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Pediatric neuropalliative medicine is an emerging area of subspecialty practice that emphasizes the human experience elements of serious neurologic illness. Child neurologists care daily for patients who can benefit from the communication strategies and management practices central to pediatric neuropalliative medicine, whether at the primary or subspecialty level. In this episode, Gordon Smith, MD, FAAN, speaks with Lauren Treat, MD, author of the article "Neuropalliative Medicine in Pediatric Neurology" in the Continuum® December 2025 Neuropalliative Care 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. Treat is an associate professor in the divisions of child neurology and palliative medicine at the University of Colorado School of Medicine in Aurora, Colorado. Additional Resources Read the article: Neuropalliative Medicine in Pediatric Neurology 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 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 Gordon Smith. Today I've got the great pleasure of interviewing my good friend Dr Lauren Treat about her article on neuropalliative medicine in pediatric neurology practice. This article appears in the December 2025 Continuum issue on neuropalliative care. Lauren, welcome to the Continuum podcast, and maybe you can introduce yourself to our listeners. Dr Treat: Such a delight to be here, Gordon. Thank you. I am a pediatric neurologist and palliative medicine doctor at the University of Colorado, Children's Hospital Colorado, and I am practicing in both areas. I do general child neurology, and I also run a pediatric neuropalliative medicine clinic. So, I'm happy to be here to talk about it. Dr Smith: And, truth in advertising, I tried very hard to get Dr Treat to move to VC to work with me. And I haven't given up yet. I'm looking forward to the conversation. And Lauren, I wonder- one, I'm really excited about this issue, by the way. This is the second podcast I've done. And I'd like to ask the same question I asked of David Oliver, who's amazing. What a great article and conversation we had. And that question is, can you define palliative care? I think a lot of people think of it as, like, end-of-life care or things like that. And is the definition a little different in the pediatric space than it is in the adult space? Dr Treat: Such a great place to start, Gordon. I absolutely think that there are nuances that are very important in pediatrics. And we especially acknowledge in pediatrics that there is a very longitudinal component of this. And even moreso, I think, then in adult neuropalliative medicine, in pediatrics, we are seeing people=even prenatally or early in their first hours and days of life, and walking with them on a journey that might last days or weeks, but might last years or decades. And so, there is this sense that we are going to come alongside them and be part of the ups and the downs. So yes, neuropalliative medicine is a kind of medicine that is a very natural partner to where neurology is in its current field. We're doing a lot of exciting things with modifying diseases, diagnosing things early, and we have a very high reliance on the things that we can measure in medicine. And not all things can be measured that are worthwhile about one's quality of life. A family very poignantly told me very recently, making sure someone stays alive is different from making sure they have a life. And that's what neuropalliative medicine is about. Dr Smith: Well, great summary, and I definitely want to follow up on several aspects of that, but there's one point I was really curious about as I've been thinking about this, you know, these are really exciting times and neurology in general and in child neurology in particular. And we've got all of these exciting new therapies. And as you know, I'm a neuromuscular person, so it's hard not to think back on SMA and not be super excited. And so, I wonder about the impact of these positive developments on the practice of neuropalliative care in kids. You know, I'm just thinking, you know, you mentioned it's a journey with ups and downs. And I wonder, the complexity of that must be really interesting. And I bet your job looks different now than it did seven or eight years ago. Dr Treat: That's absolutely true. I will self-reference here one of the figures in the paper. Figure 2 in my section is about those trajectories, about how these journeys can have lots of ups and downs and whether this person had a normal health status to begin with or whether they started out life with a lot of challenges. Those ups and downs inherently involve a lot of uncertainty. And that's where palliative medicine shines. Not because we have the answer---everyone would love for us to have the answer---but because we consider ourselves uncertainty specialists in the way that we have to figure out what do we know, what can we ground ourselves in, and how can we continue to move forward even if we don't have all the answers? That is a particular aspect of neurology that is incredibly challenging for families and clinicians, and it can't stand as a barrier to moving forward and trying to figure out what's best for this child, what's best for this family. What do we know to be true about them as people, and how can we integrate that with all of the quantitative measures that we know and love in neurology? Dr Smith: So, I love the comment about prognostication, and this really ties into positive uncertainty or negative undercertainty in terms of therapeutic development. I wonder if you can talk a little bit about your approach to prognostication, particularly in a highly fluid situation. And are there pearls and pitfalls that our listeners should consider when they're discussing prognosis for children, particularly maybe young children who have severe neurological problems? Dr Treat: It's such a pivotal issue, a central issue, to child neurology practice. Again, because we are often meeting people very, very early on in their journey---earlier than we ever have before, sometimes, because of this opportunity to have a diagnosis, you know, prenatally or genetically or whatever else it is---sometimes we are seeing the very early signs of something as compared to previously where we wouldn't have a diagnosis until something was in its more kind of full-blown state. This idea of having a spectrum and giving people the range of possible outcomes is absolutely still what we need to do. However, we need to add on another skill on top of that in helping people anchor into what feels like the most likely situation and what the milestones are going to be in the near future, about how we're going to walk this journey and what we'll be on the lookout for that will help us branch into those different areas of the map down the road. Dr Smith: So, I wonder if we can go back to the framework you mentioned, two answers ago, I think? You and the article, you know, provide four different types of situations kind of based on temporal progression. I wonder if maybe the best way of approaching is to give an example and how that impacts your thoughts of how you manage a particular situation. Dr Treat: Absolutely. So, this figure in particular is helpful in multiple ways. One is to just give a visual of what these disease trajectories are doing, because we're doing that when and we take a history from a patient. But actually, to put it into an external visual for yourself, for your team, but also perhaps for the family can be really powerful. It helps you contextualize the episode of care in which you're meeting the family right now. And it also helps, sometimes, provide some sense of alignment or point out some discrepancies about how you're viewing that child's health and quality of life as compared to how the family might be viewing it. And so, if you say, you know, it sounds like during those five years before we met, you were up here, and now we find ourselves down here, and we're kind of in the middle of the range of where I've seen this person's health status be. Do I have that right? Families feel really seen when you do that and when you can get it accurately. And it also invites a dialogue between the two parties to be able to say, well, maybe I would adjust this. I think we had good health or good quality of life in this season. But you're right, it's getting harder. It's kind of that "show, don't tell" approach of bringing together all the facts to put together the relative position of where we are now in the context of everything they've been through. Dr Smith: You know, I wonder if you could talk a little bit more about the differences between palliative care and adult patients and in children? Dr Treat: Absolutely. One of the key features in pediatrics is this kind of overriding sense of an out-of-order event in the family's life. Children are not supposed to have illness. Children are not supposed to have disability. Children are not supposed to die before their parents. And that layer of tragedy is incredibly heavy and pervasive. It's not every encounter that you have in child neurology, but it does kind of permeate some of the conversati

Patients with Parkinson disease and other movement disorders have significant palliative care needs that are poorly met under traditional models of care. Clinical trials demonstrate that specialist palliative care can improve many patient and family outcomes. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Benzi M. Kluger, MD, MS, FAAN, author of the article "Neuropalliative Care in Movement Disorders" in the Continuum® December 2025 Neuropalliative Care issue. Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology at the University of California San Francisco in the Department of Neurology in San Francisco, California. Dr. Kluger is the Julius, Helen, and Robert Fine Distinguished Professor of Neurology in the Departments of Neurology and Medicine (Palliative Care) at the University of Rochester in Rochester, New York. Additional Resources Read the article: Neuropalliative Care in Movement Disorders 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: @AaronLBerkowitz Guest: @BenziKluger 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 Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Benzi Kluger about his article on neuropalliative care in Parkinson disease and related movement disorders, which is found in the December 2025 Continuum issue on neuropalliative care. Welcome to the podcast, Dr Kluger, and could you please introduce yourself to our audience? Dr Kluger: I'm Benzi Kluger. I'm a professor of neurology and palliative medicine at the University of Rochester. I'm the chief of our neuropalliative care service, I'm the director of our Palliative Care Research Center, and I'm also the founding president of the International Neuropalliative Care Society. Dr Berkowitz: Wow, that is a large number of hats that you wear in a very important area of palliative care. So, your article is a fantastic article that covers a lot of concepts in palliative care that I myself was not familiar with and really applies them in a very nuanced way to patients with Parkinson's disease and related disorders. So, I'm looking forward to learning from you today to discuss some of the concepts you talk about in the article and how you apply them in your daily practice of palliative care in this particular patient population. So, one of the key points in your article is that we're often so focused on treating the motor symptoms of Parkinson's disease and other degenerative movement disorders that we are often at risk of underdiagnosing and undertreating the nonmotor symptoms, which in some cases, as you mentioned in the article, are more disabling to the patient than the motor symptoms that we tend to focus on. So, from a palliative care perspective, what are some of the nonmotor symptoms that you find tend to be underdiagnosed and undertreated in this patient population? Dr Kluger: The literature suggests---and we've replicated it, actually, Lisa Schulman published a paper twenty-five years ago and the data is almost exactly the same when it comes to things like depression, pain, fatigue, constipation, sleep---that you miss it about 50% of the time. And there's a number of reasons for that. One is that these are subjects that people don't always like to talk about. People don't like talking about depression. People don't like talking about poop and constipation. And I think there are things that neither the patient or the caregiver nor the physician are necessarily comfortable with. And they're also sometimes confusing of, which doctor should I talk to this about? Should I talk to my primary care doctor, should I talk to my neurologist? And so I think the key here is really having a checklist and being proactive about it. In the article, I suggest a template or previsit questionnaire that you can use, but I think it's just about being automatic about it. And it just takes the burden off of the patient and the family to bring them up and letting them know that this is a safe space and this is the right space to talk about these symptoms. Dr Berkowitz: That's very helpful to know. So, having some type of checklist or template just so we go all through them and, as you said, it sort of destigmatizes, just, this is the list of things, and I'm going to just ask about all of them. So we check in on those particular symptoms, whether they're present or not. Are there any particular symptoms that jump out to you as ones that tend to be missed---either because we don't ask about them or patients are less comfortable mentioning them---that in your practice, when you've elicited them, have allowed for particular intervention that's really improved the quality of life for patients in this group? Dr Kluger: Yeah, I'll mention a few that I think come up and are very pertinent. One is mood. And, to use depression---but we could also use anxiety as an example---again, these are topics that people don't always want to talk about. And I think it's important---we may get to this a little bit more later---is being careful to distinguish between depression and grief, sadness, normal worry, frustration. A lot of times the way I'll ask that when I'm talking to a patient is, you know, I hear you're using the word depressed. I want to make sure. does this feel to you like normal sadness given that you have an illness that sucks, or does this really feel like it's above and beyond that and you feel like you'd need a little extra help to get your emotions under control? The second one, which is kind of related, is other behavioral symptoms, including PD psychosis and hallucinations. And there, I think, the thing is that people are quite frankly afraid that they're losing their mind or going insane. So, I think that's another critical one. And then one that, you know, it's kind of a low-hanging fruit but people don't want to talk about, is constipation. And when we did our large randomized control trial of palliative care, our single biggest effect size was actually that we did a better job of treating constipation than usual care. And I think the only trick there is that we asked about it. Dr Berkowitz: I see. So, do you then as part of your routine practice and seeing these patients with Parkinson's disease in particular, you have a particular checklist you go through during the appointment or, as you mentioned, you- one could do it before the appointment. But you tend to go through this in the visit, and is there any palliative care wisdom you have for us, those who are not trained in palliative care, to making sure we really elicit these symptoms in an effective way and how much they're bothering the patient? Dr Kluger: Two things that I've seen work---and we've done a lot of implementation studies. One is that, if it works for your practice, having patients fill out a questionnaire or survey in advance. And I think one of the highest-yield things there too is for blank lines to allow patients to write in what their top three problems are. And I've found when we've used it, and I think other people have found, that it's a huge time saver. People hand them the form, they look to see what's at checked a yes or what's checked as high, and then that becomes the agenda for the visit. The other thing that I think works equally well is just having a template, and at this point its just kind of, like, hard-wired into my neurons that, you know, no matter what we talked about in the HPI, I'll always ask about sleep and mood and bowel and bladder and pain to make sure that I don't miss those things. Dr Berkowitz: You mentioned in your article that palliative care needs in patients with Parkinson's disease really differ over the course of the illness and may be different at the time the initial diagnosis is given versus as the disease progresses versus the latest, most advanced stages of the disease. Can you talk a little bit more about how your approach to these patients changes over time from a palliative care perspective? Dr Kluger: Yes. And I'll also add, I think some of this is going to be more relevant to our listeners than to me. I'm now almost entirely in a neuropalliative care clinic, but for early-stage illness, it's really primary palliative care. And just to reinforce, this is palliative care that's provided by neurologists and primary care doctors, not specialist palliative care. I think that mindset's particularly important around the time of diagnosis. One of the things that, for me, was most eye-opening when we were doing qualitative interviews and studies was how devastating the diagnosis of Parkinson's disease was for patients and their families. And that was not something that I really anticipated. I think, like a lot of people and a lot of movement disorder doctors, I kind of thought of Parkinson's disease as a relatively good-news diagnosis. And that was often the way I pitched it, and we talked about Sinemet and DBS and exercise and all these things, but I have a relativity bias. And that bias is, I know that Parkinson's is better than PSP or MSA or brain cancer. But for the individual getting that diagnosis, that's it's not good news because their relativity bias is, I didn't have Parkinson's before and now I do. And for the rest of my life I'm going to have Parkinson's. And for the rest of my life, there may be things that I can do today that I won't be able to do tomorrow or next week. And

Dementia is often a highly burdensome disease process for patients, their caregivers and families, and the community at large. Palliating symptoms and providing guidance surrounding advance care planning and prognostication are integral components of the management plan. In this episode, Katie Grouse, MD, FAAN, speaks with Neal Weisbrod, MD, an author of the article "Neuropalliative Care in Dementia" in the Continuum® December 2025 Neuropalliative Care 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. Weisbrod is a neurologist at Hartford Healthcare with the Ayer Neuroscience Institute in Mystic, Conneticut. Additional Resources Read the article: Neuropalliative Care in Dementia 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 Neal Weisbrod about his article on neuropalliative care in dementia, which appears in the December 2025 Continuum issue on neuropalliative care. Welcome to the podcast, and please introduce yourself to our audience.  Dr Weisbrod: Thank you. I'm really excited to be here. I'm Neal Weisbrod. I'm a neurologist and palliative care physician currently working at Hartford Healthcare in Mystic, Connecticut. Dr Grouse: To start, I'd like to ask why you think it's important that neurologists read your article? Dr Weisbrod: The primary reason I think it's really important to read the article is because these are just really common problems that neurologists run into in clinical practice. So, Alzheimer disease and many other dementias are extremely common, and managing the burdensome symptoms and the complex discussions that we have to have with the patients and their families as they go through the course of dementia is something that is very common in clinical practice. And so my hope is that by reading this article, clinicians will pick up a few tools, a few new ideas for how to make these conversations easier and for how to help these patients get through the disease with a little bit less suffering. Dr Grouse: I learned a lot from reading your article, and I really encourage our listeners to check it out. But I was curious what you feel that you discussing your article would come as the biggest surprise to our listeners? Dr Weisbrod: So, I think that the most surprising thing a lot of people will see reading this article is the section on prognosis. A lot of times it seems families are counseled, when they're talking about the prognosis of Alzheimer disease, that it could be ten years or longer. But really, the data show that for many patients, the median prognosis is closer to three to eight years. And that is a little bit longer for Alzheimer disease than many other types of dementia, but also gets significantly shorter as patients get older. So, we're looking at a closer to three-year median prognosis for patients who are over eighty-five, whereas patients in their sixties are probably closer to the eight or nine-year median prognosis. And so I think that piece will hopefully help people give a little bit more accurate counseling about prognosis.  Dr Grouse: I'm glad you brought that up because I was wondering, why is it so important that we are careful to make sure that we're giving prognostic information for our patients and maybe even updating it as their clinical status changes? Dr Weisbrod: I think first of all, it's a really common thing that patients and families are thinking about and worried about. They don't necessarily always seem to ask as much as they want to know. I think there's a lot of fear around that conversation, even though it's really important. And then there's also often tension between the family and caregivers tend to want to know more than patients do. I think that it really helps people plan for the future as well as possible to know what their future might be. And we have a lot of limitations in predicting the future, but using the best information we can, laying out what we think the likely range is, allows people to make a lot more clear plans for their future. Dr Grouse: I'd imagine it's also pretty helpful for hospice referrals, too, having that data.  Dr Weisbrod: Yeah, definitely. And there's a lot of angst about when to refer patients who have dementia to hospice. The most important thing I think about when I'm making a hospice referral is that I don't have to be right. And I think it takes a lot of that concern off to just say, all I'm doing is making a connection, getting someone who's potentially interested in the hospice, who has a really advanced serious illness connected to a hospice agency. And then they can go through the full evaluation with the hospice and the hospice medical director and determine whether they're eligible. So, I think there are really helpful thresholds to think about that would be a good trigger. Like a patient who we think has advanced dementia, who has a hospitalization for pneumonia or a fracture of the hip or some other really serious acute medical condition, I think is a really good trigger to start to think about hospice. But most importantly, it's just the connection, and I tell the patients that upfront. I tell them that you're going to have a conversation and we'll decide whether you're a good fit, and if not, the hospice will usually just check in with you over time and decide when is the right time in the future. Dr Grouse: That's really helpful. And I think just a really great reminder to our listeners about thinking about hospice sooner or at certain critical points in their patient care rather than waiting, maybe, before it's gone on too long and may be of less use later on. I was wondering, in your own clinical practice, what do you think is the most challenging aspect of providing care to patients with dementia?  Dr Weisbrod: I think this one's easy. I would say managing the time has to be the most difficult part. I think that taking care of patients who have dementia is time-consuming. There's a lot of different priorities that we have to manage the time around. How much time are we going to spend doing cognitive testing? How much time are we going to spend doing counseling? How much time are we going to spend making up a treatment plan and discussing medications? How much time are we going to spend on advanced care planning? And the way I try to combat that is really just trying to think about what I'm going to prioritize in a certain visit and not try to accomplish everything. I'll tell patients and their families, the next time you come in, we're going to have a conversation focusing on advanced care planning. Or, the next time you come in, we're going to sit down and try to talk through all the questions you have about what the future might hold. That way I in that visit, I don't feel like, oh, I have to do updated cognitive testing and I have to review all the next steps in medication, and that allows me to take it in more bite-sized chunks. Dr Grouse: You made some of the great points, and specifically you mentioned advanced care planning. Your article makes a really strong case for the importance of advanced care planning, yet you definitely acknowledge the many barriers to initiating discussions that clinicians face. In your patients with dementia, can you walk us through how you integrate discussions about advanced care planning with your patients and their families?  Dr Weisbrod: Yeah, I think this is still something that is evolving in my practice, and I don't think there's any perfect way of doing it. I think there's a lot of right ways of doing it, and as long as we're thinking about it a lot and bringing it up periodically, that's probably the best. What I try to do, though, is after I discuss what I think is the most likely diagnosis with patients and their families, I try to have a fairly close follow-up visit after that. Allow them to digest that information, to often do a little bit of their own research, to talk about it as a family. And then when they come in for that next appointment, I try to at least lay some groundwork about advanced care planning, asking them what they've completed already, and then based on what they've already done to that point, talking to them about what I think the next step would be. If they have done nothing, usually it's just, hey, I really think you should start to think about who would be making decisions for you if you lose the ability to make your own decisions and counsel them about power of attorney paperwork and establishing a healthcare surrogate. When it's patients who have already done some of that initial prep, I think that it's really important to keep in mind it's a longitudinal discussion and you can take it in small pieces over time. Often that helps because you can really establish that rapport and that trust. And then I like to just keep checking in whenever there's major changes in the patient's health or condition, like admission to the hospital or transfer to an assisted living facility or memory care clinic. Those are good times to remember, hey, I really need to revisit this conversation.  Dr Grouse: It's probably good to also mention another really important point from your article, which was that impairment of decision-maki

Careful assessment and individualized care, provided by a skilled multidisciplinary care team, are emphasized in the holistic approach to neuropalliative care, which considers physical, psychological, social, spiritual, and existential aspects for people with neuromuscular diseases. In this episode, Gordon Smith, MD, FAAN, speaks with David J. Oliver, PhD, FRCP, FRCGP, FEAN, author of the article "Neuropalliative Care in Neuromuscular Disorders" in the Continuum® December 2025 Neuropalliative Care 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. Oliver is an honorary professor of Tizard Centre at the University of Kent in Canterbury, United Kingdom. Additional Resources Read the article: Neuropalliative Care in Neuromuscular Disorders 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 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: Hello, this is Dr Gordon Smith. Today I've got the great pleasure of interviewing Dr David Oliver about his article on neuropalliative care and neuromuscular disorders, which appears in the December 2025 Continuum issue on neuropalliative care. David, welcome to the Continuum podcast, and please introduce yourself to our audience. Dr Oliver: Thank you. It's a pleasure and a privilege to be here. I'm a retired consultant in palliative medicine in the UK. I worked at the Wisdom Hospice in Rochester for over thirty years, and I'm also an honorary professor at the University of Kent in Canterbury in the UK. I've had a long interest in palliative care in neurological diseases. Hopefully we can talk about a bit later. Dr Smith: I really look forward to learning a little bit more about your path and experiences. But I wonder if, before we get into the meat of neuropalliative care with a focus on neuromuscular, if maybe you can kind of set the stage by just defining palliative care. I mean, my experience is that people think of this in different ways, and a lot of folks think- hear palliative care, and they immediately go to end-of-life care or comfort care. So, what- how should we think about maybe the discipline of palliative care or neuropalliative care? Dr Oliver: I see palliative care as very much responding to people's needs, whether that's physical needs, psychological needs, social or spiritual or existential. So, it can be much earlier in the disease progression. And I think particularly for neurological diseases, early involvement may be very important. Dr Smith: That was actually going to be my first substantive question, really, was when to begin the conversation and what does that look like and how does it evolve over time. You have a really great figure in the article that kind of emphasizes the various stages within a patient's journey that, you know, palliative care can become involved. But I wonder if you could use ALS as a good example and describe what that looks like from when a patient is first diagnosed with ALS through their course? Dr Oliver: I think particularly in ALS at the beginning, soon after diagnosis, someone may have a lot of distress and a lot of questions that they need answering. This is a disease they've not had any contact with before. And they don't understand what's going on, they don't understand the disease. So, there may be a great need to have the opportunity to talk about the disease, what may happen, what is happening, how it's going to affect them and their family. As think time goes on, there may be later they develop swallowing problems, and that will need to be talking about a feeding tube and gastrostomy. And again, there may be a lot of issues for the person and their family. As they deteriorate, they may have respiratory problems and need to have discussion about ventilatory support, either by PAP, noninvasive ventilation, or even tracheostomy. And again, I think that's a big issue that needs wide discussion. And then it may be at the final few months of the disease, where they are deteriorating, that they may have increased needs, and their families may have those needs after the death. And I think often families bereaved from someone with a neurological disease such as ALS need a great deal of support, having many mixed emotions. There may be a feeling of relief that they're not involved in that caring, but then a feeling of guilt that they shouldn't be having those feelings. So, I think that can happen over a period of… what with ALS it may be two, three, four years, but it may be similar changes over time with any patient with a neurological disease. It may be ten or fifteen years with Parkinson's or five to ten years with a progressive supranuclear palsy, but there'll be this similar need to look at palliative care during their disease progression. Dr Smith: So, I'm curious at the time of diagnosis of ALS, how far out in the future do you provide information? So a specific question would be, do you talk about end-of-life management? In my experience, ALS patients are sometimes interested in knowing about that. Or do you really focus on what's in front of you in the next three to six months, for instance? Dr Oliver: I think it's both. Obviously, we need to talk about the next three to six months, but often giving patients the opportunity to talk about what's going to happen in the future, what may happen at the end of life, I think is important. And I think a disease like ALS, if they look it up on the Internet, they may have a lot of very distressing entries there. There's a lot about how distressing dying with ALS is. And actually confront those and discuss those issues early is really important. Dr Smith: So of course, the other thing that comes up immediately with an ALS diagnosis---or, for that matter, with any other neurodegenerative problem---is prognosis. Do you have guidance and how our listeners who are giving a diagnosis of ALS or similar disorder should approach the prognostication discussion? Dr Oliver: It's often very difficult. Certainly in the UK, people may have- be a year into their disease from their first symptoms before they're diagnosed, and I've seen figures, that's similar across the world. So, people may be actually quite way through their disease progression, but I do think we have to remember that the figures show that at five years, 25% of people are still alive, and 5 to 10% are still alive at ten years. We mustn't say you are going to die in the next two or three years, because that may not be so. And I think to have the vagueness but also the opportunity to talk, that we are talking of a deterioration over time and we don't know how that will be for you. I always stress how individual I think ALS is for patients. Dr Smith: One of the other concepts that is familiar with anyone who does ALS and clearly comes through in your article---which is really outstanding, by the way. So, thank you and congratulations for that---is the importance of multidisciplinary teams. Can you talk a little bit about how neuropalliative care sits within a multidisciplinary care model? Dr Oliver: I think the care should be multidisciplinary. Certainly in the UK, we recommended multidisciplinary team care for ALS in particular, from the time of diagnosis. And I think palliative care should be part of that multidisciplinary team. It may be a member of the team who has that palliative care experience or someone with specialist experience. Because I think the important thing is that everyone caring for someone with ALS or other neuromuscular diseases should be providing palliative care to some extent: listening to people, discussing their goals, managing their symptoms. And a specialist may only be needed if those are more complicated or particularly difficult. So, I think it is that the team needs to work together to support people and their families. So, looking at the physical aspects where the physiotherapist or occupational therapist may be very important, the psychologicals are a counsellor or psychologist. The social aspects, most of our patients are part of wider families, and we need to be looking at supporting their carers and within their family as well as the person. And so that may involve social work and other professionals. And the spiritual, the why me, their fears about the future, may involve a spiritual counsellor or a chaplain or, if appropriate, a religious leader appropriate to that- for that person. So, I think it is that wider care provided by the team. Dr Smith: I'm just reflecting on, again, your earlier answers about the Continuum of neuropalliative care. Knowing your patient is super valuable here. So, having come to know someone through their disease course must pay dividends as you get to some of these harder questions that come up later during the disease progression. Dr Oliver: I think that's the very important use of palliative care from early on in the diagnosis. It's much easier to talk about, perhaps, the existential fears of someone while they can still talk openly. To do that through a communication aid can be very difficult. To talk about someone's fear of death through a communication aid is really very, very difficult. The multidisciplinary team, I think, works well if all the membe

Severe acute brain injury presents acute and longitudinal challenges. Addressing total pain involves managing physical symptoms and providing emotional, social, and spiritual support to enhance quality of life for patients and their families. In this episode, Kait Nevel, MD, speaks with Claire J. Creutzfeldt, MD, author of the article "Neuropalliative Care in Severe Acute Brain Injury and Stroke" in the Continuum® December 2025 Neuropalliative Care issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Liewluck is a professor in the department of neurology at the University of Washington in Seattle, Washington. Additional Resources Read the article: Neuropalliative Care in Severe Acute Brain Injury and Stroke With Dr. Claire Creutzfeldt 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: @IUneurodocmom Guest: @cj_creutzfeldt 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 Nevel: Hello, this is Dr Kait Nevel. Today I'm interviewing Dr Claire Creutzfeldt about her article on neuropalliative care in severe acute brain injury and stroke, which appears in the December 2025 Continuum issue on neuropalliative care. Claire, welcome to the podcast, and please introduce yourself to the audience. Dr Creutzfeldt: Thanks, thanks for having me. Yeah, I'm an associate professor of neurology at the University of Washington. I'm a stroke neurologist and palliative care researcher and really have focused my career on how we can best integrate palliative care principles into the care of patients with severe stroke and other neurocritical illness. Dr Nevel: Wonderful. Well, I'm looking forward to talking to you today about your excellent article that I really enjoyed reading. To get us started, can you tell us what you feel is the most important takeaway from your article for the practicing neurologist? Dr Creutzfeldt: Yeah. You know, I think one is always a little biased by what one is working on currently. And I think what I'm most excited about or feel more strongly about is this idea that stroke and severe acute brain injury are not an event, but really a chronic illness that people are left with usually for the rest of their lives, that change their life radically. And I think that education, research funding, also the clinical setting, current healthcare models aren't set up for that. And this idea that severe acute brain injury, you know, should be viewed as a lifelong condition that requires support across all ranges of goals of care. So curative, restorative, palliative and end-of-life care. Dr Nevel: Yeah, I love that part of your article, how you really highlighted that concept. And I think obviously that's something that we see in neurology and learn, especially as we transition out of our residency stages. But I think especially for the trainees listening, can sometimes be hospital inpatient-heavy, if you will, that kind of you can lose sight of that, that these acute strokes, severe acute brain injury, it turns into a chronic illness or condition that patients are dealing with lifelong. Dr Creutzfeldt: Often what we do in a very acute setting is like, is really cool and sexy and like, we can cure people from their stroke if they come, you know, at the right time with the right kind of stroke to the right hospital. And often the symptoms that people come in with much later on are harder to treat and address, partly because the focus in education, clinical and research just hasn't been as much on that time. Dr Nevel: Yeah, absolutely. So, can you talk to us about this concept of total pain? What does it mean, and how do we incorporate this concept into the way that we view our approach, our patient care? Dr Creutzfeldt: Total pain is a very old word, but it's sort of coming back into fashion in the palliative care world because it really describes all those sources of suffering or sources of distress, like, beyond what we sort of really think of as sort of the physical symptoms in recovery of stroke. As many of you know, palliative care often thinks in this multidimensional way of the physical distress, physical pain, but also psychological, emotional, social and spiritual, existential. And both- we sort of created sort of a figure that incorporates all of them and also includes both patients and their family members. They share some of these sources of distress, but they also have distinct ones that need to be addressed. And at the core of that total pain is what we need to provide, is sort of optimal communication and goals-of-care prognosis. Dr Nevel: Yeah, I'm thinking about all of those aspects and not just focusing on one. How does the disease trajectory of severe acute brain injury and stroke play a role in the palliative care approach? And how should we kind of going back to that original point of this idea of severe acute brain injury being an acute event and then oftentimes turning into kind of a chronic condition? How does that play a role in how we address palliative care with our patients, or kind of the stages of palliative care with our patients? Dr Creutzfeldt: Yeah, I think several things, especially for neurologists, is the more traditional palliative care illnesses, like cancer or congestive heart failure, illnesses where people are diagnosed when they're still functioning at a relatively high level and tend to have time to consider their prognosis and their goals of care in the end of life wishes and to meet with palliative care and to consider their personhood. Who am I? What's most important for me? And stroke, people with stroke, they not only present at their worst, they meet us at their worst, at a time when the patient themselves usually can't speak for themselves, when their personhood has been stripped from them. And then as providers, we, you know, we often really just get that one opportunity to get the conversation right and to guide people towards, you know, what we would call optimal and goal-concordant care. So, the challenges are many. I do think that the burden of these early conversations is on neurologists and really requires the neurologists to show compassion, to learn communication skills, think really hard about how you want to communicate prognosis and goals of care early on, because it's going to color people's experiences and decisions longitudinally. You asked about, sort of, this trajectory. And I do think it's important to think about, you know, what really happens even after the thrombectomy or even after we discharge people, especially from the ICU. Because for us, often after sort of day five or six, you know, we're sort of done. We're thinking about secondary stroke prevention. And, you know, how do I get the patient to rehab or out of the hospital? For the patients and families, this is when it really all just starts. You know, this is when they- when they're first memories are usually, you know, they hardly remember that acute setting. And so, when they are medically stable, we're done with the acute blood pressure treatment where we've removed the Foley, we've made a decision about nutrition. For us that tends to be a time where we let go a little; for patients and families that tends to actually be the time when they have to think about how am I going to live with this and what are the next several months or years going to look like? And so being there for them is important. Dr Nevel: That's such a, I think, important point, that when we have our plan in place, we know medically what the plan is for that patient and we're starting to step back, think about rehab or discharge. That's when oftentimes more quote-unquote "reality" steps in for patients and families about what their future is going to look like. Dr Creutzfeldt: And medical stability is not even close to neurological stability. And so, they are still in the middle of real prognostic uncertainty, and often waxing and waning symptoms or new symptoms coming up for them. Like pain, you know, post thalamic pain syndrome, just as an example, tends to be something that doesn't develop until later. Dr Nevel: Right, right. Absolutely. And since you touched on this concept of prognostic uncertainty, and, you know, that's something that's so challenging in severe acute brain injury, especially the early days when you talk about this, you know, that things tend to become a little bit more certain as more time passes. But these are really hard conversations because a lot of times feel like big decisions that need to be made early on, you know? Dr Creutzfeldt: Huge! Dr Nevel: Sometimes things like trach and PEG and things like that. How do you approach that conversation? I know you talk about that a little bit in your article. You touch on that, some of the, kind of, strategies or concepts that we use in palliative care to approach this prognostic uncertainty with patients. Dr Creutzfeldt: Yeah, I think the challenge is to balance this acknowledging uncertainty with still being able to guide the families and allow them to trust you. So, there are a few things that I have said in the past, and I have taught in the past, and I don't use anymore. They include sentences like I don't have a crystal ball, for example. Nobody was asking you for one. The other one that I want us to avoid, I think, is the sentence we are t

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. Chou 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

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 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

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 a

Dystrophinopathies are heritable muscle disorders caused by pathogenic variants in the DMD gene, leading to progressive muscle breakdown, proximal weakness, cardiomyopathy, and respiratory failure. Diagnosis and management are evolving areas of neuromuscular neurology. In this episode, Kait Nevel, MD, speaks with Divya Jayaraman, MD, PhD, an author of the article "Dystrophinopathies" in the Continuum® October 2025 Muscle and Neuromuscular Junction Disorders issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Jayaraman is an assistant professor of neurology and pediatrics in the division of child neurology at the Columbia University Irving Medical Center in New York, New York. Additional Resources Read the article: Dystrophinopathies 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: @IUneurodocmom 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 Nevel: Hello, this is Dr Kate Nevel. Today I'm interviewing Dr Divya Jayaraman about her article on dystrophinopathies, which she wrote with Dr Partha Ghosh. This article appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Divya, welcome to the podcast, and please introduce yourself to the audience. Dr Jayaraman: Thank you so much, Dr Nevel. My name is Divya, and I am an assistant professor of Neurology and Pediatrics at Columbia University Irving Medical Center, and also an attending physician in the Pediatric Neuromuscular program there. In that capacity, I see patients with pediatric neuromuscular disorders and also some general pediatric neurology patients and also do research, primarily clinical research and clinical trials on pediatric neuromuscular disorders. Dr Nevel: Wonderful. Thank you for sharing that background with us. To set us on the same page for our discussion, before we get into some more details of the article, perhaps, could you start with some definitions? What comprises the dystrophinopathies? What are some of the core features? Dr Jayaraman: So, the dystrophinopathies, I like that term because it is a smaller subset from the muscular dystrophies. The dystrophinopathies are a spectrum of clinical phenotypes that are all associated with mutations in the DMD gene on chromosome X. So, that includes DMD---or, Duchenne muscular dystrophy---, Becker muscular dystrophy, intermediate muscular dystrophy (which falls in between the two), dilated cardiomyopathy, asymptomatic hyperCKemia, and manifesting female carriers. In terms of the core features of these conditions, so, there's some variability, weakness being prominent in Duchenne and also Becker. The asymptomatic hyperCKemia, on the other hand, may have minimal symptoms and might be found incidentally by just having a high CK on their labs. They all will have some degree of elevated CK. The dilated cardiomyopathy patients, and also the Becker patients to a lesser degree, will have cardiac involvement out of proportion to skeletal muscle involvement, and then the manifesting carriers likewise can have elevated CK and prominent cardiac involvement as well as some milder weakness. Dr Nevel: Now that we have some definitions, for the practicing neurologists out there, what do you think is the most important takeaway from your article about the dystrophinopathies? Dr Jayaraman: I like this question because it suggests that there's something that, really, any neurologist could do to help us pick up these patients sooner. And the big takeaway I want everyone to get from this is to check the CK, or creatine kinase, level. It's a simple, cheap, easy test that anyone can order, and it really helps us a lot in terms of setting the patient on the diagnostic odyssey. And in terms of whom you should be thinking about checking a CK in, obviously patients who present with some of the classic clinical features of Duchenne muscular dystrophy. This would include young boys who have toe walking, as they're presenting, sign; or motor delayed, delayed walking. They may have calf hypertrophy, which is what we say nowadays. You might have seen calf pseudohypertrophy in your neurology textbooks, but we just say calf hypertrophy now. Or patients can often have a Gowers sign or Gowers maneuver, which is named after a person called Gowers who described this phenomenon where the child will basically turn over and use their hands on the floor to stand up, usually with a wide-based gait, and then they'll sort of march their hands up their legs. That's the sort of classic Gowers maneuver. There are modified versions of that as well. So, if anyone presents with this classic presentation, for sure the best first step is to check a CK. But I would also think about checking a CK for some atypical cases. For example, any boy with any kind of motor or speech delay for whom you might not necessarily be thinking about a muscle disorder, it's always good practice to check a CK. Even a boy with autism for whom you may not get a good clinical exam. This patient might present to a general pediatric neurology clinic. I always check a CK in those patients, and you'll pick up a lot of cases that way. For the adult folks in particular, the adult neurologist, a female patient could show up in your clinic with asymptomatic hyperCKemia. And I think it's an important differential to think about for them because this could have implications not just for their own cardiac risks, but also for their family planning. Dr Nevel: So, tell us a little bit more about the timing of diagnosis. Biggest takeaway: check a CK if this is anywhere on your radar, even if somewhat of an atypical case. Why is it so important to get kiddos started on that diagnostic odyssey, as you called it, early? Dr Jayaraman: This is especially important for kids because if they especially get a Duchenne muscular dystrophy diagnosis, you might be making them eligible for treatments that we've had for some time, and also treatments that were not available earlier that hinge on making that diagnosis. So, for example, people may be skeptical about steroids, but there's population data to suggest that initiation and implementation of steroids could delay the onset of loss of ambulation as much as three years. So, you don't want to deprive patients of the chance to get that. And then all the newer emerging therapies---which we'll be talking about later, I'm sure---require a Duchenne muscular dystrophy diagnosis. So, that's why it's so important to check a CK, have this on your radar, and then get them to a good specialist. Dr Nevel: I know that you alluded already, or shared a few of the kind of exam paroles or findings among patients with dystrophinopathy. But could you share with us a little bit more how you approach these patients in the clinic who are presenting with muscle weakness, perhaps? And how do you approach this or think about this in terms of ways to potentially differentiate between a dystrophinopathy versus another cause of motor weakness or delay? Dr Jayaraman: It's helpful to think through the neuraxis and what kinds of disorders can present along that neuraxis. A major differential that I'm always thinking about when I'm seeing a child with proximal weakness is spinal muscular atrophy, which is a genetic anterior horn cell disorder that can also present in this age group. And some of the key differences there would be things like reflexes. So, you should have dropped reflexes in spinal muscular atrophy. In DMD, surprisingly, they might have preserved Achilles reflexes even if their patellar reflexes are lost. It may only be much later that they go on to lose their Achilles reflex. So, if you can get an Achilles reflex, that's quite reassuring, and if you cannot, then you need to be thinking about spinal muscular atrophy. They can both have low muscle tone and can present quite similarly, including with proximal weakness, and can even have neck flexion weakness. So, this is an important distinction to make. The reason for that is, obviously there are treatments for both conditions, but for spinal muscular atrophy, timing is very, very important. Time is motor neurons, so the sooner you make that diagnosis the better. Other considerations would be the congenital muscular dystrophies. So, for those that they tend to present a lot younger, like in infancy or very early on, and they can have much, much higher CKS in that age range than a comparable Duchenne or Becker muscular dystrophy patient. They can also have other involvement of the central nervous system that you wouldn't see in the dystrophinopathies, for example. My mnemonic for the congenital muscular dystrophies is muscle-eye-brain disease, which is one of the subtypes. So, you think about muscle involvement, eye involvement, and brain involvement. So, they need an ophthalmology valve. They can have brain malformations, which you typically don't see in the dystrophinopathies. I think those are some of the major considerations that I have. Obviously, it's always good to think about the rest of the neuraxis as well. Like, could this be a central nervous system process? Do they have upper motor neuron signs? But that's just using all of your exam tools as a neurologist. Dr Nevel: Yeah, absolutely. So, let's say you have a patient in clinic and you suspect they may have a dystr

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 o

Genetic variants that underlie skeletal muscle channelopathies and rhabdomyolysis can also cause persistent and progressive muscle weakness. The availability and expanded use of genetic testing allows for the identification of new genes causing periodic paralysis and rhabdomyolysis. In this episode, Teshamae Monteith, MD, FAAN speaks with Hani Kushlaf, MD, MS, FAAN, author of the article "Muscle Channelopathies and Rhabdomyolysis" in the Continuum® October 2025 Muscle and Neuromuscular Junction Disorders 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. Kushlaf is a professor of neurology and pathology as well as the director of the Neuromuscular Division, director of Neuromuscular Research, and director of the Neuromuscular Medicine Fellowship in the Department of Neurology and Rehabilitation Medicine and the Department of Pathology and Laboratory Medicine at the University of Cincinnati College of Medicine in Cincinnati, Ohio. Additional Resources Read the article: Muscle Channelopathies and Rhabdomyolysis 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: @HaniKushlaf 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 Hani Kushlaf about his article on muscle channelopathies and rhabdomyolysis, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Hi, Hani. How are you? Dr Kushlaf: Good. How are you doing? Thank you for having me. Dr Monteith: Well, thank you for coming on our podcast. So why don't you introduce yourself? Dr Kushlaf: So, I'm Hani Kushlaf. I'm a professor of Neurology and Pathology in the Department of Neurology and Rehabilitation Medicine at the University of Cincinnati in Cincinnati, Ohio. Dr Monteith: And what got you interested in muscle disorders? Dr Kushlaf: So, this is a long story. At first in residency, I was interested in epilepsy, but the moment I started doing a rotation in neuromuscular, I became enamored with neuromuscular disorders. I remember seeing the first patient in the rotation who had myofibrillar myopathy, and I found out that there is very little known about muscle disease at the time. So, I became very interested and I immediately changed direction as I started doing nerve conduction studies and EMGs and having that procedure base, I just decided that I want to pursue neuromuscular disorders. Dr Monteith: Well, that doesn't sound like a long story. It sounds like love at first sight. Dr Kushlaf: Yes, I think part of it is not very far from neuromuscular disorders and that it does have some electrophysiology involved. But muscle disease and nerve disorders, they need that detailed neurologic examination, which I love in terms of doing the localization exercise. Dr Monteith: Great. So why don't we talk about the objectives of your article? Dr Kushlaf: This article was written to review muscle channelopathies that include myotonic disorders and periodic paralysis, and also rhabdomyolysis, with emphasis on genetic causes of rhabdomyolysis more than acquired causes. Dr Monteith: So, why was this update so important? Dr Kushlaf: I think this area of muscle disorders hasn't seen a lot of progress in recent years, but there are interesting findings that we're learning that spark, hopefully, more research into the area, because we do have significant gaps that are related to understanding pathophysiology of some of these disorders. For example, in patients with periodic paralysis, it's clearly known now that these patients over time develop muscle weakness, and the muscle weakness is unrelated to how many episodes of weakness they have---basically, the episodic paralysis part of the disease. So, this is an important finding that I think we need to look more into it and understand that these disorders actually progress, even though that they may not have episodes of paralysis. In addition, there are genetic therapies that have been introduced into most of neuromuscular medicine at this time, including muscle disorders, while this specific part of muscle diseases has not had that luxury yet. And I'm hoping over time that there will be an introduction of gene therapies for these diseases. Dr Monteith: Great. So, it sounds like there's some clinical advances, then, as well as genetic advances. Now, you also spoke about rhabdomyolysis and that there's newer ways of thinking about that from perhaps when I was in residency. So why don't you update me on these newer approaches? Dr Kushlaf: The rhabdomyolysis… first, the definition of it is changing. We used to use a cut off, a CK of about a thousand, to call it rhabdomyolysis. And very recently it's clear that that level of CK is not sufficient to call it rhabdomyolysis. So, now the level went up in terms of exertion of rhabdomyolysis, up to ten thousand, has to be more than ten thousand. And in patients who haven't had exercise, the level is up to five thousand. So, it's no longer actually one thousand. And that refinement in the definition is important because there are some patients who exercise all the time and they may exercise at an athletic level and they have very high CK's. And those patients should not be labeled as having rhabdomyolysis. Basically, they are doing strenuous physiologic exercise. In addition, not only the definition of rhabdomyolysis is changing, it is our approach to which disorders to consider first and how we should work up patients with rhabdomyolysis. So, acquired rhabdomyolysis remains the most important etiology to be ruled out first. So, I always tell my fellows and residents that, think about acquired rhabdomyolysis first before you think about the genetic disorder. After you rule out the fact that it is not a toxic or metabolic or medication-induced rhabdomyolysis, then think about a genetic etiology. But when you get that consultation from the hospital that the patient has rhabdomyolysis and we want you to figure it out, always look at the medication list and make sure that there isn't anything on it that causes, actually, a rhabdomyolysis. And in many instances, you find out that it's actually a toxic or metabolic etiology for the rhabdomyolysis. And as part of this article, there's also an acronym that's now being used to identify those patients who would benefit from genetic testing. The acronym is called RHABDO. It's as is the word, RHABDO. R refers to Recurrent exertion of rhabdomyolysis. So, it's not just one episode. And the H refers to HyperCKemia, and the hyperCKemia should persist more than eight weeks after the episodes of rhabdomyolysis. And if it is exertional, then the person has not done an unaccustomed exercise. So, they have changed the way that they do exercise and now they are exercising for two hours instead of one hour or they have introduced a new way of exercise into their exercise regimen. Then that should not be considered. It's not considered necessary to test these patients for a genetic cause. Also, the muscle enzyme typically, in genetic causes of rhabdomyolysis, goes more than fifty times above the upper limit of normal, which is more than a thousand. So that has to be taken into account. And then for the D it's Drugs and medications. This has to be ruled out before you say yes, we need to find the genetic cause of rhabdomyolysis. And then the O, it's basically family history. If you find that there is other family members who are affected or they have a high CK, then of course that would point you toward doing genetic testing. Dr Monteith: Great. So, it sounds like there's some advances there in how we approach these patients. In what way is this practice changing? You mentioned, you know, really important to rule out these potentially reversible causes first. Dr Kushlaf: Yeah. So, once you identify the theology, it becomes easier to manage the patient. So, if it is a statin-induced rhabdomyolysis, you know that you want to stop the statin and you are not going to have this problem again. So, that's quite important. The statins, of course, will have to not be reintroduced in the future for that specific patient who developed statin-induced rhabdomyolysis. But for the genetic causes of rhabdomyolysis, if you go down the path of genetic rhabdomyolysis, of course we have no cures for these disorders. We may have treatments. One of the conditions that I have alluded to as one of the case presentations in the article is a patient who has riboflavin responsive multiple acid CoA dehydrogenase deficiency, and I wanted to highlight this disorder because it's a disorder not to be missed. It does have a treatment, which is riboflavin, and that comes from the name riboflavin-responsive. So that's why I put there in the article as part of the manuscript. However, some of these disorders, once you find the genetic etiology, there may be a way of preventing it in the future generation. Family planning, reproductive medicine technologies, can help in this instance and prevent this disease from occurring in the future generations. Dr Monteith: So, why don't we move on to episodic skeletal disorders? What is your general approach for these types of diseases? Dr Kushlaf: Muscle channelopathies, skeletal muscle channelopathies,

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 f

Inclusion body myositis (IBM), the most common myopathy in adults, is a disease of aging characterized by slowly progressive weakness. Diagnosis of IBM requires the integration of historical, clinical, and laboratory data, while management consists of a multidisciplinary approach to address comorbidities and potential complications. In this episode, Aaron Berkowitz, MD, PhD, FAAN speaks with Elie Naddaf, MD, author of the article "Inclusion Body Myositis" in the Continuum® October 2025 Muscle and Neuromuscular Junction Disorders issue. Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology at the University of California San Francisco in the Department of Neurology in San Francisco, California. Dr. Naddaf is an associate professor of neurology at the Mayo Clinic College of Medicine in Rochester, Minnesota. Additional Resources Read the article: Inclusion Body Myositis 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: @AaronLBerkowitz Guest: @ElieNaddaf3 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 Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Elie Naddaf about his article on inclusion body myositis, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Welcome to the podcast, Dr Naddaf, and would you please introduce yourself to our audience? Dr Naddaf: Thank you for having me. I am Elie Naddaf, a neuromuscular neurologist at Mayo Clinic in Rochester, Minnesota, and one of my main focus research-wise is about inclusion body myositis. Dr Berkowitz: Fantastic. Well, this is a great article on inclusion body myositis, or IBM, as we may refer to it today. It has a lot of clinically practical tips for examining patients at the bedside and a lot of important updates for us on how to diagnose this condition. So, I encourage our listeners to check out the article, and I look forward to discussing some of the key aspects here and learning from your expertise. First, tell us about the classic presentation of IBM, when the disease is pretty easy to recognize at the bedside based on the history and exam. Dr Naddaf: Luckily, IBM is one of those diseases that has a very particular pattern of weakness that makes it easier to diagnose. However, in real life it can be very challenging for several reasons, which we will cover in this podcast and in the article. However, a typical presentation of IBM is that of an older patient, more likely to be a male---twice more likely to be a male---,presenting with slowly progressive weakness over a couple years or so. And the weakness predominantly affects the deep finger flexors in the hand. So, they most commonly present with hand grip weakness, or the quadriceps muscle presenting with some lower limb weakness. However, some patients can present with one or the other, not necessarily with both at the same time. It is usually a painless disease,, and because of the lingering course, patients tend to present within two to three years from their symptom onset. So, with that, on examination, if the patient is presenting with the hand weakness, they would demonstrate weakness in the deep finger flexors, which are the muscles that we use to flex the distal intralaryngeal joints. This weakness is often asymmetric and can be in only one hand; and also, even within the same hand, you can have a variable severity from one finger to the other. And that's one reason, although it sounds a classic phenotype, if you can imagine a patient just presenting with hand weakness, a lot of other things come to mind, whether it's a compressive neuropathy or whether it's a radiculopathy or motor neuron disease. Similarly, in the leg, the quadriceps is a big and strong muscle. So, it's often that patients' symptoms originally or in the beginning get dismissed because the physician did not demonstrate any weakness on manual motor testing. Because it's a strong muscle, it needs to lose a certain amount of strength to be able to demonstrate that weakness by just pushing against the patient trying to extend their knee from about a 90 degree or so. That's why another way in those cases would be to examine them more functionally whether they're kneeling or squatting. It is usually a pure motor disease, although patients can commonly have a peripheral neuropathy. But typically, on exam, you mainly see muscle weakness. Dr Berkowitz: Perfect. So, if we see a patient who's an older man with progressive painless weakness of the finger flexors, quadriceps, this is sort of the classic presentation where we would consider IBM. But you mentioned in your article that some patients can present somewhat atypically when we might not immediately think of this diagnosis. What are some of the atypical presentations we should be aware of that should lead us to think about IBM as a possible etiology for the patient's pattern of weakness? Dr Naddaf: So, IBM indeed can present in any muscle group. That's why about 14% of patients may have the weakness onset beyond the finger flexors or knee extensions. And there are very particular phenotypes that stand out. Especially the most common in that scenario would be patients presenting with pure difficulty swallowing, isolated dysphasia that can sometimes precede the limb weakness by several years, and that's especially common in females. Other phenotypes including just a proximal weakness, like a limb-girdle weakness; an axial weakness, for example, head drop or camptocormia or a foot drop. And because it's an asymmetric disease, you can see the challenge there---if someone just presenting with a foot drop on one side, that it could be challenging to just think of IBM. So, those are the main phenotype. One particular phenotype that is super interesting is, patients present with severe facial weakness as if they have severe bilateral Bell's palsy. And that's the, usually, the most common first misdiagnosis. And all these patients reported so far in the literature are only females. This has not been reported in any male patients. So yes, the finger flexor quadriceps weakness is the most common typical presentation. However, IBM can present, technically, in any other muscle in the body. Dr Berkowitz: Great. Well that's very helpful information that especially comes from experts like you who see a lot of these patients and are able to make these diagnoses of these rare phenotypes. Whereas many of us general neurologists, like myself, might think of IBM only with finger flexor weakness and quadriceps weakness, perhaps with some foot drop dysphagia associated. Sounds like this is a diagnosis to consider in atypical presentations or atypical presentations of myopathy that aren't fitting other phenotypes or aren't yielding diagnostic results for other phenotypes. And you have in your article a very helpful table that goes through some of the common sites of weakness in IBM and the differential diagnosis for myopathies and other conditions to consider in patients who have the classic and less typical presenting features. So, let's say that we see a patient with clinical features suggestive of IBM. How do we go about confirming the diagnosis? What are the main diagnostic tests we would use to try to make a firm diagnosis here? Dr Naddaf: So, the gold standard so far for diagnosis for inclusion body myositis, as it is an acquired disease, has been a muscle biopsy. So, muscle biopsy is the probably most important tool in the diagnostic approach to IBM. Even in patients with a classical phenotype, that all like in any other test, it depends on your pretest probability and how sure you are the patient has IBM. But even with the classic phenotype, it is characteristic of IBM, but not pathognomic of IBM. Because if we see a high number of patients with similar phenotypes, we will run into a lot of other disorder that present similarly. And some patients---especially for instance, with myotonic dystrophies, specially type two---may be very difficult to distinguish from IBM, especially those that present in adulthood that they don't have the classic picture of a myotonic dystrophy patient you would think of. And some of them may not even have percussion myotonia. Because of that, the biopsy is very important to confirm your diagnosis in that regard. And on the biopsy, you want to see evidence of inflammation, basically, and the mesial inflammation, without going into a lot of details, to set it apart from those genetic ones. But in IBM it's not a pure inflammatory disease. There are other features on the biopsy that are very particular to IBM, two main other things we need to find. One is that of the accumulation of autophagic vacuole and protein aggregates and that of mitochondrial dysfunction. So, the other test for patients, presenting with weakness---again that depends on your clinical suspicion---would be first to establish that the underlying process is a myopathy; and hence, the EMG. And also, that's particularly important in patient with symptoms in one limb to differentiate it from compressive neuropathies or from a motor neuron disorder or other. So, the EMG tells you it's a myopathy with fibrillation potential, helps you also choose a muscle for biopsy. So as far as blood tests, the main blood test is that of the cytosolic nucleosidase 1A, or people call them IBM antibody. That's present in about half of the

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 onl

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

While genetic testing has replaced muscle biopsy in the diagnosis of many genetic myopathies, clinical assessment and the integration of clinical and laboratory findings remain key elements for the diagnosis and treatment of muscle diseases. In this episode, Casey Albin, MD, speaks with Margherita Milone, MD, PhD, FAAN, FANA, author of the article "A Pattern Recognition Approach to Myopathy" 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. Milone is a professor of neurology and the director of the Muscle Pathology Laboratory at Mayo Clinic College of Medicine and Science in Rochester, Minnesota. Additional Resources Read the article: A Pattern Recognition Approach to Myopathy 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, this is Dr Casey Albin. Today I'm interviewing Dr Margherita Milone on her article on a pattern recognition approach to myopathy, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Welcome to the podcast, Dr Milone. Thank you so much for joining us. I'll start off by having you introduce yourself to our listeners. Dr Milone: Hello Casey, thank you so much for this interview and for bringing the attention to the article on muscle diseases. So, I'm Margherita Milone. I'm one of the neuromuscular neurologists at Mayo Clinic in Rochester. I have been interested in muscle disorders since I was a neurology resident many years ago. Muscle diseases are the focus of my clinical practice and research interest. Dr Albin: Wonderful. Thank you so much. When I think about myopathies, I generally tend to think of three large buckets: the genetic myopathy, the inflammatory myopathies, and then the necrotizing myopathies. Is that a reasonable approach to conceptualizing these myopathies? Dr Milone: Yeah, the ideology of the myopathies can be quite broad. And yes, we have a large group of genetic muscle diseases, which are the most common. And then we have immune-mediated muscle diseases, which include inflammatory myopathies as well as some form of necrotizing myopathies. Then we have some metabolic myopathies, which could be acquired or could be genetic. And then there are muscle diseases that are due to toxins as well as to infection. Dr Albin: Wow. So, lots of different etiologies. And that really struck me about your article, is that these can present in really heterogeneous ways, and some of them don't really read the rule book. So, we have to have a really high level of suspicion, for someone who's coming in with weakness, to remember to think about a myopathy. One of the things that I like to do is try to take us through a little bit of a case to sort of walk us through how you would approach if someone comes in. So, let's say you get, you know, a forty-year-old woman, and she's presenting with several months of progressive weakness. And she says that even recently she's noted just a little bit of difficulty swallowing. It feels to her like things are getting stuck. What are some of the things when you are approaching the history that would help you tease this to a myopathy instead of so many other things that can cause a patient to be weak? Dr Milone: Yes. So, as you mentioned, people who have a muscle disease have the muscle weakness often, but the muscle weakness is not just specific for a muscle disease. Because you can have a mass weakness in somebody who has a neurogenic paralysis. The problem with diagnosis of muscle diseases is that patients with these disorders have a limited number of symptom and sign that does not match the large heterogeneity of the etiology. So, in someone who has weakness, that weakness could represent a muscle disease, could represent an anterior horn cell disease, could represent a defect of neuromuscular junction. The clinical history of weakness is not sufficient by itself to make you think about a muscle disease. You have to keep that in the differential diagnosis. But your examination will help in corroborating your suspicion of a muscle disease. Let's say if you have a patient, the patient that you described, with six months' history of progressive weakness, dysphagia, and that patient has normal reflexes, and the patient has no clinical evidence for muscle fatigability and no sensory loss, then the probability that that patient has a myopathy increases. Dr Albin: Ah, that's really helpful. I'm hearing a lot of it is actually the lack of other findings. In some ways it's asking, you know, have you experienced numbness and tingling? And if not, that's sort of eliminating that this might not be a neuropathy problem. And then again, that fatigability- obviously fatigability is not specific to a neuromuscular junction, but knowing that is a hallmark of myasthenia, the most common of neuromuscular disorders. Getting that off the table helps you say, okay, well, it's not a neuromuscular junction problem, perhaps. Now we have to think more about, is this a muscle problem itself? Are there any patterns that the patients describe? I have difficulty getting up from a chair, or I have difficulty brushing my hair. When I think of myopathies, I historically have thought of, sort of, more proximal weakness. Is that always true, or not so much? Dr Milone: Yeah. So, there are muscle diseases that involve predominantly proximal weakness. For example, the patient you mentioned earlier could have, for example, an autoimmune muscle disease, a necrotizing autoimmune myopathy; could have, perhaps, dermatomyositis if there are skin changes. But a patient with muscle disease can also present with a different pattern of weakness. So, myopathies can lead to this weakness, and foot drop myopathies can cause- can manifest with the weakness of the calf muscles. So, you may have a patient presenting to the clinic who has no the inability to stand on tiptoes, or you may have a patient who has just facial weakness, who has noted the difficulty sealing their lips on the glasses when they drink and experiencing some drooling in that setting, plus some hand weakness. So, the muscle involved in muscle diseases can vary depending on the underlying cause of the muscle disease. Dr Albin: That's really helpful. So, it really is really keeping an open mind and looking for some supporting features, whether it's bulbar involvement, extraocular eye muscle involvement; looking, you know, is it proximal, is it distal? And then remembering that any of those patterns can also be a muscle problem, even if sometimes we think of distal being more neuropathy and proximal myopathy. Really, there's a host of ranges for this. I really took that away from your article. This is, unfortunately, not just a neat way to box these. We really have to have that broad differential. Let me ask another question about your history. How often do you find that patients complain of, sort of, muscular cramping or muscle pain? And does that help you in terms of deciding what type of myopathy they may have? Dr Milone: Many patients with muscle disease have muscle pain. The muscle pain could signal a presence of inflammation in skeletal muscle, could be the result of overuse from a muscle that is not functioning normally. People who have myotonia experience muscle stiffness and muscle pain. Patients who have a metabolic myopathy usually have exercise-induced muscle pain. But, as we know, muscle pain is also very nonspecific, so we have to try to find out from the patient in what setting the pain specifically occurs. Dr Albin: That's really helpful. So, it's asking a little bit more details about the type of cramping that they have, the type of pain they may be experiencing, to help you refine that differential. Similarly, one of the things that I historically have always associated with myopathies is an elevation in the CK, or the creatinine kinase. How sensitive and specific is that, and how do you as the expert sort of take into account, you know, what their CK may be? Dr Milone: So, this is a very good point. And the elevation of creatine kinase can provide a clue that the patient has a muscle disease, but it is nonspecific for muscle disease because we know that elevation of creatine kinase can occur in the setting of a neurogenic process. For example, we can see elevation of the creatine kinase in patients who have ALS or in patients who have spinal muscular atrophy. And in these patients---for example, those with spinal muscular atrophy---the CK elevation can be also of significantly elevated up to a couple of thousand. Conversely, we can have muscle diseases where the CK elevation does not occur. Examples of these are some genetic muscle disease, but also some acquired muscle diseases. If we think of, for example, cases where inflammation in the muscle occurs in between muscle fibers, more in the interstitium of the muscle, that disease may not lead to significant elevation of the CK. Dr Albin: That's super helpful. So, I'm hearing you say CK may be helpful, but it's neither completely sensitive nor completely specific when we're thinking about myopathic disorders. Dr Milone:

Functional movement disorders are a common clinical concern for neurologists. The principle of "rule-in" diagnosis, which involves demonstrating the difference between voluntary and automatic movement, can be carried through to explanation, triage, and evidence-based multidisciplinary rehabilitation therapy. In this episode, Gordon Smith, MD, FAAN speaks Jon Stone, PhD, MB, ChB, FRCP, an author of the article "Multidisciplinary Treatment for Functional Movement Disorder" in the Continuum® August 2025 Movement 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. Stone is a consultant neurologist and honorary professor of neurology at the Centre for Clinical Brain Sciences at the University of Edinburgh in Edinburgh, United Kingdom. Additional Resources Read the article: Multidisciplinary Treatment for Functional Movement Disorder 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: @gordonsmithMD Guest: @jonstoneneuro Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. This exclusive Continuum Audio interview is available only to you, our subscribers. We hope you enjoy it. Thank you for listening. Dr Smith: Hello, this is Dr Gordon Smith. Today I've got the great pleasure of interviewing Dr Johnstone about his article on the multidisciplinary treatment for functional neurologic disorder, which he wrote with Dr Alan Carson. This article will appear in the August 2025 Continuum issue on movement disorders. I will say, Jon, that as a Continuum Audio interviewer, I usually take the interviews that come my way, and I'm happy about it. I learn something every time. They're all a lot of fun. But there have been two instances where I go out and actively seek to interview someone, and you are one of them. So, I'm super excited that they allowed me to talk with you today. For those of our listeners who understand or are familiar with FND, Dr Stone is a true luminary and a leader in this, both in clinical care and research. He's also a true humanist. And I have a bit of a bias here, but he was the first awardee of the Ted Burns Humanism in Neurology award, which is a real honor and reflective of your great work. So welcome to the podcast, Jon. Maybe you can introduce yourself to our audience. Dr Stone: Well, thank you so much, Gordon. It was such a pleasure to get that award, the Ted Burns Award, because Ted was such a great character. I think the spirit of his podcasts is seen in the spirit of these podcasts as well. So, I'm a neurologist in Edinburgh in Scotland. I'm from England originally. I'm very much a general neurologist still. I still work full-time. I do general neurology, acute neurology, and I do two FND clinics a week. I have a research group with Alan Carson, who you mentioned; a very clinical research group, and we've been doing that for about 25 years. Dr Smith: I really want to hear more about your clinical approach and how you run the clinic, but I wonder if it would be helpful for you to maybe provide a definition. What's the definition of a functional movement disorder? I mean, I think all of us see these patients, but it's actually nice to have a definition. Dr Stone: You know, that's one of the hardest things to do in any paper on FND. And I'm involved with the FND society, and we're trying to get together a definition. It's very hard to get an overarching definition. But from a movement disorder point of view, I think you're looking at a disorder where there is an impairment of voluntary movement, where you can demonstrate that there is an automatic movement, which is normal in the same movement. I mean, that's a very clumsy way of saying it. Ultimately, it's a disorder that's defined by the clinical features it has; a bit like saying, what is migraine? You know? Or, what is MS? You know, it's very hard to actually say that in a sentence. I think these are disorders of brain function at a very broad level, and particularly with FND disorders, of a sort of higher control of voluntary movement, I would say. Dr Smith: There's so many pearls in this article and others that you've written. One that I really like is that this isn't a diagnosis of exclusion, that this is an affirmative diagnosis that have clear diagnostic signs. And I wonder if you can talk a little bit about the diagnostic process, arriving at an FND diagnosis for a patient. Dr Stone: I think this is probably the most important sort of "switch-around" in the last fifteen, twenty years since I've been involved. It's not new information. You know, all of these diagnostic signs were well known in the 19th century; and in fact, many of them were described then as well. But they were kind of lost knowledge, so that by the time we got to the late nineties, this area---which was called conversion disorder then---it was written down. This is a diagnosis of exclusion that you make when you've ruled everything out. But in fact, we have lots of rule in signs, which I hope most listeners are familiar with. So, if you've got someone with a functional tremor, you would do a tremor entrainment test where you do rhythmic movements of your thumb and forefinger, ask the patient to copy them. It's very important that they copy you rather than make their own movements. And see if their tremor stops briefly, or perhaps entrains to the same rhythm that you're making, or perhaps they just can't make the movement. That might be one example. There's many examples for limb weakness and dystonia. There's a whole lot of stuff to learn there, basically, clinical skills. Dr Smith: You make a really interesting point early on in your article about the importance of the neurological assessment as part of the treatment of the patient. I wonder if you could talk to our listeners about that. Dr Stone: So, I think, you know, there's a perception that- certainly, there was a perception that that the neurologist is there to make a diagnosis. When I was training, the neurologist was there to tell the patient that they didn't have the kind of neurological problem and to go somewhere else. But in fact, that treatment process, when it goes well, I think begins from the moment you greet the patient in the waiting room, shake their hand, look at them. Things like asking the patient about all their symptoms, being the first doctor who's ever been interested in their, you know, horrendous exhaustion or their dizziness. You know, questions that many patients are aware that doctors often aren't very interested in. These are therapeutic opportunities, you know, as well as just taking the history that enable the patient to feel relaxed. They start thinking, oh, this person's actually interested in me. They're more likely to listen to what you've got to say if they get that feeling off you. So, I'd spend a lot of time going through physical symptoms. I go through time asking the patient what they do, and the patients will often tell you what they don't do. They say, I used to do this, I used to go running. Okay, you need to know that, but what do they actually do? Because that's such valuable information for their treatment plan. You know, they list a whole lot of TV shows that they really enjoy, they're probably not depressed. So that's kind of useful information. I also spend a lot of time talking to them about what they think is wrong. Be careful, that they can annoy patients, you know. Well, I've come to you because you're going to tell me what's wrong. But what sort of ideas had you had about what was wrong? I need to know so that I can deal with those ideas that you've had. Is there a particular reason that you're in my clinic today? Were you sent here? Was it your idea? Are there particular treatments that you think would really help you? These all set the scene for what's going to come later in terms of your explanation. And, more importantly, your triaging of the patient. Is this somebody where it's the right time to be embarking on treatment, which is a question we don't always ask yourself, I think. Dr Smith: That's a really great point and kind of segues to my next question, which is- you talked a little bit about this, right? Generally speaking, we have come up with this is a likely diagnosis earlier, midway through the encounter. And you talked a little bit about how to frame the encounter, knowing what's coming up. And then what's coming up is sharing with the patient our opinion. In your article, you point out this should be no different than telling someone they have Parkinson's disease, for instance. What pearls do you have and what pitfalls do you have in how to give the diagnosis? And, you know, a lot of us really weren't trained to do this. What's the right way, and what are the most common land mines that folks step on when they're trying to share this information with patients? Dr Stone: I've been thinking about this for a long time, and I've come to the conclusion that all we need to do with this disorder is stop being weird. What goes wrong? The main pitfall is that people think, oh God, this is FND, this is something a bit weird. It's in a different box to all of the other things and I have to do something weird. And people end up blurting out things like, well, your scan was normal or, you haven't got epilepsy or, you haven't got Parkinson's disease. That's not what you normally do. It's weird. What you normally do is you take a deep breath and you say, I'm sorry to tell you've got Parkinson's disease or, you have this type of dystonia. That's what you normal

Paroxysmal movement disorders refer to a group of highly heterogeneous disorders that present with attacks of involuntary movements without loss of consciousness. These disorders demonstrate considerable and ever-expanding genetic and clinical heterogeneity, so an accurate clinical diagnosis has key therapeutic implications. In this episode, Kait Nevel, MD, speaks with Abhimanyu Mahajan, MD, MHS, FAAN, author of the article "Paroxysmal Movement Disorders" in the Continuum® August 2025 Movement Disorders issue. Dr. Nevel is a Continuum® Audio interviewer and a neurologist and neuro-oncologist at Indiana University School of Medicine in Indianapolis, Indiana. Dr. Mahajan is an assistant professor of neurology and rehabilitation medicine at the James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders at the University of Cincinnati in Cincinnati, Ohio. Additional Resources Read the article: Paroxysmal Movement Disorders 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: @IUneurodocmom Guest: @MahajanMD Full episode transcript available here Dr Jones: This is Doctor 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 Nevel: Hello, this is Dr Kait Nevel. Today I'm interviewing doctor Abhi Mahajan about his article on diagnosis and management of paroxysmal movement disorders, which appears in the August 2025 Continuum issue on movement disorders. Abhi, welcome to the podcast and please introduce yourself to the audience. Dr Mahajan: Thank you, Kait. Thank you for inviting me. My name is Abhi Mahajan. I'm an assistant professor of neurology and rehabilitation medicine at the University of Cincinnati in Cincinnati, Ohio. I'm happy to be here. Dr Nevel: Wonderful. Well, I'm really excited to talk to you about your article today on this very interesting and unique set of movement disorders. So, before we get into your article a little bit more, I think just kind of the set the stage for the discussion so that we're all on the same page. Could you start us off with some definitions? What are paroxysmal movement disorders? And generally, how do we start to kind of categorize these in our minds? Dr Mahajan: So, the term paroxysmal movement disorders refers to a group of highly heterogeneous disorders. These may present with attacks of involuntary movements, commonly a combination of dystonia and chorea, or ataxia, or both. These movements are typically without loss of consciousness and may follow, may follow, so with or without known triggers. In terms of the classification, these have been classified in a number of ways. Classically, these have been classified based on the trigger. So, if the paroxysmal movement disorder follows activity, these are called kinesigenic, paroxysmal, kinesigenic dyskinesia. If they are not followed by activity, they're called non kinesigenic dyskinesia and then if they've followed prolonged activity or exercise they're called paroxysmal exercise induced dyskinesia. There's a separate but related group of protogynous movement disorders called episodic attacks here that can have their own triggers. Initially this was the classification that was said. Subsequent classifications have placed their focus on the ideology of these attacks that could be familiar or acquired and of course understanding of familiar or genetic causes of paroxysmal movement disorders keeps on expanding and so on and so forth. And more recently, response to pharmacotherapy and specific clinical features have also been introduced into the classification. Dr Nevel: Great, thank you for that. Can you share with us what you think is the most important takeaway from your article for the practicing neurologist? Dr Mahajan: Absolutely. I think it's important to recognize that everything that looks and sounds bizarre should not be dismissed as malingering. Such hyperkinetic and again in quotations, "bizarre movements". They may appear functional to the untrained eye or the lazy eye. These movements can be diagnosed. Paroxysmal movement disorders can be diagnosed with a good clinical history and exam and may be treated with a lot of success with medications that are readily available and cheap. So, you can actually make a huge amount of difference to your patients' lives by practicing old-school neurology. Dr Nevel: That's great, thank you so much for that. I can imagine that scenario does come up where somebody is thought to have a functional neurological disorder but really has a proximal movement disorder. You mentioned that in your article, how it's important to distinguish between these two, how there can be similarities at times. Do you mind giving us a little bit more in terms of how do we differentiate between functional neurologic disorder and paroxysmal movement disorder? Dr Mahajan: So clinical differentiation of functional neurological disorder from paroxysmal movement disorders, of course it's really important as a management is completely different, but it can be quite challenging. There's certainly an overlap. So, there can be an overlap with presentation, with phenomenology. Paroxysmal nature is common to both of them. In addition, FND and PMD's may commonly share triggers, whether they are movement, physical exercise. Other triggers include emotional stimuli, even touch or auditory stimuli. What makes it even more challenging is that FND's may coexist with other neurological disorders, including paroxysmal movement disorders. However, there are certain specific phenom phenotypic differences that have been reported. So specific presentations, for example the paroxysms may look different. Each paroxysm may look different in functional neurological disorders, specific phenotypes like paroxysmal akinesia. So, these are long duration episodes with eyes closed. Certain kinds of paroxysmal hyperkinesia with ataxia and dystonia have been reported. Of course. More commonly we see PNES of paroxysmal nonepileptic spells or seizures that may be considered paroxysmal movement disorders but represent completely different etiology which is FND. Within the world of movement disorders, functional jerks may resemble propiospinal myoclonus which is a completely different entity. Overall, there are certain things that help separate functional movement disorders from paroxysmal movement disorders, such as an acute onset variable and inconsistent phenomenology. They can be suggestibility, distractibility, entrainment, the use of an EMG may show a B-potential (Bereitschaftspotential) preceding the movement in patients with FND. So, all of these cues are really helpful. Dr Nevel: Great, thanks. When you're seeing a patient who's reporting to these paroxysmal uncontrollable movements, what kind of features of their story really tips you off that this might be a proximal movement disorder? Dr Mahajan: Often these patients have been diagnosed with functional neurological disorders and they come to us. But for me, whenever the patient and or the family talk about episodic movements, I think about these. Honestly, we must be aware that there is a possibility that the movements that the patients are reporting that you may not see in clinic. Maybe there are obvious movement disorders. Specifically, there's certain clues that you should always ask for in the history, for example, ask for the age of onset, a description of movements. Patients typically have videos or families have videos. You may not be able to see them in clinic. The regularity of frequency of these movements, how long the attacks are, is there any family history of or not? On the basis of triggers, whether, as I mentioned before, do these follow exercise? Prolonged exercise? Or neither of the above? What is the presentation in between attacks, which I think is a very important clinical clue. Your examination may be limited to videos, but it's important not just to examine the video which represents the patient during an attack, but in between attacks. That is important. And of course, I suspect we'll get to the treatment, but the treatment can follow just this part, the history and physical exam. It may be refined with further testing, including genetic testing. Dr Nevel: Great. On the note of genetic testing, when you do suspect a diagnosis of paroxysmal movement disorder, what are some key points for the provider to be aware of about genetic testing? How do we go about that? I know that there are lots of different options for genetic testing and it gets complicated. What do you suggest? Dr Mahajan: Traditionally, things were a little bit easier, right, because we had a couple of genes that have been associated with the robust movement disorders. So, genetic testing included single gene testing, testing for PRRT2 followed by SLC2A. And if these were negative, you said, well, this is not a genetic ideology for paroxysmal movement disorders. Of course, with time that has changed. There's an increase in known genes and variants. There is increased genetic entropy. So, the same genetic mutation may present with many phenotypes and different genetic mutations may present with the similar phenotype. Single gene testing is not a high yield approach. Overall genetic investigations for paroxysmal movement disorders use next generation sequencing or whole exome sequence panels which allow for sequencing of multiple genes simultaneously. The reported diagnostic yield with let's say next generation sequencing is around 3

Tics are movements or sounds that are quick, recurrent, and nonrhythmic. They fluctuate over time and can be involuntary or semivoluntary. Although behavioral therapy remains the first-line treatment, modifications to comprehensive behavioral intervention have been developed to make treatment more accessible. In this episode, Casey Albin, MD, speaks with Jessica Frey, MD, author of the article "Tourette Syndrome and Tic Disorders" in the Continuum® August 2025 Movement 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. Frey is an assistant professor of neurology, Movement Disorders Fellowship Program Director, and Neurology Student Clerkship Director at the Rockefeller Neuroscience Institute in the department of neurology at West Virginia University in Morgantown, West Virginia. Additional Resources Read the article: Tourette Syndrome and Tic Disorders 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 Transcript 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: Hi all, this is Dr Casey Albin. Today I'm interviewing Dr Jessica Frey about her article Tourette Syndrome and Tic Disorders, which appears in the August 2025 Continuum issue on movement disorders. Dr Frey, thank you so much for being here, and welcome to the podcast. I'd love for you to briefly introduce yourself to our audience. Dr Frey: Thank you for having me here today. My name is Jessica Frey, and I am a movement disorder specialist at West Virginia University. I'm also the movement disorder fellowship director, as well as the neurology clerkship student director. Dr Albin: Dr. Frey, I feel like this was one of the things I actually had no exposure to as a resident. For trainees that kind of want to get a better understanding of how these are managed, what kind of counseling you do, what kind of interventions you're using, how can they get a little bit more exposure? Dr Frey: That's a great question, and I actually had a similar experience to you. I did not see that many patients with Tourette syndrome while I was in my residency training. I got a lot more exposure during my fellowship training, and that's when I actually fell in love with that patient population, caring for them, seeing them be successful. I think it depends on the program that you're in. During the pediatric neurology rotation might be your best bet to getting exposure to patients with Tourette syndrome, since a lot of them are going to be diagnosed when they're quite young, and sometimes they'll even continue to follow through young adulthood in the pediatric neurology clinic. However, up to 20% of patients with Tourette syndrome will have persistent tics during adulthood. And so, I think it is important for neurology trainees to understand how to manage them, understand what resources are out there. So, if you have an interest in that, absolutely try to follow either in the pediatric neurology department, or if you have a movement disorder program that has a Tourette clinic or has a movement disorder specialist who has an interest in Tourette syndrome, definitely try to hang out with them. Get to know that patient population, and educate yourself as much as you're able to educate the patients as well. Dr Albin: Yeah, I think that's fantastic advice. You wrote a fantastic article, and it covers a lot of ground. And I think let's start at some of the basics. When I think of Tourette syndrome and tics, I think of Tourette syndrome having tics, but maybe not all patients who have tics have Tourette syndrome. And so, I was wondering, A, if you could confirm that's true; and then could you tell us a little bit about some of the diagnostic criteria for each of these conditions? Dr Frey: Sure. So, a tic is a phenomenological description. So basically, what you're seeing is a description of a motor or phonic tic, which is a particular type of movement disorder. Tourette syndrome is a very specific diagnosis, and the diagnostic criteria for Tourette syndrome at this point in time is that you need to have had at least one phonic tic and two or more motor tics over the course of at least a year before the age of eighteen. Dr Albin: Got it. So, there's certainly more specific and a lot more criteria for having Tourette syndrome. I was struck in reading your article how many myths there are surrounding Tourette syndrome and tic disorders kind of in general. What's known about the pathophysiology of Tourette syndrome, and what are some common misconceptions about patients who have this disorder? Dr Frey: Yeah, so I think that's a really excellent question because for so many years, Tourette syndrome and tic disorders in general were thought to be psychogenic in origin, even dating back to when they were first described. The history of Tourette syndrome is quite interesting in that, when Tourette---who, you know, it's named after---was working with Charcot, a lot of the initial descriptors were of actual case reports of patients who had more psychogenic descriptions, and eventually they became known as tic disorders as well. It wasn't until the discovery of Haldol and using Haldol as a treatment for tic disorders that people started to change their perception and say, okay, maybe there is actually a neurologic basis for Tourette syndrome. So, in terms of the pathophysiology, it's not completely known, but what we do know about it, we think that there is some sort of hyperactivity in the corticostriatal-thalamocortical circuits. And we think that because of this hyperactivity, it leads to the hyperactive movement disorder. We think similar circuitry is involved in conditions like OCD, or obsessive compulsive disorder; as well as ADHD, or attention deficit hyperactivity disorder. And because of that, we actually do tend to see an overlap between all three of these conditions in both individuals and families. Dr Albin: And hearing all of that, does this all come back to, sort of, dopamine and, sort of, behavioral motivation, or is it different than that? Dr Frey: It's probably more complex than just dopamine, but there is the thought that dopamine does play a role. And even one of the hypotheses regarding the pathophysiology is actually that these tics might start as habits, and then when the habits become more common, they actually reshape the dopaminergic pathways. And each time a tic occurs, there's a little bit of a dopaminergic reward. And so over time, that reshapes those hyperactive pathways and changes the actual circuitry of the brain, leading it to be not just a habit but part of their neurologic makeup. Dr Albin: It's fascinating to hear how that actually might play into our neural circuitry and, over time, rewire our brain. Fascinating. I mean, this is just so interesting how movement disorders play into such behavioral regulation and some comorbid conditions like ADHD and OCD. I thought it would be really helpful, maybe, to our listeners to kind of think through a case that I suspect is becoming more common. So, if it's okay with you, I'll present sort of a hypothetical. Dr Frey: Absolutely. Dr Albin: This is a father bringing in his seventeen-year-old daughter. She's coming into the clinic because she's been demonstrating, over the past four to six weeks, some jerking movement in her right arm. And it's happened multiple times a day. And it was a pretty sudden onset. She had not had any movement like this before, and then several weeks ago, started moving the right hand. And then it became even more disruptive: her right leg was involved, she had some scrunching her face. This is all happening at a time where she was dealing with some stress, maybe a little bit of applications around college that she was having a lot of anxiety about. How do you sort of approach this case if this is someone who comes to your office? Dr Frey: Sure. So, I think the first thing that you want to get is a good solid history, trying to understand, what is the origin of these abnormal movements and what led to the abnormal movements. Now, a key thing here is that in Tourette syndrome, and most physiologic tic syndromes, there's a pretty early onset. So, in Tourette syndrome, the expected age of onset is between the ages of five and seven years old. So, to have kind of acute new abnormal movements as a seventeen-year-old would be very unusual for a new-onset diagnosis of Tourette syndrome. However, there's a couple of things from the history that could help you. One would be, were there ever tics in the past? Because sometimes, when you think retrospectively, a lot of these patients might have had a simple eye-blinking tic or a coughing tic when they were a child. And perhaps they did have Tourette syndrome, a very mild case of it. But because the tics were never that pronounced, they never went to see anyone about it and it was never known that they had Tourette syndrome in the first place. If there is no history like that and the movements are completely new, out of the blue, of course you want to rule out anything acute that could be going on that could be causing that. Looking at the phenomenology of the movements can also be very helpful. When you're looking at abnormal tic movements, you would expect most cases of som

Ataxia is a neurologic symptom that refers to incoordination of voluntary movement, typically causing gait dysfunction and imbalance. Genetic testing and counseling can be used to identify the type of ataxia and to assess the risk for unaffected family members. In this episode, Katie Grouse, MD, FAAN, speaks with Theresa A. Zesiewicz, MD, FAAN, author of the article "Ataxia" in the Continuum® August 2025 Movement 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. Zesiewicz is a professor of neurology and director at the University of South Florida Ataxia Research Center, and the medical director at the University of South Florida Movement Disorders Neuromodulation Center at the University of South Florida and at the James A. Haley Veteran's Hospital in Tampa, Florida. Additional Resources Read the article: Ataxia 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 Theresa Zesiewicz about her article on ataxia, which appears in the August 2025 Continuum issue on movement disorders. Welcome to the podcast, and please introduce yourself to our audience.  Dr Zesiewicz: Well, thank you, Dr Grouse. I'm Dr Theresa Zesiewicz, otherwise known as Dr Z, and I'm happy to be here. Dr Grouse: I have to say, I really enjoyed reading your article. It was a really great refresher for myself as a general neurologist on the topic of ataxia and a really great reminder on a great framework to approach diagnosis and management. But I wanted to start off by asking what you feel is the key message that you hope our listeners will take away from reading your article. Dr Zesiewicz: Yes, so, thanks. I think one of the key messages is that there has been an explosion and renaissance of genetic testing in the past 10 years that has really revolutionized the field of ataxia and has made diagnosis easier for us, more manageable, and hopefully will lead to treatments in the future. So, I think that's a major step forward for our field in terms of genetic techniques over the last 10 years, and even over the last 30 years. There's just been so many diseases that have been identified genetically. So, I think that's a really important take-home message. The other take-home message is that the first drug to treat Friedreich's ataxia, called omaveloxolone, came about about two years ago. This was also a really landmark discovery. As you know, a lot of these ataxias are very difficult to treat. Dr Grouse: Now pivoting back to thinking about the approach to diagnosis of ataxia, how does the timeline of the onset of ataxia symptoms inform your approach? Dr Zesiewicz: The timeline is important because ataxia can be acute, subacute or chronic in nature. And the timeline is important because, if it's acute, it may mean that the ataxia took place over seconds to hours. This may mean a toxic problem or a hypoxic problem. Whereas a chronic ataxia can occur over many years, and that can inform more of a neurodegenerative or more of a genetic etiology. So, taking a very detailed history on the patient is very important. Sometimes I ask them, what is the last time you remember that you walked normal? And that can be a wedding, that can be a graduation. Just some timeline, some point, that the patient actually walked correctly before they remember having to hold onto a railing or taking extra steps to make sure that they didn't fall down, that they didn't have imbalance. That sometimes that's a good way to ask the patient when is the last time they had a problem. And they can help you to try to figure out how long these symptoms have been going on. Dr Grouse: I really appreciate that advice. I will say that I agree, it can sometimes be really hard to get patients to really think back to when they really started to notice something was different. So, I like the idea of referencing back to a big event that may be more memorable to them. Now, given that framework of, you know, thinking through the timeline, could you walk us through your approach to the evaluation of a patient who presents to your clinic with that balance difficulties once you've established that? Dr Zesiewicz: Sure. So, the first thing is to determine whether the patient truly has ataxia. So, do they have imbalance? Do they have a wide base gait? That's very important because patients come in frequently to your clinic and they'll have balance problems, but they can have knee issues or hip issues, neuropathy, something like that. And sometimes what we say to the residents and the students is, usually ataxia or cerebellar symptoms go together with other problems, like ocular problems are really common in cerebellar syndromes. Or dysmetria, pass pointing, speech disorder like dysarthria. So, not only do you need to look at the gait, but you should look at the other symptoms surrounding the gait to see if you think that the patient actually has a cerebellar syndrome. Or do they have something like a vestibular ataxia which would have more vertigo? Or do they have a sensory ataxia, which would occur if a person closes his eyes or has more ataxia when he or she is in the dark? So, you have to think about what you're looking at is the cerebellar syndrome. And then once we look to see if the patient truly has a cerebellar syndrome, then we look at the age, we look at---as you said before, the timeline. Is this acute, subacute, or chronic? And usually I think of ataxia as falling into three categories. It's either acquired, it's either hereditary, or it's neurodegenerative. It can be hereditary. And if it's not hereditary, is it acquired, or is it something like a multiple system atrophy or a parkinsonism or something like that? So, we try to put that together and start to narrow down on the diagnosis, thinking about those parameters. Dr Grouse: That's really a helpful way to think through it. And it is true, it can get very complex when patients come in with balance difficulties. There's so many things you need to think about, but that is a great way to think about it. Of course, we know that most people who come in to the Movements Disorders clinic are getting MRI scans of their brains. But I'm curious, in which cases of patients with cerebellar ataxia do you find the MRI to be particularly helpful in the diagnosis? Dr Zesiewicz: So, an MRI can be very important. Not always, but- so, something like multiple system atrophy type C where you may see a hot cross bun sign or a pontine hyperintensity on the T2-weighted image, that would be helpful. But of course, that doesn't make the diagnosis. It's something that may help you with the diagnosis. In FXTAS, which is fragile X tremor/ataxia syndrome, the patient may have the middle cerebellar peduncle sign or the symmetric hyperintensity in the middle cerebellar peduncles, which is often visible but not always. Something like Wernicke's, where you see an abnormality of the mammillary bodies. Wilson's disease, which is quite rare, T2-weighted image may show hyperintensities in the putamen in something like Wilson's disease. Those are the main MRI abnormalities, I think, with ataxia. And then we look at the cerebellum itself. I mean, that seems self-evident, but if you look at a sagittal section of the MRI and you see just a really significant atrophy of the cerebellum, that's going to help you determine whether you really have a cerebellar syndrome. Dr Grouse: That's really encouraging to hear a good message for all of us who sometimes feel like maybe we're missing something. It's good to know that information can always come up down the line to make things more clear. Your article does a great review of spinal cerebellar ataxia, but I found it interesting learning about the more recently described syndrome of SCA 27B. Would you mind telling us more about that and other really common forms of SCA that's good to keep in mind? Dr Zesiewicz: Sure. So, there are now 49 types of spinal cerebellar ataxia that have been identified. The most common are the polyglutamine repeat diseases: so, spinocerebellar ataxia type 3 or type 2, type 6, are probably the most common. One of the most recent spinocerebellar ataxias to be genetically identified and clinically identified is spinocerebellar ataxia 27B. This is caused by a GAA expansion repeat in the first intron of the fibroblast growth factor on chromosome 13. And the symptoms do include ataxia, eye problems, downbeat nystagmus, other nystagmus, vertical, and diplopia. It appears to be a more common form of adult-onset ataxia, and probably more common than was originally thought. It may account for a substantial number of ataxias, like, a substantial percentage of ataxias that we didn't know about. So, this was really a amazing discovery on SCA 27B. Dr Grouse: Now a lot of us I think feel a little anxious when we think about genetic testing for ataxia simply because there's so many forms, things are changing quickly. Do you have a rule of thumb or a kind of a framework that we can think of as we approach how we should be thinking about getting genetic testing for the subset of patients? Dr Zesiewicz: Sure. And I think that this is where age comes into play a lot. So, if you have a child who's 10, 11, or