refer to a really great case in your article. There are several of them, but this is a patient, a FKRP patient, who was originally thought to have dermatomyositis based on a low-titer ME2 antibody. You guys figured out the correct diagnosis. We send a lot of antibody panels out. Wonder if you have any wisdom, pearls, pitfalls, for how to interpret antibody tests in patients with chronic myopathies? We send a lot of them. And that's the sort of population where we need to be thinking about limb-girdle muscular dystrophies. It's a great case for those, which I hope is everyone who read your article in detail. What do you have to say about that? Dr Liewluck: Yes, so myositis antibodies, we already revolutionized a few of muscle diseases. I recall when I finished my fellowship thirteen years ago, so we don't really have much muscle myositis antibodies to check. But now the panel is expanded. But again, the antibodies alone cannot lead to diagnosis. You need to go back to your clinical. You need to make sure the clinical antibodies findings are matched. For example, if the key that- if the myocytes specific antibodies present only at the low positive title, it's more often to be false positive. So, you need to look carefully back in the patient, the group of phenotypes, and when in doubt we need to do muscle biopsies. Now on the opposite end, the other group of the antibody is the one for necrotizing autoimmune myopathy; or, the other name, immune-mediated necrotizing myopathy. This is the new group that we have learned only just recently that some patients may present as a typical presentation. I mean, when even thinking about the whole testing autoimmune myopathy, we think about those that present with some acute rapidly progressive weakness, maybe has history of sudden exposures. But we have some patients that present with very slowly progressive weakness like muscular dystrophies. So now in my practice, if I encounter a patient I suspect LGMD, in addition to doing genetic testing for LGMD, I also test for necrotizing doing with myopathy antibodies at the same time. And we typically get antibody back within what, a week or two, but projected testing would take a few months. Dr Smith: Yeah. And I guess maybe you could talk a little bit about pitfalls and interpretation of genetic tests, right? I think you have another case in your article, and I've certainly seen this, where a patient is misdiagnosed as having a genetic myopathy, LGMD, based on, let's say, just a misinterpretation of the genetic testing, right? So, I think we need to think of it on both sides. And I like the fact that the clinical aspects of diagnosis really are first and foremost most important. But maybe you can talk about wisdom in terms of interpretation of the genetic panel? Dr Liewluck:Yes. So genetic testing, I think, is a complex issue, particularly for interpretation. And if you're not familiar with this, it's probably best to have your colleagues in genetics that help looking at this together. So, I think the common scenario we encounter is that in those dystrophies that are autosomal recessive, so we expect that the patient needs to have two abnormal copies of the genes to cause the disease. And if patients have only one abnormal copy, they are just a carrier. And commonly we see patients refer to us as much as dystrophy is by having only one abnormal copy. If they are a carrier, they should not have the weakness from that gene abnormality. So, this would be the principle that we really need to adhere. And if you run into those cases, then maybe you need to broaden your differential diagnosis. Dr Smith: I want to go back to the clinical phenomenology, and I've got a admission to make to you, Teerin. And I find it really hard to keep track of these disorders at, you know, thirty-four and climbing a lot of overlap, and it's hard to remember them. And I'm glad that I'm now going to have a Continuum article I can go to and look at the really great tables to sort things out. I'm curious whether you have all these top of mind? Do you have to look at the table too? And how should people who are seeing these patients organize their thoughts about it? I mean, is it important that you memorize all thirty-four plus disorders? How can you group them? What's your overall approach to that? Dr Liewluck: I need to admit that I've not memorize all twenty-four different subtypes, but I think what I triy to do even in my real-life practice is group it all together if you can. For example, I think that the biggest group of these LGMD is what we call alpha-dystroglycanopathies. So, this include already ten different subtypes of recessive LGMD. So alpha-dystroglycan is the core of the dystrophin-associated glycoprotein complex. And it's heavy glycosylated protein. So, the effect in ten different genes can affect the glycosylation or the process of adding sugar chain to this alpha-dystroglycan. And they have similar features in terms of the phenotype. They present with proximal weakness, calf pseudohypertrophy, very high CK, some may have recurrent rhabdomyolysis, and cardiac and rhythmic involvement are very common. This is one major group. Now the second group is the limb-girdle muscular dystrophy due to defective membrane repair, which includes two subtypes is the different and on dopamine five. The common feature in this group is that the weakness can be asymmetric and despite proximal weakness, they can have calf atrophy. On muscle biopsy sometimes you can see a myeloid on the muscle tissues. And the third group is the sarcoglycanopathy, which includes four different subtypes, and the presentation can look like we share. For the rest, sometimes go back to the table. Dr Smith: Thank you for that. And it prompts another question that I always wonder about. Do you have any theories about why such variability in the muscle groups that are involved? I mean, you just brought up dystroglycanopathy, for instance, as something that can cause a very distal predominant myopathy; others do not. Do we at this point now have an understanding given the better genetics that we have on this and work going on in therapeutic development, which I want to get to in a minute, that provides any insight why certain muscle groups are more affected? Dr Liewluck: Very good question, Gordon. And I would say the first question that led me interested in muscle disease---and this happened probably back in 2000 when I just finished medical school---is why, why, why? Why does muscle disease tend to affect proximal muscles? I thought by now, twenty-five years later, we'd have the answer. I don't. I think this, you don't know clearly why muscle diseases, some affect proximal, some affect distal. But the hypothesis is, and probably my personal hypothesis is, that maybe certain proteins may express more in certain muscles and that may affect different phenotypes. But, I mean, dysferlin has very good examples that can confuse us because some patients present with distal weakness, some patients present with proximal weakness, that's by the same gene defect. And in this patient, when we look at the MRI in detail, actually the patterns of fatty replacements in muscle are the same. Even patient who present clinically as a proximal or distal weakness, the imaging studies show the same finding. Bottom line, we don't know. Dr Smith: Yeah, who knew it could be so complex? Teerin, you brought up a really great point that I wanted to ask about, which is muscle MRI scan, right? We're now seeing studies that are doing very broad MR imaging. Do you use some muscle MRI very frequently in your clinical evaluation of these patients? And if so, how? Dr Liewluck: Maybe I don't use it as much as I could, but the most common scenario I use in this setting is when I have the genetic testing come back with the VUS. So, we look at each VUS, each gene in detail. And if anything is suspicious, what I do typically go back to the literature to see if that gene defect in particular has any common pattern of muscle involvement on the MRI. And if there is, I use MRI as one of the two to try to see if I can escalate the pathogenicity of that VUS. Dr Smith: And a VUS is a "Variant of Unknown Significance," for our listeners. I'm proud that I remember that as a geneticist. These are exciting times in neurology in general, but particularly in an inherited muscle disease. And we're seeing a lot of therapeutic development, a lot going on in Duchenne now. What's the latest in terms of disease-modifying therapeutics and gene therapies in LGMD? Dr Liewluck: Yes. So, there are several precritical and early-phase critical trials for gene therapy for the common lymphoma of muscular dystrophies. For example, the sarcoglycanopathies, and they also have some biochemical therapy that arepossible for the LGMD to FKRP. But there are many things that I expect probably will come into the picture broader or later phase of critical tryouts, and hopefully we have something to offer for the patients similar to patients with Duchenne muscular dystrophy. Dr Smith: What haven't we talked about, I mean, holy cow? There's so much in your article. What's one thing we haven't talked about that our listeners need to hear? Dr Liewluck: Good questions. So, I think we covered all, but often we get patients with proximal weakness and high CK, and they all got labeled as having limb-girdlemuscular dystrophy. What I want to stress is that proximal weakness and high CK is a common feature for muscle diseases, so they need to think broad, need to think about all possibilities. Particularly don't want to miss something treatable. Chronic, slowly progressive cause, as I mentioned earlier, we think more about muscle dystrophy, but at the cranial range, we know that rare patients with necrotic autonomyopathy and present with limb good of weakness at a slowly progressive cost. So, make sure you think about these two when suspecting that LGMD patient diabetic testing has come back inconclusive. Dr Smith: Well, that's very helpful. And fortunately, there's several other articles in this issue of Continuum that help people think through this issue more broadly. Teerin, you certainly don't disappoint. I enjoyed listening to you about a month ago, and I enjoyed reading your article a great deal and enjoy talking to you even more. Thank you very much. Dr Liewluck: Thank you very much, Gordon. Dr Smith: Again, today I've been interviewing Dr Teerin Liewluck about his article on limb-girdle muscular dystrophy, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Please be sure to check out Continuum Audio episodes for this and other issues. And thanks to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy, affecting individuals across the lifespan with variable severity. Advances in genetic understanding and therapeutic development have led to an era of promising disease-modifying strategies. In this episode, Katie Grouse, MD FAAN, speaks with Renatta N. Knox, MD, PhD, author of the article "Facioscapulohumeral Muscular Dystrophy" in the Continuum® October 2025 Muscle and Neuromuscular Junction Disorders issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Knox is an assistant professor of neurology in the Division of Pediatric Neurology and Neuromuscular Section at Washington University School of Medicine in St. Louis, Missouri. Additional Resources Read the article: Facioscapulohumeral Muscular Dystrophy Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Renatta Knox about her article on fascioscapulohumeral muscular dystrophy, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Welcome to the podcast, and please introduce yourself to our audience. Dr Knox: Hi Katie, thank you so much for the invitation for the audio interview. I'm looking forward to our conversation. As she mentioned, my name is Renata Knox. It's a pleasure to be here today. Dr Grouse: I'd like to start by asking, what is the key message that you hope your readers will take from your article? Dr Knox: I would say two things. The first is an appreciation and understanding of the unique genetic mechanism that leads to FSHD. And the second is the really exciting therapy landscape that we find ourselves in. So, we're hopeful that there will actually be disease-modifying therapies for FSHD soon. Dr Grouse: We're really looking forward to learning more about that. Now, before we get to that piece, could you just remind us of the clinical manifestations and features that are specific to FSHD? Dr Knox: So, one of the most unique things about FSHD that we see clinically is the pattern of weakness. So, one of the first features is that it's asymmetric. And then there are certain muscle groups that typically are affected, and that's partly where the name comes from. So, we see effects in the face, the limbs, the trunk; and so, those are some of the unique features that we see clinically. Dr Grouse: I'd love it if you could walk us through how you approach diagnosing a patient who presents with proximal weakness where FSHD is in your differential. Dr Knox: Yeah, it's a really great question. So, I would say it depends. So, I actually focus on FSHD in my clinical practice. So, many times patients are referred to me because there's a very high suspicion or there's a known family history of FSHD. So, that's one category of cases. I would say the other category of case is where it's, as you said, maybe more proximal weakness more broadly. Someone that's before me who has a known family history, they really have some of the characteristic physical features---which I'm pretty attuned to, as this is, you know, part of my subspecialty---I'll actually go directly to FSHD genetic testing. And that is one of the unique features of this disease, that the next-generation sequencing panels that are typically used for some of our other muscle diseases, FSHD is not captured on those. So, we actually have to send targeted testing for FSHD to diagnose it. So, that is one category where, again, I have a very high suspicion either based on their clinical presentation and/or a known family history, then I will actually go directly to FSHD-targeted genetic testing. In the second case, where it is one of the conditions that I'm considering among others, I will do more broad testing. So, I will get a CK level to see if there's evidence of muscle breakdown. I'll likely also do one of the next-generation sequencing panels that we have access to, which will allow us to identify, potentially, one to two hundred potential muscle diseases. And then again, if FSHD is higher on my differential in that second group of patients, then I will also send targeted FSHD-specific testing. Dr Grouse: That's really helpful. And I'm wondering if you have any thoughts about common pitfalls that you've seen when providers are trying to work this up? Dr Knox: I don't know if I would say pitfalls. I think I would acknowledge that it's challenging. My subspecialty training in neuromuscular medicine and also gene therapy. And so FSHD is pretty high on my radar. But I would say in neurology in general---and then, you know, the general medical population---,it really isn't something that many people are seeing. So, I would say what patients will communicate to us sometimes is some frustration that maybe it took time to make the diagnosis, but I just have a deep understanding that it's not something that is on many people's radars. And I think, again, it's tricky because it's not picked up on these next-generation sequencing panels, which many of us can send pretty easily. It will be missed. And I will say the biggest pitfall is, again, if you're not thinking about it and you don't send that testing, you actually- it's very difficult to diagnose it. Dr Grouse: Thank you so much for highlighting that. I think there are many people who are not aware that those different panels really aren't picking that up and that they have to test specifically. So, I think that's a great thing for all of us to keep in mind. Are there any tips or tricks to the diagnosis, other than the genetic issues that you mentioned, that sometimes can really bring this diagnosis to the forefront? Dr Knox: I think things that really tip me off to having a higher suspicion for FSHD is facial weakness that we can detect on our exam. Scapular winging---again, there's a small subset of disorders which can impact that. Someone who's presenting with foot drop, you know, with facial weakness, I think definitely about FSHD more. Also, clinically, kind of the presentation or things that they're beginning to have difficulty with is a tip-off. So, if someone is an athlete, like, they're a volleyball player or basketball player and they say, oh, I'm having difficulties, you know, with movements that require them to elevate their arm, which can be a sign of the shoulder weakness that we classically see. Or someone who says, oh, I'm having a harder time shampooing my hair or combing my hair. So those can be tip-offs again, which are basically referencing the type of weakness that they have. Another feature of FSHD which isn't necessarily as broadly appreciated is that pain and fatigue are very common. So, if someone is coming in and saying, actually, I also have a significant amount of fatigue as well or a lot of pain, that's something that can tip me off to it. Hearing loss is something that we can also see in up to 20% of patients with FSHD. So, if they are having those symptoms or saying they're ringing in their ears, these are some things that will make me begin to think about it more. Dr Grouse: Oh, really helpful. I also found it really fascinating reading some of the very FSHD-specific clinical signs, some interesting- some diagrams and pictures as well, that are very specific to the pattern of weakness that develops in FSHD. So, I encourage our listeners to check that out. But are there any highlights from those little clinical pearls that you'd like to point out? Dr Knox: I think the poly-hill sign---so, these are these literal hills that we can see in the shoulders of patients with FSHD---is pretty classic. Popeye arms, which is this older term that we still use that has to do with which muscle groups are preserved versus those that have atrophy. So that's a common feature. And then I would say, really, the asymmetry is something that is a unique feature in FSHD. And again, we did our best to provide good representative images. So again, as you mentioned, Katie, I would really encourage people to look at those images and then think about cases that they may have seen and how similar they are so they can begin to recognize those signs as well. Dr Grouse: Now going back to the genetic topic, the complex genetic underpinnings of FSHD are really well-explained in your article; and again, worth taking a look at to remind ourselves of everything that's of that pathology. Now, I was wondering though, if you could give us a brief overview of how we should approach genetic testing in a suspected case of FSHD? You mentioned some specific panels, but it does sound like there's some more complexity to it as well. Dr Knox: Yes, and I'll just kind of briefly explain that complexity. Part of the thing that we're detecting in the genetic testing is the repeat number. And so, we're actually looking for a contraction in a repeat number. So, not an expansion, which were typical for some of the diseases that we think about, the trinucleotide repeat disorders. And this is why it's not captured in the next-generation sequencing panels, because they do not currently have the ability to do that. And so, again, what the type of testing that I do really depends on my suspicion. So again, if my suspicion is very high for FSHD---they have a family history, they have the classic features---then I will actually go directly to an FSHD-specific testing, which is available from various sources. If, again, it's among different things that I'm thinking about, I will get a CK lab. I typically will also send a next-generation sequencing panel specific for muscle diseases, perhaps muscular dystrophy; again, depending on what I'm thinking about. And then I will also send in a specific FSHD genetic test as well. People are beginning to use whole-genome sequencing, which is capturing some of our true nucleotide repeat disorders and becoming more comprehensive. So, my hope is that as that becomes more standard of care---like, whole-exome sequencing can be gotten pretty routinely now---that it may be easier for us to make some of these diagnoses. Dr Grouse: Well, that's really helpful, and thanks for that overview. Now another thing that you mentioned that I thought was really interesting in your article was that patients with, you know, history of FSHD, perhaps in the family, who are pregnant and want to screen for this disease would not be able to use sort of the more common screening tests like cell-free DNA testing and may have to go to other means to do that. What is generally their route to this type of testing? Dr Knox: Yeah, great question, and really important question for family planning purposes, and it definitely comes up in clinical practice. And so again, because of the unique genetics of FSHD, you actually have to do invasive genetic testing currently to be able to test it. And so that's, you know, amnio or chorio, and then send it to a lab that can perform, again, FSHD-specific testing on the samples that are presented. And there are obviously labs that are capable of doing that and centers that are capable of doing that, but it is not picked up on the cell-free DNA panels that are being very routinely used. You or your provider has to be thinking about it to send that specific testing, similar to our patients that come into clinic and have not yet been diagnosed. Dr Grouse: Once you have the diagnosis, what are our options for therapy? I think it sounds like at this current time, it looks to be mostly supportive. What are some of the supportive care options we should keep in mind? Dr Knox: Yes, so that is definitely accurate. Care today is supportive, but again, we're very excited about the clinical trial and therapy landscape for FSHD. So, I work very closely with my physical therapy colleagues that are in clinic with me. So, we work very closely with physical and occupational therapists to help with supportive measures, adaptive measures, doing assessments, helping our patients to be able to move and exercise safely and effectively. As I mentioned, pain is very common in FSHD and so we can treat that with medications. The most common medication that we use to treat for pain in FSHD are NSAIDs. And then other than that it's really, you know, supportive measures. Do they need to see other subspecialists? There are some surgical options. Those are used very rarely to help with some of the scapular weakness, but typically it's physical therapy, occupational therapy, supportive devices. We treat the pain as we're able to, and then we work with other subspecialists to screen, monitor and support our patients to the best of our ability. Dr Grouse: Well, without further ado, I'd love to hear more about what's coming down the pipeline in clinical trials. What can we look forward to seeing, hopefully, in future years to treat these patients? Dr Knox: Yes. And so, this is actually what got me interested in the neuromuscle space in general is that, because we now for many years have known the genetic cause of many of these disorders as well as some of the underlying mechanisms, we can actually use advances in therapeutics to do what we call targeted therapies. So, rather than treating symptoms or indirect methods or doing kind of broad drug screens---which, again, still do take place and still do have their place---we actually can target mechanisms directly. And so, we know that the underlying biology of FSHD is due to this protein called DUX4 being expressed when it should not be. So, it's what we call a toxic gain of function. And so, the targeted way to address this is to suppress DUX4 expression. And so, kind of broadly speaking, what we're really excited about are a couple of products that are currently in clinical trials right now that actually caused DUX4 suppression to be suppressed. And again, these are targeted pathways. And so, again, the hope is that by doing that, we can hopefully slow the progression of the disease, potentially stop progression of the disease, and potentially reverse. Again, we don't know if that might be possible, but that is one of the hopes. Dr Grouse: Well, that's really exciting, and I know we're all looking forward to more coming down the pipeline soon, and hopefully more things that can really offer some exciting treatments for our patients with this condition. Now, a little more deep-dive into our patients who are diagnosed. You've reviewed some of the treatments currently available and hopefully may someday soon be available. Are there other things that we should be keeping in mind in this population? For instance, screenings that we should be doing for other extramuscular manifestations that we need to be thinking about? Dr Knox: I will answer that question two ways. I think something that's very important to acknowledge is the impact that these diagnoses and these conditions have on our patient practically, psychologically. One of the other unique features of FSHD is, it's autosomal-dominant. So, if it is in a family, you can have many family members who are affected, but the variability is very high. And so, you can have in the same family someone who is wheelchair-dependent, and someone else in the family with the same underlying genetics who has no signs or symptoms or is very mildly affected. And that is something that is definitely challenging for our families and patients to navigate if they're very different than their family members with the same condition. And just navigating the world with a condition that, you know, can be physically debilitating and cause changes to what they're able to do or not able to do, progression is something that's very difficult to handle. So, I think that's one set of things. And we try our best, you know, with my team and my other colleagues in the space, to support our families and patients in the best way that we can. Secondly, there is very important screening that needs to be done for this condition. So, one of the things- and the current guidelines which are actually being updated, the last update was in 2015 is all patients that undergo pulmonary function testing or PFTs. And so that's something we do at baseline and we do at least annually in my practice. Young kids who are presenting very early or patients with certain genetics that we know are more predisposed to extra muscular manifestations, we recommend screening for hearing, which is one of the manifestations, and ophthalmologic exam to look for retinovascular changes, which is one of the manifestations as well. Those are the more common ones that are typically done. There's also some evidence in pediatric patients with very severe manifestations that there may be some cognitive impacts, learning impacts. And so, that is something we're also thinking about screening and supporting our patients in that way. And again, we typically work with these patients in a multidisciplinary team depending on what manifestations and the degrees to which they're impacted by the disorder. Dr Grouse: Thank you so much for that answer. I think a lot of us forget sometimes when we get really focused on what can we do now, that we forget to kind of stop and reflect on sort of the more holistic approach. How is this affecting the patient? How is this affecting the patient's family dynamic, and what other ways are they going through life with this condition that we need to be thinking about? So, I appreciate you bringing that up. I wanted to ask, sort of based on what you're talking about and what you mentioned already, you happened to mention that what initially drew you that to this work was your interest in some of the really exciting breakthroughs in the field. Well, was there anything else that drew you to, specifically, congenital neuromuscular diseases, and FSHD in particular? Dr Knox: I'm a physician scientist by training, and so I would describe myself also as a molecular biologist. So, I love getting into the nitty gritties of disease mechanisms, what genes are doing in bodies, how they function. And so, as I mentioned earlier, in the neuromuscle space, we've known for many years the genetic cause of many of these disorders and have done great, you know, mechanistic work to kind of define why we see the disease. And then now we're at this intersection of that knowledge marrying with these really novel therapeutic approaches, gene therapy approaches, being able to intersect and then in very creative ways actually target diseases very directly. And so, I would say it really is the combination of those two things. FSHD has a really fascinating unique biology, which again, we encourage everyone to read about more in the article. That really drew me to it. I'm very interested in gene regulation, transcription. This is one of the underlying mechanisms that is gone awry in the disorder, and then that being married to advances in therapeutics. So, you could wed those two pieces of information and actually meaningfully impact patient 's lives. And again, that's the real privilege and honor to witness is how these therapies can transform lives. And I saw it happened with this one case for this one disorder when I was a resident where there was no treatment. Young children, unfortunately, would not survive the disease. And then I saw the therapy come be in development and literally change the trajectory. And this is what we're very hopeful for in the FSHD space, that wedding, this wonderful basic science research, translational research, companies working together to develop these therapies that can transform lives. It is just so beautiful to witness and see, and it's something that I get to do. You know, it's a part of my job, so it's a real privilege. Dr Grouse: Well, I have to say, it's really inspiring hearing you talk about it. And I imagine that many neurologists-in-training who are listening to this may be inspired as well and may be convinced to go into this field for that very reason. So, thank you so much for sharing all of this information with us today. I learned a lot, and I think all of our listeners have too. Dr Knox: Thank you. It's really been a pleasure. Dr Grouse: Again, today I've been interviewing Dr Renatta Knox about her article on fascioscapulohumeral muscular dystrophy, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.