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  • Facioscapulohumeral Muscular Dystrophy With Dr. Renatta Knox
    Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy, affecting individuals across the lifespan with variable severity. Advances in genetic understanding and therapeutic development have led to an era of promising disease-modifying strategies. In this episode, Katie Grouse, MD FAAN, speaks with Renatta N. Knox, MD, PhD, author of the article “Facioscapulohumeral Muscular Dystrophy” in the Continuum® October 2025 Muscle and Neuromuscular Junction Disorders issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Knox is an assistant professor of neurology in the Division of Pediatric Neurology and Neuromuscular Section at Washington University School of Medicine in St. Louis, Missouri. Additional Resources Read the article: Facioscapulohumeral Muscular Dystrophy Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN  Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Grouse: This is Dr Katie Grouse. Today I'm interviewing Dr Renatta Knox about her article on fascioscapulohumeral muscular dystrophy, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Welcome to the podcast, and please introduce yourself to our audience. Dr Knox: Hi Katie, thank you so much for the invitation for the audio interview. I'm looking forward to our conversation. As she mentioned, my name is Renata Knox. It's a pleasure to be here today. Dr Grouse: I'd like to start by asking, what is the key message that you hope your readers will take from your article? Dr Knox: I would say two things. The first is an appreciation and understanding of the unique genetic mechanism that leads to FSHD. And the second is the really exciting therapy landscape that we find ourselves in. So, we're hopeful that there will actually be disease-modifying therapies for FSHD soon. Dr Grouse: We're really looking forward to learning more about that. Now, before we get to that piece, could you just remind us of the clinical manifestations and features that are specific to FSHD? Dr Knox: So, one of the most unique things about FSHD that we see clinically is the pattern of weakness. So, one of the first features is that it's asymmetric. And then there are certain muscle groups that typically are affected, and that's partly where the name comes from. So, we see effects in the face, the limbs, the trunk; and so, those are some of the unique features that we see clinically. Dr Grouse: I'd love it if you could walk us through how you approach diagnosing a patient who presents with proximal weakness where FSHD is in your differential. Dr Knox: Yeah, it's a really great question. So, I would say it depends. So, I actually focus on FSHD in my clinical practice. So, many times patients are referred to me because there's a very high suspicion or there's a known family history of FSHD. So, that's one category of cases. I would say the other category of case is where it's, as you said, maybe more proximal weakness more broadly. Someone that’s before me who has a known family history, they really have some of the characteristic physical features---which I'm pretty attuned to, as this is, you know, part of my subspecialty---I'll actually go directly to FSHD genetic testing. And that is one of the unique features of this disease, that the next-generation sequencing panels that are typically used for some of our other muscle diseases, FSHD is not captured on those. So, we actually have to send targeted testing for FSHD to diagnose it. So, that is one category where, again, I have a very high suspicion either based on their clinical presentation and/or a known family history, then I will actually go directly to FSHD-targeted genetic testing. In the second case, where it is one of the conditions that I'm considering among others, I will do more broad testing. So, I will get a CK level to see if there's evidence of muscle breakdown. I'll likely also do one of the next-generation sequencing panels that we have access to, which will allow us to identify, potentially, one to two hundred potential muscle diseases. And then again, if FSHD is higher on my differential in that second group of patients, then I will also send targeted FSHD-specific testing. Dr Grouse: That's really helpful. And I'm wondering if you have any thoughts about common pitfalls that you've seen when providers are trying to work this up? Dr Knox: I don't know if I would say pitfalls. I think I would acknowledge that it's challenging. My subspecialty training in neuromuscular medicine and also gene therapy. And so FSHD is pretty high on my radar. But I would say in neurology in general---and then, you know, the general medical population---,it really isn't something that many people are seeing. So, I would say what patients will communicate to us sometimes is some frustration that maybe it took time to make the diagnosis, but I just have a deep understanding that it's not something that is on many people's radars. And I think, again, it's tricky because it's not picked up on these next-generation sequencing panels, which many of us can send pretty easily. It will be missed. And I will say the biggest pitfall is, again, if you're not thinking about it and you don't send that testing, you actually- it's very difficult to diagnose it. Dr Grouse: Thank you so much for highlighting that. I think there are many people who are not aware that those different panels really aren't picking that up and that they have to test specifically. So, I think that's a great thing for all of us to keep in mind. Are there any tips or tricks to the diagnosis, other than the genetic issues that you mentioned, that sometimes can really bring this diagnosis to the forefront? Dr Knox: I think things that really tip me off to having a higher suspicion for FSHD is facial weakness that we can detect on our exam. Scapular winging---again, there's a small subset of disorders which can impact that. Someone who's presenting with foot drop, you know, with facial weakness, I think definitely about FSHD more. Also, clinically, kind of the presentation or things that they're beginning to have difficulty with is a tip-off. So, if someone is an athlete, like, they're a volleyball player or basketball player and they say, oh, I'm having difficulties, you know, with movements that require them to elevate their arm, which can be a sign of the shoulder weakness that we classically see. Or someone who says, oh, I'm having a harder time shampooing my hair or combing my hair. So those can be tip-offs again, which are basically referencing the type of weakness that they have. Another feature of FSHD which isn't necessarily as broadly appreciated is that pain and fatigue are very common. So, if someone is coming in and saying, actually, I also have a significant amount of fatigue as well or a lot of pain, that's something that can tip me off to it. Hearing loss is something that we can also see in up to 20% of patients with FSHD. So, if they are having those symptoms or saying they're ringing in their ears, these are some things that will make me begin to think about it more. Dr Grouse: Oh, really helpful. I also found it really fascinating reading some of the very FSHD-specific clinical signs, some interesting- some diagrams and pictures as well, that are very specific to the pattern of weakness that develops in FSHD. So, I encourage our listeners to check that out. But are there any highlights from those little clinical pearls that you'd like to point out? Dr Knox: I think the poly-hill sign---so, these are these literal hills that we can see in the shoulders of patients with FSHD---is pretty classic. Popeye arms, which is this older term that we still use that has to do with which muscle groups are preserved versus those that have atrophy. So that's a common feature. And then I would say, really, the asymmetry is something that is a unique feature in FSHD. And again, we did our best to provide good representative images. So again, as you mentioned, Katie, I would really encourage people to look at those images and then think about cases that they may have seen and how similar they are so they can begin to recognize those signs as well. Dr Grouse: Now going back to the genetic topic, the complex genetic underpinnings of FSHD are really well-explained in your article; and again, worth taking a look at to remind ourselves of everything that's of that pathology. Now, I was wondering though, if you could give us a brief overview of how we should approach genetic testing in a suspected case of FSHD? You mentioned some specific panels, but it does sound like there's some more complexity to it as well. Dr Knox: Yes, and I'll just kind of briefly explain that complexity. Part of the thing that we're detecting in the genetic testing is the repeat number. And so, we're actually looking for a contraction in a repeat number. So, not an expansion, which were typical for some of the diseases that we think about, the trinucleotide repeat disorders. And this is why it’s not captured in the next-generation sequencing panels, because they do not currently have the ability to do that. And so, again, what the type of testing that I do really depends on my suspicion. So again, if my suspicion is very high for FSHD---they have a family history, they have the classic features---then I will actually go directly to an FSHD-specific testing, which is available from various sources. If, again, it's among different things that I'm thinking about, I will get a CK lab. I typically will also send a next-generation sequencing panel specific for muscle diseases, perhaps muscular dystrophy; again, depending on what I'm thinking about. And then I will also send in a specific FSHD genetic test as well. People are beginning to use whole-genome sequencing, which is capturing some of our true nucleotide repeat disorders and becoming more comprehensive. So, my hope is that as that becomes more standard of care---like, whole-exome sequencing can be gotten pretty routinely now---that it may be easier for us to make some of these diagnoses. Dr Grouse: Well, that's really helpful, and thanks for that overview. Now another thing that you mentioned that I thought was really interesting in your article was that patients with, you know, history of FSHD, perhaps in the family, who are pregnant and want to screen for this disease would not be able to use sort of the more common screening tests like cell-free DNA testing and may have to go to other means to do that. What is generally their route to this type of testing? Dr Knox: Yeah, great question, and really important question for family planning purposes, and it definitely comes up in clinical practice. And so again, because of the unique genetics of FSHD, you actually have to do invasive genetic testing currently to be able to test it. And so that's, you know, amnio or chorio, and then send it to a lab that can perform, again, FSHD-specific testing on the samples that are presented. And there are obviously labs that are capable of doing that and centers that are capable of doing that, but it is not picked up on the cell-free DNA panels that are being very routinely used. You or your provider has to be thinking about it to send that specific testing, similar to our patients that come into clinic and have not yet been diagnosed. Dr Grouse: Once you have the diagnosis, what are our options for therapy? I think it sounds like at this current time, it looks to be mostly supportive. What are some of the supportive care options we should keep in mind? Dr Knox: Yes, so that is definitely accurate. Care today is supportive, but again, we're very excited about the clinical trial and therapy landscape for FSHD. So, I work very closely with my physical therapy colleagues that are in clinic with me. So, we work very closely with physical and occupational therapists to help with supportive measures, adaptive measures, doing assessments, helping our patients to be able to move and exercise safely and effectively. As I mentioned, pain is very common in FSHD and so we can treat that with medications. The most common medication that we use to treat for pain in FSHD are NSAIDs. And then other than that it's really, you know, supportive measures. Do they need to see other subspecialists? There are some surgical options. Those are used very rarely to help with some of the scapular weakness, but typically it's physical therapy, occupational therapy, supportive devices. We treat the pain as we're able to, and then we work with other subspecialists to screen, monitor and support our patients to the best of our ability. Dr Grouse: Well, without further ado, I'd love to hear more about what's coming down the pipeline in clinical trials. What can we look forward to seeing, hopefully, in future years to treat these patients? Dr Knox: Yes. And so, this is actually what got me interested in the neuromuscle space in general is that, because we now for many years have known the genetic cause of many of these disorders as well as some of the underlying mechanisms, we can actually use advances in therapeutics to do what we call targeted therapies. So, rather than treating symptoms or indirect methods or doing kind of broad drug screens---which, again, still do take place and still do have their place---we actually can target mechanisms directly. And so, we know that the underlying biology of FSHD is due to this protein called DUX4 being expressed when it should not be. So, it's what we call a toxic gain of function. And so, the targeted way to address this is to suppress DUX4 expression. And so, kind of broadly speaking, what we're really excited about are a couple of products that are currently in clinical trials right now that actually caused DUX4 suppression to be suppressed. And again, these are targeted pathways. And so, again, the hope is that by doing that, we can hopefully slow the progression of the disease, potentially stop progression of the disease, and potentially reverse. Again, we don't know if that might be possible, but that is one of the hopes. Dr Grouse: Well, that's really exciting, and I know we're all looking forward to more coming down the pipeline soon, and hopefully more things that can really offer some exciting treatments for our patients with this condition. Now, a little more deep-dive into our patients who are diagnosed. You've reviewed some of the treatments currently available and hopefully may someday soon be available. Are there other things that we should be keeping in mind in this population? For instance, screenings that we should be doing for other extramuscular manifestations that we need to be thinking about? Dr Knox: I will answer that question two ways. I think something that's very important to acknowledge is the impact that these diagnoses and these conditions have on our patient practically, psychologically. One of the other unique features of FSHD is, it's autosomal-dominant. So, if it is in a family, you can have many family members who are affected, but the variability is very high. And so, you can have in the same family someone who is wheelchair-dependent, and someone else in the family with the same underlying genetics who has no signs or symptoms or is very mildly affected. And that is something that is definitely challenging for our families and patients to navigate if they're very different than their family members with the same condition. And just navigating the world with a condition that, you know, can be physically debilitating and cause changes to what they're able to do or not able to do, progression is something that's very difficult to handle. So, I think that's one set of things. And we try our best, you know, with my team and my other colleagues in the space, to support our families and patients in the best way that we can. Secondly, there is very important screening that needs to be done for this condition. So, one of the things- and the current guidelines which are actually being updated, the last update was in 2015 is all patients that undergo pulmonary function testing or PFTs. And so that's something we do at baseline and we do at least annually in my practice. Young kids who are presenting very early or patients with certain genetics that we know are more predisposed to extra muscular manifestations, we recommend screening for hearing, which is one of the manifestations, and ophthalmologic exam to look for retinovascular changes, which is one of the manifestations as well. Those are the more common ones that are typically done. There's also some evidence in pediatric patients with very severe manifestations that there may be some cognitive impacts, learning impacts. And so, that is something we're also thinking about screening and supporting our patients in that way. And again, we typically work with these patients in a multidisciplinary team depending on what manifestations and the degrees to which they're impacted by the disorder. Dr Grouse: Thank you so much for that answer. I think a lot of us forget sometimes when we get really focused on what can we do now, that we forget to kind of stop and reflect on sort of the more holistic approach. How is this affecting the patient? How is this affecting the patient's family dynamic, and what other ways are they going through life with this condition that we need to be thinking about? So, I appreciate you bringing that up. I wanted to ask, sort of based on what you're talking about and what you mentioned already, you happened to mention that what initially drew you that to this work was your interest in some of the really exciting breakthroughs in the field. Well, was there anything else that drew you to, specifically, congenital neuromuscular diseases, and FSHD in particular? Dr Knox: I'm a physician scientist by training, and so I would describe myself also as a molecular biologist. So, I love getting into the nitty gritties of disease mechanisms, what genes are doing in bodies, how they function. And so, as I mentioned earlier, in the neuromuscle space, we've known for many years the genetic cause of many of these disorders and have done great, you know, mechanistic work to kind of define why we see the disease. And then now we're at this intersection of that knowledge marrying with these really novel therapeutic approaches, gene therapy approaches, being able to intersect and then in very creative ways actually target diseases very directly. And so, I would say it really is the combination of those two things. FSHD has a really fascinating unique biology, which again, we encourage everyone to read about more in the article. That really drew me to it. I'm very interested in gene regulation, transcription. This is one of the underlying mechanisms that is gone awry in the disorder, and then that being married to advances in therapeutics. So, you could wed those two pieces of information and actually meaningfully impact patient 's lives. And again, that's the real privilege and honor to witness is how these therapies can transform lives. And I saw it happened with this one case for this one disorder when I was a resident where there was no treatment. Young children, unfortunately, would not survive the disease. And then I saw the therapy come be in development and literally change the trajectory. And this is what we're very hopeful for in the FSHD space, that wedding, this wonderful basic science research, translational research, companies working together to develop these therapies that can transform lives. It is just so beautiful to witness and see, and it's something that I get to do. You know, it's a part of my job, so it's a real privilege. Dr Grouse: Well, I have to say, it's really inspiring hearing you talk about it. And I imagine that many neurologists-in-training who are listening to this may be inspired as well and may be convinced to go into this field for that very reason. So, thank you so much for sharing all of this information with us today. I learned a lot, and I think all of our listeners have too. Dr Knox: Thank you. It's really been a pleasure. Dr Grouse: Again, today I've been interviewing Dr Renatta Knox about her article on fascioscapulohumeral muscular dystrophy, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.
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  • A Pattern Recognition Approach to Myopathy With Dr. Margherita Milone
    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: You are correct. Dr Albin: Great. So, coming back to our patients, you know, she says that she has this dysphasia. How do bulbar involvement or extraocular eye movement involvement, how do those help narrow your differential? And what sort of disorders are you thinking of for patients who may have that bulbar or extraocular muscle involvement? Dr Milone: Regarding dysphagia, that can occur in the setting of acquired myopathies relatively frequent; for example, in inclusion body myositis or in other forms of inflammatory myopathy. Your patient, I believe, was in their forties, so it's a little bit too young for inclusion body myositis. Involvement of the extraocular muscles is usually much more common in genetic muscle diseases and much less frequent in hereditary muscle disease. So, if there is involvement of the extraocular muscles, and if there is a dysphagia, and if there is a proximal weakness, you may think about oculopharyngeal muscular dystrophy, for example. But obviously, in a patient who has only six months of history, we have to pay attention of the degree of weakness the patient has developed since the symptom onset. Because if the degree of weakness is mild, yes, it could still be a genetic or could be an acquired disease. But if we have a patient who, in six months, from being normal became unable to climb stairs, then we worry much more about an acquired muscle disease. Dr Albin: That's really helpful. So, the time force of this is really important. And when you're trying to think about, do I put this in sort of a hereditary form of muscle disease, thinking more of an indolent core, something that's going to be slowly progressive versus one of those inflammatory or necrotizing pathologies, that's going to be a much more quick onset, rapidly progressive, Do I have that right? Dr Milone: In general, the statement is correct. They tend, acquired muscle disease, to have a faster course compared to a muscular dystrophy. But there are exceptions. There have been patients with immune mediated necrotizing myopathy who have been misdiagnosed as having limb-girdle muscular dystrophy just because the disease has been very slowly progressive, and vice versa. There may be some genetic muscle diseases that can present in a relatively fast way. And one of these is a lipid storage myopathy, where some patients may develop subacutely weakness, dysphagia, and even respiratory difficulties. Dr Albin: Again, I'm hearing you say that we really have to have an open mind that myopathies can present in a whole bunch of different ways with a bunch of different phenotypes. And so, keeping that in mind, once you suspect someone has a myopathy, looking at the testing from the EMG perspective and then maybe laboratory testing, how do you use that information to guide your work up? Dr Milone: The EMG has a crucial role in the diagnosis of muscle diseases. Because, as we said earlier, weakness could be the result of muscle disease or other form of neuromuscular disease. If the EMG study will show evidence of muscle disease supporting your diagnostic hypothesis, now you have to decide, is this an acquired muscle disease or is this a genetic muscle disease? If you think that, based on clinical history of, perhaps, subacute pores, it is more likely that the patient has an acquired muscle disease, then I would request a muscle biopsy. The muscle biopsy will look for structural abnormalities that could help in narrowing down the type of muscle disease that the patient has. Dr Albin: That's really helpful. When we're sending people to get muscle biopsies, are there any tips that you would give the listeners in terms of what site to biopsy or what site, maybe, not to biopsy? Dr Milone: This is a very important point. A muscle biopsy has the highest diagnostic yield if it's done in a muscle that is weak. And because muscle diseases can result in proximal or distal weakness, if your patient has distal weakness, you should really biopsy a distal muscle. However, we do not wish to biopsy a muscle that is too weak, because otherwise the biopsy sample will result just in fibrous and fatty connected tissue. So, we want to biopsy a muscle that has mild to moderate weakness. Dr Albin: Great. So, a little Goldilocks phenomenon: has to be some weak, but not too weak. You got to get just the right feature there. I love that. That's a really good pearl for our listeners to take. What about on the flip side? Let's say you don't think it's an acquired a muscular disease. How are you handling testing in that situation? Dr Milone: If you think the patient has a genetic muscle disease, you pay a lot of attention to the distribution of the weakness. Ask yourself, what is the best pattern that represent the patient's weakness? So, if I have a patient who has facial weakness, dysphagia, muscle cramping, and then on examination represent myotonia, then at that point we can go straight to a genetic test for myotonic dystrophy type one. Dr Albin: That's super helpful. Dr Milone: So, you request directly that generic test and wait for the result. If positive, you will have proof that your diagnostic hypothesis was correct. Dr Albin: You're using the genetic testing to confirm your hypothesis, not just sending a whole panel of them. You're really informing that testing based on the patient's pattern of weakness and the exam findings, and sometimes even the EMG findings as well. Is that correct? Dr Milone: You are correct, and ideally, yes. And this is true for certain muscle diseases. In addition to myotonic dystrophy type one, for example, if you have a patient who has fascial scapulohumeral muscular weakness, you can directly request a test for FSHD. So, the characterization of the clinical phenotype is crucial before selecting the genetic test for diagnosis. Dr Albin: Wonderful. Dr Milone: However, this is not always possible, because you may have a patient who has just a limb-girdle weakness, and the limb-girdle weakness can be limb-girdle muscular dystrophy. But we know that there are many, many types of limb-girdle muscular dystrophies. Therefore, the phenotype is not sufficient to request specific genetic tests for one specific form of a limb-girdle muscular dystrophy. And in those cases, more complex next-generation sequencing panels have a higher chance of providing the answer. Dr Albin: Got it, that makes sense. So, sometimes we're using a specific genetic test; sometimes, it is unfortunate that we just cannot narrow down to one disease that we might be looking for, and we may need a panel in that situation. Dr Milone: You are correct. Dr Albin: Fantastic. Well, as we wrap up, is there anything on the horizon for muscular disorders that you're really excited about? Dr Milone: Yes, there are a lot of exciting studies ongoing for gene therapy, gene editing. So, these studies are very promising for the treatment of genetic muscle disease, and I'm sure there will be therapists that will improve the patient's quality of life and the disease outcome. Dr Albin: It's really exciting. Well, thank you again. Today I've been interviewing Dr Margarita Malone on her article on a pattern recognition approach to myopathy, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Be sure to check out Continuum Audio episodes from this and other issues, and thank you to our listeners for joining us today. And thank you, Dr Milone. Dr Milone: Thank you, Casey. Very nice chatting with you about this. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.
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  • Multidisciplinary Treatment for Functional Movement Disorder With Dr. Jon Stone
    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 normally say. If you follow the normal- what goes wrong is that people don't follow the normal rules. The patient picks up on this. What's going on here? This doctor's telling me what I don't have and then they're starting to talk about some reason why I've got this, like stress, even though I don't- haven't been told what it is yet. You do the normal rules, give it a name, a name that you're comfortable with, preferably as specific as possible: functional tremor, functional dystonia. And then do what you normally do, which is explain to the patient why you think it's this. So, if someone's got Parkinson's, you say, I think you've got Parkinson's because I noticed that you're walking very slowly and you've got a tremor. And these are typical features of Parkinson. And so, you're talking about the features. This is where I think it's the most useful thing that you can do. And the thing that I do when it goes really well and it's gone badly somewhere else, the thing I probably do best, what was most useful, is showing the patient their signs. I don't know if you do that, Gordon, but it's maybe not something that we're used to doing. Dr Smith: Wait, maybe you can talk more about that, and maybe, perhaps, give an example? Talk about how that impacts treatment. I was really impressed about the approach to physical therapy, and treatment of patients really leverages the physical examination findings that we're all well-trained to look for. So maybe explore that a little bit. Dr Stone: Yeah, I think absolutely it does. And I think we've been evolving these thoughts over the last ten or fifteen years. But I started, you know, maybe about twenty years ago, started to show people their tremor entrainment tests. Or their Hoover sign, for example; if you don't know Hoover sign, weakness of hip extension, that comes back to normal when the person's flexing their normal leg, their normal hip. These are sort of diagnostic tricks that we had. Ahen I started writing articles about FND, various senior neurologists said to me, are you sure you should write this stuff down? Patients will find out. I wrote an article with Marc Edwards called “Trick or Treat in Neurology” about fifteen years ago to say that actually, although they're they might seem like tricks, there really are treats for patients because you're bringing the diagnosis into the clinic room. It's not about the normal scan. You can have FND and MS. It's not about the normal scan. It's about what you're seeing in front of you. If you show that patient, yes, you can't move your leg. The more you try, the worse it gets. I can see that. But look, lift up your other leg. Let me show you. Can you see now how strong your leg is? It's such a powerful way of communicating to the patient what's wrong with them diagnostically, giving them that confidence. What it's also doing is showing them the potential for improvement. It's giving them some hope, which they badly need. And, as we'll perhaps talk about, the physio treatment uses that as well because we have to use a different kind of physio for many forms of functional movement disorder, which relies on just glimpsing these little moments of normal function and promoting them, promoting the automatic movement, squashing down that abnormal pattern of voluntary movement that people have got with FND. Dr Smith: So, maybe we can talk about that now. You know, I've got a bunch of other questions to ask you about mechanism and stuff, but let's talk about the approach to physical therapy because it's such a good lead-in and I always worry that our physical therapists aren't knowledgeable about this. So, maybe some examples, you have some really great ones in the article. And then words of wisdom for us as we're engaging physical therapists who may not be familiar with FND, how to kind of build that competency and relationship with the therapist with whom you work. Dr Stone: Some of the stuff is the same. Some of the rehabilitation ideas are similar, thinking about boom and bust activity, which is very common in these patients, or grading activity. That's similar, but some of them are really different. So, if you have a patient with a stroke, the physiotherapist might be very used to getting that person to think and look at their leg to try and help them move, which is part of their rehabilitation. In FND, that makes things worse. That's what's happening in Hoover sign and tremor entrainment sign. Attention towards the limb is making it worse. But if the patient's on board with the diagnosis and understands it, they'll also see what you need to do, then, in the physio is actively use distraction in a very transparent way and say to the patient, look, I think if I get you to do that movement, and I'll film you, I think your movement's going to look better. Wouldn't that be great if we could demonstrate that? And the patient says, yeah, that would be great. We're kind of actively using distraction. We're doing things that would seem a bit strange for someone with other forms of movement disorder. So, the patients, for example, with functional gait disorders who you discover can jog quite well on a treadmill. In fact, that's another diagnostic test. Or they can walk backwards, or they can dance or pretend that they're ice skating, and they have much more fluid movements because their ice skating program in their brain is not corrupted, but their normal walking program is. So, can you then turn ice skating or jogging into normal walking? It's not that complicated, I think. The basic ideas are pretty simple, but it does require some creativity from whoever's doing the therapy because you have to use what the patient's into. So, if the patient used to be a dancer- we had a patient who was a, she was really into ballet dancing. Her ballet was great, but her walking was terrible. So, they used ballet to help her walk again. And that's incredibly satisfying for the therapist as well. So, if you have a therapist who's not sure, there are consensus recommendations. There are videos. One really good success often makes a therapist want to do that again and think, oh, that's interesting. I really helped that patient get better. Dr Smith: For a long time, this has been framed as a mental health issue, conversion disorder, and maybe we can talk a little bit about early life of trauma as a risk factor. But, you know, listening to you talk, it sounds like a brain network problem. Even the word “functional”, to me, it seems a little judgmental. I don't know if this is the best term, but is this really a network problem? Dr Stone: The word “functional”, for most neurologists, sounds judgmental because of what you associate it with. If you think about what the word actually is, it's- it does what it says on the tin. There's a disordered brain function. I mean, it's not a great word. It's the least worst term, in my view. And yes, of course it's a brain network problem, because what other organ is it going to be? You know, that's gone wrong? When software brains go wrong, they go wrong in networks. But I think we have to be careful not to swing that pendulum too far to the other side because the problem here, when we say asking the question, is this a mental health problem or a neurological one, we're just asking the wrong question. We're asking a question that makes no sense. However you try and answer that, you're going to get a stupid answer because the question doesn't make sense. We shouldn't have those categories. It's one organ. And what's so fascinating about FND---and I hope what can incite your sort of curiosity about it---is this disorder which defies this categorization. You see some patients with it, they say, oh, they've got a brain network disorder. Then you meet another patient who was sexually abused for five years by their uncle when they were nine, between nine and fourteen; they developed an incredibly strong dissociative threat response into that experience. They have crippling anxiety, PTSD, interpersonal problems, and their FND is sort of somehow a part of that; part of that experience that they've had. So, to ignore that or to deny or dismiss psychological, psychiatric aspects, is just as bad and just as much a mistake as to dismiss the kind of neurological aspects as well. Dr Smith: I wonder if this would be a good time to go back and talk a little bit about a concept that I found really interesting, and that is FND as a prodromal syndrome before a different neurological problem. So, for instance, FND prodromal to Parkinson's disease. Can you talk to us a little bit about that? I mean, obviously I was familiar with the fact that patients who have nonepileptic seizurelike events often have epileptic seizures, but the idea of FND ahead of Parkinson's was new to me. Dr Stone: So, this is definitely a thing that happens. It's interesting because previously, perhaps, if you saw someone who was referred with a functional tremor---this has happened to me and my colleagues. They send me some with a functional tremor. By the time I see them, it's obvious they've got Parkinson's because it's been a little gap. But it turns out that the diagnosis of functional tremor was wrong. It was just that they've developed that in the prodrome of Parkinson's disease. And if you think about it, it's what you'd expect, really, especially with Parkinson's disease. We know people develop anxiety in the prodrome of Parkinson's for ten, fifteen years before it's part of the prodrome. Anxiety is a very strong risk factor for FND, and they're already developing abnormalities in their brain predisposing them to tremor. So, you put those two things together, why wouldn't people get FND? It is interesting to think about how that's the opposite of seizures, because most people with comorbidity of functional seizures and epilepsy, 99% of the time the epilepsy came first. They had the experience of an epileptic seizure, which is frightening, which evokes strong threat response and has somehow then led to a recapitulation of that experience in a functional seizure. So yeah, it's really interesting how these disorders overlap. We're seeing something similar in early MS where, I think, there's a slight excess of functional symptoms; but as the disease progresses, they often become less, actually. Dr Smith: What is the prognosis with the types of physical therapy? And we haven't really talked about psychological therapy, but what's the success rate? And then what's the relapse rate or risk? Dr Stone: Well, it does depend who they're seeing, because I think---as you said---you're finding difficult to get people in your institution who you feel are comfortable with this. Well, that's a real problem. You know, you want your therapists to know about this condition, so that matters. But I think with a team with a multidisciplinary approach, which might include psychological therapy, physio, OT, I think the message is you can get really good outcomes. You don't want to oversell this to patients, because these treatments are not that good yet. You can get spectacular outcomes. And of course, people always show the videos of those. But in published studies, what you're seeing is that most studies of- case series of rehabilitation, people generally improve. And I think it's reasonable to say to a patient, that we have these treatments, there's a good chance it's going to help you. I can't guarantee it's going to help you. It's going to take a lot of work and this is something we have to do together. So, this is not something you're going to do to the patient, they're going to do it with you. Which is why it's so important to find out, hey, do they agree with you with the diagnosis? And check they do. And is it the right time? It's like when someone needs to lose weight or change any sort of behavior that they've just become ingrained. It's not easy to do. So, I don't know if that helps answer the question. Dr Smith: No, that's great. And you actually got right where I was wanting to go next, which is the idea of timing and acceptance. You brought this up earlier on, right? So, sometimes patients are excited and accepting of having an affirmative diagnosis, but sometimes there's some resistance. How do you manage the situation where you're making this diagnosis, but a patient's resistant to it? Maybe they're fixating on a different disease they think they have, or for whatever reason. How do you handle that in terms of initiating therapy of the overall diagnostic process? Dr Stone: We should, you know, respect people's rights to have whatever views they want about what's wrong with them. And I don't see my job as- I'm not there to change everyone's mind, but I think my job is to present the information to them in a kind of neutral way and say, look, here it is. This is what I think. My experience is, if you do that, most people are willing to listen. There are a few who are not, but most people are. And most of the time when it goes wrong, I have to say it's us and not the patients. But I think you do need to find out if they can have some hope. You can't do rehabilitation without hope, really. That's what you're looking for. I sometimes say to patients, where are you at with this? You know, I know this is a really hard thing to get your head around, you've never heard of it before. It's your own brain going wrong. I know that's weird. How much do you agree with it on a scale of naught to ten? Are you ten like completely agreeing, zero definitely don't? I might say, are you about a three? You know, just to make it easy for them to say, no, I really don't agree with you. Patients are often reluctant to tell you exactly what they're thinking. So, make it easy for them to disagree and then see where they're at. If they're about seven, say, that's good. But you know, it'd be great if you were nine or ten because this is going to be hard. It's painful and difficult, and you need to know that you're not damaging your body. Those sort of conversations are helpful. And even more importantly, is it the right time? Because again, if you explore that with people, if a single mother with four kids and, you know, huge debts and- you know, it's going to be very difficult for them to engage with rehab. So, you have to be realistic about whether it's the right time, too; but keep that hope going regardless. Dr Smith: So, Jon, there's so many things I want to talk to you about, but maybe rather than let me drive it, let me ask you, what's the most important thing that our listeners need to know that I haven't asked you about? Dr Stone: Oh God. I think when people come and visit me, they sometimes, let's go and see this guy who does a lot of FND, and surely, it’ll be so easy for him, you know? And I think some of the feedback I've had from visitors is, it's been helpful to watch, to see that it’s difficult for me too. You know, this is quite hard work. Patients have lots of things to talk about. Often you don't have enough time to do it in. It's a complicated scenario that you're unravelling. So, it's okay if you find it difficult work. Personally, I think it's very rewarding work, and it's worth doing. It's worth spending the time. I think you only need to have a few patients where they've improved. And sometimes that encounter with the neurologist made a huge difference. Think about whether that is worth it. You know, if you do that with five patients and one or two of them have that amazing, really good response, well, that's probably worth it. It's worth getting out of bed in the morning. I think reflecting on, is this something you want to do and put time and effort into, is worthwhile because I recognize it is challenging at times, and that's okay. Dr Smith: That's a great number needed to treat, five or six. Dr Stone: Exactly. I think it's probably less than that, but… Dr Smith: You're being conservative. Dr Stone: I think deliberately pessimistic; but I think it's more like two or three, yeah. Dr Smith: Let me ask one other question. There's so much more for our listeners in the article. This should be required reading, in my opinion. I think that of most Continuum, but this, I really truly mean it. But I think you've probably inspired a lot of listeners, right? What's the next step? We have a general or comprehensive neurologist working in a community practice who's inspired and wants to engage in the proactive care of the FND patients they see. What's the next step or advice you have for them as they embark on this? It strikes me, like- and I think you said this in the article, it's hard work and it's hard to do by yourself. So, what's the advice for someone to kind of get started? Dr Stone: Yeah, find some friends pretty quick. Though, yeah, your own enthusiasm can take you a long way, you know, especially with we've got much better resources than we have. But it can only take you so far. It's really particularly important, I think, to find somebody, a psychiatrist or psychologist, you can share patients with and have help with. In Edinburgh, that's been very important. I've done all this work with the neuropsychiatrist, Alan Carson. It might be difficult to do that, but just find someone, send them an easy patient, talk to them, teach them some of this stuff about how to manage FND. It turns out it's not that different to what they're already doing. You know, the management of functional seizures, for example, is- or episodic functional movement disorders is very close to managing panic disorder in terms of the principles. If you know a bit about that, you can encourage people around you. And then therapists just love seeing these patients. So, yeah, you can build up slowly, but don't- try not to do it all on your own, I would say. There's a risk of burnout there. Dr Smith: Well, Dr Stone, thank you. You don't disappoint. This has really been a fantastic conversation. I really very much appreciate it. Dr Stone: That's great, Gordon. Thanks so much for your time, yeah. Dr Smith: Well, listeners, again, today I've had the great pleasure of interviewing Dr Jon Stone about his article on the multidisciplinary treatment for functional neurologic disorder, which he wrote with Dr Alan Carson. This article appears in the August 2025 Continuum issue on movement disorders. Please be sure to check out Continuum Audio episodes from this and other issues. And listeners, thank you once again for joining us today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. We hope you've enjoyed this subscriber-exclusive interview. Thank you for listening.
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  • Paroxysmal Movement Disorders With Dr. Abhimanyu Mahajan
    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 35 to 50 percent. Specific labs at centers have developed their own panels which may improve the yield of course. In children, microarray may be considered, especially the presentation includes epilepsy or intellectual disability because copy number variations may not be detected by a whole exome sequencing or next generation sequencing. Overall, I will tell you that I'm certainly not an expert in genetics, so whenever you're considering genetic testing, if possible, please utilize the expertise of a genetic counsellor. Families want to know, especially as an understanding of the molecular underpinnings and knowledge about associated mutations or variations keeps on expanding. We need to incorporate their expertise. A variant of unknown significance, which is quite a common result with genetic testing, may not be a variant of unknown significance next year may be reclassified as pathogenic. So, this is extremely important. Dr Nevel: Yeah. That's such a good point. Thank you. And you just mentioned that there are some genetic mutations that can lead to multiple different phenotypes. Seemingly similar phenotypes can be associated with various genetic mutations. What's our understanding of that? Do we have an understanding of that? Why there is this seeming disconnect at times between the specific genetic mutation and the phenotype? Dr Mahajan: That is a tough question to answer for all paroxysmal movement disorders because the answer may be specific to a specific mutation. I think a great example is the CACNA1A mutation. It is a common cause of episodic ataxia type 2. Depending on when the patient presents, you can have a whole gamut of clinical presentations. So, if the patient is 1 year old, the patient can present with epileptic encephalopathy. Two to 5 years, it can be benign paroxysmal torticollis of infancy. Five to 10 years, can present with learning difficulties with absence epilepsy and then of course later, greater than 10 years, with episodic ataxia (type) 2 hemiplegic migraine and then a presentation with progressive ataxia and hemiplegic migraines has also been reported. So not just episodic progressive form of ataxia has also been reported. I think overall these disorders are very rare. They are even more infrequently diagnosed than their prevalence. As such, the point that different genetic mutations present with different phenotypes, or the same genetic mutation I may present with different phenotypes could also represent this part. Understanding of the clinical presentation is really incomplete and forever growing. There's a new case report or case series every other month, which makes this a little bit challenging, but that's all the more reason for learning about them and for constant vigilance for patients who show up to our clinic. Dr Nevel: Yeah, absolutely. What is our current understanding of the associated pathophysiology of these conditions and the pathophysiology relating to the genetics? And then how does that relate to the treatment of these conditions? Dr Mahajan: So, a number of different disease mechanisms have been proposed. Traditionally, these were all thought to be ion channelopathies, but a number of different processes have been proposed now. So, depending on the genetic mutation that you talk about. So certain mutations can involve ion channels such as CACMA1A, ATP1A3. It can involve solute carriers, synaptic vesicle fusion, energy metabolism such as ECHS1, synthesis of neurotransmitters such as GCH1. So, there are multiple processes that may be involved. I think overall for the practicing clinician such as me, I think there is a greater need for us to understand the underlying genetics and associated phenotypes and the molecular mechanisms specifically because these can actually influence treatment decisions, right? So, you mentioned that specific genetic testing understanding of the underlying molecular mechanism can influence specific treatments. As an example, a patient presenting with proximal nocturnal dyskinesia with mutation in the ADCY5 gene may respond beautifully to caffeine. Other examples if you have SLC2A1, so gluc-1 (glucose transporter type 1) mutation, a ketogenic diet may work really well. If you have PDHA1 mutation that may respond to thiamine and so on and so forth. There are certain patients where paroxysmal movement disorders are highly disabling and you may consider deep brain stimulation. That's another reason why it may be important to understand genetic mutations because there is literature on response to DBS with certain mutations versus others. Helps like counselling for patients and families, and of course introduces time, effort, and money spent in additional testing. Dr Nevel: Other than genetic testing, what other diagnostic work up do you consider when you're evaluating patients with a suspected paroxysmal movement disorder? Are there specific things in the history or on exam that would prompt you to do certain testing to look for perhaps other things in your differential when you're first evaluating a patient? Dr Mahajan: In this article, I provide a flow chart that helps me assess these patients as well. I think overall the history taking and neurological exam outside of these paroxysms is really important. So, the clinical exam in between these episodic events, for example, for history, specific examples include, well, when do these paroxysms happen? Do they happen or are they precipitated with meals that might indicate that there's something to do with glucose metabolism? Do they follow exercise? So, a specific example is in Moyamoya disease, they can be limb shaking that follows exercise. So, which gives you a clue to what the etiology could be. Of course, family history is important, but again, talking about the exam in between episodes, you know, this is actually a great point because out– we've talked about genetics, we've talked about idiopathic paroxysmal movement disorders, –but a number of these disorders are because of acquired causes. Well, of course it's important because acquired causes such as autoimmune causes, so multiple sclerosis, ADEM, lupus, LGI1, all of these NMDAR, I mentioned Moyamoya disease and metabolic causes. Of course, you can consider FND as under-acquired as well. But all of these causes have very different treatments and they have very different prognosis. So, I think it's extremely important for us to look into the history with a fine comb and then examine these patients in between these episodes and keep our mind open about acquired causes as well. Dr Nevel: When you evaluate these patients, are you routinely ordering vascular imaging and autoimmune kind of serologies and things like that to evaluate for these other acquired causes or it does it really just depend on the clinical presentation of the patient? Dr Mahajan: It mostly depends on the clinical presentation. I mean, if the exam is let's say completely normal, there are no other risk factors in a thirty year old, then you know, with a normal exam, normal history, no other risk factors. I may not order an MRI of the brain. But if the patient is 55 or 60 (years) with vascular risk factors, then you have to be mindful that this could be a TIA. If the patient has let's say in the 30s and in between these episodes too has basically has a sequel of these paroxysms, then you may want to consider autoimmune. I think the understanding of paraneoplastic, even autoimmune disorders, is expanding as well. So, you know the pattern matters. So, if all of this is subacute started a few months ago, then I have a low threshold for ordering testing for autoimmune and paraneoplastic ideology is simply because it makes such a huge difference in terms of how you approach the treatment and the long-term prognosis. Dr Nevel: Yeah, absolutely. What do you find most challenging about the management of patients with paroxysmal movement disorders? And then also what is most rewarding? Dr Mahajan: I think the answer to both those questions is, is the same. The first thing is there's so much advancement in what we know and how we understand these disorders so regularly that it's really hard to keep on track. Even for this article, it took me a few months to write this article, and between the time and I started and when I ended, there were new papers to include new case reports, case series, right? So, these are rare disorders. So most of our understanding for these disorders comes from case reports and case series, and it's in a constant state of advancement. I think that is the most challenging part, but it's also the most interesting part as well. I think the challenging and interesting part is the heterogeneity of presentation as well. These can involve just one part of your body, your entire body can present with paroxysmal events, with multiple different phenomenologies and they might change over time. So overall, it's highly rewarding to diagnose such patients in clinic. As I said before, you can make a sizeable difference with the medication which is usually inexpensive, which is obviously a great point to mention these days in our health system. But with anti-seizure drugs, you can put the right diagnosis, you can make a huge difference. I just wanted to make a point that this is not minimizing in any way the validity or the importance of diagnosing patients with functional neurological disorders correctly. Both of them are as organic. The importance is the treatment is completely different. So, if you're diagnosing somebody with FND and they do have FND and they get cognitive behavioral therapy and they get better, that's fantastic. But if somebody has paroxysmal movement disorders and they undergo cognitive behavioral therapy and they're not doing well, that doesn't help anybody. Dr Nevel: One hundred percent. As providers, obviously we all want to help our patients and having the correct diagnosis, you know, is the first step. What is most interesting to you about paroxysmal movement disorders? Dr Mahajan: So outside of the above, there are some unanswered questions that I find very interesting. Specifically, the overlap with epilepsy is very interesting, including shared genes, the episodic nature, presence of triggers, therapeutic response to anti-seizure drugs. All of this I think deserves further study. In the clinic, you may find that epilepsy and prognosis for movement disorders may occur in the same individual or in a family. Episodic ataxia has been associated with seizures. Traditionally this dichotomy of an ictal focus. If it's cortical then it's epilepsy, if it's subcortical then it's prognosis for movement disorders. This is thought to be overly simplistic. There can be co-occurrence of seizures and paroxysmal movement disorders in the same patient and that has led to this continuum between these two that has been proposed. This is something that needs to be looked into in more detail. Our colleagues in Epilepsy may scoff this, but there's concept of basal ganglia epilepsy manifesting as paroxysmal movement disorders was proposed in the past. And there was this case report that was published out of Italy where there was ictal discharge from the supplementary sensory motor cortex with a concomitant discharge from the ipsilateral coordinate nucleus in a patient with paroxysmal kinesigenic cardioarthidosis. So again, you know, basal ganglia epilepsy, no matter what you call it, the idea is that there is a clear overlap between these two conditions. And I think that is fascinating. Dr Nevel: Really interesting stuff. Well, thank you so much for chatting with me today. Dr Mahajan: Thank you, Kait. And thank you to the Continuum for inviting me to write this article and for this chance to speak about it. I'm excited about how it turned out, and I hope readers enjoy it as well. Dr Nevel: Today again, I've been 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. I encourage all of our listeners to be sure to check out the Continuum Audio episodes from this and other issues. As always, please read the Continuum articles where you can find a lot more information than what we were able to cover in our discussion today. And thank you for our listeners for joining today. And thank you, Abhi, so much for sharing your knowledge with us today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.
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  • Tourette Syndrome and Tic Disorders With Dr. Jessica Frey
    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 something like Tourette syndrome to occur first in the midline and go in a rostrocoidal distribution. So, you mostly see things happening with eye blinking, throat clearing, sniffling, neck snapping. These are some of the immediate tics that start to happen. We also usually start to see simple tics, as opposed to complex tics, at the beginning. Now, over the course of time, many patients do develop more complex tics that might involve the arms or the extremities, but that would be unusual to see this as a presenting feature of new-onset Tourette syndrome. Dr Albin: Got it. So, I'm hearing that the history really matters and that sometimes, like those, like, first-onset seizures, I imagine as a neurointensivist, we see a lot of patients who've had seizures who think that they're presenting the first time. And then we go back and we say, well, actually they have had some abnormal movements at night. Sounds like it's very similar with these movement disorders where you have to really go back and ask, well, was there some sniffling? Did they go through a phase where they were grunting frequently? Because I can imagine that many children make those behaviors, and that it may not have registered as something that was cause for concern. Dr Frey: Absolutely. Dr Albin: And then the other thing I heard from you was that the phenomenology really matters and that there is a typical presentation, starting from sort of the face and working the way down. And that can be really helpful. But in this case, the family is quite clear. No, no, no. She's never had movements like this before. This is- nothing like this. We promise you, did not go through a phase where she was coughing or blinking, or, this is all totally new. And the phenomenology, they say, no, no, she did not start with blinking. It definitely started in the arm and then progressed in its complex movements. So, knowing that about her, how does that sort of shape how you move forward with the diagnosis? Dr Frey: Yeah. So, really good question. And this is something that I think really peaked during the Covid-19 pandemic. We saw an influx of patients, especially teenage girls or young adult girls, who basically would come in and have these new, acute-onset, abnormal movements. We weren't sure what to call them initially. There was some discussion of calling them “explosive tic disorder” and things like that. A lot of these actually looked very similar to psychogenic nonepileptic seizures, where they would come into the emergency department and have many abnormal movements that were so severe, that they were having a “tic attack” and couldn't stop the abnormal movements from occurring. And we saw so many of these cases during the Covid-19 pandemic that it eventually became known as a distinctive diagnostic criteria with the name of “functional ticlike behavior”, or FTLB. When we think about functional ticlike behavior, we think that these tics are driven more by anxiety and stress. A lot of times, the backstory of these patients, they were in a very stressful situation, and that's when the abnormal movement started. So, a very similar kind of backstory to patients that might develop psychogenic nonepileptic seizures. These tics were popularized, for lack of a better term, via social media during the Covid-19 pandemic. One article is out there that even has called these functional ticlike behaviors as “a pandemic within a pandemic”, because there was such a strong showing of ticlike behavior in the clinics during the Covid-19 pandemic. Although social media was thought to play a big role in these functional ticlike behaviors, we think that there's probably a little bit more complexity and nuance to why these functional ticlike behaviors develop. There is probably a little bit of a genetic predisposition. There's probably some other psychosocial factors at play. And when we see cases like this, the best thing that you can do is educate your patients about the differences between functional ticlike behaviors and tics that we see associated with conditions like Tourette syndrome. And then the best types of treatments that we have seen thus far are treating any underlying stressors, if any of those exist, as well as cognitive behavioral therapy has been shown to be somewhat helpful. As the Covid-19 pandemic has wound down, we have actually seen a lot less cases in our clinic. And one reason we think is less stressors, less uncertainty for the future, which we think was a driving precipitant of some of these cases. But it also is not as popularized in the media as well. There were a lot of TikTok users in particular, which lent itself to the name “TikTok tic”. These videos are not as viewed or not as popular as they were during the Covid-19 pandemic. One reason being that because we are not all relegated to our homes, constantly looking to online sources of information---just in general, we have kind of not been on the Internet as much as we were during the Covid-19 pandemic---as a society as a whole. Dr Albin: This is really fascinating how the environmental milieu, for lack of a better word, like, really influenced how patients were experiencing, sort of, functional neurologic disorders. In your article you describe really these three baskets of primary tic---which can then be a part of Tourette syndrome---,functional ticlike behaviors---which really were a unique manifestation of stress and anxiety specifically during the Covid-19 pandemic---, and then tics as a manifestation of some either different underlying etiology or medication side effect. So, when do you get concerned about that secondary etiology? Dr Frey: So secondary tics can occur in a variety of instances. I think some of the more common examples would be in genetic disorders. So, Huntington's disease is a really good example. I think we all associate chorea with Huntington's disease. That's probably the most commonly associated phenomenology that we see with Huntington's disease. But we can see a variety of movement disorders in Huntington's, and one of them is tics. So, when we see tics in association with other types of movement disorders, we should be thinking about a possible genetic etiology. If we see tics in association with other neurologic symptoms, such as seizures or cognitive changes, we should be thinking that this is something besides a primary tic disorder. You also mentioned medication use, and it's really important to think about tardive tics. I know we often think about tardive dyskinesia, and the first kind of phenomenology that jumps into our brain is usually chorea because it's those abnormal lip movements, finger movements, toe movements that we see after a patient has been on, for example, an antipsychotic or an antiemetic that has antidopaminergic properties. However, we can see a variety of abnormal movement disorders that occur secondary to antidopaminergic medications, especially after abrupt withdrawal of these antidopaminergic medications. And tics are one of them. There have been cases reported where people that have tardive tics will still report that they have a premonitory urge, as well as a sense of relief after their tics. So, it actually can seem very similar to Tourette syndrome and the tics that people with Tourette syndrome experience on a regular basis. The key here is that the treatment might differ because if it's due to an antidopaminergic medication or abrupt withdrawal of that antidopaminergic medication, you might need to treat it a little bit differently than you would otherwise. Dr Albin: I love that you bring in, it's not just looking at their specific movement disorder that they may be coming to clinic with, that tic disorder, but are there other movement disorders? Has there been a change in their medication history? Have they had cognitive changes? So really emphasizing the importance of that complete and comprehensive neurologic history, neurologic physical exam, to really get the complete picture so that it's not honing in on, oh, this is a primary tic. That's all there is to it, because it could be so much more. I know we're getting close to sort of the end of our time together, but I really wanted to switch to end on talking about treatment. And your article does such a beautiful job of talking about behavioral interventions and really exciting new medical interventions. But I would like to, if you don't mind, have you focus on, what behavioral counseling and what education do you provide for patients and their families? Because I imagine that the neurologist plays a really important role in educating the patient and their family about these disorders. Dr Frey: Absolutely. When we think about treatment, one of the most important things you can do for patients with Tourette syndrome or other primary tic disorders is educate them. This remains true whether it's a primary tic disorder that we see in Tourette syndrome or the functional ticlike behavior that we've discussed here. A lot of times, because there is such a stigma against people with tic disorders and Tourette syndrome, when they hear that they have Tourette syndrome or they are diagnosed with that, sometimes that can be an upsetting diagnosis. And sometimes you have to take time explaining what exactly that means and debunking a lot of the myths that go along with the stigmas associated with Tourette syndrome. I think a lot of times people are under the false assumption that people with Tourette syndrome cannot lead normal lives and cannot hold down jobs and cannot be productive members of society. None of that is true. Most of my patients have great lives, good quality of life, and are able to go about their day-to-day life without any major issues. And one of the reasons for that is we do have a lot of great treatment options available. Another important stigma to break down is that people with tic disorders are doing this for attention or doing this because they are trying to get something from someone else. That is absolutely false. We do think that the tics themselves are semivolitional because people with Tourette syndrome have some degree of control over their tics. They can suppress them for a period of time. But a lot of people with tic disorders and Tourette syndrome will describe their tics as if you're trying to hold onto a sneeze. And you can imagine how uncomfortable it is to hold in a sneeze. We're all able to do it for a period of time, but it's much easier to just allow that sneeze to occur. And a lot of times that's what they are experiencing, too. So, although there is some degree of control, it's not complete control, and they're certainly not doing these tics on purpose or for attention. So that's another important myth to debunk when you're counseling patients and their families. I think the dynamic between young patients that are presenting with their parents or guardians, sometimes that dynamic is a little bit challenging because another faulty assumption is that parents feel they are responsible for having this happen to their child. There used to be a really strong sense that parents were responsible for the tics that occurred in their children, and that is also absolutely not true. Parenting has nothing to do with having the tics or not. We know that this is a neurodevelopmental disorder. The brain is indeed wired differently and it's important to counsel that with the parents, too, so that they understand what tools they need to be successful for their children as well. Dr Albin: I love that. So, it's a lot of partnership with patients and their families. I really like that this is just a wire different, and I hope over time that working together we as neurologists can help break down some of that stigmatization for these patients. This has been an absolutely phenomenal discussion. I have so enjoyed learning from your article. For the listeners out there, there are some really phenomenal tables that go into sort of how to approach this from the office perspective, how to approach it from the treatment perspective. So, thank you again, Dr Jessica Frey, for your article on Tourette syndrome and tic disorders, which appears in the August 2025 Continuum issue on movement disorders. Be sure to check out Continuum Audio episodes from this and other issues, and thank you so much to our listeners for joining us today. Dr Frey: Thank you for having me. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.
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Continuum Audio features conversations with the guest editors and authors of Continuum: Lifelong Learning in Neurology, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. AAN members can earn CME for listening to interviews for review articles and completing the evaluation on the AAN’s Online Learning Center.
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