Continuum Audio

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Cheryl Bushnell, MD, MHS, who served as the guest editor of the June 2026 Cerebrovascular Disease issue. They provide a preview of the issue, which publishes on June 3, 2026.
Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota.
Dr. Bushnell is a Professor of Neurology and Director of the Center for Transformative Stroke Care at Wake Forest University School of Medicine in Winston-Salem, North Carolina.
Additional Resources
Read the issue: continuum.aan.com
Subscribe to Continuum®: shop.lww.com/Continuum
Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud
More about the American Academy of Neurology: aan.com
Social Media
facebook.com/continuumcme
@ContinuumAAN
Host: @LyellJ
Guest: @CBushnellMD 
Full episode transcript available here
Dr Jones: One of the core tenets of our field is that we learn neurology one stroke at a time. But what do we have to learn about preventing them altogether? The science of stroke prevention, acute treatment, and recovery are evolving rapidly, and it's hard to keep up. Today, we're speaking with Dr. Cheryl Bushnell, guest editor of our latest Continuum issue on Cerebrovascular Disease, to discuss these topics and much more. 
Dr Jones: This is Dr. Lyell Jones, editor-in-chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about subscribing to the journal, listening to verbatim recordings of the articles, and exclusive access to interviews not featured on the podcast. 
Dr Jones: This is Dr. Lyell Jones, editor-in-chief of Continuum: Lifelong Learning in Neurology. Today, I'm interviewing Dr. Cheryl Bushnell, who is Continuum's guest editor for our latest issue on Cerebrovascular Disease. Dr. Bushnell is a professor of neurology and the director of the Center for Transformative Stroke Care at the Wake Forest University School of Medicine in Winston-Salem, North Carolina, where she specializes in the care of stroke patients and their social and functional determinants of recovery and health, and is an internationally recognized expert on those topics. Dr. Bushnell, welcome. Thank you for joining us today. Why don't you introduce yourself to our listeners? 
Dr Bushnell: Absolutely. Thank you for the invitation. It's really an honor to be here. So, as you mentioned, I am the director of the Center for Transformative Stroke Care at Wake Forest. It's a really fun transition for me to be involved with different care models for stroke, and I think a lot of the Continuum topics are directly relevant to some of the things that I'm doing now as an administrator and sort of a facilitator of new research. So, thanks again for having me. 
Dr Jones: Yeah, and, and you have a wonderful perspective, and we're gonna pull that out today in our interview questions, and I'm looking forward to sharing that with our listeners. But before we get to the questions, we're gonna start off today's podcast with another Continuum Audio trivia question for our listeners. Anticoagulation has played a critical role in secondary ischemic stroke prevention for a long time now. While direct oral anticoagulants have taken on a greater role in the treatment of prevention of stroke, there are still some use cases for vitamin K antagonists like warfarin. The trivia question for our listeners is this: How was warfarin discovered, and how did it get its name? Stick around and we'll share the answer to that question toward the end of our interview today. So, Dr. Bushnell, let's get right to it. You alluded to your various roles, and your leadership in the field has been exemplary. The interventions for acute ischemic stroke have really exploded over the last decade or so, and they get a lot of attention and discussion, but prevention and recovery are just as important in the care of these patients. Tell us a little more about how you approached this issue, about the article topics you chose, etc. 
Dr Bushnell: Well, once I was chosen to lead the guest editorship, I wanted to come up with a group of topics that were maybe a little bit different from previous issues. So, I kind of looked at the previous issues and saw, as you said, an emphasis on acute stroke, and that's really important because it has been evolving. But my thought was, how about what happens to patients after they get the intervention and they're discharged home? And because a lot of trainees may not get to see these patients ever again, or it's months before they might see them, or if they're readmitted, which is what we don't want to see, but that certainly is a lot of the exposure is in the inpatient setting. So, I thought I would kind of transport the education into the outpatient and transitional setting, as well as prevention, not only secondary, but primary prevention, with an emphasis on brain health. Some of the populations that may not get as much attention. So, sex differences, stroke in women, pregnancy, the transitions of care, and also the emphasis on holistic view of patients and their challenges, which includes the non-medical factors that drive health, otherwise known as social determinants of health. 
Dr Jones: I appreciate that perspective, and obviously th-this is an area of your deep expertise, and it's great to have an issue that really digs into some of those topics a little more deeply. As an educator, I'm really glad you mentioned that about the trainee's perspective. You know, especially junior neurology trainees that are in the hospital all the time. They're seeing patients in the middle of a cerebrovascular catastrophe. But there's a long tail of recovery, right? And they'll get to see that in continuity clinic, but it's a good message to share from an evidence and, um, experiential perspective in the issue. So, appreciate that perspective. You've just read all these articles and edited them. Was there anything that you ran across that was a surprise to you? 
Dr Bushnell: Well, I personally chose a lot of the authors based on my knowledge of their work. So, I wouldn't say that it was completely surprising, but I do think that I was just genuinely impressed with the quality of the writing and the synthesis of information. I just was incredibly proud of the work that these co-authors have put together. I'd say that that was-- it wasn't surprising so much as just a sense of pride that I had with the product that's coming out. But of course, there have been some new trials that had to be incorporated at the last minute, some of which were presented at the International Stroke Conference just a few weeks ago. 
Dr Jones: Yeah. We try to be as up-to-date as we can, and I will completely agree with you. We have some really good writers in our field, and it's really just a pleasure when you read an article that's by an expert, and it's a joy to read. I can tell you it's one of the best parts of this job, and you get to learn a lot. I think one of the more challenging scenarios that I hear about from colleagues in recent years has been optimal management of patients with asymptomatic extracranial atherosclerosis. The pivotal trials that inform how we manage those patients were from a long time ago, decades ago, predating a lot of the more intensive medical management tools that we have today. In that scenario, Dr. Bushnell, what's the latest on that, and what should our listeners know? 
Dr Bushnell: Well, obviously, the CREST 2 trial has been long awaited. It's been going on for over ten years, I believe. Of course, it's, uh, two different trials all in one, the carotid stenting and angioplasty versus intensive medical management. And of course, each of the carotid vascularization arms of the trial also had intensive medical management. And then the other trial is the carotid endarterectomy as the form of revascularization. And it interestingly did not show any benefit of carotid endarterectomy compared to intensive medical management. But of course, the somewhat surprising result was that carotid angioplasty and stenting truly was superior, although it was a small number of events in the trial overall. But that stenting plus intensive medical management was somewhat better than intensive medical management alone. And I think stenting has come a long way in terms of safety, and so I think that's been part of the evolution of the field. I do wanna say that I'm a huge fan of the intensive medical management, and I think that what the protocol does in terms of blood pressure management, cholesterol management is very much above and beyond what's done in private practice even. And the health coaching for all the other things related to diabetes and weight loss and smoking cessation and physical activity, that is what we need to be doing to actually decrease the risk of stroke, and I think that it's very effective. I can't say enough about the design of the study for that reason, that everyone gets the intensive medical management, and then you just layer on the type of revascularization on top of it. So, I wouldn't have been surprised if this was a completely negative trial overall. They just happened to have some better outcomes in the stenting arm. 
Dr Jones: I recall a few years ago when the series of endovascular therapy trials for acute stroke came out, and I think there was a, a period of time where the field had to adapt to that. I wonder what you think about with the CREST 2 findings on stenting. I mean, is that gonna be a big change? Because obviously atherosclerosis is highly prevalent. Is that gonna be a big change? Is the field ready for that? How much adjustment do we have in store? 
Dr Bushnell: I'm not sure it's gonna be a really big change. If you read the editorial that accompanied the trial in the New England Journal, just a few patients in either direction would have changed the outcome. I kind of look at it as an absolute difference that's relatively small. So, I'm not sure that it will have a huge impact on the field. I do think that the specialists who insert the stents may have some differences of opinion of who should be stented and who shouldn't. Because I think, you know, all of the specialists who do procedures were involved with the trial. But I would say there's a larger percentage of vascular surgeons who were involved, and so I'd say they may have a change of their practice. And neurologists may not even get involved at all. 
Dr Jones: Right. 
Dr Bushnell: That was one of the challenges for getting patients in the trial is that, you know, not all of us see the asymptomatic carotid stenosis, that they tend to get referred to vascular surgery. So, I think maybe in a corner of the practices of vascular surgeons is where you might see the differences. 
Dr Jones: Your point about the way the trial was designed or the trials were designed, that intensive medical management is really important, and we have huge gaps in that. In our specialty, it's, you know, we have probably an opportunity in primary care even to address that. And that leads me to my next question. You know, given your perspective and your expertise, what do you think is the biggest practice gap in the care of patients with stroke or with cerebrovascular disease of any kind? 
Dr Bushnell: I think by far the biggest gap is transitions of care and access to follow-up in a specialty clinic after discharge and continuous secondary prevention. We only call it secondary prevention because it happened to come after a stroke, but I really feel like we should just focus on prevention and call it that. There are a lot of people who are trying to kind of, get us away from primary versus secondary prevention. And, and Mitch Elkind is phenomenal and had a beautiful chapter weaving in prevention and brain health. So, I highly recommend that people, if they don't read any other chapters of the Continuum to read his, because I think that it's getting to your point about where the gaps are, and I think prevention is the biggest one. I think we could do so much more in models of care to ensure that there is a pathway once patients are discharged. We have no quality metrics. We have no measurement of how well people are doing after they're discharged. We have all of these fancy things and sophisticated acute treatments, but all of those are for naught if somebody goes home and they fall and they have a severe head injury or hip fracture because they weren't properly supervised or they didn't have the help that they needed at home. So, you got me on my soapbox here for a second, but that is definitely what I see as the gap. 
Dr Jones: That's an important soapbox, an important gap, and obviously, if it was a simple problem, we could solve it. But it's obviously something that education is a valuable tool for that, and that's part of why we are including so much content in this issue of Continuum. So, if we put that aside as a gap that we would love to close, when you look into the near future or distant future, Dr. Bushnell, and what's the next big thing on the horizon? New interventions, new prevention tools, or something else entirely? What do you think? 
Dr Bushnell: There are two things that I would mention. One is sort of the new category of anticoagulants, antithrombotics, the factor XIa inhibitors. We had an amazing presentation of the oceanic stroke trial at the International Stroke Conference, and this is probably going to be a game changer for the arsenal of antithrombotic therapies that we can offer to patients that do not have a reason for anticoagulation. So, they, they don't have atrial fibrillation, for example, or something else that requires anticoagulation. And so, the factor XI, asundexian, is the drug that they used in that trial. The safety profile is pretty amazing. There was very little bleeding complications and a great benefit in those patients with some degree of atherosclerosis, but, you know, of course, not enough to require carotid revascularization, but then also, um, small vessel disease and cryptogenic stroke. I think those are the three categories of patients, and that's a lot of the strokes that we see all benefited from this new drug. So, I think that's gonna be exciting. There, of course, it has to go through the FDA approval process, and so it might take a little bit of time before that's on the market, and we don't know how much it's gonna cost, but I think it is a, a major breakthrough. And of course, there are other similar medications in that category that are coming. And then I think the other thing is the emphasis on brain health and lifestyle factors and the things that we can do to prevent stroke and dementia because they are the same, essentially. Those are really important. And when we have someone in the hospital with a stroke or a TIA in particular, it's a great teaching opportunity for those patients to say, "Hey, here's what you can do to protect your brain." These are things that we always tell people to prevent a stroke, but just think about it as protecting your brain and keeping your brain as healthy as possible. 
Dr Jones: That's a great message, and one that you get to share with patients directly. You're joining us today for this interview. You're on stroke service, so you're actively involved in caring for patients with stroke. What in your practice is the most rewarding aspect of caring for these patients? What is it that you find most rewarding? 
Dr Bushnell: I've been involved in a clinical trial that has focused on managing blood pressure and also coaching and other aspects of stroke recovery. I think that has probably been the most rewarding aspect of my career. Until I was involved with this trial, I didn't necessarily do intensive blood pressure monitoring, but I'm seeing the benefits of having data from home, what those blood pressures are over a span of time. I see the immediate or intermediate effects of the blood pressure medication changes that I've made, and I see how the patients respond. So, I have to say that this is not part of usual practice, but I think it should be. And I think it's been incredible from the perspective of a neurologist who is really intensively trying to make the patients' lives better. And it's not just what I do, it's what the health coaches do as part of this intervention. And again, very similar to intensive medical management. So, I, I feel like I've been living it in a slightly different setting than in the CREST 2 trials. But there are other trials that have used the intensive medical management as approach as well. But I would say that's the most rewarding. I've seen people who've lost weight, who are physically fit, who are able to get off of blood pressure medications practically by the end of six months, and that's amazing. And then they continue doing it because they see the benefits. 
Dr Jones: You've had a front row seat to a lot of that. That's really got to feel rewarding. 
Dr Bushnell: It is, absolutely. 
Dr Jones: You know, when you put it that way, it makes me want to go home and check my blood pressure, which I haven't done in a while. But I think that's a message to all of our listeners that we do have plenty of opportunity for risk factor optimization and following the evidence that has been generated and is being generated. Huge opportunity, not only at the population level, but I think the, um, individual patient level too. Okay, so now we're back to our Continuum Audio trivia question, and I'll repeat it for our listeners. How was warfarin discovered, and how did it get its name? Dr. Bushnell and I were talking about this earlier, so I'll just go ahead and share the answer. So, in the early 20th century in the U.S. Midwest, there were epidemics of a hemorrhagic disease in cattle, of all places, and this was eventually traced to moldy cattle feed that was made from sweet clover. And in 1940, researchers at the University of Wisconsin discovered that the anticoagulant in the sweet clover was a compound that was later synthesized for therapeutic use in 1954 as warfarin. And the name came from, uh, the support for the research. The research support came from the Wisconsin Alumni Research Foundation, or WARF, and the end of the word came from the underlying compound, which was coumarin. So that was a little bit of trivia that I had never heard. It's not in the issue, everyone, so you're getting something extra here on the podcast. But been using the drug forever. It still has its uses, even though it's become less advantageous than some of the newer agents. But-- And of course, Dr. Bushnell already knew that when I brought it up, but I just thought that was an interesting bit of history. Well, Dr. Bushnell, thank you for joining us. Thank you for such a great conversation about the latest in cerebrovascular disease. I learned a lot today. I learned a lot in reading these wonderful articles. I hope our listeners learned a lot today as well. I'm really grateful for your hard work on the issue, which I think will come in handy for junior readers and subscribers, as well as our more experienced neurologists as well. Sometimes it's hard to keep up with a rapidly changing subspecialty of our field. So, thank you for joining us today. 
Dr Bushnell: Thank you for having me. It's been my pleasure. 
Dr Jones: Again, today we've been speaking with Dr. Cheryl Bushnell, guest editor of Continuum's most recent issue on cerebrovascular disease. Please check it out, and thank you to our listeners for joining today. 
Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. Thank you for listening to Continuum Audio.

Balancing disease control with pregnancy and neonatal considerations in people with neuroinflammatory disease throughout the family planning, pregnancy, and postpartum periods is crucial. Modern treatment paradigms enable women to safely become pregnant and breastfeed alongside effective disease management. Shared decision making is an important part of this process.
In this episode, Kait Nevel, MD, speaks with Ruth Dobson, MD and Kerstin Hellwig, MD, authors of the article "Family Planning in Neuroinflammatory Disease" in the Continuum® April 2026 Multiple Sclerosis and Related 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. Dobson is a professor in the Centre for Preventive Neurology at the Wolfson Institute of Population Health, Queen Mary University of London, and a consultant neurologist in the Department of Neurology at the Royal London Hospital, Barts Health NHS Trust, in London, United Kingdom.
Dr. Hellwig is a professor in the Department of Neurology at Katholisches Klinikum, Ruhr‑Universität Bochum, in Bochum, Germany.
Additional Resources
Read the article: Family Planning in Neuroinflammatory Disease
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: @drruthdobson
Full episode transcript available here

Palliative care in multiple sclerosis spans the disease course, from early screening and support after diagnosis to symptom management and quality‑of‑life optimization in midstage disease, and end‑of‑life care in advanced MS. This episode outlines a staged approach to palliative care, highlights the roles of neurology and primary care teams, and discusses tools such as patient‑reported outcomes and symptom scales to support ongoing assessment of patients and care partners.
In this episode, Katie Grouse, MD, FAAN, speaks with Penelope Smyth, MD, FRCPC and Janis M. Miyasaki, MD, MEd, FRCPC, coauthors of the article "Palliative Care in Multiple Sclerosis" in the Continuum® April 2026 Multiple Sclerosis and Related 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. Smyth is the director of the Division of Neurology in the Department of Medicine at the University of Alberta in Edmonton, Alberta, Canada.
Dr. Miyasaki is a professor in the Division of Neurology in the Department of Medicine at the University of Alberta and the zone clinical department head for Clinical Neurosciences at Alberta Health Services in Edmonton, Alberta, Canada.
Additional Resources
Read the article: Palliative Care in Multiple Sclerosis
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 Grouse: With the new treatments for MS, people might be saying palliative care is not relevant at all. It's about giving up hope and hopelessness. But this article covers why palliative care is important for your patients and families throughout their illness trajectory.
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 Drs Penelope Smyth and Janis Miyasaki about their article on palliative care in multiple sclerosis, which appears in the April 2026 Continuum issue on multiple sclerosis. Welcome to the podcast, and please introduce yourselves to our audience. 
Dr Smyth: Thank you, Katie. I'm Penny Smyth. I am a neurologist at the University of Alberta, a professor in neurology, and a clinical multiple sclerosis specialist. 
Dr Miyasaki: Hi, Katie. Thanks for having us. I'm Janis Miyasaki. I am a movement disorder neurologist primarily who also provides neuropalliative care at the University of Alberta in Edmonton, Canada. 
Dr Grouse: It's so great having you today to talk with us about your article. I thought this article was really a wonderful take on the topic. I learned a lot, and I'm really hoping all of our listeners will take advantage of this article and take advantage of all the learning they can get from reading about this topic. So, I wanted to start with a more general question, which is, what is the key message from this article that you're hoping your readers will take away? 
Dr Smyth: In terms of key takeaways, I think it's our hope that neurologists will come away from reading this article with, really, an expanded understanding of what palliative care is and how that might be applicable to them in their care for their patients with MS along a continuum of treating people with MS, that there can be components of palliative care and strategies that can be integrated early after diagnosis in, really, anywhere along the continuum of caring for people with MS. We've called that kind of mid-stage. And then there are particular needs for people with MS and their care partners in late-stage or severe MS and end of life that might require different palliative care strategies. I think we kind of have maybe a bit of a bias sometimes in thinking of palliative care as more directed towards those that are near end-of-life. But in fact, it's a much expanded concept. 
Dr Miyasaki: And I'll just add that we also discuss a palliative approach, that palliative care skills and philosophies can be used by generalists---in this case, neurologists who are providing care to people with MS---and that adopting certain skills and communication techniques can help us better address our patients' and their families' symptoms. And also to keep in mind that for most people with neurologic illness, the unit of care is not only the patient, but it's the patient and the family, however that family looks. 
Dr Grouse: Now, Penny, I'm curious, how are early-stage and mid-stage multiple sclerosis palliative care strategies different from, say, a typical evaluation and counseling that a neurologist would give, say, an MS specialist or even a general neurologist? 
Dr Smyth: Thank you, Katie. That's a great question, and something that actually I learned in writing this piece with Janice and from her as a neuropalliative care expert. I think in terms of early strategies around palliative care that can be helpful to the general neurologist in their office, palliative care is about holistic support for patients and their care providers spiritually, emotionally, physically. There are components of palliative care and symptom management and making sure that the patient is at the center of the care, as well as support for their care partners with their holistic approach of relief of suffering as well as offering hope. When I started this piece, I was thinking that many of us neurologists, I think, often informally utilize many of these components already when we're dealing with patients early on after diagnosis in terms of communication, counseling, and education; going through their fear of an uncertain future; spiritual well-being; and then connecting them with supports for adaptive coping strategies. And then as well in mid-stage, which is really around what we can do in symptom management and improving quality of life, with screening tools and patient-reported outcome measures. However, I have to say that there are many unmet needs for people with MS and their care partners that they identify that are clearly not being met by us neurologists in this day and age. So even though we may be incorporating some of these strategies, I don't think we're meeting the mark all the time and hitting the target, especially in our busy office practices, in various ways.
Dr Grouse: Given that, at a high level, what are some important early-stage MS palliative care concepts that we should be keeping in mind when we are counseling patients in these stages of the disease?
Dr Miyasaki: An important concept to keep in mind for neurologists dealing with early-stage MS patients is that for us, we feel successful that we have made a diagnosis. And yet for the patient, it is taking away that hope. Maybe it's not MS. Maybe I just have a numb hand and it's gonna go away. And for us to appreciate that while we make this diagnosis multiple times a week---or, for MS specialists multiple times a day---for this person, it is the first time, the first experience, and it shakes their entire foundation of who they are as a person, how they will perform all the tasks and roles that they have in society, in their professional lives, in their family structures, and in their close, intimate relationships. As physicians, we may be overwhelmed by acknowledging that. I feel that it's important for us to understand the needs that our patients have and to allow them to have their feelings. You know, feelings can feel messy and time-consuming, and yet when we fully see our patients, I feel that this is the best of medicine. And it certainly is, in terms of palliative care, the principle that we seek. We accept all of the patient, the joy and the sorrow, the anger and the frustration. We accept it all, and we try to determine what will serve this person who is suffering in front of us now. 
Dr Smyth: There's another piece to this, which came up as Janice and I were writing together. We were talking about offering a prognosis to a patient as to how they would do, and this was something that I thought deeply about, because I said, we always communicate how uncertain the prognosis is and how we can't predict the future. And then she said to me, well, what about offering a roadmap to a person with MS soon after diagnosis as to how you're gonna determine how they do over the next couple of years? Which are really important years in terms of determining how patients are doing on their disease-modifying therapies, whether they're having progression or not, and things. It's a pivotal time. So, if you can offer a roadmap to a person with MS and say, look, this is when we will be following you up. This is how we will be following you with MRI and biomarkers if you have that available, and this is how we will determine how responsive you are and then how we move forward from there.
Dr Grouse: Really important concepts. And the roadmap certainly makes a lot of sense to me and something that, apart from just being useful to the patient for so many reasons to help set expectations, you know, is useful for us to better partner with the patient so they understand this is sort of how we do things and everyone's sort of expectations are met. So, I think those sound like really great goals and things to keep in mind. Now, we talked about early-stage MS palliative care concepts. How does that change as you get into the mid-stage of the disease? 
Dr Smyth: Yeah. So, this is reflecting the fact that the course of MS is so different and the experience of MS is so different person to person. And so, what do we do as neurologists when we follow these people long-term over years and decades of living with their MS as their needs evolve, as their symptoms evolve, and as their disability evolves? Well, really, this is about the time of getting into, what are the symptoms that they're struggling with, what are the causes of their suffering at various points? And then how do we identify that, maybe with use of patient-reported outcome measures, screening scales, things like that. And then how do we direct symptomatic management to the specific symptoms that are causing distress to the patient? As well as trying to improve their quality of life in various ways, treating their comorbidities, making sure to check on exercise, healthy living, and that kind of thing. 
Dr Grouse: Now getting into, I think, topics that we're more used to thinking about when we think about palliative care: a lot of us, I think, are really unsure of the right time to discuss advanced care directives in the course of multiple sclerosis, and I think that's not helped by the fact that many of us are just, in general, not terribly comfortable talking about those types of things in general. What is your advice to questions like this? 
Dr Smyth: And this is something that, again, Janice and I had to come together on, because there is no universal accepted time for when is the right time in multiple sclerosis to discuss advanced care directives and goals of care. And in fact, when they have looked at it in the literature, different things have come out. It has come out that neurologists can be uncomfortable discussing this. There's unique challenges to people with MS in that they have a diagnosis at a young age with an uncertain trajectory of how their course of disease is going to go. And many of these things lead care providers to be somewhat hesitant as to when is the right time, as well as, there were identified barriers within patients themselves as to when the right time might be to discuss. In that, you know, some of the coping strategies might be, as identified by some of the qualitative studies that have been done on this, around the fact that they would prefer to focus on the present rather than the future. In some studies expressed an ambivalence as to when they thought the right time might be, as well as some negative experiences that they might have had from providers trying to discuss these things in their previous experience. So, I went back to looking at the European guidelines for palliative care in MS, who suggested when a person might have severe MS---which they define as walking with bilateral aids for at least twenty meters or an EDSS of six or higher---or trigger-based, when there has been a change in the patient's status, when there's been a decline in some way or progression. Now, this is a little different, actually, than what we offer other people with neurologic diseases, and I don't know if that's the right answer. And this is where I'm going to turn it over to Janice, because I think we could learn something, as neurologists who treat people with MS, from our palliative care specialists. 
Dr Miyasaki: I think of advanced care planning in a very different way. I think what a lot of the patients were expressing in the studies was that being asked about advanced care planning signaled to them in some way that they have reached this point in their illness where things aren't going so great and I anticipate that you may run into complications. Whereas in our movement disorder clinic, one of our fellows did a study looking at capacity for decision-making. And even in people who scored normally on the Montreal Cognitive Assessment, they had impairments in some of the domains of decision-making. And so, our philosophy in movement disorders at least---and some of our patients are quite young who have multiple system atrophy, they could be in their forties---we take the philosophy that everyone over the age of decision-making capacity, which is generally eighteen, should have some goals of care established. And how I introduce it in my clinic is, you know, for the young resident, you want the full-meal deal, because the likelihood of the resident surviving the ICU admission is very high. And then when we look at me, who… I am older, the likelihood of surviving an ICU admission is considerably lower. And so, the appropriate goals of care might be that I am willing to go to the ICU, and if things go well, then they can continue. But if things are not going well, they can have a discussion with my personal directive or power of attorney to talk about what the goals of care should be. And then the other aspect is sometimes having the conversation with family is really important because most of our families in hospital express an uncertainty. Am I doing the right thing? And they want to do the right thing for their loved ones. And most people actually say, if you ask them, I don't want to burden my family with making decisions that are going to tear at their hearts. So, then we can't actually make good informed decisions for our loved ones unless we have clear conversations. I think it does speak to our superstitious beliefs that if we talk about death, it's going to happen. But I hope the listeners will take my word for it, it really doesn't. And someone had a really good saying about the advanced directive. They're kind of like evening clothes. You should take them out every once in a while and make sure they still fit. And so, when you normalize it in this way, it helps people to just say, oh, yeah, it's once a year. Dr. Miyasaki is gonna ask me about how do I feel about those goals of care. And then it doesn't have this portent of, oh, I'm not doing well. Instead, it's just, this is what we should all be doing for our sake and for our family's sake. 
Dr Smyth: Now, one thing that I have to add on to this is that it is important to try to establish advanced care directives before patients experience cognitive decline, because then that can make it a much more challenging conversation and brings nuances of challenge into the interactions, which, you know, are hard. 
Dr Grouse: And Penny, I'm glad you brought that up, because I was really struck by that point too when reading this article, how easy it is to miss the subtle signs that cognitive changes are happening. I think it's just- it's a good kind of segue into that topic in general, but it is such an important link to, you know, making sure that you get those advanced directives at a time when the patient's really able to express and understand what they're talking to you about. Now, on the topic of the cognitive screenings, what's a good way to do this type of screening, and why is this type of screening so particularly important in the case of multiple sclerosis? 
Dr Smyth: Yeah. Thank you, Katie. I think that it's important for our listeners to think about and recognize when we see our patients with MS because it is one of the invisible symptoms that people with MS can live with and may not be apparent on regular conversation in the office. So, it's important to deliberately ask about subjective challenges in cognition. Ask the partner about how they're doing in terms of their cognition in various ways. As well as asking them and exploring then, how are they doing in their professional roles if they're working or in their surroundings? How are they coping on a daily basis on a cognitive level in addition to a physical level? We know that cognitive issues are actually the biggest contributor for not working and are a huge driver of disability in MS in terms of functioning, even more than physical decline in many ways. So, it is important for us neurologists to keep top of mind and to think about and deliberately attend to. There are screening tests that we can do in the office. The easiest for us, which measures the verbal processing speed, is the SDMT test, which is a ninety-second test matching symbols and numbers. It's easy to do. You can train a MOA to do it before you see the patient and things like that, and it just gives you an idea as to where the patient is at. And usually they're having difficulties if they're greater than two standard deviations below the norm for their age, or if there's a significant drop of four or eight points, and that might signal to you that there might be more going on. You can explore it, and then if you do have this available, the ability to refer for neuropsychological testing if there's questions. But often we can't get it with the MoCA score, unfortunately. 
Dr Grouse: Talking about all these concepts, I think they all sound great. I think a lot of us hearing this will naturally say, "Yes, these are absolutely things we should be incorporating in the care of these patients." What I wondered about was, certainly we're all very busy, it is really hard to find time for a lot of these things. We don't always have access to specialists who can help us with some of these conversations. How can we find time, and how can we work this into the care of our patients effectively and still make time for all the other things we have to talk about, and make sure that we're seeing all of our other patients and staying on time and all of those things? 
Dr Miyasaki: Yes. I think that's the challenges of dealing with people who actually, over time, their care needs increase, is huge in neurology. I can't think of a single subspecialty where care actually gets easier. It's constantly getting harder. You know, having come from private practice, I completely understand my colleagues' challenges in the community. Some of the ways that other groups have managed this when they don't have government or university support in their center is actually to look at not-for-profits. There are a lot of not-for-profits that can help in terms of wayfinding for social services, explaining to the patients and the family what is available to them. And in fact, some of them can also provide some cognitive supports, as well as point them in the way of day programs. And many of them have very established caregiver support groups, as well as patient support groups for various stages of their illness. So, I think it requires for the individual or small or even a large group practice to be inventive, to look in your community and see what resources are available and free for your patients in order to establish that loose team without boundaries to help your patients. Of course, for those in academic centers, I know that times are tight for all of us, and if you haven't established a team, it is a challenge; and then learning how to write a business plan or a briefing note for your institution and to learn how to speak the love language of administrators, is really key to putting forward the needs of our patients. Which, compared to heart attack patients or hips and knees, they are very rare, and yet our patients can result in significant cost to the healthcare system. So, we do have an opportunity to make the case that putting a little bit of investment in the ambulatory setting can result in significant cost savings to the system when it comes to acute care hospitalization. 
Dr Smyth: So, I was thinking, Janis, as you were talking about that, when you were talking about not-for-profit groups, it's really the MS societies in various countries that are very active in this and have a lot of resources available, especially for care partners. 
Dr Grouse: Those are really great tips. Thank you for bringing those up as potential other resources we can take advantage of. I wanted to ask specifically about physician-assisted death and assisted suicide, which certainly does come up, especially in later-stage parts of the disease. How can palliative care specialists be helpful when patients do express interest in these types of interventions? 
Dr Miyasaki: As you know, Katie, in Canada, we've had a legislative right to access to what we call medical assistance in dying. When the legislation passed, one of my other colleagues and I felt that these were the only conversations we were having with our patients. In all this experience, I have sort of developed in my mind a framework of people who are what we call MAID-curious. They want to know what their rights are and how it would look, when they feel the time is close, for them to exercise that right. And then there are those who are fearful of future suffering. And some of them may have a very unrealistic view of what the future will look like. And this may be in particular for multiple sclerosis because many of the public's view is based on what treatment was like thirty years ago. It may not be informed by more recent treatment where patients actually do quite well, and the majority never get to progressive MS. And so, to explore and be open to that request is the first thing that is important. And then if the person has unresolved symptoms that, traditionally, we can't care for, the palliative care specialist can be very helpful because they just have inventive ways of looking at things. They look at it outside the box, and they have a different toolkit available to them. I would not want all neurologists to just send all these patients requesting physician-assisted death to their palliative care colleagues. But I think for those who are having unaddressed symptoms, it can be very helpful. Certainly, if there is an acute event in the hospital, then this is a time of crisis. And often hospitals will have an in-hospital palliative care team who can come and speak to the patient about what is going on and address some of their needs. And I would also like to emphasize the importance of spiritual care, because for many of our patients, they are not just having the physical suffering, they are also having the spiritual suffering of hopelessness or of feeling that they are a burden or that they just are not seen because a lot of the symptoms in MS are invisible. To have that understanding by a spiritual care counselor is really helpful for the people to feel understood and to reduce some of that suffering. 
Dr Grouse: That's a really great point, I think, to end on, and I think it really ties in a lot of the themes that we've been talking about today. Thank you so much for coming to talk with us today. It's been such a pleasure having you both here.
Dr Smyth: Thank you.
Dr Miyasaki: Thank you, Katie.
Dr Grouse: Again, today I've been interviewing Drs Penelope Smyth and Janis Miyasaki about their article on palliative care in multiple sclerosis, which appears in the April 2026 Continuum issue on multiple sclerosis. 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.

Advances in immunotherapies for multiple sclerosis and related disorders have increased the risk of infections and raised important questions about vaccination efficacy. This episode reviews infection risks across treatment classes, emphasizes the importance of monitoring and patient education, and discusses optimal vaccine timing to preserve protective immune responses.
In this episode, Aaron L. Berkowitz, MD, PhD, FAAN, speaks with Avindra Nath, MBBS, FAAN, coauthor of the article "Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders" in the Continuum® April 2026 Multiple Sclerosis and Related Disorders issue.
Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology in the Department of Neurology at the University of California, San Francisco, in San Francisco, California.
Dr. Nath is the chief of the Section of Infections of the Nervous System at the National Institute of Neurological Disorders and Stroke, National Institutes of Health, in Bethesda, Maryland
Additional Resources
Read the article: Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders
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Earn CME (available only to AAN members): continpub.com/AudioCME
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More about the American Academy of Neurology: aan.com
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Host: @AaronLBerkowitz
Full episode transcript available here
Dr Berkowitz: Over the last decades, there has been a revolution in the treatment of multiple sclerosis, neuromyelitis optica spectrum disorder, and other immune-mediated neurologic conditions with countless new, highly effective medications. However, with every new treatment comes new risks; and in the case of immunomodulatory therapy, many of those risks relate to infection. Today, I have the privilege of talking with an expert on this topic, Dr Avindra Nath, about the infectious risks of treatments for multiple sclerosis and other immune-mediated neurologic disorders. 
Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. 
Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Avi Nath about his article on vaccine considerations and infection risk in multiple sclerosis and related disorders, which he coauthored with Dr Amit Bar-Or. This article appears in the April 2026 Continuum issue on multiple sclerosis. Welcome to the podcast, Dr Nath, and could you please introduce yourself to our audience? 
Dr Nath: Thanks very much for inviting me to this podcast. I'm absolutely delighted to have the opportunity to discuss our areas of interest and expertise related to infections and vaccinations for MS patients. My area has been studying the infections of the nervous system since the beginning of the AIDS pandemic, and over the years and decades, we've developed expertise related to various types of CNS infections. That includes ones that are developing in individuals who have immune compromise due to a variety of different reasons.
Dr Berkowitz: Fantastic. Well, glad to have the opportunity to speak with you today. When I was in medical school---and you were my attending, actually, we were just reminiscing, which we probably think was not that long ago, but is now over twenty years ago---there were just two medications for MS, right? Beta interferon and glatiramer acetate. And now we have over a dozen, and it's amazing to think of all the progress in these last two decades, as well as for related diseases like NMO. I don't think we even had the aquaporin-four biomarker, right, when I was working with you as a med student in the early 2000s.
Dr Nath: And that certainly dates me a lot. 
Dr Berkowitz: Both of us. 
Dr Nath: Yeah. 
Dr Berkowitz: Of course, with all these new treatments, these have been amazing advances for our patients, right? But these come with new treatment-related risks to monitor for with the immunomodulatory medications for MS and related disorders. And one of those most important risks is that of infection. So, your article reviews the potential infectious complications of medications used to treat MS, NMO, etc, and also covers considerations related to thinking about vaccines in this patient population. So, as the MS treatment landscape grows, I can say as a general neurologist, keeping up with all these medications and what to screen for and what to worry about and when to vaccinate just becomes more challenging every year. And your article has so many helpful tables, some organized by medicine, some organized by- sorry, medication, some organized by infection, some by vaccines. So, this is gonna be a great resource for our providers to print out and tape up in their clinic rooms. We won't be able to get into all the depth and detail that you have in this article today, but I do want to focus on some of the key points here related to the common medications we use for MS and which infections to think about and which vaccine considerations we might need to keep in mind for these medications. But before we delve into the drugs, I just wanna ask you more broadly, you talk in the article about the challenge of patients with immune-mediated diseases who are on immunomodulatory therapy being at risk for both flares of their disease and for infections; and these infections can present somewhat atypically, right, in immunomodulated hosts, to maybe coin a term you can correct me on, because they can't mount the full inflammatory response. So how do you approach new symptoms in patients on these immunomodulatory medicines as far as distinguishing disease flare from a treatment-related infection? 
Dr Nath: So, I have to say that although a lot of new treatments have come along for MS, and they've really, you know, improved the outcome tremendously and there are so many different options, it has also kept people like me relevant because they cause a lot of various types of infections, and so keeps me in business all the same. But just as you mentioned, there's so many of them, even I have difficulty keeping track of what does what. So, you do need to be able to refer back to published literature, and the tables, I hope, will be quite useful in that regard. You're absolutely right, and you can get new infections, you can get reactivation of existing infections, and you can get atypical presentations of various types of infections that you may not normally think of. So that presents multiple challenges to the treating physician. The other interesting thing about MS is, just as you mentioned, that you already have CNS lesions to begin with. Now, on top of it, you have an infection, so now how to sort out what is the existing disease and what is the infection, it can again become challenging. But one thing is for sure: all these infections are caused by an organism. So, what you really need to do is, the underlying diagnostic is to demonstrate the presence of the organism. Whether you demonstrate it depending on the infection in the spinal fluid or in the brain or, you know, some peripheral organ system, that is going to be key to making the diagnosis. So, all your clinical acumen is good, but that alone may not be sufficient.
Dr Berkowitz: Very good. So, when you see a, a patient now who has a new neurologic symptom in the context of an immune-mediated disease who's on immunomodulatory therapy, what goes through your mind? Are you thinking this disease and this drug, and sort of what are the infections, and does the syndrome match? Or are you thinking, you know, you can't always rely on the imaging to distinguish between, say, a flare of an MS and PML because white matter lesions could look similar? How do you sort of approach this scenario when it comes up? 
Dr Nath: So, you're right. You have to keep an open mind so that even though you know some infections are more likely to occur with certain types of medications, that doesn't mean that others cannot occur. So, I think when you first see the patient, you should not jump to conclusions, but rather have an open mind. But yes, for example, your patient is on natalizumab, the chances of PML are going to be high. It's a very interesting drug. It does not cause immune compromise in the periphery, but what it's doing is preventing these cells from getting into the brain. So, because then it's acting at the blood-brain barrier. So that means that organisms that are already present in the brain have an opportunity to get reactivated. Turns out you don't have a lot of organisms in the brain, except JC virus seems to be one of them that does somehow, in some individuals, manage to reside out there. And so that can get reactivated. It can get reactivated in the periphery and then enter the brain, too. So, where the very specific mutations have to occur in that virus in order to take residence in the brain. That would be a suspicion that you might have, and MRI can be useful in, again, helping you think about that possibility. If you have typical lesions involving the U fibers, they're demyelinating, usually you do not have much edema around them because patient is immune compromised, but certainly within the brain in these individuals. And so, then you need to demonstrate the organism. The demonstration of the organism should be in the spinal fluid and not in the blood because in the virus, it can-- is reservoir in the kidneys and in the lymph nodes, and periodically it'll shed into the blood. Detection of the organism in the blood can be a false positive, but in the spinal fluid, it shouldn't be there unless you have an infection. Or if you cause a traumatic tap, I guess, if a patient is viremic, that's a possibility, but those are extremely rare. So at least for PML, that's the way that you would diagnose it. Now, you can develop, for example, if an individual is on fingolimod, you can get a wide variety of infections. Here it's a totally different type of mechanism of action. Here the cells are trapped within the lymph nodes, so that means now your entire periphery is immune compromised, right?  So here you can get viral infections, bacterial infections, fungal infections. So here, if a patient presents with new neurological symptoms, you have to have a really open mind for all these possibilities. Now, let's say a patient was on dimethyl fumarate, and dimethyl fumarate causes neutropenia early on. So here you have to worry about an individual developing bacterial infections, so latent tuberculosis or bacterial meningitis can occur in these individuals. That's something to keep in mind. It's not that other infections cannot occur with dimethyl fumarate, you can see PML and other things too, but the chances of bacterial infections are greater. So, you got to make sure that you draw all the cultures for that purpose. Similarly, if you're on a complement inhibitor, like a C5 inhibitor or the thing that I could use in NMO, there are the chances of meningococcal meningitis. So, these patients, you need to prevaccinate them before you start these kinds of treatments and look for that possibility. When you suspect bacterial infections, particularly acute bacterial meningitis, there time is of essence. Also, in some of the acute viral infections, for example---herpes encephalitis is another one---you have to be so careful, and if you suspect any of them, even if they're with possibly atypical manifestations, you treat first and then diagnose later, and draw all your cultures, whatever you need to, and just treat them. And these infections can also cause cerebral edema, so one has to be careful about doing spinal taps in these individuals. You want some kind of neuroimaging before you do them. In the days when we didn't have neuroimaging, we used to say, "Okay, if your patient has focal neurological signs or is comatose, you don't do it." But these days, you can get imaging very quickly and very easily. All the-- Because of our stroke management, we've learned how to do them so quickly. So, I think there's little excuse not to do imaging and prevent herniation from occurring. 
Dr Berkowitz: That's very helpful. So, using the information we know about the drug, and we're going to rapid-fire review some of that in a bit to know what infections the patient is susceptible to, but acknowledging that any patient can get any infection, right? Whether they're on particular medications or not. And then if you're not sure, based on the neuroimaging, which as you said, is helpful, but not always helpful in distinguishing between infections and flares or, as you said, in the case of meningitis, encephalitis, early on at least, especially in immunocompromised or immunomodulated, quote unquote, patient might not see the typical imaging. So really, when safe, getting CSF or cultures, PCRs, and other infectious studies too is really gonna be the definitive diagnostic maneuver here. Is that fair summary across the board? 
Dr Nath: I think you said that absolutely right. And you summarized that correctly. And, you know, thing about infection, a lot of neurological diseases are, you know, diagnosed by clinical acumen, like your Parkinson's and Alzheimer's and others. Think about infections is caused by an organism, demonstrate the organism, right? That should be your goal. It doesn't mean that clinical acumen is not important, but here you have an opportunity to demonstrate the organism, so you should depend upon that. 
Dr Berkowitz: Okay. Well, you gave us a nice segue by talking about some of the infections to worry about with some of the medications. So what I'd like to do now for the sort of second half of our interview here is to go through some of the more common medications used for MS, and if we have time, for NMO, and just sort of go kind of rapid fire here, and for each medication, if you can tell us the kind of top infectious concerns and whether when to consider them or what screening needs to take place before or during administration of the medication, and then any vaccine considerations we should be aware of. Some of these will obviously be quite short depending on the medicine. So, going back to the two medications I alluded to earlier that were the only ones in play when you and I last saw each other on the wards when I was a medical student, beta interferon, glatiramer acetate, any infections or vaccine considerations with these medications? 
Dr Nath: No, I think they're probably your safest medications now as far as immunomodulatory therapies are concerned. These two, and IVIG, if you ever use them, are probably the safest, do not require any vaccine considerations, per se.
Dr Berkowitz: Perfect. Okay. So, moving on to fingolimod and others in the sphingosine-one phosphate receptor modulator family, what are the infectious considerations? Any prescreening or vaccination considerations? 
Dr Nath: I think all your patients should be prescreened for antibodies to JC virus, because there is a risk for PML, and those who are positive should be closely monitored. So, it's not an absolute contraindication for using these medications, but they just require closer monitoring. With this class of drugs, PML is of consideration. Also, these varicella-zoster virus infection, yeah, with that you can develop zoster encephalitis or myelitis. It can present with motor symptoms as well, which can be atypical. You don't usually see them otherwise in immune-competent individuals. So, varicella-zoster, sometimes you can develop encephalitis, also vasculitis with varicella-zoster, so one has to be careful. So, getting the shingles vaccine can be actually very helpful to prevent these things. And then some patients can even develop herpes simplex encephalitis also, and that can be extremely atypical. So, they don't- they can involve the basal ganglia, can involve the brain stem and cerebellum. So again, your index of suspicion should be very high. Interestingly, although HSV encephalitis has been associated with NMDA receptor encephalitis, those reports of NMDA receptor encephalitis have not been published yet with NMS patients. Not sure why, maybe they just have been missed. But that doesn't seem to be a major concern. And then there are a whole host of other infections that can occur with this class of drugs, and that can include toxo; fungal infections, particularly crypto. There's a case report of histoplasmosis; hepatitis virus, particularly hepatitis C; and then the poxvirus is a good example. You can get molluscum contagiosum; warts with papillomavirus; you can get atypical mycobacteria; and even Kaposi sarcoma, which is HHV8. So, there's a huge variety of infections with the sphingosine one phosphate receptor modulators. 
Dr Berkowitz: And any- aside from screening for JC virus before initiating these, any- and then continuing to monitor for JC antibody index, any other considerations as far as labs to send, monitoring before or on the drug or vaccine considerations for patients on fingolimod and the others in this category, siponimod, etcetera? 
Dr Nath: Yeah, there are a lot of things to consider. All the details are really available in the chapter if you look at them. But briefly, all the things that one could potentially vaccinate patients for, all these infections I mentioned, one should do so. The timing is critical so that if you can do it before treatment, I think, before starting treatment, that is absolutely important. And you got to give them at least, you know, two to three weeks for these vaccines to take effect before starting your medication. If your patient already arrives on a medication, then you got to play this game of you know, before the next dose, give them again two to three weeks before the next dose and start vaccinating them and get all the vaccines in. Broadly, about the things to worry about the vaccines are you have live vaccines, and you've got the inactivated vaccines or the subunit vaccines. You have to be careful with live vaccines, because if your patient is immunocompromised, that virus can sometimes itself cause harm. For example, you know, yellow fever is one, and there you can develop encephalitis from it. Measles, mumps, rubella, these are all live vaccines. Now, the good thing is that a lot of us have been immunized very early in childhood, but that may not be the case any longer. And so, these things, one has to be very careful with when you're giving live vaccines, that we want to avoid them as much as possible, and individuals are gonna be immune-compromised. But all the others, meningococcus, for example, you should- the HPV vaccines, the varicella zoster vaccines, all these things, you've got to pre-vaccinate and make sure that they have an antibody response to them before starting immunocompromising therapy.
Dr Berkowitz: Perfect. Okay, moving on to some of the other orals. What infectious and/or vaccine considerations do we have with teriflunomide? 
Dr Nath: Okay, yeah. Teriflunomide is a very interesting drug. It's relatively safe. There is concern about the possibility of varicella zoster infection, people have reported that, and also tuberculosis. But PML is extremely rare, if not at all, and we haven't seen herpes encephalitis quite yet. 
Dr Berkowitz: Got it. How about dimethyl fumarate?
Dr Nath: Yeah. So dimethyl fumarate is... as I mentioned earlier, it's interesting because it causes this neutropenia. It's transient, but it occurs early on, and these patients can be at risk of PML, although small. They can develop varicella zoster virus infection, herpes encephalitis, and also fungal infections. For example, cryptococcal infection has been reported with dimethyl fumarate.
Dr Berkowitz: Okay. We've spoken a bit about natalizumab and PML, and you have extensive information on this in your article, and I'll defer the reader to that. But for natalizumab, what are the key points every neurologist should know about natalizumab and PML as far as from the practical perspective, screening, frequency of screening, when to worry, when to not use natalizumab at all in the first place based on what you find in your screening for JC virus? What are the key points every neurologist should know? 
Dr Nath: Uh, yes. You bring up an important point, and that is all patients should be monitored for JC virus. If they're JC virus-negative, so that's your most ideal patient to go on natalizumab, but that doesn't mean they cannot get infected with the virus. In fact, there's an interesting study claiming that, you know, patients, when they get these infusions, they're all sitting in the same room getting infused. Some have JC virus, some don't have JC virus, and so there's the potential that we may be aiding the transmission here in some way or another. The virus is an interesting one. It comes out in urine, and then it's spread through oral contamination, gets into the tonsils, and then spreads from there to your marrow and resides in the kidney and the marrow, as well as the lymph nodes, forever. So, you, you have to monitor these patients to see that during the course, even if they're negative, they could turn out positive. So, every six months or a year, an antibody test should be done on all patients irrespective. If a patient already has antibodies, that's not an absolute contraindication. It just means you've got to monitor them closely for development of new symptoms, and if, whenever there are new symptoms, don't just assume this is due to MS, but just make sure the MRI is done with and without contrast. The- and if there's still a suspicion, that you do a CSF evaluation for JC virus. Just detecting, looking for JC virus in the blood, a rising titer is another thing that can help you. And so, the titer is also important. And the reason you have rising titers is it means that there's an infection that's already occurred in the brain, and the immune system is reacting to that infection by increasing titers. But that alone is not sufficient to make the diagnosis. You still- that gives you an index of suspicion. You've got to then do the MRI and the spinal tap to, you know, be absolutely certain. So, each patient is a little bit different, so the way you monitor them is going to depend on where they are. You know, if they've had prior immunomodulatory therapy before starting natalizumab, or if they're on natalizumab for more than two years, then the chances of PML are much greater, so you may want to monitor them more closely. Uh, they never had any prior immunomodulatory therapy, you're just starting natalizumab, maybe once a year is sufficient. So, I think you've got to tailor it depending on what your risks are for each patient.
Dr Berkowitz: Perfect. That's very helpful. And again, you write extensively about PML and natalizumab and PML considerations in your article. So, for a more detailed and in-depth discussion of what we just discussed, definitely hope readers will take a look at your article. Okay. Last but not least---certainly not least, 'cause we're using these probably, it seems, the most commonly in many places I've worked---rituximab, ocrelizumab are B-cell therapies for MS. What are some of the infectious and vaccine considerations related to these infusion medications? 
Dr Nath: So, there's concern for PML with anti-B-cell therapies also, maybe not to the same degree as natalizumab, but the same principles should be applied. A lot of people think that these are relatively safe. I don't think so. I think we see enough number of patients on B-cell therapies with PML. So, I would use the same caution because these infections are... you know, can be fatal. So, one should be very careful, even with anti-B-cell therapies. And just with natalizumab, you also have the risk of VZV infection causing shingles. HSV1 has been reported, but there's another interesting complication that has been reported with anti-B-cell therapies, and that is severe West Nile encephalitis. And as mosquitoes-borne diseases are getting more and more prevalent, and we're seeing West Nile cases erupting every summer, I think one's got to be, you know, very cognizant of the fact that this can occur. These patients should take precautions to prevent mosquito bites from occurring and not expose themselves to areas where they could be at risk for it. Unfortunately, there is no vaccine for it and no specific treatment for West Nile. So, all one can do is use prevention strategies for mosquito bites. 
Dr Berkowitz: Yeah, I'm glad you mentioned that. I think the only really truly severe neuroinvasive cases I've seen of West Nile virus have indeed been in patients who were being treated with B-cell therapy. Not, if I'm remembering correctly, for immune-mediated disease, but for a lymphoma, so probably other confounding factors there. But yeah, it's a disease we learn about and think about, but I've only seen the most severe cases in patients who had abnormal immune systems, so I'm glad you flagged that. This has been a very helpful discussion, and I've learned a lot from you. I learned a lot from your article, just as I did when you were my attending some 20-something years ago on the wards when I was a medical student. So, it's good to continue learning from you through your writing and research, and today from getting to talk to you again. I encourage our readers to read your article and to bookmark those tables for when these considerations come up for your patients on these immunomodulatory therapies and you're wondering which infections to worry about and how to manage vaccines in this patient population. So again, today I've been interviewing Dr. Avi Nath about his article on vaccine considerations and infection risk in multiple sclerosis and related disorders, which he wrote with Dr. Amit Bar-Or. This article appears in the April 2026 Continuum issue on multiple sclerosis. Be sure to check out Continuum Audio episodes from this and other issues, and thank you again to our listeners for joining today. 
Dr Nath: Thank you so much, Aaron, for that wonderful interview, and I'm extremely proud of all your accomplishments over the last 20 years. You've done an amazing job, and it was such a pleasure to see you and to be able to do this interview with you. Thank you again. 
Dr Berkowitz: Thanks. That means a lot. I never would have imagined- we won't say 20, how many, but 20-something years ago as the medical student looking up to you and all your expertise on these infections and all of your research that led to so much of our understanding on these, that I would find myself interviewing you two decades later. So, for all the students listening, you never know where you'll end up, but I appreciate your very kind words. 
Dr Nath: That's what we hope for all our students. Thank you so much. 
Dr Berkowitz: Thanks again. 
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.

There are many treatment options for people with relapsing MS. Patients should be carefully monitored to assess treatment response, and a change in treatment approach should be considered if safety concerns emerge.
In this episode, Teshamae Monteith, MD, FAAN, speaks with Ellen M. Mowry, MD, MCR, and Daniel Ontaneda, MD, PhD, coauthors of the article "Treatment of Multiple Sclerosis" in the Continuum® April 2026 Multiple Sclerosis and Related Disorders issue.
Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida.
Dr. Mowry is the director of the Multiple Sclerosis Experimental Therapeutics Program and a professor of neurology at The Johns Hopkins University School of Medicine in Baltimore, Maryland.
Dr. Ontaneda is the director of research at the Mellen Center for Multiple Sclerosis and a professor of neurology at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Cleveland, Ohio.
Additional Resources
Read the article: Treatment of Multiple Sclerosis
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More about the American Academy of Neurology: aan.com
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Host: @headacheMD
Guest: @EllenMowryMD
Full episode transcript available here
Dr. Monteith: There are so many new treatment strategies for multiple sclerosis, which is a blessing, but it does come with the complexity of really just trying to nail down the approach. I just got finished talking to Drs Ellen Mowry and Daniel Ontaneda about their article on treatment of multiple sclerosis. We discussed relapses, weighing escalation versus early high-effective treatment and progressive disease. This is a must-listen-to podcast. I hope you enjoy it as much as I enjoyed talking to them. 
Dr. Jones: This is Dr. Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.
Dr. Monteith: This is Dr. Teshamae Monteith. Today, I'm interviewing Ds Ellen Mowry and Daniel Ontaneda about their article on treatment of multiple sclerosis, which they wrote with Dr. Darin Okuda. This article appears in the April 2026 Continuum issue on multiple sclerosis. Welcome, both of you. How are you? 
Dr. Mowry: Great. And thank you so much for having us. 
Dr. Monteith: Absolutely. So, why don't you both introduce yourself? 
Dr. Ontaneda: All right. My name is Daniel Ontaneda. I'm a neurologist at the Cleveland Clinic. I spend the majority of my time doing research, but I still dedicate about a day a week to seeing people with MS in clinic. 
Dr. Mowry: I'm Ellen Mowry. I'm also a neurologist, but practice at the Johns Hopkins University. And similar to Dan, I mostly work on research, but also have an active clinical care component, taking care of people with MS. 
Dr. Monteith: Well, thank both of you for writing this article and being on our podcast. I assume you guys have probably known each other for quite a while now. 
Dr. Mowry: Yes.
Dr. Ontaneda: Yes.
Dr. Monteith: What inspired you to get into multiple sclerosis research and then clinical care? 
Dr. Ontaneda: I always loved neurology, and I think a lot of us who go into neurology are attracted to the complexity of the human brain and how the nervous system works. But what really hit home to me was a family member of mine who had multiple sclerosis, and he was being treated in a time where we really didn't have super effective disease-modifying medications. And so, as I went through my medical career, I always kind of kept an eye on what was happening with multiple sclerosis, and I started my training at a time where it was really flourishing in terms of the medications available, so that's what inspired me to go into MS. It's a disease that we can definitely treat, and you can change outcomes for people. So, that was it. 
Dr. Monteith: Yeah, that personal experience can be very impactful. 
Dr. Mowry: My journey started, actually, because I was thinking about whether I wanted to be a physician at all, and I happened to land, just after high school, a position with a neurologist who happened to mostly focus on multiple sclerosis and taking care of folks with multiple sclerosis. And by the end of the summer, I knew I wanted to go to med school and I wanted to be a neurologist and I wanted to work with people with MS. I thought I would be a clinician exclusively, but I think as time went on and I started to hear the consistent questions that people I served were asking in the clinic and realizing that those questions could be turned into research projects that could address their concerns, I moved more and more towards research.
Dr. Monteith: Great. There are a lot of really detailed information in the article, so I think that research mind is very useful, and I see that in the writing. Why don't we talk about the goal of the article?
Dr. Ontaneda: So, I think the goal of the article was to set out kind of what the large view of what treatment for multiple sclerosis looks like. And, you know, many times we divide the treatment of multiple sclerosis into these large pillars, and I think that's what we did in the article. The first was, you know, what do you do with a person who has an MS attack or relapse? The second is, what medications do we use to treat the relapsing forms of multiple sclerosis where there is a lot of acute inflammation, focal inflammatory lesions that are occurring? And then the final one is, what do you do with individuals who have a more progressive form of the disease where they're accruing disability slowly and gradually?
Dr. Monteith: And what were some of the main points?
Dr. Mowry: Dr. Okuda provided a really nice section on the treatment of acute relapses in multiple sclerosis, and it's important to understand what we talk about when we are saying "relapse". For people with MS, many symptoms can fluctuate and occur and then get better over time, and sometimes people with MS use the same term of "relapse" to describe those symptom fluctuations. As neurologists, when we're thinking about relapse, we're really trying to think about symptoms that can be attributed to new focal inflammatory events somewhere in the central nervous system. Typically, these are accompanied---if you were to get an MRI at the same time---by a new lesion or MS spot, as I like to call them, on MRI scan. And so, it's important to distinguish when somebody is talking about symptoms, whether they are true new symptoms that could be mapped to a place in the central nervous system. Because alternatively, a lot of people who've had attacks or relapses in the past can have what we call pseudo-relapses, and these are essentially recrudescence of old symptoms, typically in a similar pattern as what had occurred in the past. And these can be brought out by things like fever or infection, sometimes stress. And pseudo-relapses are not thought to be due to new development of immune system-induced injury and therefore would be less likely to respond to treatment; and in fact, treatment may be contraindicated for those events. We also talked a little bit in that article about how relapses are treated, talking about the use of high-dose steroids for true new relapses, but also kind of cautioning that those are not necessarily free of concerns, especially if you have a pseudo-relapse or there could be an infection going on. And that ultimately, the decision as to whether to treat a relapse really is a shared decision-making because it's thought that although the steroids can speed up recovery from a relapse, they may not have a major impact on ultimate recovery. And so, a lot of the shared decision-making comes in here because for a mild relapse, you might choose to forego a course of high-dose steroids. 
Dr. Monteith: Daniel, any other main points? 
Dr. Ontaneda: Yeah. On the side of treating relapses, I think one of the other things that probably has changed a lot, at least during the course of my training, is that in the past, whenever we had identified a relapse, as Dr. Mowry has clearly defined, we would typically treat with intravenous high-dose corticosteroids, typically with methylprednisolone. And that was kind of our go-to. We would either do it in an infusion center or we would set it up with home care. And I think one of the things that our field learned over, I would say, the last five or ten years is there's an abundance of studies that show that you can give that same dose of methylprednisolone. Rather than giving it IV, you can give it orally. No pun intended, as I tell my patients, a lot of pills to swallow because we use fifty-milligram prednisone pills, and they have to take 1,250 a day. The pharmacy always pushes back on that many pills, but really the advantage of being able to take steroids orally that way for three to five days is really, I think, one, better for people with MS because they can do it in the comfort of their own home, and two, I think also when you look at the costs associated with that treatment, it is the most cost-effective option.
Dr. Monteith: And what are some of the latest developments that you're really excited about that weren't in the article? 
Dr. Mowry: A lot of the article focused on the approach to treatment of people with what we've traditionally called relapsing/remitting multiple sclerosis. So, this is the kind of MS that traditionally presents with a relapse or an attack initially, although some of that nomenclature is changing, actually. And the article focused a lot on the strategies surrounding treatment of somebody with newly diagnosed relapsing MS, and thinking about this vast number of disease-modifying therapies that are available to people with MS and their clinicians, and how to think about the strategy with respect to largely centered around the efficacy class of the medication, whether people should take an approach of using a higher-efficacy therapy---meaning a medicine that in clinical trials was more likely on average to suppress relapses as well as new lesions---or whether there's still a good argument for the case of using an escalation approach, using some of the more modest efficacy medications that also probably in general have lower risks, monitoring for response to treatment and changing if the medication isn't working. And so, there's still a lot of debate in the field, I would say, even though many people have moved towards a one-size-fits-all kind of approach. I think there's still a lot of debate in the field about the evidence underlying that. And, you know, full disclosure, Dr. Ontaneda and I are each running parallel and very complementary clinical trial programs to address this very question, the results of which should be available within the next year, year and a half. 
Dr. Monteith: Well, we can't wait that long. Give me some clinical pearls to how we initiate these modifying therapies. Like, what are the pearls that we need to have in our mind? 
Dr. Ontaneda: Yeah. I think when we think about starting the disease-modifying therapy in an individual who has an active form of multiple sclerosis, I think, you know, one of the cornerstones I would say of making that decision is shared decision-making. I think we tend to sit down with the patient and analyze the data that we have at hand, what we know about their multiple sclerosis, and we use several factors to inform how likely we think their disease is gonna be active or potentially might not respond to the initial treatment you give. And we look heavily at the MRI. The MRI is really a useful marker because it shows us, one, how many lesions a person might have---both, you know, where those lesions are and also kind of the amount of lesions. Lesions, certainly, that are in the spinal cord, a very large burden of diseases. A lot of active lesions, which we determine by the presence of contrast-enhancing lesions, really helps us inform on disease severity. I would say that was our number one tool that we use to decide and help us decide how we think that person's MS is gonna do over time. And then the second thing that we put into the equation also is, you know, how well do we think this person is going to tolerate our medications? All our disease-modifying medications act through suppression of the immune system, and we know that that carries some risks associated with it. Some of those risks are stuff like infections. Some of those can be simple infections that really don't have major consequences, but some of them can be quite serious, including the need for hospitalizations or prolonged antibiotic treatment courses. And so, we also look at what, you know, the underlying risk of a person has for infection. This kind of is determined by, one, A, how many infections they've had up to date, and also how much disability they had. I would say in our average patient who when we see them, they're probably typically pretty young, in their twenties, thirties, forties, they typically don't have a lot of infectious risks. And therefore, I think there's kind of a move to saying, "Well, actually their risk of infections is quite low." And we put that together with, you know, also what the preference of the patient might want. So, do they prefer to take a pill, for example? Do they prefer a medication where they receive that via infusion every six months and they don't really have to think about it? There are some people that don't like going into a hospital, and they might prefer an injection type of those medications. And so, after a complex discussion of all those factors, we take into consideration how much risk the patient wants to take as well, and we come up with a rational choice of a couple of medication options. So, I think it's challenging sometimes because we have over two dozen medications. There's the risk of you saying, "There are these twenty-four medications, you can pick one." And I think our job as neurologists is to kind of pare those down, talk about, in a person like yourself, these are the two or three medications that I would recommend using. Why don't you review them? And then we bring them back, and we kind of make a final decision with, one of the key factors that I think is important to remind people is that you're gonna start this medication, and we are gonna monitor to make sure it's working. We're gonna monitor to make sure you're tolerating it well. And although it's an important, the first decision you make, I think one key theme that we tell people is, we can revise our strategy whenever we like. We just have to think about it and do it in a way that we think is gonna make sure that their MS is under the best control. And then we think about the ultimate goal of treatment, which, in multiple sclerosis, is the absence of any attacks and also the absence of any new lesions on MRI. And that's where whether you are offering more of the high-effective medications or more moderate- or low-efficacy medications, that's where there's a little bit of controversy still in our field, and that's what our trials are trying to answer. 
Dr. Monteith: Excellent. So now we've selected a particular option- and I love those points with shared decision-making, using the MRI to guide and then kind of risk tolerance related to infection. But now a patient's still having relapses, and I know the goal is zero, but, you know, there's some margin. What are the pearls to advance to more high-efficacy therapies? 
Dr. Mowry: Yeah, that's a great question. Dr. Ontaneda in the article actually talked about the literature surrounding monitoring for breakthrough disease and when to say this much is too much, and there's actually not a definite right answer. It's clear that more active disease early in the course is probably more of concern than, say, developing, you know, a new spot in your fifties or something to that effect. So, different people have different thresholds. I know at our center, we tend to be pretty on top of making changes for breakthrough disease. So, what we typically do is reimage people about six months after they start a medication to establish a new baseline. And sometimes, because of delays in starting or because the medications take a while to kick in, there might be a new spot or two. So, if that's the case, I really only get concerned if the spots are also taking up the dye or enhancing to indicate they're really quite recent, and I think, "Ugh, that's not something I'd like to see six months after starting a medication." And so that otherwise is sort of the reference scan, moving forward, to evaluate the medication, and I have a very low threshold for changing, particularly if somebody is on a moderate-efficacy therapy. To me, I think, well, our goal of trying the moderate efficacy therapy is essentially to see if we could get away with a medicine that is probably, on average, safer and that will still work for your MS. But if the answer is no, I personally don't like to stick around too much on them. One caveat I would say is that if somebody develops what appears to be a new lesion or spot on higher-efficacy therapy, before presuming that that new area of activity is a definite new MS event, I always like to rethink carefully, did I get the diagnosis correct? Or could this be an early infection such as, you know, progressive multifocal leukoencephalopathy in people on natalizumab in particular? Because I see breakthrough activity so rarely in people on higher-efficacy therapies that I just like to rethink my diagnosis and the differential prior to making switches to, typically, another higher-efficacy therapy in that case. But that, again, is a little bit of shared decision-making. It's sometimes contextual. If a person is using a self-administered medication and they have a little breakthrough, sometimes you can solicit some history, saying, "Oh, I actually kind of stopped taking it for a few weeks because something was going on, and I really want to retry." And that's very reasonable as well. Dan, do you have any other thoughts? 
Dr. Ontaneda: No, I think I agree. That's really close to how I practice myself as well, and the majority of people at my center. I think that we are learning that when you start a treatment, many times---depending on how deeply you look---you can find evidence of ongoing disease, and that's something that we struggle with. It's almost like we have tools to treat inflammation in terms of new MS lesions and new relapses. And so, when those are present, it's pretty clear that you probably have to switch medication. I think a slightly trickier issue is when, for example, you have a person who might be stable. They don't have an attack. But you notice that they're worsening, and they tell you they're worsening. I think our ability and tools for that is a little bit harder, and we recognize that that can actually happen fairly early in the disease. And that's why we're trying to rethink this mantra that we've had for many years, where we kind of divide MS up into relapsing and progressive, and we see people develop progressive MS 10 to 15 years after they've had a relapsing form of the disease. So, I think that's just a reality of clinical practice. And we don't have as many tools to treat that gradual worsening, which is kind of what the rest of our article spent some time talking about.
Dr. Monteith: You've also written about the clinical trial long-term extension studies. And what are the few points that you take away from the emergence of these types of publications over the past few years?
Dr. Mowry: Yeah, well, long-term extension studies can be really helpful to understand whether the findings that are evidenced during the randomized portion of trials themselves continue into a longer term. And for people with MS, understanding these data can be really helpful because, particularly when we're looking for impact of a given treatment or a strategy on disability worsening, often it takes longer than the short-term portion of the trial to truly understand if the medication or strategy has an impact on insidious worsening that Dan is speaking about. Many trials have demonstrated a short-term benefit, but we think a lot of times that benefit is probably because of the reduction in relapses, which sometimes leave a permanent mark on neurologic function. But the extension studies are trying to understand a little bit more about whether the effect on disability worsening is sustained, and also to look a little bit more deeply at long-term safety, especially when it comes to medications that do increase the risk of infection. The caveats, though, in interpreting those types of studies are that people drop out, and so probably the people who drop out of those studies are really different. They may be either less disabled and they think, "Oh, you know, I'm done. I feel good." Or potentially more disabled and they think, "Ugh, I have more things to do I've got to take care of. What's going on?" And so that kind of dropout can produce some bias in interpreting the results. Dan, any other thoughts? 
Dr. Ontaneda: No, I think that's spot on. I mean, I think that when we're trying to decide on what general philosophy to use, right? Like, you're seeing a patient for the first time. They've recently been diagnosed with MS, and you have... you know, I kind of bin them into three options. You can start a low-efficacy, a moderate, or a high-efficacy medication. And the first piece of information you could use is clinical trials, and Dr Mowry very clearly identified why some of that data might be a little bit biased and isn't, you know, completely applicable to the patient who's in front of you. The second thing that we might look at is observational data, and there's a wealth of observational data that shows that, in general, people on higher-efficacy medications tend to do better over time. But one of the challenges we have is that there's always biases related to those observational study designs. And so, I think you have to interpret them with a little bit of caution because there are reasons people start specific medications in people. And when you look at them in a purely observational study, even if you do some fancy way of addressing those biases, such as propensity, there always is the possibility of some residual bias. You know, that's part of the reason why we're doing the trials that Dr Mowry described, because we really need kind of long-term evidence to show that these medications actually can affect disability ten, twelve years after started. And I think pragmatic clinical trials, like the ones we're running, are really gonna be the key to answer those questions. We all have our favorite approaches right now, but I think that the data to actually demonstrate what's best for people with MS is really needed. 
Dr. Monteith: Great, and there's so much in this article. I mean, we didn't even touch on radiological isolated syndrome, monitoring MS therapeutically, and treatment of progressive MS. Any final take-home points? 
Dr. Ontaneda: Yeah. Maybe I will touch a little bit on the side of progressive MS, because it has been, you know, the MS that we historically have not been able to treat as much. So, we described there's over two dozen therapies approved for relapsing forms of MS. For purely progressive forms of MS that don't have any evidence of activity, we really only have one approved therapy, and it appears that that therapy actually does work through active inflammation anyway. And in the article, we highlighted examples of studies that have been negative, but also some recent examples of studies that have been positive, specifically with a new class of medication called BTKI, or Bruton tyrosine kinase inhibitors. We just recently heard of a second molecule that also had positive results in this realm. So, we're excited that, you know, in the next four to five years- 
Dr. Monteith: I'm sorry. Can you just go ahead and say what that molecule...You're leaving people hanging. 
Dr. Ontaneda: One molecule is tolebrutinib, which already has a positive study in secondary progressive MS in individuals without activity. And then the second compound that has been studied with positive trial results, we only have summary results from that, is a medication called fenobrutinib. And we think these two compounds that are part of a single class, the hope is that maybe they can address some of that gradual worsening that occurs in MS. And then the question comes whether we should use those from the get-go or if we should just use them later. So, a whole sort of variety of different questions. But I think important to call out for clinicians that this area where we had no available treatments for so many years might be changing. 
Dr. Monteith: Well, thank you both. I really loved this conversation. I learned a lot listening to both of you, and I look forward to your clinical trial results. 
Dr. Mowry: Thank you so much for having us.
Dr. Ontaneda: Thanks so much. It was our pleasure.
Dr. Monteith: Again, today I've been interviewing Doctors Ellen Mowry and Daniel Ontaneda about their article on treatment of multiple sclerosis, which they wrote with Dr. Darin Okuda. This article appears in the April 2026 Continuum issue on multiple sclerosis. 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.