Podcasts about Aan

In the second episode of this series, Dr. Tesha Monteith and Dr. Peter Goadsby discuss the prediction of treatment responses for personalized medicine. Show transcript: Dr. Tesha Monteith:  Hi, this is Tesha Monteith with The Neurology Minute. Today I'm speaking with Peter Goadsby from the Division of Biomedical Sciences at King Abdullah University of Science and Technology about key trends in headache medicine and some of the most impactful research presented at the AAN annual meeting. Can you talk a little bit about prediction of treatment response for personalized medicine? Dr. Peter Goadsby I hope that AI gives us some direction. I haven't seen anything yet, but I don't think we've done enough with it to make it stunning yet. I think that the AI systems ... I'd love to know, for example ... I've been using triptans for 30 years and apart from using sumatriptan first when [inaudible 00:00:51] had a triptan simply because it's the commonest triptan, which is generally what I do, that's a pretty naff rule when you think about it. I'd like to think that AI systems could work out where we should be going in terms of acute therapy, preventive therapy, whether there are particular red flags or amber flags you might say in a person's broad history. I don't think we've got there yet, but I actually think we will get there. I think we'll be surprised and we'll learn things about the biology of the disorder and about the pharmacology of these medicines, which must have subtle differences because we all see people who respond to one and don't respond to another, and you sort of scratch your head, but you're happy that it happens. Dr. Tesha Monteith:  I agree with you, and I think the future is really bright for headache medicine and the potential of AI to move the needle. Peter, thank you again for joining us and sharing your insights. I really appreciate you being on. This is Tesha Monteith. Thank you for listening to The Neurology Minute.

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

In deze aflevering van De Interieur Club Podcast gaat Evelien Reich in gesprek met ontwerper Carole Baijings.Als je aan Carole Baijings denkt, denk je aan kleur. Aan gradients, grids, transparantie, fluo details en een bijna wetenschappelijke liefde voor nuance. Maar in dit gesprek wordt vooral duidelijk: kleur is voor Carole geen decoratief laagje achteraf. Kleur is onderdeel van het materiaal, van de plek, van het maakproces en van de emotie van een ontwerp.Evelien en Carole praten over haar jeugdherinneringen aan geur en kleur, haar liefde voor roze, haar start in de creatieve wereld en hoe ze uiteindelijk in design terechtkwam. Ook vertelt Carole over haar ateliermatige manier van werken: zelf kleuren mengen, modellen maken, materialen testen en ruimte laten voor wat er onder je handen ontstaat.Het gesprek gaat langs samenwerkingen met onder andere HAY, Arita, Herman Miller/MillerKnoll, Japanse ambachtsmensen, sieraden, brillen, bloempotten, meubels en telefoonhoesjes. Klein of groot, industrieel of uniek: Carole benadert elk object met dezelfde intensiteit.In deze aflevering hoor je onder andere:Hoe Carole kleur ziet als onderdeel van materiaalWaarom roze voor haar meer is dan een lievelingskleurHoe geur en kleur verbonden kunnen zijnWat een ateliermatige manier van werken haar oplevertWaarom je als ontwerper niet altijd van A naar B moet willenHoe gradients, transparantie en fluo details haar signatuur vormenWaarom samenwerking met ambachtsmensen zo waardevol isHoe belangrijk doorzettingsvermogen is in het ontwerpvakWaarom elk detail klopt: van product en prijs tot verpakking en merkWat interieurprofessionals kunnen leren van haar manier van kijkenEen inspirerende aflevering voor interieurontwerpers, architecten, stylisten, makers en iedereen die met meer aandacht naar kleur, materiaal en detail wil kijken.Luister nu naar S5A32 van De Interieur Club Podcast: Evelien Reich in gesprek met Carole Baijings.Muziek/producent: Music from #Uppbeathttps://uppbeat.io/t/hartzmann/sunnyLicense code: TUXOJDHYFVJS1TBH

In the final episode of this series, Dr. Justin Abbatemarco and Dr. Ruth Dobson discuss navigating conversations with women and their families about potential ocrelizumab exposure during pregnancy and breastfeeding.  Read more about this abstract on the AAN website.   Show transcript: Dr. Justin Abbatemarco: Hello and welcome back. This is Justin Abbatemarco on our final episode with Ruth Dobson from Queen Mary University of London on our AAN annual meeting abstract humoral vaccine response and one year follow-up of infants potentially exposed to ocrelizumab during pregnancy and breastfeeding. Our previous two episodes, we've talked about this wider world of monoclonal antibodies during pregnancy and then we've talked about the data specifically around ocrelizumab. But Ruth, I think the million-dollar question is how do we approach this in clinical care? How can we talk to women and their families during this really exciting time and how do you employ this, especially within the MS space? Dr. Ruth Dobson: So it's a really exciting time for women in our families, but it can be really hard to talk about. And many of my patients have loads of anxieties about living with a chronic disease, thinking about pregnancy and breastfeeding, worrying about how to balance effective treatment against wanting not to cause any potential harm or risk to their child. A lot of this is actually about informed decision making and having those discussions and having the data to back up those discussions. What this data really helps us to do is have those discussions in a way that is meaningful for women so we can say, "Well, actually where you have received treatment up until the point of conception, we can see that babies are being born with normal B cell levels, that the drug is not causing long term effects to the best of our knowledge in your babies." And similarly, when people are thinking about restarting treatment postpartum, we know specifically in MS that the relapse risk is highest in those postpartum three months. So often people feel quite anxious about that and want to get on top of their disease, but don't want to forego breastfeeding for that. We are now in a situation where women no longer have to choose. We know that the drug doesn't get into breast milk. We can reassure them. Certainly in Europe, we've had a label change around CD20s now being safe for use in breastfeeding. So we can have that discussion and enable people to actually have that pregnancy and breastfeeding experience that they want to have without having to make compromises in the way that maybe people have previously. Dr. Justin Abbatemarco: I love that message because our messaging before was compromising. But now we can really have an informed discussion with patients and their families that MS does not define them and does not define their family planning needs. I love that idea about breastfeeding as well. I think that's a really anxious time. It's a really intimate moment that we as the medical community shouldn't dictate that we should allow that to be a time that the families get to choose on how they want to approach that. And so this data helps so much. Maybe we could just talk about that label change, how we could think about keeping up with our governing bodies and how they talk about these medications, because it's really challenging if a patient checks on the internet and sees something different from our FDA or other European governing bodies. How do you think through that? Dr. Ruth Dobson: Yeah, it's really hard and it creates lots of anxieties for patients. And I think even at the moment, the label washout is different across CD20 drugs. It's different between Europe and America. And that in itself causes anxiety. But in some ways that helps with those discussions to say, these labels, they're not always based in the kind of evidence that we need that's really helped us to recruit women studies to get people taking part in this research. And also in Europe, it shortened the washout period. These studies work in terms of changing that policy. I think that regulators are increasingly recognizing, certainly in Europe, class effects. They're increasingly recognizing the importance of including people considering pregnancy, lactating mothers in studies so that we can actually better answer these questions without having to wait eight, 10 years for these kind of data to come out before we can allow our patients to really partake in informed decision making. Dr. Justin Abbatemarco: And your work, work like it is so important for these conversations. So we'll hopefully have some really great discussions and be able to come back and have better conversations with patients because of it. So Ruth, thanks. Dr. Ruth Dobson: Thank you.  

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.

Begin dit jaar klaagde Trump zijn eigen belastingdienst aan voor tien miljard dollar. De zaak leek juridisch geen kans van slagen te hebben, maar nu is er toch een schikking: een fonds van bijna twee miljard dollar voor Trumps politieke bondgenoten, betaald door de belastingbetaler. Bovendien zou Trump en zijn familie voortaan onschendbaar zijn voor toekomstige vervolging. Democraten stellen dat dit corruptie op klaarlichte dag is. Daarover Björn Soenens, oud VS-correspondent voor de VRT. (07:17) Aan het front in Libanon Vandaag melden Libanese autoriteiten zeker 19 doden door Israëlische aanvallen. Inmiddels zijn al sinds maart meer dan 3000 mensen gedood in Libanon. En dat terwijl er vrijdag nog een het staakt-het-vuren tussen Israël en Libanon is verlengd. Wat betekent dit staakt het vuren in de praktijk? En welke gevolgen ondervinden journalisten die er verslag van doen? We vragen het correspondent Gilad Perez en collega-journalist Bram Vermeulen, die net terug is uit Libanon.   Presentatie: Nadia Moussaid

Ping! is uit. De nieuwe roman van Tweakers-journalist Arnoud Wokke en GZ-psycholoog Sarah Sporken laat zien hoe een algoritme een 18-jarige opslokt. Aan tafel ontleden ze het driekoppige monster van smartphoneverslaving, en Randal bekent dat hij normaal met TikTok doucht. In Ping! volg je Emmy, die net 18 is, een nieuwe telefoon uitpakt en per ongeluk viral gaat. Vanaf daar trekt het algoritme haar steeds dieper naar binnen. Arnoud Wokke (tiende keer aan tafel, jubileum aankomend) en Sarah Sporken schreven twee jaar lang aan de roman: een psychologische vertelling vanuit twee perspectieven, Emmy en haar telefoon, met verzonnen social media om toekomstbestendig te blijven en een handgetekende cover. Aan tafel pakken ze de thema’s uit het boek beet: cognitieve dissonantie, FOMO, het driekoppige monster van smartphoneverslaving, en waarom Sarah het in twintig jaar spreekkamer steeds vaker langs ziet komen. Plus de ironie van het maakproces: een boek tegen social media, gecoördineerd via Slack. Use the social media. Destroy the social media. Kill it from within. Over de gasten Arnoud Wokke is techjournalist bij Tweakers, schrijft sinds de eerste iPhone over smartphones en sociale media, en waarschuwt al jaren voor algoritmische verslaving. Tien jaar geleden schreef hij het non-fictieboek I Love/Hate Smartphones. Ping! is zijn eerste roman. LinkedIn: Arnoud Wokke Website: arnoudensarah.nl Sarah Sporken werkt twintig jaar in de GGZ en de afgelopen tien jaar als GZ-psycholoog. Ze ziet sociale media en aandachttrekkende apps steeds vaker een rol spelen bij haar cliënten, vooral bij jongeren. Ping! is haar eerste boek. Website: arnoudensarah.nl Sponsor: Vodafone Alleen met Vodafone True Unlimited heb je altijd het snelste internet (tot wel 1 gbit/sec). Check voor meer info en alle Unlimited-abonnementen vodafone.nl/unlimited of loop even een winkel binnen voor extra info!In deze aflevering 0:00:00 Tiende keer aan tafel, en de jubileum-rekensom loopt mis0:02:17 Een 18-jarige, een nieuwe telefoon, en het idee voor Ping!0:04:30 Wat Sarah in twintig jaar spreekkamer ziet veranderen0:11:09 Wie Emmy is en waarom haar viraliteit nodig was voor het verhaal0:15:29 Bovenmenselijk: op de wc gaan zonder je telefoon0:20:12 Cognitieve dissonantie, of hoe je jezelf praat in de verslaving0:23:08 Randal’s 24 uur zonder telefoon (en de vergeten verjaardag)0:25:24 De douchescène die niemand had verwacht0:33:05 Wat je kind ziet als jij twintig keer per uur checkt0:36:28 Verveling als verloren superkracht0:38:01 Het driekoppige monster: bestaat smartphoneverslaving eigenlijk wel?0:46:01 De goede kanten van social media (want die zijn er ook)0:51:01 Is de smartphone de draak in dit verhaal?0:52:31 Fictieve social media: toekomstbestendig schrijven1:01:43 De handgetekende cover en de doelgroep1:06:49 De Slack waarin Arnoud en Sarah het boek bouwden1:07:59 Volgende week: het complete maakproces in een tweede aflevering Genoemd in deze aflevering Ping!, de psychologische roman van Arnoud en Sarah over smartphoneverslaving I Love/Hate Smartphones, Arnoud’s non-fictieboek van tien jaar geleden over smartphones Tweakers, waar Arnoud al sinds de eerste iPhone over tech schrijft Jetty Sporken, Sarah’s zus en ontwerper van de handgetekende cover van Ping! Tips van de tafel Sarah: Probeer eens 24 uur zonder telefoon. Je krijgt klap op klap, maar je ziet ook wat je mist. En vooral: hoe verslaafd iedereen om je heen blijkt te zijn.Sarah: Zet een app-limiet op de NOS-app of een andere reflex-app. Niet omdat het je echt stopt, maar omdat het je heel even bewust maakt.Randal: Doe je telefoon de wc uit. Bovenmenselijk, weet hij, maar het scheelt schermtijd.Jurian: Tijdens therapie: smartwatch af, telefoon uit het zicht. Anders gebeurt er nog wel iets belangrijks in dat ene uurtje.See omnystudio.com/listener for privacy information.

Het verhaal van Jordan Belfort is spraakmakend en door Martin Scorsese vastgelegd in The Wolf of Wallstreet. Een geweldige film, die wat sales betreft, echt tijdloos is en meerdere facetten van het salesvak belicht. Zowel de goede als de slechte.In deze aflevering behandelen we een aantal salestips die in de Wolf of Wallstreet voorbijkomen. Aan het einde zetten we deze salestips in een top 5 met een onbetwiste nummer 1. Uiteraard zit er ook een  AI-blokje in de aflevering waarin Pepijn uitlegt wat hij precies doet met AI-agents en welke taken je zo'n AI-agent kunt laten doen.Mocht je aanvullingen of opmerkingen hebben, of een luistervraag, reageer dan op Spotify, LinkedIn of stuur ons een e-mail via contact@verkoopisalles.nl.

In deze aflevering is Josephine van der Hoeven van Funny Business te gast. Ze is gedragseconoom, criminologe en faciliteert culturele transformatie met behulp van humor. Orly Polak en Joriene Beks gaan met haar in gesprek over hoe humor helpt om lastige onderwerpen bespreekbaar te maken en hoe het kan bijdragen aan gedragsverandering en cultuurontwikkeling. We verkennen waarom humor spanning verlaagt, schaamte doorbreekt en mensen ontvankelijker maakt voor feedback en verandering. Aan de hand van praktijkvoorbeelden bespreken we hoe je met luchtigheid beweging creëert in complexe groepsdynamieken. Een gesprek over timing, veiligheid, zelfspot, groepsgedrag en de kunst van het spiegelen. Veel luisterplezier!

Stel dat je de economie opnieuw kon ontwerpen, net zoals Montesquieu ooit de politieke macht opsplitste. Dat is precies wat duurzaamheidsonderzoeker en auteur Babette Porcelijn voor ogen heeft met haarTrias Economica.In deze aflevering gaat Marnix Kluiters met haar in gesprek over de verborgen machtsstructuren in onze economie. Wie voelt de gevolgen, zonder ooit een stem te hebben gehad? Babette laat zien hoe de drie economische machten: de publieke macht, de financiële macht en de bedrijfsmacht, steeds verder verstrengeld raken, en wat dat betekent voor onze democratie.Verder bespreken ze geldschepping en groeidwang, aandeelhoudersmacht versus stakeholderszeggenschap, rechten voor de natuur en toekomstige generaties, de rol van Europa als tegenmacht, en hoe je kleine maar fundamentele stappen kunt zetten. te beginnen bij Big Tech.

De discussie over de centenindex laait opnieuw op. Nu er ook een alternatief wordt aangereikt, lijken de regeringspartijen het maar niet eens met elkaar. Gaat er effectief iets doorgevoerd worden? En moet wie in een fermette woont schrik beginnen krijgen voor een nieuwe belasting? Of werd er aan paniekvoetbal gedaan voor niets? Aan tafel: Bart Eeckhout, Stavros Kelepouris, Joline MaenhoutProductie: Laurens Bervoets (hoorstroom) & Dries VermeulenEindredactie: Sam Feys & Rik Boey Wil je reageren? Mail naar podcasts@demorgen.beSee omnystudio.com/listener for privacy information.

In part one of this series, Dr. Justin Abbatemarco and Dr. Ruth Dobson discuss current evidence on monoclonal antibodies in pregnancy and breastfeeding and prior understanding of CD20 therapies.  Read more about this abstract on the AAN website.  

Deze aflevering gaat over de psychologie achter onze Engelse spreekangst en hoe we die handrem er definitief afhalen. Aan het einde deel ik een primeur over mijn gloednieuwe Engelse Community die de eerste week van juni opengaat: the English Confidence Club!Wil je de boot niet missen en direct de aanmeldlink ontvangen zodra de deuren openen? Stuur me dan nu alvast een mailtje via tess@mail.learnenglishwithtess.com en dan krijg je de aanmelding zodra ik live ga!

­Over een maand wil FC Emmen graag 22 spelers onder contract hebben. Nu is dat de helft. Dus is het spitsuur voor de nieuwe directeur voetbalzaken Ernst Söllner. Na het gedwongen vertrek van technisch directeur Nico Haak en het opstappen van de voltallige raad van commissarissen, is ook het contract met clubicoon Michel van Oostrum als hoofdscout niet verlengd, laat Söllner weten. „Nee. Dat was geen fijn telefoontje om te plegen. Michel is toch mister Emmen. Die had ik liever met een leukere boodschap opgebeld'', vertelt de voormalig profvoetballer. Söllner vervolgt: „We zijn een club die op elke euro moet letten. Dus gaan we verder met mensen met een doorlopend contract, anders blijf je afkopen. Ik ben me bewust dat je in deze functie niet met iedereen vrienden kunt zijn en af en toe een harde boodschap moet brengen.'' ­ Aan de andere kant verwelkomt de club Björn Zwikker in de technische staf voor zijn stage tot trainer in het betaalde voetbal. „Dat is een zeer talentvolle trainer met frisse ideeën over het voetbal. We moeten altijd waken dat we een club worden van ouwe-jongens-krentenbrood.'' Voor de selectie geldt dat FC Emmen meer wil doen met minder centen. Het spelersbudget is met 2,2 miljoen euro tonnen lager dan vorig seizoen. Omdat de club niet wil inboeten op kwaliteit op het veld, moet de groep flink inkrimpen. „We willen naar maximaal 22 spelers. Dat waren er dik dertig'', stelt Söllner. Gijs Bolk is daar straks niet meer bij. De talentvolle verdediger vertrekt zo goed als zeker naar De Graafschap. „We hebben er alles aan gedaan om hem te behouden. We hebben zelfs zijn ouders thuis uitgenodigd en zijn samen uit eten geweest. We hebben ons verhaal verteld en voor Emmer-bergrippen een goede aanbieding gedaan. Dat vond de kamp Bolk ook. Als ze dan alsnog voor een prachtige club als De Graafschap kiezen dan gaan we straks gewoon goed uit elkaar.'' ­ Ook het behouden van doelman Luca Unbehaun lijkt een schier onmogelijke klus. „Unbehaun heeft van ons een maximale aanbieding gekregen. Natuurlijk wil hij nog eens een stap omhoog maken, maar als hij bijtekent dan speelt hij gewoon iedere week in de schijnwerpers.'' Goed nieuws is er ondertussen voor de fans van Freddy Quispel. De Emmenaar blijft gewoon bij zijn club, zo laat Söllner doorschemeren. De voetbaldirecteur blikt ook terug op het pijnlijke vertrek van technisch directeur Nico Haak en waarom hij als bestuurslid zelf diens takenpakket grotendeels overnam. „We wilden Nico Haak graag behouden als hoofd voetbalontwikkeling en dat ik dan de plek in de directie overnam. Nico heeft veel verstand van voetbal, maar ik denk dat ik zakelijke beslissingen beter kan nemen. We kwamen er helaas niet uit met elkaar en raakten in conflict.'' ­ Na een lange praatsessie hebben directie en de huidige technische staf onder leiding van hoofdtrainer Menno van Dam inmiddels de samenwerking voor volgend seizoen beklonken. „We willen ook geen trainerskerkhof zijn in Emmen. Er was een roep om het vertrek van Menno van Dam, maar we wilden geen derde trainer in korte tijd ontslaan. Hij is als jonge coach bij ons gekomen en we laten hem nu zeker niet verzuipen.'' Aan de tafel van Radio Meerdijk wordt verder besproken wie van het dozijn aan proefspelers in de smaak valt en waarom aan sommige voetballers wordt gevraagd zich te specialiseren op een andere positie. Verder wordt duidelijk met welke oud bekenden gesproken wordt voor een nieuwe rol bij FC Emmen. ­ * Vragen voor in de podcast? Mail naar: william.pomp@dvhn.nl * FC Emmen op de voet volgen? Abonneer je hier op onze nieuwsbriefSee omnystudio.com/listener for privacy information.

Aan tafel deze week: bijzonder hoogleraar onderzoeksjournalistiek Nikki Sterkenburg, burgemeester Doetinchem Mark Boumans, burgemeester Apeldoorn Ton Heerts, rechtbankverslaggever van De Telegraaf Saskia Belleman, raadsheer aan het Gerechtshof Amsterdam Annemarieke Kleene, Mpanzu Bamenga Tweede Kamerlid voor D66 en NOS-correspondent Afrika Elles van Gelder. Presentatie: Twan Huys Wil je meer weten over de gasten in Buitenhof? Op onze website vind je meer informatie. Daar kan je deze aflevering ook terugkijken en je vindt er natuurlijk nog veel meer gesprekken: https://bit.ly/buitenhof-17-mei-26 Burgemeesters in Nederland zijn het zat. Democratisch genomen besluiten worden steeds vaker ondermijnd door intimidatie, bedreiging, geweld en ontregeling, schrijven ze aan politiek Den Haag. Dit naar aanleiding van de protesten tegen asielopvang die in verschillende gemeenten steeds vaker flink uit de hand lopen. Na weer een week vol ongeregeldheden schuiven aan in Buitenhof: burgemeesters Ton Heerts en Mark Boumans en hoogleraar onderzoeksjournalistiek Nikki Sterkenburg. Duizenden doden, hongersnood en seksueel geweld; in Soedan vindt de grootste humanitaire crisis ter wereld plaats, maar aandacht voor het conflict is er nauwelijks. Sinds 2023 bevechten het regeringsleger en paramilitaire rebellen in het land elkaar. Waarom grijpt de internationale gemeenschap niet in? We gaan het erover hebben met Elles van Gelder, NOS-correspondent in Afrika, en D66-Kamerlid Mpanzu Bamenga. De strafzaken tegen Ali B en Marco Borsato toonden opnieuw aan hoe ingewikkeld een zedenzaak kan zijn. Hoeveel aangiftes leiden tot een zaak? En hoeveel daders worden uiteindelijk veroordeeld? De nieuwe zedenwet is nu ruim een jaar van kracht. Staan de slachtoffers sterker? Aan tafel raadsheer aan het Gerechtshof Amsterdam Annemarieke Kleene en rechtbankverslaggever van De Telegraaf Saskia Belleman.  

Een merk bouw je niet alleen met een goed product. Je bouwt het door te durven starten, te blijven bewegen en telkens opnieuw te kiezen voor de lange termijn. Dat is precies wat Pleuni Holthausen doet met MOAI, het watersportmerk dat begon met SUP-boards en inmiddels doorgroeit richting kajaks, lifestyleproducten en internationale expansie.Pleuni begon al op haar 21e met ondernemen. Tijdens haar studie reisde ze met haar vader naar China, waar een fabriek een importeur zocht voor zeilboten in Nederland. Wat begon met zeilboten, groeide uit tot distributie en groothandel in SUP-boards. In 2017 besloot Pleuni haar eigen merk te starten: MOAI.Ze zag een gat in de markt. Aan de ene kant waren er goedkope boards van mindere kwaliteit. Aan de andere kant dure merken met een sterke focus op de mannelijke watersportscene. Pleuni wilde iets anders bouwen: een kwalitatief goed board dat beter aansloot bij gezinnen, vrouwen en recreatieve watersporters die vooral willen genieten op het water.In aflevering 88 vertelt Pleuni hoe ze haar merk vanaf het begin internationaal heeft neergezet. Niet door te wachten tot kansen vanzelf kwamen, maar door beurzen te bezoeken, winkels te benaderen en letterlijk met boards in een huurauto door Amerika te rijden. “Het is gewoon bij iedere winkel heel lief lachen, je verhaal vertellen en hopen dat ze erin trappen”, zegt ze met een glimlach.Wat haar verhaal sterk maakt, is dat ze niet alleen het succes laat zien. Pleuni vertelt ook eerlijk over de moeilijke kanten van ondernemen. Na de coronapiek kwam er een enorme omzetdaling, ontstond er te veel voorraad en kwamen marges onder druk te staan door hogere inkoopprijzen, transportkosten en internationale onzekerheid. Het dwong haar om opnieuw naar haar bedrijf te kijken.Haar belangrijkste les? Groei vraagt om structuur. “Ik had eerder iemand moeten aanhaken die me kon helpen met structuur”, vertelt ze. Als creatieve ondernemer zit Pleuni vol ideeën, maar ze ontdekte dat een bedrijf pas echt schaalbaar wordt als processen, verantwoordelijkheden en keuzes helder zijn.Toch blijft haar grootste kracht juist haar ondernemerslef. Pleuni gelooft in doen, testen, reizen, praten met klanten en leren door te vallen en weer op te staan. Ze wil niet per se de grootste worden, maar wel een merk bouwen met betekenis. Een merk waar mensen fan van worden. Haar droom is helder: MOAI laten groeien van watersportmerk naar lifestylemerk, vergelijkbaar met hoe O'Neill ooit begon.Wat haar blij maakt? Mensen op het water zien met een board dat zij heeft gemaakt. “Elke keer als ik iemand op mijn SUP zie staan, denk ik: hoe cool is dit?”Wil je het hele gesprek horen? Luister naar aflevering 88 via Spotify of https://femaleleadersclub.nl/podcastOver de Female Leaders Club Dé community voor succesvolle vrouwelijke ondernemers die niet alleen dromen van groei en impact, maar het ook waarmaken. Wij geloven in ‘lift as you grow'. Wil je meer weten over onze missie en events? Bekijk dan de website: https://femaleleadersclub.nlZelf een keer te gast zijn in de podcast? We interviewen alleen vrouwen die verder zijn in hun ondernemerschap of leiderschap. Ben jij dat? Aanmelden kan via: https://femaleleadersclub.nl/podcastMeer weten over Pleuni Holthausen? Ga naar www.moaithebrand.com voor meer informatie over haar werk.

In aflevering #143 duiken we in het verse CPB-rapport De hoogste bomen vangen minder wind: belastingdruk op inkomens en vermogens (mei 2026). Het CPB constateert vrij helder: op papier is ons belastingstelsel progressief, in de praktijk niet. De bv is de belangrijkste ontsnappingsroute, de doorschuifregeling maakt uitstel praktisch tot afstel, de Bedrijfsopvolgingsregeling kost 1,1 miljard per jaar ten gunste van enkele duizenden personen, en de hypotheekrenteaftrek jaagt de huizenprijzen aan zonder dat het eigenwoningbezit toeneemt. Het CPB zegt het zelf, woordelijk: het belastingstelsel remt de groeiende ongelijkheid niet af en draagt er soms zelfs aan bij. En Den Haag? Het coalitieakkoord Aan de slag van D66, VVD en CDA spreekt niet over vermogensongelijkheid, behoudt expliciet de BOR, de doorschuifregeling, de hypotheekrenteaftrek en het lage vpb-tarief, en legt in de hervormingsagenda alvast vast dat belastingen "niet verder worden genivelleerd". D66-fractievoorzitter Paternotte stelde dat er een grens zit aan hoe zwaar je bedrijven nog kunt belasten — als antwoord op de vraag of vermogens zwaarder belast zouden moeten worden. Dat is dus de meest progressieve coalitiepartner. Ondertussen waarschuwt het SCP dat de bezuinigingen op zorg en sociale zekerheid de ongelijkheid juist verder vergroten. We leggen uit hoe het stelsel werkt, voor wie het werkt, en waarom een rapport dat een aardverschuiving zou moeten veroorzaken, in Den Haag wordt afgedaan als kennisnemen. Deze aflevering werd gemaakt met ondersteuning van Wim Brons van remotepodcast.nl. Een aanrader voor als je op afstand een podcast wil maken met fantastische geluidskwaliteit. Wil je ons steunen? Dat kan: je kunt vriend van de show worden: https://vriendvandeshow.nl/studio-tegengif ***SHOWNOTES*** CPB, ‘De hoogste bomen vangen minder wind: belastingdruk op inkomens en vermogens' (2026) https://www.cpb.nl/publicatie/de-hoogste-bomen-vangen-minder-wind-belastingdruk-op-inkomens-en-vermogens Ministerie van Financiën, ‘Ambtelijk rapport Aanpak fiscale regelingen' (2023) https://open.overheid.nl/documenten/3da70b0e-9ec0-4619-a4eb-d01bc0198a05/file Ministerie van Financiën, IBO vermogensverdeling ‘Licht uit, spot aan: de vermogensverdeling' https://www.rijksfinancien.nl/sites/default/files/rapporten/vermogensverdeling/IBO-Vermogensverdeling-rapport.pdf NRC, Hoofdredactioneel commentaar, ‘Politieke onwil om iets aan de groeiende ongelijkheid te doen schaadt uiteindelijk heel Nederland' https://www.nrc.nl/nieuws/2026/05/08/politieke-onwil-om-iets-aan-de-groeiende-ongelijkheid-te-doen-schaadt-uiteindelijk-heel-nederland-a4927169?utm_source=clipboard&utm_medium=clipboard&utm_campaign=share&utm_term=share-modal NRC, Marieke Stellinga, ‘Wanneer gaan we eindelijk eens minder scheef belasten' https://www.nrc.nl/nieuws/2026/05/08/wanneer-gaan-we-eindelijk-eens-minder-scheef-belasten-a4927367

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 Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz 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.

In dit gesprek bij De Nieuwe Wereld analyseert emeritus hoogleraar Paul Frissen de transformatie van de overheid naar een 'gevaarlijke staat'. Aan de hand van zijn nieuwe boek, De Neutrale Staat, fileert hij hoe de overheid gedreven door technocratie en morele maakbaarheid steeds verder doordringt in het private leven van de burger. Van de Schijf van Vijf tot de Toeslagenaffaire: Frissen legt bloot hoe de roep om maatwerk en redelijkheid onbedoeld leidt tot disciplinering, ongelijkheid en de uitholling van de democratische rechtsstaat. Een pleidooi voor een staat die weer afstand bewaart en de ruimte laat aan het fundamentele verschil tussen mensen.------------------Steun DNWMaak het geluid van de Nieuwe Wereld mogelijk. Zonder uw steun geen DNW! Word lid of doneer:

In the May episode of the President's Spotlight, Dr. Jason Crowell and Dr. Natalia Rost provide a leadership perspective on the 2026 Annual Meeting.  Stay informed by watching the President's Spotlight video.   Show transcript:  Dr. Jason Crowell: Hey, this is Jason Crowell with today's Neurology Minute. Once again, we have Natalia Rost joining us for our monthly check-in. Of course, Natalia is the president of the AAN. Natalia, thanks for joining us again this month. Dr. Natalia Rost: Hi, Jason. Dr. Jason Crowell: So what have you been up to since we last spoke a month ago? Dr. Natalia Rost: Well, as you know, we just came back from Chicago, where our 2026 AAN annual meeting took place, and of course, it's the largest gathering of neurologists and neuroscience professionals worldwide, so not a small feat. We welcome this time a record-breaking 16,000 plus participants in person in Chicago and online, representing 110 countries and all 50 states, what I call a microcosm of the global neurology community. It was amazing, and an opportunity to step back, reflect, and be reminded that progress in neurology happens not in isolation, but through our shared purpose and collaboration, and the energy and optimism coming out of this meeting is something I'm so proud of. Dr. Jason Crowell: I can only imagine what a whirlwind week that is for you. So now that it's past us and you reflect back, what stands out to you from the week? Dr. Natalia Rost: Well, it was clear during that meeting that we're advancing what comes next and that's why science and research was at the heart of the week and why sustained investment in discovery matters. I had the privilege of seeing colleagues modeling leadership in neurology, both on stage and behind the scenes and attendees engaged with cutting-edge science, shared insights across disciplines, and bringing those new insights and techniques home to their practices, institutions, and communities. Dr. Jason Crowell: Now, your presidential plenary at the meeting was about neuroscience at the crossroads. What would you say is the most urgent challenge facing our neurology community right now? Dr. Natalia Rost: You know, as a physician scientist myself, I'm focused on how to sustain progress at this moment of rapid scientific advancement. Our neurology community is gathering extraordinary volume of knowledge, but translating that momentum into durable impact requires continued commitment to research, workforce development and collaboration across disciplines are key topics. And I feel that this is a pivotal time for our field. Dr. Jason Crowell: And if I could ask you to just briefly take off your president hat for a moment, personally, what was your favorite thing about the week? Dr. Natalia Rost: What always been for me for over two decades now, the chance to come together as a community. I always say AAN is our home and the annual meeting is like one big homecoming for us. There's a unique energy that comes from being in the same space with colleagues from across neurology, sharing ideas, learning from each other, and just reconnecting with people who care deeply about this field, your colleagues. And while our work can be demanding, as we know on a day-to-day basis, the meeting helps remind us why we chose this profession and why it matters. Dr. Jason Crowell: And lastly, what would you say for anyone who was not able to make it to this homecoming in Chicago? Dr. Natalia Rost: We got you. We have great resources for those who weren't able to join live and you can get high-level highlights or diving into programming online. Access it all at theaan.com/am. Dr. Jason Crowell: Natalia, thanks so much. Dr. Natalia Rost: Thanks for having me.  

In deze uitzending van De Nieuwe Wereld analyseert Harry Geels samen met filosoof Ad Verbrugge de diepe gezagscrisis die onze samenleving ontregelt. Aan de hand van Verbrugge's nieuwste boek verkennen zij hoe de roep om individuele vrijheid ontaardde in een kille expertocratie, waarin de menselijke maat is opgeofferd aan KPI's en bureaucratie.Van de invloed van de jaren '60 op het huidige neoliberalisme tot Harry's persoonlijke ervaringen voor de klas: dit gesprek legt bloot waarom jongeren snakken naar echte rolmodellen en waarom we dringend terug moeten van 'branding' naar karaktervorming. Een pleidooi voor bezieling, lokale gemeenschappen en het herstel van de menselijke waardigheid in een digitale wereld.------------------------------------Haal je kaartjes voor de Theater Tour! ⭐19 mei: Grote Kerk Alkmaar met Maurice de Hond: https://grotekerkalkmaar.nl/tickets/seizoen-25-26/de-nieuwe-wereld-ondergang-van-het-avondland/?showId=3878151937-177159177816 juni: De Maagd, Bergen op Zoom: Willem Middelkoop: https://www.demaagd.nl/agenda/ondergang-van-het-avondland-de-nieuwe-wereld-4xn6

Aan tafel deze week: veiligheidsexpert van Instituut Clingendael Bob Deen, gouverneur van Limburg Emile Roemer, hoogleraar virologie Marion Koopmans, topwetenschapper Rosa Rademakers.  Presentatie: Maaike Schoon Wil je meer weten over de gasten in Buitenhof? Op onze website vind je meer informatie. Daar kan je deze aflevering ook terugkijken en je vindt er natuurlijk nog veel meer gesprekken: https://bit.ly/buitenhof-10-mei-26 Een militaire parade zonder materieel en een tribune met nauwelijks internationale gasten; de Russische viering van de overwinning op nazi-Duitsland staat in schril contrast met die van voorgaande jaren. De oorlog in Oekraïne is vastgelopen en de positie van Poetin staat onder druk. Hoe stevig zit de Russische president nog in het zadel nu de gevolgen van de oorlog voor de bevolking steeds voelbaarder worden? Te gast in Buitenhof: Bob Deen, veiligheidsexpert van Instituut Clingendael. Gouverneur van Limburg Emile Roemer maakt zich zorgen over uitholling van onze democratie. Burgers voelen dat ze over steeds minder zaken wat te zeggen hebben en politici lossen grote probleemdossiers als stikstof, wonen, migratie en vestigingsklimaat niet op. Zijn woedende mensen bij een gemeentehuis een ondermijning van de democratie?  De Vlaamse topwetenschapper Rosa Rademakers heeft onlangs in Los Angeles een van de Breakthrough Prizes gewonnen – de prestigieuze “Oscars van de wetenschap”. Ze krijgt de prijs voor haar baanbrekende ontdekking van een genetische fout die zowel ALS als frontotemporale dementie kan veroorzaken. Een doorbraak die het internationale onderzoek de voorbije vijftien jaar in een stroomversnelling bracht. Rademakers schuift zondag aan. Het hantavirus zorgde deze week voor grote bezorgdheid. Hoewel dit virus geen extreme dreiging vormt, laat het zien dat het belangrijk is dat landen zich wapenen tegen toekomstige virusuitbraken. Hoe goed is Nederland voorbereid op een nieuwe pandemie? We gaan erover in gesprek met Marion Koopmans, hoogleraar virologie. 

Het moest de kers zijn op de grootse carriere-taart van entrepreneur par excellence, Hennie van der Most; Rivoli. Een attractiepark aan de Maas in Rotterdam. En na het succesvol ombouwen van een ziekenhuis, een watertoren en een ongebruikte kerncentrale was het in Rotterdam tijd om aan de slag te gaan met een voormalige vuilverbrander. Aan enthousiasme geen gebrek, maar door tal van andere oorzaken lukt het maar niet om het park te openen. Het drama dat zich heeft afgespeeld aan de Maas in Rotterdam en in het onstuimige leven van Hennie is gefilmd door documentaire-maker Max Ploeg. Hij volgde Hennie anderhalf jaar lang voor de film Pretpark Hennie en Willemijn en Dolf stappen graag in de achtbaan van het leven van Hennie van der Most. Verder: * Je leeft om te sporten, maar kun je er ook van leven? * Het WK is voor 'Hard Gras' een kleedkamer vol dictators en dode Duitsers. * En wie schrijft, die blijft bewijst de 100 jarige David Attenborough Presentatie: Dolf Jansen & Willemijn Veenhoven Cabaret: Owen Schumacher, Aron Elstak, Lotte Velvet, en Marcel Harteveld Column: Teun van den Elzen Livemuziek: Marlon Pichel (met special featuring van Danny Vera)

De tweede etappe in de Giro d'Italia was er een met twee gezichten. Aan de ene kant schreef Guillermo Thomas Silva geschiedenis door als eerste Uruguayaan ooit een rit in een grote ronde te winnen, aan de andere kant was er weer een vreselijke valpartij. Nu met nog grotere gevolgen dan gisteren. Niek Goedvolk neemt de schade op met Roxane Knetemann en wielerverslaggever Daniël Dwarswaard. Wie zijn de grootste slachtoffers? Werd de koers na de neutralisatie niet te snel weer hervat? En hoe lekker is het dat Thymen Arensman vandaag geen tijd verliest, maar zelfs een paar secondes wint? We bespreken het allemaal in een nieuwe aflevering van In Het Wiel.See omnystudio.com/listener for privacy information.

Geopolitieke omwentelingen laten allerlei nieuwe allianties ontstaan. De meest opmerkelijke is wel die van Canada met de Europese Unie. In hoog tempo verdiept, verbreedt en intensiveert die coalitie zich. Buitengewoon symbolisch hierbij was de uitnodiging aan premier Mark Carney om als eregast de Top bij te wonen van de Europese Politieke Gemeenschap in Jerevan, Armenië. Jaap Jansen en PG Kroeger duiken in de zwaartepunten, de focus en de opmerkelijke inspiratiebronnen. Van het ontstaan van Canada in de 15e eeuw, cognac-export in het begin van de 20ste eeuw tot Havèl in 1978 en de Finse president nu. *** Deze aflevering is mede mogelijk gemaakt met donaties van luisteraars die we hiervoor hartelijk danken. Word ook vriend van de show! Heb je belangstelling om in onze podcast te adverteren of ons te sponsoren? Zend ons een mailtje en wij zoeken contact. *** De jonge Jean Monnet was als avontuurlijke cognac-handelaar al gefascineerd door Canada, zijn ondernemende migrantencultuur, innovatieve geest en openheid. Het eerste verdrag van 'zijn' EEG buiten Europa was dan ook met dat land, over hightech samenwerking rond kernenergie. En die avant garde rol werd traditie. In 1976 sloot de EEG een breed kaderakkoord met premier Pierre Trudeau, in 2017 met zijn zoon Justin het CETA-vrijhandelsakkoord met meteen weer zo'n brede opzet erbij, de Strategische Partnerschapovereenkomst. Deze aanpak is het model geworden voor alomvattende akkoorden die de EU wereldwijd sluit, zoals met India, Japan, Australië, Vietnam en Mercosur. Met Canada gaat deze coalitievorming in hoog tempo de diepte in. Bij de ruimtevaart in de ESA, Horizon Europe rond R&D, als enig niet-Europese land in het lange-termijn defensie-investeringen programma SAFE, met Oekraïne en in de JEF-coalitie rond de Pool en Oostzee. En nu als eerste niet-Europees land actief in de door Emmanuel Macron geïnitieerde Europese Politieke Gemeenschap die samenkwam in de Kaukasus, dichtbij een aantal spanningshaarden in de actuele geopolitiek. Mark Carney benut dit nadrukkelijk om met de EU samen afstand te nemen van allereerst Amerika, maar ook van China. Daarmee vult hij zijn geruchtmakende speech in Davos, eerder dit jaar, heel concreet in. Hij riep de ‘middelmachten’ op zich te emanciperen van 'hegemonen' als Poetin, Xi en Trump en realistisch te bezien wat zij met elkaar kunnen waarmaken. Alleen zo kunnen ze hun soevereiniteit bewaren. À la het kabinet-Jetten: “Aan tafel, niet op het menu.” Canada moest als een van de eersten meemaken wat zo'n 'middle power' existentieel kon bedreigen, schetste Carney scherp. Betreuren dat Trump, Poetin en Xi zich zo gedragen noemde hij zinloos. “Nostalgie is geen strategie.” Macron, Friedrich Merz, Mario Draghi en Alexander Stubb bouwen hier nadrukkelijk op voort. In de campagne in ons land klonk de echo ervan door in 'Het kan anders' en 'Het kan wél'. In Canada is inmiddels forse steun voor - zelfs – het lidmaatschap van de EU. Stubb noemt dit idee ‘a marriage made in heaven’. De Europese Commissie houdt het formeel braaf af, maar wijst op mechanismen als 'speciale partnerschapsovereenkomsten' met verwante landen. Ook voor Oekraïne en Moldavië wordt dit verkend en voor Noorwegen is het al een feit. Canada zou als hoogontwikkeld rijk land van 41 miljoen inwoners, met een bbp van 10% van de EU, ongeveer zo groot zijn als Italië en iets groter dan de Benelux of Spanje. Carney wil daarbij met zijn land de brug slaan tussen de EU en het Trans-Pacific Partnership waarin Canada een belangrijke rol speelt. Een hoogontwikkeld, vrijheidsgezind 'handelsblok' van 1,5 miljard mensen zou daarmee tegenover de 'hegemonen' geplaatst worden. En zou zoiets bij Canada zelf passen, gelet op de wortels van dit land? Wie daarin duikt ziet verrassende overeenkomsten. Hun Rudolf Thorbecke was diens tijdgenoot Lord Durham. Van een reeks losse, soevereine provincies werd na 1870 een coherente confederatie opgebouwd, die qua opbouw sterk doet denken aan de EU van nu. Warm bepleiter daarvan was nota bene queen Victoria. Drijfveer was toen al de schrik voor 'tariffs' en de expansiedrift uit Washington. Bewust koos men voor een Europese traditie met multiculturele vrijheden, een constitutionele monarchie en nadruk op betrouwbare, lange termijn relaties als land dat in essentiële, nu ook vaak zeer kritische grondstoffen op zekerheid van afnemers wilde kunnen rekenen. Carney's visioen voor zijn land als partner in de geopolitieke rol van de EU bouwt dus voort op een stevig fundament in historie en cultuur. *** Verder kijken Mark Carney speech in Jerevan Mark Carney speech in Davos Alexander Stubb: Canada in EU 'marriage made in heaven' *** Verder luisteren 578 - Oorlog voeren in een verdeelde wereld: misverstanden en mislukkingen 575 - Nederland staat niet langer op het menu, maar zit aan tafel 571 - Het kabinet-Jetten in een geopolitieke orkaan 567 - De geschiedenis beukt op Europa's deur. Caroline de Gruyter over zondagskinderen in een ruige wereld 558 – Poetins rampjaar, Jettens kans 528 - ‘Europa, ontwaak!’ Manfred Weber en de eenzaamheid van Europa 492 – Macrons Europese atoombom 484 - Hoe Trump chaos veroorzaakt en de Europeanen in elkaars armen drijft 458 - De gedroomde nieuwe wereldorde van Poetin en Xi 447 - Als Trump wint staat Europa er alleen voor 427 - Europa wordt een grootmacht en daar moeten we het over hebben 236 – Václav Havel, de dissident die president werd 137 – Joeri van den Steenhoven over slim investeren in kenniseconomie Canada 124 - 95 jaar Jacques Delors 107 - Jean Monnet, de vader van Europa *** Tijdlijn 00:00:00 – Deel 1 00:30:27 – Deel 2 01:07:06 – Deel 3 01:30:00 – EindeSee omnystudio.com/listener for privacy information.

LES 127Er is geen liefde dan die van God.Jij denkt misschien dat er verschillende soorten liefde mogelijk zijn. Jij denkt misschien dat er een soort liefde is voor dit, en een soort voor dat; een manier om de een lief te hebben, en een andere manier om een ander lief te hebben. Liefde is één. Ze kent geen afzonderlijke delen en geen gradaties, geen soorten of niveaus, geen verschillen en geen onderscheidingen. Ze is zichzelf gelijk, volkomen onveranderlijk. Ze verandert nooit naar gelang de persoon of de omstandigheid. Ze is het Hart van God en tevens van Zijn Zoon.De betekenis van liefde is duister voor ieder die denkt dat liefde veranderen kan. Hij ziet niet in dat veranderlijke liefde nu eenmaal onmogelijk is. En dus denkt hij dat hij nu eens liefhebben, en dan weer haten kan. Hij denkt bovendien dat liefde aan de een kan worden geschonken, en toch zichzelf kan blijven hoewel ze anderen wordt onthouden. Zulke dingen over liefde geloven betekent niet begrijpen wat liefde is. Als ze dergelijke onderscheidingen kon maken, zou ze tussen de rechtvaardige en de zondaar moeten oordelen, en de Zoon van God in afzonderlijke delen waarnemen.Liefde kan niet oordelen. Omdat ze zelf één is, ziet ze alles als één. Haar betekenis ligt in eenheid. En ze moet wel ontgaan aan de denkgeest die denkt dat ze partijdig of gedeeltelijk is. Er is geen liefde dan die van God, en alle liefde is de Zijne. Waar liefde afwezig is regeert geen ander principe. Liefde is een wet zonder tegendeel. Haar heelheid is de kracht die alles bijeenhoudt, de schakel tussen de Vader en de Zoon die Hen beiden voor eeuwig als hetzelfde samenbindt.Geen cursus die tot doel heeft jou te leren je te herinneren wat jij werkelijk bent, kan nalaten te benadrukken dat er nooit een verschil kan zijn tussen wat jij werkelijk bent en wat liefde is. De betekenis van liefde is jouw betekenis en wordt gedeeld door God Zelf. Want wat jij bent, is wat Hij is. Er is geen liefde dan die van Hem, en wat Hij is, is al wat er is. Hemzelf is geen beperking opgelegd, en dus ben jij eveneens onbeperkt.Geen wet waaraan de wereld gehoorzaamt, kan jou helpen de betekenis van liefde te bevatten. Wat de wereld gelooft, werd gemaakt om de betekenis van liefde te verbergen en die duister en geheim te houden. Er is geen enkel principe dat door de wereld hooggehouden wordt, dat niet indruist tegen de waarheid van wat liefde is en wat jij bent.Probeer niet in de wereld jouw Zelf te vinden. Liefde wordt niet gevonden in duisternis en dood. Toch is ze volkomen duidelijk voor ogen die zien en oren die de Stem van de liefde horen. Vandaag oefenen we om je denkgeest vrij te maken van alle wetten waaraan jij denkt te moeten gehoorzamen, van alle beperkingen waaronder je gebukt gaat en alle veranderingen die volgens jou deel uitmaken van het menselijk lot. Vandaag zetten we de allergrootste stap die deze cursus verlangt in je voortgang naar zijn vastgestelde doel.Als je vandaag ook maar het vaagste begrip verkrijgt van wat liefde betekent, heb jij een onmetelijke afstand en een in tijd ontelbaar aantal jaren overbrugd op de weg naar je verlossing. Laten we dan samen vandaag met blijdschap enige tijd aan God geven en begrijpen dat dit het allerbeste gebruik van de tijd is dat er is.Ontsnap vandaag gedurende twee keer vijftien minuten aan elke wet waarin jij nu gelooft. Stel je denkgeest open en rust. Aan de wereld die jou gevangen schijnt te houden, kan iedereen ontsnappen die er niet aan is verknocht. Neem alle waarde terug die jij aan haar povere aanbiedingen en onzinnige geschenken hebt gehecht, en laat de gave van God ze allemaal vervangen.Roep je Vader aan, in de zekerheid dat Zijn Stem zal antwoorden. Hijzelf heeft dit beloofd. En Hijzelf zal een vonk van waarheid in je denkgeest plaatsen, overal waar jij een onjuiste overtuiging of een duister waanbeeld van je eigen werkelijkheid en van wat liefde betekent, opgeeft. Hij zal vandaag door je loze gedachten heenstralen en je helpen de waarheid van de liefde te begrijpen. In liefdevolle mildheid zal Hij bij jou verblijven, wanneer je Zijn Stem toestaat om aan je schone en open denkgeest de betekenis van liefde te leren. En Hij zal de les met Zijn Liefde zegenen.Vandaag vallen de talloze toekomstige jaren van wachten op de verlossing weg tegenover de tijdloosheid van wat jij leert. Laten wij vandaag dankzeggen dat ons een toekomst zoals het verleden blijft bespaard. Vandaag laten we het verleden achter ons, om het voorgoed te vergeten. En we slaan onze ogen op naar een ander heden, waarin een toekomst daagt die in elk opzicht van het verleden verschilt.Deze prille wereld is als een pasgeboren kind. En wij zullen haar in gezondheid en kracht zien groeien om haar zegen uit te stralen over allen die komen leren de wereld aan de kant te zetten waarvan zij dachten dat die was gemaakt in haat om de vijand van de liefde te zijn. Nu zijn zij allen samen met ons bevrijd. Nu zijn zij allen onze broeders in Gods Liefde.We zullen de hele dag door aan hen denken, omdat we geen deel van onszelf kunnen uitsluiten van onze liefde als we ons Zelf willen kennen. Denk minstens drie keer per uur aan iemand die de reis met jou maakt en gekomen is om te leren wat jij leren moet. En zodra hij in je gedachten opkomt, geef hem dan deze boodschap van jouw Zelf:Ik zegen jou, broeder, met de Liefde van God, die ik met jou delen wil.Want ik wil de vreugdevolle les leren dat er geen liefde is dan die van God, van jou, van mij, van iedereen.Alle tekst- werk en handboek klassen van Een Cursus in Wonderen met Elbert nu te beluisteren en te bekijken op https://decursusmetelbert.nl

Vaar mee over de Caraïbische Zee in deze heerlijke feelgoodserie! 'Gestrand met jou' van Saskia M.N. Oudshoorn is het romantische, grappige en zonnige eerste deel van de Aan boord-serie. Uitgegeven door Z&K Sprekers: Sophie Veldhuizen, Pascal Vanenburg

In the last episode of this series, Dr. Justin Abbatemarco and Dr. Benjamin P. Trewin discuss how to apply this data into clinical practice.   Read more about this abstract on the AAN website.   Show transcript:  Dr. Justin Abbatemarco: Hello, and welcome back. This is Justin Abbatemarco and I'm joined by Benjamin Trewin where we're reviewing top abstracts from the AAN annual meeting in Chicago. Today we're talking about his abstract maintenance immunotherapy and MOGAD, early steroid benefit, dose thresholds, and disability risk. Ben, we've done this really great job of dissecting the data, steroids, non-steroidal agents. How do you think about the treating MOGAD cases in clinic though? How do you try to put this data and the data we've talked about into clinical practice? Dr. Benjamin P. Trewin: It's obviously a very good and actionable question, and our research has always tried to focus on these dilemmas facing the clinician at the bedside. And so the way that we think about this is, of course, we try to come up with some rules or some guidelines to treat all patients, as that's the most effective way of giving the message, but we need to acknowledge there is variation within MOGAD patients. There are people with low relapsing propensity who will take a very long time to relapse. You'll need to follow them for a long time. And there are ones with high relapsing propensity. So some of our previous work, we actually reviewed thousands of MOGAD patients in the literature and found that if you follow them for more than five years, over 70% actually relapse. It's just a matter of following them. So acknowledging this variation in the patients is important, but at the same time, the guideline we would probably endorse based on our research is that all patients with MOGAD after a first attack should be treated with oral corticosteroid taper, including at least five months of 12.5 milligrams per day oral corticosteroids. Now, how does that work in practice? Well, you would probably start them, and I say probably here because we don't have the strength of evidence for the very start of the course and the very end. But what did we do? Well, we start them at about one milligram per kilogram. And over probably about two to three weeks, you can bring them down to about 12.5 milligrams per day, or in children, 0.16 milligram per kilogram per day. And then you'll do that four or five months. And then over two or three weeks after that, you would step them down. Of course, you want to be careful that you don't have any adrenal issues. You would want to go slow enough for that. But at the same time, you don't want to prolong the course too long and put yourself at risk of side effects. Dr. Justin Abbatemarco: I think that's really helpful and practical. And you don't need these huge doses, it looks like, to treat these patients well and trying to really be mindful of those side effects that are truly dose dependent. And then yeah, we have some really great data. We need some randomized data to help us inform next steps, but this retrospective data, we're starting to put together this picture around B-cell depleting IVIG like we talked about. So super helpful. Ben, really excited to see you at the annual meeting. And yeah, thank you for your time and expertise. 

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 Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @headacheMD Guest: @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.

Achter de gepolijste glimlach van de VVD-top schuilt een ijzeren regime waar geen ruimte is voor discussies.Maarten van Rossem en Tom Jessen ontleden de schokkende werkwijze van de grootste machtspartij van Nederland. Aan de hand van de onthullende biografie De negen levens van Dilan Yesilgöz leggen zij bloot hoe de partijdemocratie systematisch is vervangen door een waterdichte machtsmachine.Hoe veranderde de VVD van een liberaal debatcentrum in een gesloten bolwerk waar dissonante geluiden direct worden geëlimineerd?In deze aflevering: wat de buitenwereld niet ziet van de VVD.Kijk hier deze podcast met beeld

Aan het begin van de week begon president Trump met het nodige aplomb 'Operation Freedom': een militaire actie om de vastzittende schepen in de straat van Hormuz te bevrijden. Vandaag, binnen drie dagen, kondigt hij alweer een 'pauze' van die operatie aan. Volgens Trump is deze bedoeld om de onderhandelingen met Iran een kans te geven. Maar critici wijzen op de grilligheid van het Witte Huis en constateren een gebrek aan strategie. Legt Amerika het in dat opzicht af tegen Iran? Daarover Rob de Wijk, directeur van het Centrum voor Strategische Studies. (10:37) Cruciaal moment voor Starmer In het Verenigd Koninkrijk gaan deze week miljoenen mensen naar de stembus. Hoewel het gaat om lokale besturen en de parlementen van Schotland en Wales, zijn alle ogen gericht op de landelijke politiek. Want de Labour-partij van premier Keir Starmer lijkt er ongenadig van langs te zullen krijgen, en dat brengt ook zijn positie aan het wankelen. Daarover politicoloog en kenner van het VK Casper Kirkels van de Radboud Universiteit. Presentatie: Laila Frank.

In dit gesprek op Bevrijdingsdag reflecteren Jelle van Baardenwijk en filosoof Ad Verbrugge op de diepere betekenis van vrijheid en de evolutie van de Nederlandse herinneringscultuur. Ze verkennen hoe de beleving van de Tweede Wereldoorlog door de jaren heen is getransformeerd: van de collectieve wederopbouw en de sterke sociale verbanden van de verzuiling, naar de cultuurkritiek van de jaren '60 en de hedendaagse focus op individuele rechten en maatschappelijke pluriformiteit.Aan de hand van denkers als Hegel en Kuyper analyseren zij de spanning tussen de burger en de overheid. Daarbij trekken zij scherpe parallellen met actuele ontwikkelingen, zoals de impact van de coronacrisis op onze grondrechten en de toenemende invloed van globalisering op nationale instituties. Het gesprek eindigt met een filosofische blik op de etymologie van het woord 'vrijheid', waarbij Verbrugge pleit voor een herwaardering van vrijheid als een vorm van liefdevolle zorg en gemeenschapszin in plaats van louter individuele autonomie.---------------Koop nu je kaartjes voor de Theater Tour! ⭐Deze donderdag!7 mei: Op Hodenpijl, Schipluiden met Kees de Kort: https://ophodenpijl.nl/evenement/nieuwe-wereld-kees-de-kort/?occurrence=2026-05-0719 mei: Grote Kerk Alkmaar met Maurice de Hond: https://grotekerkalkmaar.nl/tickets/seizoen-25-26/de-nieuwe-wereld-ondergang-van-het-avondland/?showId=3878151937-177159177816 juni: De Maagd, Bergen op Zoom: Willem Middelkoop: https://www.demaagd.nl/agenda/ondergang-van-het-avondland-de-nieuwe-wereld-4xn6

Aan tafel deze week: waarnemend burgemeester Wijdemeren Mark Verheijen, directeur Justice for Prosperity Jelle Postma, minister van Klimaat en Groene Groei Stientje van Veldhoven, IT-ondernemer Ludo Baauw, directeur Theater Na de Dam Jaïr Stranders. Presentatie: Joost Vullings Wil je meer weten over de gasten in Buitenhof? Op onze website vind je meer informatie. Daar kan je deze aflevering ook terugkijken en je vindt er natuurlijk nog veel meer gesprekken: https://bit.ly/buitenhof-3-mei-26 Waarnemend burgemeester van Wijdemeren Mark Verheijen stond ook deze week weer in het brandpunt van de slepende asieldiscussie. Het protest in zijn gemeente mondde uit in vernielingen aan het gemeentehuis. Is er nog wel discussie mogelijk als mensen grijpen naar geweld?   Jelle Postma is oud-AIVD'er en oprichter van het onderzoeksplatform Justice for Prosperity. Dat onderzocht in hoeverre extreemrechtse groeperingen betrokken zijn bij de anti-migratierellen in Nederland. Zondag publiceert de organisatie haar rapport. Om welke groeperingen gaat het? En zijn zij ook actief in Loosdrecht?  Deze week was minister van Klimaat en Groene Groei Stientje van Veldhoven in Colombia om met ruim vijftig andere landen te kijken hoe we van fossiele brandstoffen af kunnen komen. Hoe moeten we verder in eigen land met de klimaatopdracht nu het in Nederland steeds vaker en langer niet regent? IT-ondernemer Ludo Baauw komt met een Nederlands alternatief voor het bedrijf achter DigiD: Solvinity. Tot 6 mei kan nog bezwaar worden gemaakt tegen de verlenging van het contract met het cloudbedrijf. Staatssecretaris Eric van der Burg wil het contract niet opzeggen en stelt dat er op korte termijn geen alternatief is. Volgens Baauw is dat er wel. En hoe hou je herdenken levend en betekenisvol na ruim 80 jaar in deze tijd van polarisatie? Maandag 4 mei staan we in Nederland traditiegetrouw stil bij de slachtoffers van de Tweede Wereldoorlog. Jaïr Stranders, artistiek leider van Theater Na de Dam, probeert het door theater te maken waarin gebeurtenissen uit de Tweede Wereldoorlog worden gekoppeld aan situaties uit deze tijd.

Tachtig jaar na de bevrijding bewaakt de koninklijke marechaussee de ingangen van Joodse scholen. De laatste ooggetuigen verdwijnen. En de Holocaust wordt steeds vaker ingezet als argument in een politieke strijd die niets met de Holocaust te maken heeft. Hoe houd je herdenken levend, zonder het te verliezen aan de polarisatie?Aan de vooravond van de Nationale Dodenherdenking gaan Adriaan van Dis, David Wertheim, Frida Boeke en Willem Wagenaar met elkaar in gesprek over wat het betekent te gedenken in een verdeelde samenleving, en welke eisen dat stelt aan onderwijs, literatuur en burgerschap.Adriaan van Dis hield onlangs de eerste Loe de Jong-lezing. Hij pleit voor wat hij ‘verplaatsingskunde' noemt: het vermogen je te verplaatsen in het verhaal van de ander, ook als dat verhaal botst met het jouwe.Over Gesprek Voor de DamElk jaar organiseert De Balie in samenwerking met Theater Na de Dam Gesprek Voor de Dam. In aanloop naar de Nationale Dodenherdenking op 4 mei gaan we met gasten en publiek in gesprek over wat de herdenking in deze tijd betekent en waar het nog te weinig over gaat.In samenwerking met: Theater na de DamModerator: Lennart BooijZie het privacybeleid op https://art19.com/privacy en de privacyverklaring van Californië op https://art19.com/privacy#do-not-sell-my-info.

Het afschieten van probleemwolf Bram zorgde voor veel commotie in Nederland. Het zegt veel over ons beeld van natuur en de mens. Aan de ene kant zien we de wolf als een wild ongetemd beest, aan de andere kant geven we hem een naam. Leer van milieufilosoof Martin Drenthen over ons beeld van de grens tussen mens en natuur en hoe we samen kunnen leven met de wolf. De probleemwolf | Silent-interview met milieufilosoof Martin Drenthen Denkwerk 2026 Zaterdag 7 maart 2026 | De Lindenberg, Nijmegen Radboud Reflects en de Faculteit der Filosofie, Theologie en Religiewetenschappen Like deze podcast, abonneer je op dit kanaal en mis niks. Bekijk ook de agenda voor nog meer verdiepende lezingen: https://www.ru.nl/radboudreflects Wil je geen enkele verdiepende lezing missen? Schrijf je dan in voor de nieuwsbrief: https://www.ru.nl/rr/nieuwsbrief

Aan de vooravond van 4 mei vertelt Bert Natter over “Aan het einde van de oorlog”, dat is genomineerd voor de Libris Literatuurprijs. In de roman volgen we 31 personage tijdens de laatste dag van een vrouwenconcentratiekamp.  Als Taalschat “De kinderen van het achtste woud” van Els Pelgrom. We bespreken het met Sanne van Heijst, de schrijver van de nieuwe biografie van Pelgom. En Malou Holshuijsen heeft het verhaal “Altijd deftig” geschreven voor de speciale uitgave 5 keer 5 mei. René Appel bespreekt de TNA van wielrenster Demi Vollering

In part one of this series, Dr. Justin Abbatemarco and Dr. Benjamin P. Trewin discuss the major findings from his work.  Read more about this abstract on the AAN website.  

Although rare, recognizing NMOSD is crucial for improving patient outcomes through correct diagnostic and treatment approaches. Reports of atypical forms and increasing knowledge of clinical, imaging, and laboratory-specific features are fundamental for the accurate recognition of this condition. Research on targeted therapies and biomarkers measuring and predicting disease activity will improve NMOSD management. In this episode, Gordon Smith, MD, FAAN, speaks with Sara Mariotto, MD, PhD, coauthor of the article "Neuromyelitis Optica Spectrum Disorder" in the Continuum® April 2026 Multiple Sclerosis and Related Disorders issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Mariotto is a neurologist in the Neurology Unit in the Department of Neurosciences, Biomedicine, and Movement Sciences at the University of Verona in Verona, Italy. Additional Resources Read the article: Neuromyelitis Optica Spectrum Disorder Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @GordonSmithMD Full episode transcript available here Dr Smith: Neurology is an increasingly therapeutic specialty, and across many of our subspecialty areas, lots of new drugs are being approved. Are you interested in learning more about a historically disabling disorder for which we now have a spectrum of new therapies that, if used appropriately and promptly in the right clinical situation, promise to dramatically improve patient outcomes? If so, keep listening. My name's Dr Gordon Smith. Today I'll be talking with Dr Sara Mariotto about her article on neuromyelitis optica spectrum disorder or NMOSD, which she wrote with Dr Romain Marignier. This article appears in the April 2026 Continuum issue on multiple sclerosis.  Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.  Dr Smith: This is Dr Gordon Smith. Today, I'm interviewing Dr Sara Mariotto about her article on neuromyelitis optica spectrum disorder or NMOSD, which she wrote with Dr Romain Marignier. This article appears in the April 2026 Continuum issue on multiple sclerosis. Sara, welcome to the podcast, and maybe you can start by introducing yourself to our audience.  Dr Mariotto: Yes. Thanks, Gordon. I'm Sara Mariotto. I'm a neurologist, and I work at the Neurology Unit, University of Verona, where I do both clinical diagnosis and research into neuroimmunology---so, in particular, autoimmune encephalitis, NMOSD, and MOGAD.  Dr Smith: Well, this is a super exciting area. Whenever I hear about NMOSD, I think of one specific patient I had, and I always think of her when I come across something like your article, which is really fantastic. So, before we dive into the details, I wonder if maybe you can just explain to our listeners who aren't up to speed on what NMOSD is, what the disorder is, and maybe why it's so important that all of our listeners learn how to recognize it quickly and get people started on therapy.  Dr Mariotto: Yes, sure. So, neuromyelitis optica is an inflammatory autoimmune CNS disorder usually associated with aquaporin-4 antibodies, although there are a few cases, around 10%, who can be antibody-negative. And I think it's very much important to have in mind this disease and recognize it because it can be severe, as you pointed out; can present with very severe optic neuritis, myelitis, the brain stem, or area postrema syndrome. So, it can be really severe, affect quite young people around 40 years of age---although it can affect also the pediatric population and elderly people---and, importantly, it can be treated. It's very much important to treat this patient in the acute stage very quickly with steroids or plasma exchange in addition, and then to start a chronic treatment. So, we have treatment for this condition. So, it's very much important to, to recognize it quickly and treat the patient properly.  Dr Smith: So, I wonder if we can talk a little bit about the diagnostic criteria and boundaries of NMOSD, right? So, someone who comes in with bilateral op- severe long segment optic neuritis or long segment myelitis, we think about it. But what are the boundaries? Should we be looking for this, for instance, in someone who comes in with a unilateral optic neuritis or looks like typical multiple sclerosis? Is it important to get aquaporin-4 antibodies in those patients? What do the diagnostic criteria say about this?  Dr Mariotto: So, I wouldn't test aquaporin-4 antibodies in all patients with demyelinating conditions because although aquaporin-4 antibody assay is very specific, as for all assay and all antibody testing---also for MOG antibodies, for example---some false positive results can come out. So, I would suggest to test aquaporin-4 antibodies not in typical MS cases but in those who could be suggestive for not being MS, so in all those cases with atypical optic neuritis and myelitis or other syndromes. For those cases, it's important to test aquaporin-4 antibodies, but I wouldn't test them in all typical, classical MS cases. As I said, it's quite specific, the assay, so it's uncommon to have false positive results, but it can be.  Dr Smith: Serum, CSF, both?  Dr Mariotto: So, for aquaporin-4 antibodies, they're usually present in serum. They can be positive also in the CSF. And there are a few reports of isolated CSF positivity. But if we analyze larger samples volume, then it becomes clear that isolated CSF positivity is so, so rare that it's not recommended to test them in the CSF when serum is negative. So, for aquaporin-4 antibodies, the recommended matrix of testing is serum, which is different for MOG, which is not the topic of our article but is important to mention because MOG antibodies should be tested in serum and CSF. But aquaporin-4, I would recommend to test serum.  Dr Smith: What are the boundaries between MOGAD and NMOSD? And you talked about the differential testing of antibodies, which I was going to ask about. But when should we think of NMOSD relative to MOG? Dr Mariotto: Yeah. There are aspects which are the one mentioned in the criteria, highly suggestive for NMOSD. But the clinical spectrum can be similar to that of MOGAD. Usually, although there are some clinical aspect---like, for example cortical encephalitis or ADEM, which is more typical for MOGAD, or others like area postrema syndrome, which are more typical of NMOSD. The spectrum can be similar among the two conditions, so that's why in our clinical experience, usually they ask both aquaporin-4 and MOG antibodies in patients. It's- for experts, it can be easy to differentiate the two conditions, but for nonexperts can not be so easy.  Dr Smith: Can you define area postrema syndrome? I think not all of our listeners see that every day.  Dr Mariotto: Yeah, sure. This is a syndrome which is highly suggestive of NMOSD. That's why I mention it. And it's characterized by nausea, vomiting, hiccups are known as the syndrome. And it is very, very suggestive because of the expression of aquaporin-4 in that area of NMOSD. That's why I strongly recommend for all patients who comes out to have this syndrome to test for aquaporin-4 antibodies. MOGAD is hardly ever positive for that, so I think that whenever you see a patient with that syndrome, you should think about NMOSD.  Dr Smith: I'm just curious, aquaporin-4 is a water channel, which is kind of an interesting concept. Our conversation, I really want to make sure we give clinically important information to folks, but it's so curious to me at least, how does this actually result in a inflammatory demyelinating syndrome? For a simple neuromuscular guy, what's the immunopathogenesis of this?  Dr Mariotto: Yeah, the immunopathogenesis is quite complicated, as in all CNS disorders. And of course, aquaporin-4 antibodies are the main focus, but they are not the only one. As you said, aquaporin-4 antibodies have a target, this water channel, which is at the basis of the disease, and they are produced by the interplay between T cells, B cells, and plasma cells. But then also eosinophils, macrophages, cytokines, and chemokines are involved, enter the CNS, and then another important component is complement, which is highly activated in this disease. At the end, we have astrocyte damage because astrocytes are the main target of the disease, but also axon and myelin are involved. So, it's a quite complex pathogenesis based on the antibodies, but not only on that.  Dr Smith: And this will become important when we start talking about treatment. There seems to be a recurring theme of long segment demyelination, right? Optic neuritis is typically a large percentage of the length of the optic nerve, and obviously the myelitis se- more than three segments. Do you see other long segment areas of CNS demyelination, corpus callosum or things like that? Any ideas why that is, if that's true?  Dr Mariotto: Of note, this is quite interesting because usually when we have NMOSD, we have a longitudinal involvement, especially of the optic nerve and spinal cord, while brain lesions are quite different. Like, we usually do not have the typical Dawsen fingers-like lesions that we have in MS, for example, or the classical periventricular or subcortical extensive lesions that we can see and we have in mind when we think about MS. In some cases with NMOSD, the brain is completely negative, so we do not see anything. And Dawsen lesion's quite suggestive of NMOSD. So, you're right. I mean, this is related partially to the expression of aquaporin-4, and that's why we have this typical involvement also for area postrema, for example, and maybe also our other examples of clinical aspect that we can see in these conditions. But it's basically linked with the expression of aquaporin-4, which is the main target of the disease. And that's why usually the brain doesn't show so much involvement as we can see in MS, for example.  Dr Smith: I was actually really interested in some of the unusual manifestations or phenotypes, and I don't want to get into arcadia, really, but which of these should our listeners be familiar with that would really suggest that they should be thinking about NMOSD beyond the area postrema and other features that we've already talked about that are part of the core criteria?  Dr Mariotto: Yeah. I mean, I think that the encephalic syndromes or also ADEM, which is most typical of MOGAD but can be observed also in NMOSD or PRES, for example, are syndromes that can be considered in patients with NMOSD. There are the typical ones, which are the ones showed in the criteria, but whenever we have a brainstem involvement or, like, these encephalic syndromes or also PRES, we should think about NMOSD also.  Dr Smith: Another area I was interested in are red flags. In your article, you talk about red flags that might suggest an alternative diagnosis, right? And then this presumably is particularly important in seronegative patients, which 10% is not a reasonably high number, I suppose. What are red flags we should be thinking about for some other diagnosis?  Dr Mariotto: Yeah. I would here mention two very important red flags. The first one is a very hyperacute onset. Usually these conditions, these inflammatory conditions have a subacute onset, so whenever you have a very, very acute onset, you should think about something else. This can occur sometimes also in NMOSD, but hardly ever occur. Like, a very acute myelitis, the first thing we should think about is a vascular origin, for example, with a lot of pain and not about NMOSD, although sometimes the differential diagnosis is not so easy. The second thing is a progression independently of relapses, which hardly ever occur in NMOSD. Usually in NMOSD, we have the onset, and then we have a relapsing disease course. That's why we have to treat patients always and not to stop treatment. But we do not have progression in the meanwhile, while we can have, for example, this in MS. Same thing is for MOGAD. So, these are two things that I think is very much important to keep in mind.  Dr Smith: I want to pivot to talk about treatment because that's been super exciting. But rumor has it there are new diagnostic criteria coming for NMOSD in the next year. I bet you know a bit about those. Can you give our listeners any indication about kind of where the puck is going on this? Not so much what the criteria are specifically, but what sort of diagnostic challenges are the new criteria going to help us with once they come out?  Dr Mariotto: Yeah. So basically, we are working on that, so you will read them in the next future. This is the good point of the conversation on the new criteria. And we work a lot on the definition, on the new definition and nomenclature of NMOSD; on the definition of seronegative NMOSD, which is also quite tricky; and then on the assay we should use to test aquaporin-4 antibodies, and also on potentially new syndromes which should be included into the main feature of the disease. But hopefully you will read about this very soon.  Dr Smith: Looking forward to it. And Continuum Audio listeners, you heard it here first, so thank you. Let's pivot to treatment. This has been super exciting, and I wonder if the way to approach this is to start with acute management and then sort of chronic management. Would that make sense?  Dr Mariotto: Sure.  Dr Smith: Let's say I go on service on Friday, and I have a patient who comes in with positive aquaporin-4 and bilateral optic neuritis. What's the acute approach to managing that patient?  Dr Mariotto: So, the first approach is to administer intravenous steroids, but I would not wait to escalate to plasma exchange. There is quite good evidence that we should treat the patient with additional plasma exchange very quickly, and every day of delay of plasma exchange can cause increased disability. So, we should treat patients with steroids first, and then if we are not satisfied by the recovery, soon start with a plasma exchange. There is also some evidence, although less, for IVIG, but it's important to try to treat them very quickly, even if it's Friday, you know, there is the weekend and so on. But I think it's very much important to start with steroids after excluding other infectious causes or so on, and then to start quickly with plasma exchange. The main problem could be that we do not have the results of the antibody yet.  Dr Smith: Right. So, let me ask that question. You know, let's say my patient comes in on Friday, and clinical syndrome that really looks like NMOSD, and we're waiting for the aquaporin-4. There are many places where it's hard to get plasma exchange over weekends. And so, in that setting, are you better off doing the steroids over the weekend then PLEX on Monday, or should we just give IVIG because maybe it's as good as PLEX? What's your advice there? I'm trying to get ready for Friday because I know one's coming in.  Dr Mariotto: That's true, that's true. Usually they come on Friday or Saturday. I think it's acceptable to have three days of steroids and see how the patient improves, and then after three days to start with plasma exchange. Actually, we have a very good improvement if we start between three and five days after onset. So, I think waiting for three days is acceptable just because we can see if the steroids work properly or not, and then we can quickly start to plasma exchange. But I would not wait, like, 10 days, you know, before starting with a plasma exchange, and I would not wait for antibody results.  Dr Smith: Got it. Super helpful. And I'm actually not joking around, I learned recently that I have a reputation among our residents for having lots of optic neuritis when I'm on service, which I think is sort of karmic justice for being a peripheral nerve expert. But let me ask another question. So, let's say we do that, and the patient gets three or five days of pulse methylprednisolone and five courses of PLEX, and they're not doing well. Do you then just move right along into another agent B cell depletion therapy? I mean, what's your next step in escalation in the acute setting?  Dr Mariotto: I would for sure start to, as you said, with steroids, plasma exchange, and in case IVIG, and then quickly move to chronic treatment. And for patients who are not recovering well, I would think of something which has a quick effect so we can really start treating patients very quickly. There are different options. And all over the world, there are different rules for using immunosuppression in NMOSD. Like in Italy, for example, it's different from US or other countries, Germany, for example. There are different approved treatments and different rules of using them before or after rituximab, for example. We all know that there are treatments approved for NMOSD all over the world. But in some countries, like for example in Italy, we should use rituximab first, and then if it doesn't work, escalate to the approved treatment. I know in the US it's different. But anyway, for a patient who does not improve quickly, I would start with something which has a quick effect on the disease.  Dr Smith: And then rituximab versus inebilizumab, you know, CD20, CD19, what's your advice there? Is one preferable to the other, you know, if we have options to do either?  Dr Mariotto: Yeah. So, between rituximab and inebilizumab, we know that the target, well, is different, but is anyway B cells, so CD19 and CD20. With CD19, we can affect both plasma blast, plasma cells, and B cells. That's why the target is broader. And of note, this is an approved drug, while rituximab is, in most countries, used as off-label treatment.  Dr Smith: So inebilizumab would probably be preferable if we're able to do that.  Dr Mariotto: Unfortunately, there are not so many studies comparing rituximab with the approved drug, which is, of course, a pity, but that's the case. While we have clinical trials for all the approved drugs, and although the trials were designed differently, as we mentioned in the Continuum paper, we can argue something of the comparison between the approved drugs. But it is not so clear the comparison between rituximab and the new drugs, which is also something that we should work on.  Dr Smith: And then for chronic suppressive management, what other options are there?  Dr Mariotto: So, in addition to B cells, target can be interleukin-6, as we know with tocilizumab or satralizumab, and then complement with eculizumab. These drugs are both based on the pathogenesis of the disease. That's why we also discuss it in the paper, which shows a clear involvement of complement, and among cytokines of interleukin-6. So, targeting these made clear that could improve the disease quite well, and that's why they designed some clinical trials on these drugs, which are now approved, as we said, for NMOSD.  Dr Smith: Wow, so many options, and a lot of questions, but limited time. Let me just ask a couple of more. I see a lot of myasthenia patients, and there's a lot of variability, as you know, in patients with myasthenia, the extent to which complement is an important mechanism versus other, you know, important mechanisms. To what extent is response to a complement inhibitor kind of uniform across NMOSD? Or there's some patients who just don't respond to a complement inhibitor and others that respond really well. And then just, I'll just give my second question out is, you know, what about combination therapies for patients who have particularly challenging NMOSD?  Dr Mariotto: So usually these patients have a terrific response to complement inhibitors, and this is also shown by the clinical trials where we saw how eculizumab have a very impressive effect on the disease. And also, maybe this is also your experience, a very quick effect. So that's why there are also thoughts on using it in a very acute stage of the disease. That was what I was thinking about before. But then it has a very huge effect on complement, which is a major factor involved in the pathogenesis of NMOSD also in the chronic disease stage, and that's what also we see from clinical trials. Usually, we prefer to switch treatment from one to another and not to combine them. Of course, in very difficult cases, this can be considered, but the recommendation is to switch from one of these approved drugs to the other, or from rituximab to one of the approved drugs, and try to find out the best for our patient before combining them. Dr Smith: The complement inhibitor trials are breathtaking, at least for me. If I'm trying to convince students to go into neurology, I'll say, "Take a look at that paper," because anyone who claims that we're "diagnose and adios" is so wrong. It's so exciting. So, at a high level, this must have fundamentally changed outcomes for patients. I mean, it's still a difficult disease, but what is the kind of prognosis for that patient I described who comes in, gets the therapy you talked about? What does their long-term outcome look like in this modern therapeutic environment? Dr Mariotto: So, NMOSD is almost always a relapsing disease. That's why, as we mentioned, we have to treat patients always. But the prognosis changes a lot since we were also able to use all these drugs for the disease. So, the prognosis changes if we recognize it properly and early, and if we treat NMOSD properly with immunosuppressives. So, whatever we choose it's important to start it quickly, and this is the only way that we have to improve the prognosis of this disease. We have very active cases, but we have also cases who responds quite well to this immunosuppressive treatment, since now we have, as mentioned, these ones which are very impressive and show incredible results. So, the prognosis of the disease change in the last year, thanks also to the improvement of the diagnosis and of the treatment choices for the disease.  Dr Smith: I'm just... I- maybe my last question, you know, just at a personal level, not only for you as an expert who's caring for these patients, but in the patient community, this must have been a pretty exciting period of time, right? I mean, these, these drugs are coming fast and furious, and what a change. What's the kind of zeitgeist in the community, both your professional community and amongst the patient community about where we are? Dr Mariotto: Yeah, you're right. The last years were defined the years of NMOSD and also MOGAD because we had finally approved drugs which is relevant for all the disease that we treat and changed the landscape of the disease for clinicians, but also for patients. And we have more than one, as we said, so we have more options that we can also discuss with patients to try to choose the best one in terms of activity, but also route of administration or time. Some years ago, we just had rituximab, which is not approved in most of the countries, and now we have different approved drugs. And we improved the diagnosis of the disease thanks to the availability of live cell-based assay. And then we are working a lot also on biomarkers like GFAP, for example, which has been shown to be a very attractive biomarker able to mark disease activity and maybe also prognosis on this disease. So, you're right. I mean, in the last years, the landscape of NMOSD changed a lot.  Dr Smith: Sara, thank you so much for talking with me. I could keep going for another half an hour, but I would be in trouble with my editor, so I think we probably need to wrap it up. But thank you so much. This has been very informative.  Dr Mariotto: My pleasure. Dr Smith: Mine too. Thank you. Again, today I've been interviewing Dr Sara Mariotto about her article on NMOSD, which she wrote with Dr Romain Marignier. This article appears in the April 2026 issue of Continuum on multiple sclerosis. Be sure to check out Continuum Audio episodes from this and other issues, and thanks to you, our listeners, for joining us today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

De helft van de meer dan een miljoen Nederlanders met een zeldzame aandoening heeft nog nooit een diagnose gekregen. Geen naam voor de aandoening, geen genetische oorzaak, geen gerichte behandeling, geen houvast voor de toekomst. Dat is niet alleen een medisch probleem: het is een jarenlange odyssee vol onzekerheid voor patiënten en hun families. Op 23 en 24 april vond in het Radboudumc in Nijmegen de eerste nationale Undiagnosed Hackathon plaats, waarbij specialisten van alle zeven Nederlandse universitaire medische centra in 48 uur proberen door te dringen tot de DNA-raadsels achter die moeilijk diagnosticeerbare zeldzame aandoeningen. In deze aflevering van BNR Beter bespreekt Stijn Goossens de hackathon live op locatie. Te gast zijn Helger IJntema, hoofd laboratorium genoomdiagnostiek bij het Radboudumc, en Gijs Santen, hoogleraar en afdelingshoofd klinische genetica bij het LUMC in Leiden. Aan de hackathon doen zo'n 140 specialisten mee: klinisch genetici, laboratoriumspecialisten, bio-informatici en wetenschappers, verdeeld in interdisciplinaire teams die elk een handvol patiëntdossiers analyseren. Voor 33 patiënten wordt in 48 uur geprobeerd te vinden wat eerder niet lukte. Helger IJntema legt uit hoe het laboratoriumproces eruitziet: DNA wordt geïsoleerd uit bloed, vervolgens uitgelezen en vergeleken met een referentiegenoom, waarbij bio-informatica en AI al veel voorwerk doen door irrelevante varianten te filteren. Gijs Santen legt uit waarom een diagnose zo veel meer is dan een naam. Het beëindigt de diagnostische achtbaan, maakt gerichte behandeling mogelijk, geeft uitsluitsel over herhalingskansen bij een kinderwens en biedt soms toegang tot specifieke therapieën. Centraal in de aflevering staat de rol van nieuwe DNA-technologie, met name long read sequencing, waarbij het DNA niet in kleine fragmentjes maar in grote stukken wordt uitgelezen. De puzzelanalogie die beide gasten gebruiken maakt het verschil concreet: grotere puzzelstukjes betekenen minder gaten en een completer beeld. Radboudumc is wereldwijd koploper in de klinische implementatie van deze techniek en gebruikt long read sequencing inmiddels voor zo'n 5.000 analyses per jaar. Een uitgebreidere aflevering van BNR Beter over deze innovatie techniek is hier terug te luisteren. De aflevering bevat ook persoonlijke verhalen van betrokken families. Robin Mom vertelt over zijn zoontje Sepp, die met 8% zicht leeft en voor wie de hackathon zijn tweede kans op een diagnose is. Lonneke deelt hoe de diagnose van haar zoon Bram, gevonden tijdens een internationale hackathon twee jaar geleden, hun gezin rust en richting gaf na bijna zes jaar zoeken. Over deze podcast BNR Beter is het wekelijkse programma van BNR Nieuwsradio over een toekomstbestendige zorgsector. Elke week bespreekt presentator Nina van den Dungen met zorgprofessionals, ondernemers en beleidsmakers hoe de Nederlandse zorg met technologie, innovatie, regelgeving en wetenschap beter kan worden. BNR Beter is elke maandag om 15:30 op de radio te beluisteren bij BNR Nieuwsradio, en vanaf dat moment ook als podcast via deze feed. Over de makers Nina van den Dungen (1987) is freelance journalist en als radio- en podcastpresentator al ruim 15 jaar verbonden aan BNR. Zo is ze regelmatig te horen als presentator van de nieuwsprogramma's in de ochtend- en avondspits en daarnaast presenteert ze wekelijks de beleggingspodcast Doorgelicht en BNR Beter over de zorgsector. Stijn Goossens (1996) is de redacteur van BNR Beter en plaatsvervangend presentator. Bij BNR houdt Stijn zich bezig met onderwerpen over tech, wetenschap en innovatie. Hij presenteert ook de podcast Op de zaak en test elke vrijdag een nieuw techproduct in de Ochtendspits op BNR. Hiervoor was Stijn werkzaam voor NTR Wetenschap en techplatform Bright.See omnystudio.com/listener for privacy information.

Aan tafel deze week: aankomend voorzitter FNV Hans Spekman, historicus en Iran-kenner Peyman Jafari, schrijver Ian Buruma, fotograaf Stephan Vanfleteren, directeur Mauritshuis Martine Gosselink. Presentatie: Twan Huys Wil je meer weten over de gasten in Buitenhof? Op onze website vind je meer informatie. Daar kan je deze aflevering ook terugkijken en je vindt er natuurlijk nog veel meer gesprekken: https://bit.ly/4cKk57L De kans lijkt klein dat Iran en de VS op korte termijn zullen onderhandelen. Hoe groot is de kans op een akkoord dat stand houdt? En gaat de Straat van Hormuz dan weer open? Daarover de Nederlands-Iraanse historicus en Iran-kenner Peyman Jafari. Hans Spekman gaat per 1 mei aan het werk als voorzitter van de FNV. Het nieuwe kabinet heeft veel plannen voor de sociale zekerheid in Nederland. Wat moet er volgens de nieuwe voorzitter gebeuren met de WW? En hoe gaat Spekman ervoor zorgen dat na een lange periode van interne onrust de rijen bij de vakbond weer sluiten? Blijf in leven, het nieuwe boek van schrijver en journalist Ian Buruma, gaat over het dagelijkse leven in Berlijn tijdens de Tweede Wereldoorlog. Aan de hand van dagboeken, brieven en interviews onderzoekt hij de morele dilemma's onder een dictatuur. Het is een vraag die actueel blijft: hoe kun je fatsoenlijk blijven in een onfatsoenlijke samenleving? Voor de tentoonstelling Pentimenti gaat fotograaf Stephan Vanfleteren in dialoog met de 17de‑eeuwse meesters die in het Mauritshuis hangen. Wat zeggen zijn foto's over de huidige toestand van de wereld? Parallel verschijnt een brievenboek; de correspondentie tussen Vanfleteren en Mauritshuis-directeur Martine Gosselink over kunst, licht, troost en de wereld om hen heen. Beiden zijn te gast.

Vandaag een aflevering in de serie "In Stukken". Het Hoorntrio van Johannes Brahms wordt in stukken geknipt. Aan de hand van de fragmenten in de mooiste opnames wordt het stuk onder de loep genomen. Panelleden: hoornist Mees Vos en pianist Hans Eijsackers.

Familiarity with the clinical, MRI, CSF, and serologic features of MOGAD can help neurologists recognize this condition in clinical practice. Awareness of the utility and pitfalls of the MOG antibody test is critical. The current therapeutic approach is guided by retrospective studies and the application of immunotherapies used in other autoimmune neurologic disorders. In this episode, Gordon Smith, MD, FAAN, speaks with Eoin P. Flanagan, MBBCh, coauthor of the article "Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease" in the Continuum® April 2026 Multiple Sclerosis and Related Disorders issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Flanagan is a professor of neurology and the division chair of the Division of Multiple Sclerosis and Autoimmune Neurology in the Department of Neurology at Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: Myelin Oligodendrocyte Glycoprotein Antibody–Associated 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: @GordonSmithMD Full episode transcript available here Dr Smith: So, what neurological disorder can cause bilateral optic neuritis, transverse myelitis, ADEM, or can mimic acute flaccid myelitis, intracranial hypertension, viral encephalitis, or cause seizures? Sounds like the great imitator, perhaps. If you want to know and learn more about this syndrome and how you can treat it---and it is very treatable---keep listening. My name is Gordon Smith, and today I have the great opportunity to talk with Dr Eoin Flanagan from the Mayo Clinic on his article on myelin oligodendrocyte glycoprotein antibody associated disease, or MOGAD, which is in the April 2026 issue of Continuum on Multiple Sclerosis and Related 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 Smith: This is Dr Gordon Smith. Today I'm interviewing Dr Eoin Flanagan about his article on myelin oligodendrocyte glycoprotein associated disease, or MOGAD, which appears in the April 2026 Continuum issue on multiple sclerosis and related disorders. Eoin, welcome to the podcast, and please introduce yourself to our audience.  Dr Flanagan: Yeah, thanks so much. I'm Eoin Flanagan. I'm a neurologist at the Mayo Clinic. I'm originally from Ireland. I work in the neuroimmunology lab at the Mayo Clinic, and work and see patients with MS, MOG, and autoimmune disorders here in Rochester, Minnesota.  Dr Smith: Your article is super interesting, I think, and this has been a really rapidly evolving area over the last, you know, many years. We have many more antibodies, and MOG is something that's been around for a while, but we've certainly learned a lot more about it. This is a topic that I think will be familiar to most of our listeners, but I wonder if maybe you can just begin by laying the foundation. Like, what is MOG? What's its typical presentation?   Dr Flanagan: So, MOG is a protein on the surface of the oligodendrocyte or its CNS myelin, and it was always of interest as a potential antibody target, and initially it was investigated in multiple sclerosis. But subsequently, we recognized that the antibodies to MOG have a specific syndrome, of which about a quarter of patients are pediatric and then the remainder are adults. And they can present with a variety of syndromes, probably most commonly optic neuritis, but also acute disseminated encephalomyelitis, or ADEM. Transverse myelitis can also occur, and then some other unusual brain and brainstem cerebellar syndromes can also occur.   Dr Smith: I was really impressed in the very broad phenotypic spectrum of MOG. We'll talk more about that, of course. But I wonder if maybe you can tell us when we should be ordering MOG antibody? Given this broad variability, does anyone who has a CNS demyelinating disease need a MOG assay, only specific phenotypes? What guidance do you have for our listeners?   Dr Flanagan: Yeah. It's a great question. So, I think you have to be a little bit careful because the MOG antibody test is a little bit sticky. So sometimes we can see some low-positive false positives. So, we don't wanna order it in every single patient with classical MS. So, I suppose we'll start with who not to order it in. I think it's also a very optic nerve- and optic neuritis-central disease, so I think you really need to be considering this in a patient with optic neuritis who does not have lesions in the brain suggestive of multiple sclerosis. And then we think about some of the features: if the lesion, the enhancement along the optic nerve is long, if it's bilateral, if there's a lot of optic disc edema accompanying that, we tend to think about MOG antibodies. And then children with demyelinating disease, MOG is over-represented in that cohort, so it accounts for about a third of those. So, if you have a child with CNS demyelinating disease, particularly if they're under twelve, with ADEM presentations or other presentations, you probably want to be ordering the MOG antibody test. And then a longitudinally extensive transverse myelitis in adults, certain types of cerebral phenotypes that we can get into, you would want to consider ordering MOG antibodies too.   Dr Smith: Now, you point out in the article that it's really important that laboratories use the cell-based assay for MOG as opposed to an ELISA, for instance. Is this something folks need to be very attentive to, or are all of the commercial laboratories now using a cell-based assay?   Dr Flanagan: Yeah. I think all of the commercial labs are using cell-based assays, so we don't really get into much of an issue. There are some differences between serum and CSF, so really, serum is the optimal sample to order. There is also some differences between the live cell-based assay and the fixed cell-based assay, where the live cell-based assay may have some advantages in terms of sensitivity. And then CSF is kind of still under evaluation about its role in the condition. So in general, it's a serum test. And then we have to remember that the antibody tends to be highest at the onset, and then it goes down over time. So, if you delay your testing or you're testing a patient long after the condition, it can go negative, for example. So it tends to be highest both around the relapses and particularly at the onset of the condition.   Dr Smith: You mentioned earlier that the test is sticky, which I take to mean that there is some risk for low-titer false positives. How do you navigate that situation? When should we be suspicious about a false positive?   Dr Flanagan: Yeah. I think there's some very useful features that can help you. You know, the main differential diagnosis is going to be multiple sclerosis, particularly in the US, in regions of the northern US where MS is particularly common. So, you really wanna be making sure that if you get a positive result, low positive, that it's not multiple sclerosis. And some of the best discriminating features are CSF oligoclonal bands. They're about 85% in MS and about 15% in MOG, so an easy number to remember, 85 and 15. And then the lesions in MOG, the brain lesions, tend to disappear over time. So, if you have the advantage of that follow-up MRI a year down the line, about 70% of lesions in MOGAD will resolve, while in MS, as we know, the term means multiple scars, so the MS lesions tend to persist over time. So, they are two quite useful features that can help discriminate.   Dr Smith: And how about specific phenotypes or areas of involvement or imaging abnormalities that suggest MOG? One of the things I found really interesting in your article is there are a host of different syndromes that I think had largely been previously described, many of them, that became clear later that these were really tied to MOG antibodies. Presumably, that's helpful in interpreting the antibody assay in that patients who have, perhaps, a borderline low titer, for instance, but have a very typical phenotype are more likely to have MOG than those who have a more clearly MS-type phenotype.   Dr Flanagan: Yeah, absolutely right. Yes. So, there's certain phenotypes that we don't tend to see with MS. The acute disseminated encephalomyelitis, or ADEM, is one that's particularly common in children. And about half of people that have ADEM will be positive for the MOG antibody. So that's a syndrome you need to look out for, which would be often in children, encephalopathy, and they would have multifocal white matter lesions, sometimes involving the gray matter. A second syndrome that was an interesting discovery from a Japanese group was this unilateral cerebral cortical encephalitis, where patients can have this swelling and T2 hyperintensity, often just on one side of the brain. And it's in the cortex, and some of those patients won't have any white matter lesions. And in that situation, it's important to order the MOG antibody, and that seems to be a specific phenotype of MOGAD. But sometimes people don't think about it because the white matter is not involved. So, if you see these patients, they often present with seizures, sometimes they even have fever accompanied by it. And if you see those patients and see this radiological feature, then you really want to consider ordering the MOG antibody too.   Dr Smith: Yeah, I found that really interesting. And I- actually, my next question is perhaps a good follow-up on that, is, what are the diagnostic pitfalls? You give a lot of examples of situations and I think some cases where it's easy to get tripped up and misdiagnose someone who has MOG with another fairly common neurological problem.   Dr Flanagan: Yeah, I think some of the things that can help you when you're determining if the MOG is a true positive or false positive is the level of the antibodies. The super high titers, if it's a clear positive or very strong positive, the likelihood is that that is much more likely to be MOGAD than those low positives just above the cutoff. So that can be useful to help you discriminate from false positives. Those lesions, again, if all the lesions persist over time, that's going to be more suggestive of multiple sclerosis. Other diagnostic pitfalls, I suppose, if it's a syndrome that's not really associated with MOG, like peripheral neuropathy or other syndromes where we'll see some case reports, but usually I would be very cautious about those kind of presentations. So usually, having the antibody at a high level, and then also if they've had other symptoms suggestive of MOGAD, like if a patient has had recurrent optic neuritis and then they have an unusual brain syndrome, or they start out with an unusual brain syndrome and then have recurrent optic neuritis. You know, there are situations that make it more likely if they're having other typical phenotypes of the MOGAD where we can kind of expand the spectrum, but we have to be careful.   Dr Smith: I was really curious about the dynamic imaging findings. And you point this out both in terms of the resolution of imaging findings, but also in that patients who have an acute MOG syndrome often have very rapid evolution of the imaging abnormalities. I'm just curious, you know, why is that, and what do you make of it? Does it have a mechanistic implication, do you think?   Dr Flanagan: I don't think we know for sure. I think there's probably a lot more happening than we see on MRIs sometimes. What sometimes can happen in about 10% of patients is the initial MRI can be normal. We don't tend to see that with multiple sclerosis or NMOSD. Then what we see is it evolving over time. So, at that time, if you do a CSF, you'll often see inflammation, but we don't see the lesions. Now, that might be because the MRI is not very good at picking up cortical involvement. That can be difficult to see in MRI. Or there could be other factors. It could be a functional effect on the MOG but without frank demyelination yet, for example. Or there could be edema that you- myelin edema that you can't see as a lesion yet on MRI. But we do see that if you repeat the MRI, sometimes it'll change a lot. So, you may go from one or two lesions on the first MRI to twenty lesions on the second MRI a week later. So, it does tend to change a lot. And then over time, those lesions also resolve. So, what I say is if it's a very suspicious situation---like a child comes in with new-onset encephalitis, has inflammatory CSF---you might wanna consider repeating that MRI down the line and seeing if it's changing. And then over time, you know, a repeat MRI a year after the onset when there's brain or spinal cord lesions can be very helpful just to make sure you're on the right track, because lots of those lesions will then disappear, and that's a very clear discriminator from multiple sclerosis.   Dr Smith: Yeah, thanks. I mean, I was wondering the same thing about whether that particular feature might imply, you know, a functional abnormality as opposed to more of a structural abnormality. So probably a lot more to learn as we move forward. There are now consensus diagnostic criteria that were published a couple of years ago. I think you've already touched on kind of the general approach, but do you want to speak to those? I found your summary pretty helpful.   Dr Flanagan: Yeah, I think that those criteria are quite useful. They have three main parts to them. The first part is having a characteristic clinical syndrome. So, we talked about ADEM, we talked about cerebral cortical encephalitis, transverse myelitis that's often longitudinally extensive, and optic neuritis being the main syndromes, but sometimes other brainstem or cerebellar involvement can be seen. And then the second part is having a positive MOG antibody. And then there's some caveats there. So, if you have a high positive, then you don't really need any additional supportive criteria. On the other hand, if you're low positive, to get at those sticky antibodies that make sure it's not a false positive, you need some additional supportive clinical or MRI criteria. Or if you're only positive in CSF, you need that additional criteria. You also need to be negative for the aquaporin-4 antibody, because they can overlap clinically. And some of those supportive criteria are things that we talked about a little bit earlier, longer lesions within the optic nerve, bilateral involvement, involvement of the nerve sheath or optic disc edema. This is a situation, MOG antibody disease, where your fundoscope is useful and looking in the back of the eye and seeing swelling, because we don't tend to see that quite as often. It's less common in multiple sclerosis, but we often see prominent edema in MOGAD. And then in the spinal cord, the lesions tend to be central in the cord. Sometimes they form this H sign where it's restricted to the gray matter, and they tend to be longer, sometimes involving the conus. Patients will often have neurogenic bowel or bladder. And then in the brain, deep gray involvement, those large lesions along the cortex with swelling are some of the typical features. And then the final step is exclusion of another diagnosis. Just like with any test that we do in neurology, our final step is going to be to put that into context. So that's just a normal thing that we will always do when we get a group of test results back that we don't know what it means. We have to put it into context. So, make sure it's not multiple sclerosis, everything else does not look like multiple sclerosis, and then you can be on your way to make a diagnosis.   Dr Smith: Definitely encourage listeners to read your article. I guess I say that with every time I- or with everyone I talk to for Continuum Audio, but the images are really fantastic and the cases are fantastic. So, everything you've described is well-illustrated, including really nice schematic sort of diagrams that help differentiate NMO from MOG and MS. So, if you like MRI scans and good imaging frameworks, then this is the article for you.   Dr Flanagan: I think that's true, and the other thing is that the imaging is quite helpful because it takes a while for that antibody to come back. We're lucky at Mayo Clinic, if you work here, it, it comes back faster for you. But for many places, that time of sending it in, so a lot of times you don't know right away. So, looking at scrutinizing that MRI can be very helpful to guide you on your way and to know what you're dealing with and how to approach both the acute treatment and plans to have potentially a steroid taper after the acute treatment and those kind of things that can help guide you in that regard.   Dr Smith: Yeah. So, let's talk about treatment. You know, what's your approach to treating a patient who has an acute demyelinating syndrome related to MOG?   Dr Flanagan: So similar to other things, MOG is very steroid responsive. So, we use high-dose IV methylprednisolone in adults. That would be one gram IV for five days. And then we also will sometimes use oral steroids, twelve hundred and fifty milligrams. That's a bit of a hassle because it's twenty-five fifty-milligram tablets, it doesn't come in a larger tablet version. But it's very helpful to patients because they can get started on it right away. You don't have to set up an infusion center. So, we have used those oral steroids often in people who don't have access to an infusion center, are not in the hospital. And particularly as it's often optic neuritis, some of those patients are seen in the outpatient setting, so we can get in with treatment quickly. In patients where it's more severe, it doesn't recover quickly with steroids, then we would consider escalating to plasma exchange as our second-line treatment, and there's some retrospective data that suggests that plasma exchange can be useful. That's gonna be particularly for those people who don't have that quick response to steroids, or maybe more severe phenotypes like that brain involvement with ADEM or cerebral cortical encephalitis, where those patients might be in the hospital and quite unwell. I will say, we might get on to this, that sometimes MOG can be very, very severe and even fulminant, where there can be increased intracranial pressure, and these patients can be in the ICU, and it can be life-threatening. And so, it's really important to treat those patients aggressively, and some patients have even required hemicraniectomy or additional treatment. Sometimes IL-6 blocking medications have been used in that situation. So, monitoring and treating increased intracranial pressure in those rare patients, probably 2 or 3% that have the very severe attack, is important.   Dr Smith: I think one of the things I found interesting, and then I'd love to get your feedback on this, is that most patients with MOG seem to have a very readily treatable disorder that's monophasic, right? You treat them with steroids, and they do well. On the other extreme, there are these patients that have a much more malignant presentation, and there are some that sound like they benefit from prophylactic or some chronic therapy. What's your approach, right? In MS, we do serial scans to monitor, and obviously, our patients are on, you know, chronic disease-modifying therapy. How do you decide when you're going to provide some sort of prophylactic therapy? How do you monitor it? How long do you continue it?   Dr Flanagan: That's a great point. We don't know for sure yet, but I think for the most part, our approach has been if the patient has a single episode, they recover well from that episode. So, if that's optic neuritis, they're back to twenty/twenty vision. They have recovered well. We don't tend to use chronic maintenance immunotherapy. Sometimes after the first attack, we'll do a little bit of a slow taper, maybe over four, six weeks. We have done longer than that. And then we won't place them on any long-term treatment, because it's about 50% of patients that may have a monophasic disease, so we don't want to treat all those people who are destined never to have another relapse. On the other hand, if a patient had a very severe episode, they're in the ICU, they're intubated, some of those patients then afterwards we will start them at least temporarily on an attack prevention medication for at least a few years to get them through. Some patients will be very fearful of future relapses in that situation. Or if they don't recover well, if they're blind in one eye after an episode and then their other eye is vulnerable, or they're left with some residual deficits neurologically from a myelitis, then we would often sometimes put those patients after the first attack. But most of the time, we're gonna wait and see if they get that second attack, and then once they have the second attack, that is when we would consider a steroid-sparing medication. But I will say that there's no proven medications. We don't have any clinical trial data available yet. So some of those patients with relapsing disease, we'll either try to enroll them in a clinical trial, or we'll use an off-label treatment to try and manage their disease based on what we've learned from neuromyelitis optica or from multiple sclerosis. A few different options seem to be better, and we can maybe get into that too.   Dr Smith: Yeah, let's go there. So, what options are there? You mentioned in more fulminant disease IL-6 inhibitors, and by that I assume you mean tocilizumab, but what are the options when you want to use prophylactic therapy?   Dr Flanagan: So, that tocilizumab can be beneficial in the very acute situation, in that malignant situation. But also as an attack prevention treatment, the IL-6 blockers seem to- some of the retrospective data seems to look like it works reasonably well, so we work and see if we can get that approved. Another medication that can work well is IVIG or subcutaneous immunoglobulin as a maintenance treatment, so we would sometimes give that, like, at least one gram per kilogram once a month. The benefit of that is it doesn't lower your immune system, so there's some advantages there, particularly in people who may be more prone to infections, older people. So, we'll sometimes use that. But we do get into a lot of challenges with insurance coverage, and it can be difficult to get these approved by insurance because we only have retrospective data out there. So then for some patients, if they're in a region where there's a clinical trial available, we might try to enroll them in a clinical trial. And there are some clinical trials underway now, so hopefully in the future we'll be able to have some FDA-approved medications that can have some Class 1 data that we can follow. Because it's hard when you're just following retrospective data or anecdotal reports, it's a little bit difficult to know exactly how well you're doing with your treatments.   Dr Smith: Well, Eoin, I wonder if we could finish up by just looking into the future, right? I mean, it sounds like a fun patient population to take care of because you've got lots of great therapies and can have a durable impact. But sure would be nice to have more evidence-based therapies and an FDA approval. What trials are going on? What's the future look like?   Dr Flanagan: Yep. So, there's some trials going on in the- a couple of worldwide trials. One is on an FCRN blocker called rozanolixizumab, which is kind of like a plasma exchange-type treatment which removes your antibodies, and it's a weekly subcutaneous treatment where adults are enrolled. And the second one is called satralizumab, which is another IL-6 blocking medication. And again, that one's given once monthly under the skin. And the trial for that also includes children down to age eighteen, so for adolescents, too, that can be an option. There are trials, I believe, in Asia for tocilizumab too, and there's one starting in Australia for rituximab. So, the good news is that we're going to have some really good data down the line for lots of different agents, and we'll be able to figure out which treatments work. And this will be really of great benefit to our patients when we get that Class 1 data to kind of guide us on what we should be using and really build on the success of some of the other conditions like neuromyelitis optica spectrum disorder, where we now have four or five approved, medications that work very well.   Dr Smith: Well, Eoin, thank you. This is a great conversation. I will say that it... the topic that I was a little intimidated about. I'm a simple peripheral nerve guy, as you know. But I think moreso than any other Continuum article I've read recently, I'm, like, loaded for bear. I can't wait to go back on the inpatient service and look for some MOG patients, because your article really left me feeling kind of prepared to think through this in a clinical setting. So, thank you for the conversation, and congratulations on a really wonderful piece for Continuum.   Dr Flanagan: Yeah, thanks so much. Always a great honor to be involved in the Continuum, and thanks to all the readers out there.   Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

In part two of this series, Dr. Justin Abbatemarco and Dr. Shreya Louis discuss how this technology was developed and how it has evolved.  Read more about this abstract on the AAN website. 

In the first part of this series, Dr. Justin Abbatemarco and Dr. Shreya Louis discuss the background and evolving terminology around circulating tumor DNA, cell‑free DNA and CSF‑based testing in neurology.  Read more about this abstract on the AAN website. 

Adult‑onset leukodystrophies, though rare, can closely mimic MS on both clinical presentation and neuroimaging, posing a significant diagnostic challenge. This episode highlights key clinical and radiologic red flags that can help distinguish these disorders from MS, preventing misdiagnosis and avoiding inappropriate treatment while enabling timely genetic counseling and targeted therapies. In this episode, Teshamae Monteith, MD, FAAN, speaks with Roberta La Piana, MD, PhD, coauthor of the article "Adult-Onset Leukodystrophies Mimicking 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. La Piana is an associate professor in the Department of Neurology and Neurosurgery at the Montreal Neurological Institute, McGill University, and an associate member of the Department of Diagnostic Radiology at McGill University in Montreal, Quebec, Canada. Additional Resources Read the article: Adult-Onset Leukodystrophies Mimicking 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 Host: @headacheMD Full episode transcript available here Dr Monteith: You just saw a patient in clinic. And you're clear, the diagnosis is multiple sclerosis. Not everything fits, but it kind of looks like multiple sclerosis. You see the patient back years later. There're some treatment issues, the patient's not responding to treatment, and things look different. Have you thought about a genetic inherited problem like leukodystrophy or a genetic white matter disorder? Listen to this podcast. We're going to help you figure it out. Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Monteith: This is Dr Teshamae Monteith. Today I'm interviewing Dr Roberta La Piana about her article on adult-onset leukodystrophies mimicking multiple sclerosis, which she wrote with Dr Gabrielle Macaron. This article appears in the April 2026 Continuum issue on multiple sclerosis. Welcome to our podcast.  Dr La Piana: Thank you. Thank you for having me.  Dr Monteith: Absolutely. Why don't we start off with you introducing yourself? Dr La Piana: So, my name is Roberta La Piana. I'm a pediatric neurologist. I trained in Italy, I did my medical school, I did my residency in pediatric neurology there. And then I moved here to Montreal, to the Montreal Neurological Institute, to do a PhD in neuroscience. And that's where I specialized in adult-onset genetic white matter diseases. And after my PhD, I was recruited as an assistant professor here. So, that's where I got into this field.  Dr Monteith: This big field, highly specialized; lots of disorders, but highly specialized. And what got you into this? Neuroscience is huge. So, was it a mentor, or…?  Dr La Piana: No, actually, it was because of my background, because I trained as a pediatric neurologist and I loved the genetic white matter disorders in the pediatric population. So, when I came to the Montreal Neurological Institute, initially it was mainly to have a better expertise in imaging. And being at an adult neurology institute, I started seeing patients with adult genetic white matter diseases, and I was immediately fascinated by how different they were from their pediatric counterparts. Because in pediatric genetic white matter diseases, pediatric leukodystrophies look very diffuse, look very confluentous, so it's difficult to mistake them. But in adults, in the adult forms, I was initially driven by how often they can be misdiagnosed as multiple sclerosis or as other acquired white matter disorders. So that's why I got really interested in in this field.  Dr Monteith: You're, like, literally the perfect person for this discussion.  Dr La Piana: I'm not sure- *laughs* Dr Monteith: Why don't we start off with what your objectives were when writing this article? Dr La Piana: With writing this article, the goal is what I have been, actually, doing for the past ten years or so. So, really try to get more attention into the field because of the high rate of potential misdiagnosis of patients. So, that's exactly the reason why I really would like to raise the interest of neurologists for these disorders, because they are not considered enough in the differential diagnosis of patients, of adult patients presenting with white matter disorders. They are considered rare---which are, they are rare, definitely. But collectively, while each single form is rare, collectively they are not as rare. So- and thus, the risk of misdiagnosis and the potential impact of misdiagnosis on them with, you know, you can imagine giving patients inappropriate treatment or missing the possibility of a prenatal genetic diagnosis is so high that I really would like people to keep these disorders in the differential.  Dr Monteith: And it sounds like more than ever, this is really important because some of the newer developments in the field. Dr La Piana: Yes. Specifically, we have now tools that will allow to diagnose these patients quite quickly. All the genetic techniques that are available nowadays can really, with one single shot, we can now sequence hundreds of genes so we can have a quicker diagnosis. And this thing was impossible up until ten years ago. So that's definitely the first huge improvement that makes these disorders now easily diagnosed. Dr Monteith: Yeah. So why don't we talk a little bit about how common is this misdiagnosis for these rare subtypes? Dr La Piana: Yeah, the misdiagnosis, it depends on the cohorts. Generally speaking, I would say that the rate of that misdiagnosis for these forms is up to 25% or even more in some other cohorts. And it really depends on the forms. Like, there are clearly some forms, especially those that present with multifocal white matter diseases, that present with nonspecific clinical presentations like migraines, image---and especially for female patients, and for which migraine is so common, having multifocal with other abnormalities is so common, the rate of diagnosis increases even further. So, these are all things that we need to keep in mind. I know these are rare, but still, we need to always have them on the back of our minds.  Dr Monteith: Are there any particular disorders that are more often misdiagnosed? And you spoke about progressive forms of multiple sclerosis being a common kind of misdiagnosis.  Dr La Piana: Yeah. So, there are definitely forms that are more commonly misdiagnosed. And these are those that, as I probably repeated already too many times, is the word multifocal, which is key. So, all those genetic white matter disorders that present with multifocal white matter abnormalities are not initially considered as genetic. So, I'm thinking about all of the leukovasculopathies, so, the small vessel diseases which are genetic in origin. For example, CADASIL; for example, the disorders related to collagen-4; so, the COL4 A1 or A2-related disorders. Those are clearly more commonly misdiagnosed initially. Another big group, unfortunately, is the CSF1R-related disorders. I know I'm saying a lot of gene names, but due to the fact that they start with multifocal abnormalities and they start with quite nonspecific, slowly progressive symptoms, the rate of misdiagnosis is definitely higher. Dr Monteith: And can you discuss some of the clinical challenges when seeing patients that might lead to this misdiagnosis?  Dr La Piana: There are multiple clinical challenges. One is definitely the presence of nonspecific or initially mild clinical symptoms that sometimes don't raise initially the red flag of something, degenerative or progressive or genetic. One category that I would mention are psychiatric disturbances, especially in the form of depression, anxiety, or apathy. This is quite common in patients with some forms of genetic white matter disorders, and they are initially misdirected to psychiatrists and taken care in that domain. But it's only when some even mild neurological symptoms like a gait disturbance or hyperreflexia, or we had patients with, like, a urinary incontinence. It's only at that time, but maybe years have passed meanwhile, that these patients are finally referred to the neurologist Dr Monteith: You spoke about some of these clinical symptoms. Can you give us some other clinical red flags?  Dr La Piana: Well, some other clinical red flags can be, for example, the extraneurological involvement. So, we have patients where- and there's a reason immediately to some specific disorders. For example, infertility. The presence of infertility in a female patient with white matter disorders should immediately form the consideration of the specific genetic white matter diseases that are associated with these forms. And this is not something that neurologists tend to ask about in the collection of the clinical history. And this is something that can make the difference and can accelerate the diagnosis.  Dr Monteith: What are some other things? I mean, I know we can think about treatment, lack of a common treatment response, maybe, to steroids. You gave a great example of optic neuritis, for example. Give us some other things that we should say, hey, this doesn't fit the picture. Red flag.  Dr La Piana: In this case, I think we want to talk more about the specific misdiagnosis of MS. Because these patients are often misdiagnosed with MS, but they might sometimes be misdiagnosed with other forms of acquired white matter diseases. When we consider MS, definitely the presence of being treatment resistant: so, patients that are not responsive to the common MS-targeting treatment should be always a red flag. The evolution as well. So, for example, the presence of a more slowly progressive course is another red flag. The presence of optic neuritis. Sometimes it's tricky because it's not common in the genetic white matter disorders, it's used as a criterion to orient correctly towards a multiple sclerosis. But we need to keep in mind that there are forms, genetic forms, especially the mitochondrial forms, that can present with optic neuritis and are really at the overlap with the multiple sclerosis spectrum. Then, if we want to move forward beyond the clinical side and go into the laboratory, of course a negative lumbar puncture with no oligoclonal bands should be a major red flag. Dr Monteith: What about some of the radiographic features?  Dr La Piana: So, the radiographic features is something we are really working on in the field, especially with the new criteria used in MS. So, for example the paramagnetic rim lesions or the central vein sign, they are considered the specific forms. But it's true- and don't have an answer for that. I want to be clear, but it's true that they haven't been assessed yet extensively in patients with genetic white matter disorders. Anecdotally, I can say, because I have already reported this at conferences, that we have seen patients with genetic white matter conditions reaching a threshold for a central vein sign that can be considered diagnostic for MS. And we have seen that in some patients. Again, no study has been carried out extensively to date, but I think we should consider that with a grain of salt. But yeah, the paramagnetic rim in lesions is probably more accurate to distinguish between genetic and acquired white matter disorders.  Dr Monteith: And what about some of the genetic white matter disorders that mimic MS? You spoke about things like CADASIL; what are other things that we should keep in the back of our mind? And you have great charts, to our listeners, and they're going to have to review those charts, because they're excellent. I think maybe they need to find a way to make that a little bookmark you walk around with on the ward. But what are some other conditions that kind of commonly mischaracterized?  Dr La Piana: Two of the main groups are the one that you mentioned. So, leukovasculopathy is- so, CADASIL, is definitely one of the most common misdiagnoses of MS. And the presence, as we said, of some clinical features like migraine, especially when it's complicated migraine with visual aura, we all know that. But especially in the context of a positive family history for either a psychiatry condition or migraine as well, or strokes, these are all factors that should prompt the consideration of these disorders in the differential of a patient with white matter disorders. Another category are definitely mitochondrial disorders, which I think are more neglected than others because we don't think about mitochondrial disorders when we see white matter disease; we tend to consider that mitochondrial disorders are a problem of the gray matter, but they are not. There are white matter diseases that have definitely mitochondrial. And the third category are probably microgliocytes, which are represented by the CSF1R-related disorder. And this is also something that is clearly quite prevalent, relatively prevalent, in the field of genetic white matter disorders misdiagnosed as MS.  Dr Monteith: Yeah. Why don't we go through some of the, kind of, key history, you know, some of the key questions you would ask in the history to try and differentiate? You mentioned kind of subtle symptoms, longstanding progressive symptoms. I know things that we look at like relapsing/remitting and some trigger factors can actually be associated with some of these genetic disorders. So how do you approach a patient? What are some of the key questions? You talked about family history and you talked about medical history, but why don't you kind of give us a nice way to kind of hone in on to the patient? Dr La Piana: There are a couple of questions that we usually ask. I should make a disclaimer, though, that I work very closely with the MS clinics, so we are ready to receive patients that are prescreened. So, these are already patients that people working on acquired white matter disorders feel like they are atypical, so they want our opinion. But usually, there are two groups of questions that we always ask. One is about the family history. And by saying family history, I really dig into the family history. I don't just want to know whether there are family members with neurological disorders. I ask specifically about migraine. I ask specifically about infertility issues. I ask specifically about psychiatric issues. These three things are always on the top of my mind when asking about family history. The other thing is a family history for neurodevelopmental disorder, because you know that some people might not remember that some genetic white matter diseases can present at different ages. So, in the same family, there might be cases with a pediatric-onset leukodystrophy, and that can manifest at a later age in other family members. So, this is something that we always explore. In terms of the clinical history, one question that I recommend always to ask is really about more subtle symptoms. So, for example, many of our patients present with progressive balance problems or progressive mobility issues that have been going on for a while. So, we always ask how they were when they were in their teenage years, for instance. And it's frequent that they say, actually, I was a bit clumsy. Actually, I was not the first being picked in school at phys-ed sports. And these are all interesting aspects. Maybe they are totally incidental, and sometimes they suggest that there was probably something going on for a long time. The other thing is the presence, for example, of learning difficulties. Again, these are things that are subtle but testify that there was probably a process that was more longstanding. Dr Monteith:  You talked about things like rim lesions. Are there other types of sequences that might be useful to better characterize demyelinating diseases that are genetic in origin? I assume higher levels of MRI might be better at differentiating.  Dr La Piana: Yeah. So, in the clinical setting, there are a couple of sequences that are very useful. One is the diffusion, because as opposed to multiple sclerosis, the presence of persistently restricted areas of diffusion can point immediately towards some genetic white matter diseases. One is CSF1R-related disorders. But there are also some other, more rare tremor and ataxia syndrome that present with persistent areas of restricted diffusion as well as others. The presence of calcification. So, adding an SWI, susceptibility weighted imaging, to check not just for calcifications that can immediately orient towards some disorders, but can also identify areas of microhemorrhages that, if we are going back to the leukovasculopathies, to the genetic leukovasculopathies, can tell us that we are on the right track for excluding those type of diseases. Basically, these are the two that are available in every scanner without even going into fancy, more advanced techniques. Dr Monteith: I was going to ask you that question, how often should we think about this next-generation sequencing when you're kind of on the fence, allowing for some negative results to come back in the abundance of caution?  Dr La Piana: The problem with the panel, of course, is that you run a panel and you don't know what's coming back. So, then having to deal with variants of unknown significance in genes, then you have to deal with them, and then you have to deal with results that maybe are not as black or white as you would expect initially. So, I'll answer to your question when to do that, our recommendation would be to do that every time you are presented with a patient that presents those atypical features that we summarized in the paper, and that basically raise multiple red flags for an atypical white matter disease that is not multiple sclerosis. And then what to do when you have results? I still believe that having access, of course, to genetic counselors, to neurogeneticists, is critical, but also having access and being in contact with the network of people working on this. Because we are a network; we put the website address on the paper of the white matter rounds because this is an international network that we built over the years, and we connect monthly, on a monthly basis, with meetings to discuss exactly this type of patient. So, we are all learning together, and it's very frequent that people ask us to present cases at the white matter rounds because they have a presented with unusual or atypical genetic findings and they want the opinion of experts.  Dr Monteith: Great. Well, I'm really glad that resource is available. And I'm also really glad that you wrote that article with your colleague. Thank you so much. Dr La Piana: Thank you so much, Tesha.   Dr Monteith: Today I have been interviewing Dr Roberta La Piana about her article on adult-onset leukodystrophies mimicking multiple sclerosis, which she wrote with Dr Gabrielle Macaron. 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.

In part two of this series, Dr. Tesha Monteith and Dr. Brett Lauring discuss the clinical trial design, including the objectives and methods. Read more about this abstract on the AAN website. 

In this episode, Dr. Andy Southerland reviews the Capitol Hill Report from April 6th, focusing on news related to appropriations and several new bills. Stay updated with what's happening on the hill by visiting aan.com/chr.  Learn how you can get involved with AAN advocacy. 

Dr. H.E. Hinson and Dr. Vijay Ramanan discuss the upcoming Clinical Trials Plenary Session at the AAN Annual Meeting and the landmark studies shaping neurological care. For more information about this event, visit the AAN website.  

In part one of this series, Dr. Tesha Monteith and Dr. Brett Lauring discuss the potential role TRPM8 antagonist may play in the management of migraine.   Read more about this abstract on the AAN website. 

Dr. H.E. Hinson talks with Dr. Vijay Ramanan about the upcoming Clinical Trials Plenary Session at the AAN Annual Meeting and the landmark studies shaping neurological care. For more information about this event, visit the AAN website.   Disclosures can be found at Neurology.org.