Episode 458 -- From the 2026 CMSC Annual Meeting: Part Two with Dr. Stephen Krieger

0:18 It's June 9th, and we have a lot to talk about. This week, we're continuing our coverage of the Consortium of MS Centers annual meeting, a meeting that took place just a couple of weeks ago in Charlotte, North Carolina. Now, typically, I'd be sharing interviews with two or three of the world-class MS experts that it's always my privilege to meet up with at conferences like this one. But this week is a little different. This week, my sole guest is Dr. Stephen Krieger. And the reason Dr. Krieger is my sole guest is because at this year's CMSC meeting, Dr. Krieger seemed to be everywhere, talking about all the important things as they relate to people living with MS.

1:00 But before we get to my conversation with Dr. Stephen Krieger, there are a few other things that you should know about. If you're living with multiple sclerosis, you already know that managing your symptoms is a bit of a balancing act. You wake up, you gauge your energy, you determine where your pain levels are, check in with your other symptoms, and then you adjust. And for many people, that adjustment includes reaching for things in their pantry or medicine cabinet to help them cope. Maybe it's an extra cup of coffee to fight off fatigue, a glass of wine at night to unwind from the stress, or maybe cannabis or prescription opioids to take the edge off the pain.

1:45 Well, researchers from the University of Michigan and the University of Washington took a super close look at exactly how this plays out in real time. They tracked over 250 adults with MS who were asked to report in using their smartphones four times a day. The research team wanted to see the immediate, almost hour-by-hour relationship between the substances people with MS use and their symptoms. And what they found provides a clear snapshot of the daily habits of people who live with MS. The researchers call it a bidirectional relationship. In plain English, it's a two-way street. Your symptoms change what you reach for, and what you reach for changes your symptoms later in the day.

2:32 Let's break down a few of the most surprising twists they found because, well, it's not always what you might expect. First, let's talk about alcohol and stress. The data showed that when people felt a sudden spike in momentary stress, they actually had lower odds of reaching for a drink. However, when they did have a drink, it succeeded in reducing their stress. So it works to lower stress, but stress itself isn't always the trigger pushing people to alcohol. Patients with higher overall pain averages were less likely to drink alcohol, but they were significantly more likely to use prescription opioids, which makes complete sense for pain management.

3:18 But here's where that two-way street starts getting tricky. It's what we call the hidden tax. The study found that while caffeine did what it was supposed to do, it boosted energy and it lowered fatigue, it also predicted higher stress levels later in the day. And substances like alcohol, nicotine, and cannabis were actually linked to greater fatigue afterward. Even more surprising, cannabis use was actually tied to higher momentary pain later in the day. Now the point of the study isn't to judge anyone or tell you to throw away your morning coffee or change your routine. Living with MS is tough, and symptom regulation is what gets you out of bed every day, or at least most days.

4:04 What the scientists are trying to show us is that our bodies are in a constant dynamic feedback loop. Sometimes the very thing you reach for to fix a symptom right now might be sending you a bill that becomes due a few hours later with a different symptom. If you use caffeine for energy, you might be trading it for an anxiety or stress spike later. If you use cannabis or alcohol to relax, you might be digging a deeper fatigue hole that you'll find yourself standing in tomorrow. So here's an opportunity for each of you to become your own scientist. For the next few days, just pay attention to the timing. When you have that afternoon coffee or that evening drink, look at how you feel three or four hours later.

4:51 Understanding your personal feedback loop is one of the most powerful ways to take control of your health. Talk with your care team about what you notice, because finding a balance that doesn't cost you later, that should be the ultimate goal. Now, if you'd like to review the details of this study, you'll find that link in today's show notes. If you're a parent living with multiple sclerosis or navigating any kind of progressive mobility challenge, then you know about that unique layer of emotional weight that comes with raising kids. You worry about what they're witnessing. You worry if or how your changing body could be affecting their childhood.

5:33 You wonder about how to explain a wheelchair, a scooter, or a walker to a five-year-old without making them feel sad or afraid? Well, I want to tell you about a children's book that handles this subject with grace, heart, and honesty. It's called My Superhero with Wheels, and I think it's a book that deserves a place on the bookshelves of every parent of young children in the MS community. My Superhero with Wheels was written by Lawrence Morello, who's been living with MS for 32 years. But the story itself is told through the eyes of a young child looking at their father. And to this child, the wheels their dad uses to move through the world aren't a limitation at all. Quite the opposite.

6:18 They're part of what makes him a superhero. When an adult transitions to their first assistive device, it often comes with a lot of complex grief. That wheelchair or walker becomes a symbol of what's been lost. But kids don't have that baggage. To a child, a mobility aid is just an adaptation. It's that thing that lets dad roll fast so he can get to the park. My Superhero with Wheels beautifully normalizes disability. It shows kids that being strong doesn't have to mean standing up or running. Sometimes true strength is just showing up, adapting to the day, and loving fiercely.

6:59 It teaches kids that disability isn't something to hide, fear, or explain away. It's just one part of a full, incredibly loving family life. If you're a parent who's managing MS, I think you're going to see yourself deeply reflected in these pages. It completely validates the realities of mobility challenges, but it keeps the spotlight exactly where it belongs, on your presence, your care, and that unbreakable bond you have with your kids. And the book gives children the pride and the language they need to talk about their family's story with total confidence on the playground or in the classroom. Whether you're looking for a bedtime story for your own kids, a gift for a family navigating a new diagnosis, or even a book to donate to a local classroom or therapist's office to spread disability awareness early, this is the one.

7:54 The book is My Superhero with Wheels. You'll find the link in our show notes so you can grab a copy. So let's keep changing the narrative, one bedtime story at a time. And speaking of changing the narrative, new narratives are being written when it comes to subjects like how disease-modifying therapies can effectively manage MS, what's really needed when it comes to caring for people with advanced MS, and identifying some of the potential potholes on the road to getting an early and accurate MS diagnosis. My guest, Dr. Stephen Krieger, has thoughts to share on all of these topics. And in just a moment, we'll meet Dr. Krieger.

8:39 Dr. Stephen Krieger is a professor of neurology at the Icahn School of Medicine at Mount Sinai in New York and a multiple sclerosis specialist at the Corinne Goldsmith-Dickinson Center for MS. I learn something new every time I speak with Dr. Krieger, and it's great to see you. It's great to see you, John. Thanks again for doing this with me. This is a busy meeting for you. You're reporting the three-year results of the Phase II open-label extension for Frexalamab. So can you tell us what Frexalamab is? Sure. So, you know, there's been a lot of attention paid to other disease mechanisms and treatments in MS in these last few years, such as BTK inhibitors and CAR-T therapies, but sort of maybe hiding a little below the radar is what Frexalumab does.

9:22 It's an anti-CD40 ligand monoclonal antibody, so it's a monthly infusion, takes about an hour, and it modulates the CD40 pathway, which the hope is it will regulate both active inflammation in MS, the inflammation that causes relapses, and also this more chronic innate immune processes that we think are responsible for progression. And so what I presented at this meeting is the three-year extension after their phase two trial. So, you know. Long-term data, like long-term follow-up from a trial is always important, but especially with a novel mechanism, a drug that we don't have otherwise. There's no other one.

10:03 So the only data we have for how do people with MS do on Frexalumab for the long term is this extension trial. So this was the three-year extension. And the punchline is people did not have new lesions. They did not have new enhancing lesions. They did not have new relapses, EDSS, so disability, was stable across the board. And perhaps most distinctively compared with other things in our field. Frexalumab doesn't deplete cells. It doesn't drop the immune globulins over time. There doesn't seem like a cumulative negative consequence on the immune system with it. So all that is holding steady at three years.

10:44 And no new bad news, no new adverse events of any note. So it's a good report that Open Label Extension keeps going. And now it's in two phase three trials, one for relapsing remitting MS and one for folks with secondary progressive MS. Those are ongoing. We've got about another year, year and a half probably before we'll see those results. Well, we'll keep our fingers crossed. This sounds exciting. Thank you for sharing those results. My pleasure. You're also presenting on the needs of individuals with advanced MS, specifically preserving function, reducing symptoms. You know, the term advanced MS is a term some of my listeners may understand, but it isn't a term they often hear.

11:26 We talk about progressive MS. How do you define advanced MS? This is a great question. That was the opening portion of this program was, how do we define advanced MS? This was a course led by my dear friend and colleague, Rachel Stakem. Rachel's a nurse practitioner in MS in New York. She works at a program called Independence Care Systems, which endeavors to help people with disability live full lives, live in their homes, not have to be in an institutional type facilities, et cetera. So Rachel's been my close friend at MS for 20 years. We both got into this field together. But her career commitment is to people with significant disability.

12:11 Let's put it in those terms. You know, folks who are wheelchair-confined or wheelchair users need power devices for mobility. And in MS, we focus so much on preventing disability, which is a noble goal, but perhaps we focus on it too much. Most of our clinical trials don't include people who can't ambulate. Most of our clinical trials don't include people of advanced age. And so there's been a blind spot in some ways in our field for the people who have developed real challenges from their MS. So that's what we mean by advanced MS. In essence, significant disability. But she points out at the beginning of her course, and I was just a speaker in her course, but she points out that there is no consensus definition for advanced MS.

13:01 And without that, there's less of a sense of how big that unmet need is. What are the needs of this population? Population that needs a lot. And so one of the things she'd like to do is help to move forward a consensus definition, then estimate the size of the population, survey what their needs really are, aligned resources to meet those needs. But the theme of her course was, it takes a community, it takes an interdisciplinary team, which is very much aligned with the spirit of CMSC as a conference, that no one provider, certainly no one neurologist, can hit all the needs herself.

13:42 But it is our responsibility to look for them and recognize them. And my principle that you may know that I talk about, but is very much a part of this course, is find the good that you can do. Look for the opportunities to do some good for people and to remind clinicians in general and neurologists in particular that there's never nothing I can do for you. There's always something we can do, and we need to lean into it, listen carefully, think about the person in her world and help her navigate her life and optimize her life and not just prevent disability, not just treat symptoms, but be very holistic and proactive about it.

14:24 That's what Rachel's course was about, and that's what my talk was about. You know, I'm very familiar with that world. Until she passed away, my wife lived in that world. And I would only add, not only is it, or it should be, a neurologist, a specialist's responsibility to see that and to respond to it. When that doesn't happen, I'll say as a patient advocate, it is a patient's responsibility or their care partner's responsibility to advocate for it, to point it out. And I can tell you from personal experience very often, the answer is, yeah, I wish there was something I could do for you. I've heard that out loud.

15:09 And my response was always, there probably is. And I had some notes ready for that meeting. So we can't fix everything, but what here can we fix? And what I used to do with my wife is, what are the three biggest things that are burdensome to you every day? So it wouldn't just be a list of stuff, but it would be organized by priority. And that way, it increased the chances that one of those things could get addressed, mitigated somehow. I realized as I was saying it how resonant this is going to be for you. And this whole course, it was myself, Elaine, and Renee talking about mobility, talking about access, symptom management, keeping people out of the hospital.

16:00 Extending life when possible, making it meaningful. Yeah. The course was recorded. Not everything at CMSC is recorded, but Rachel Stakem's course on Advanced MS was recorded. So I do think it would be available for folks that watch you and listen to you if they want to hear about it. I found it very meaningful. I hope we get to do it again. But at least this one was captured by CMSC on video. So it's out there if folks want to see it. Well, I'm glad. I think the folks at CMSC recognize this was something that should be shared, so I'm glad it was recorded. You'll understand immediately where this question comes from. But when someone is living with advanced MS, how important does managing the emotional well-being of their care partner become?

16:47 Yeah, well, when we talk about thinking about someone in their life with MS, the care partner, care provider, pillar of support is an awfully important part of that person's life and navigating that life. We talk about shared decision-making in MS, but how about just shared priority setting, shared well-being, and the sharing of that between, care partner and physician and nurse practitioner and occupational therapy, physical therapy, referral, psychosocial support, social work, psychology, psychiatry.

17:33 I think these things go hand in hand. And when we say there's always something you can do, there's always someone who can do it. And it's about finding who that person is to provide the support for the person living with MS, for the people living with them and supporting them. When one leg of a chair falls off, the whole chair falls over. So we need all the legs to hold it up. Well put. You know, one of the topics either being discussed or underlying the discussions at this meeting are the latest iteration of the McDonald criteria. I've heard about that. That is a criteria used to diagnose MS. And although you aren't speaking on that topic directly at this meeting, you recently had a commentary published in a peer-reviewed journal where you shared some concerns about the most recent update to the McDonald criteria.

18:23 Now, the updated criteria significantly lower the barrier to a formal MS diagnosis, meaning patients can be diagnosed much faster, at least That is the stated goal, sometimes after just a single anatomical lesion, if specific biomarkers are present. So in your essay, you raise a cautionary flag about this leap in diagnostic sensitivity. Historically, every time the McDonald criteria are relaxed to catch MS earlier, there is a corresponding surge in misdiagnosis, often confusing MS with migraines, small vessel disease, or neuromyelitis optica spectrum disorder, right? How concerned are you that these new criteria will amplify that misdiagnosis epidemic in non-MS specialist clinics?

19:13 How much time have you got for that? So, you know, it's a couple of things. I think that the motivation of the McDonald criteria is to allow for MS to be diagnosed earlier and people in whom it might have been missed. So I applaud the principle. The challenge, I think, is a couple of fold. One is the one you raised, that if we're going to diagnose multiple sclerosis in people who've never had a symptom of it, who may have very little evidence of it on traditional MRI scans, it does open up the risk of overdiagnosis in someone who has a nonspecific brain spot.

19:58 And misdiagnosis in general, confusing the disease for something else. I do think that's a concern. I also think there's a concern more deeply that we're saying someone who has a certain marker has a disease, as opposed to saying someone who has a certain marker in the blood, or in the spinal fluid, or even on a brain MRI, has a risk for the disease. Those are two very different things. So I think we've confused the two. Someone having a risk for having a disease might merit closer monitoring, maybe even treatment to prevent things from happening.

20:39 That's what we've called radiologic isolated syndrome, RIS, all these years. It looks like MS on a scan, but the person has nothing to show for it. But in certain circumstances, these new criteria mean we're going to diagnose those folks with MS. And I think that there's something really risky about doing that, telling people they have a disease that they may never have, they may never develop for their whole lives, telling them they have it. So I wrote this letter. It touches on some other things, which maybe we'll get to. And the authors of the McDonald Criteria wrote a response to my letter and a couple of other letters.

21:20 This is in Lancet Neurology. So the journal that published the criteria, which I'm pleased that this letter got there. A lot of people writing about the McDonnell criteria in all sorts of places, but the fact that I wrote something that is critical and the journal that published the criteria itself saw fit to publish it is gratifying to me because I think what I'm raising are important points. But one of the responses from the authors to my letter was, well, we're doing this in Alzheimer's disease also. You know, there's biomarkers in Alzheimer's disease. Now we're able to diagnose that. That's actually very controversial. And a lot of folks are very unsatisfied or unhappy about that, too, because many people who have these biological markers of Alzheimer's disease are never going to develop that either.

22:10 So I think although they appealed to that as an example, I think that's a cautionary tale that we have now weighted ourselves into in the MS world. And I do think it's a setup for error. And that's not fair either to people living with uncertainty, to people who've had an MRI scan. So that's one of my concerns. I've got a couple, but that's one of them. We'll talk about another set of concerns. The updated criteria rely heavily on cutting-edge tools, checking for a select six threshold of central vein sign, on mapping PIRLS, PRLs, measuring kappa-free light chains and spinal fluid, or evaluating optic nerve involvement by OCT.

22:56 Now, these are all advanced imaging techniques and lab assays that are routine at academic settings for the most part, or at least available in most academic settings, but they're rarely standardized or available at a local community neurological practice. How do we prevent these criteria from creating really a two-tier diagnostic system where patients are going to be staged and treated based on their zip code? Yeah. I mean, I think this is the biggest concern that I have. Um, and I wrote about this in the commentary, I posted it on LinkedIn, my only social media, and there was a whole conversation there about that, including the two-tiered system concern.

23:41 Um, I'm no Luddite. I like technology and I like new science and I do think the field needs to advance. Problem is, the criteria were written by folks who've studied these techniques for 10 or 20 years. They live in that world of cutting-edge science, and they promoted those things into a diagnostic criteria, which the whole point of it is to be globally useful. Useful to general neurologists, broad-spectrum neurologists in practice. Useful to neurology residents and fellows who are training, people in rural communities, people in under-resourced areas, a diagnostic criteria that's global is supposed to be a bar that everybody can achieve so that every patient, every person who may or may not have MS can have that question answered.

24:35 But by promoting these very specialized tools and techniques into the criteria, even though they kind of couch them as optional, if they're available. I do think that it's going to make it essentially impossible for broad-spectrum neurologists, neurologists in the community, in practice, in training, to apply these criteria to their patients. Impossible. You said, these techniques are available in academic centers, and I probably smirked a little bit. We don't have them. I've never seen a pearl. I've never seen a central vein sign on a clinical scan.

25:16 Because we don't have them available to us at our well-resourced MS center. We don't have them. These criteria were announced in fall 2024. It is summer 2026. We don't have them. Many places don't have them. Now, I'm not saying we can't get them. We can get them in research. This is a thing I think that the community doesn't know, and maybe even the authors of McDonald underappreciate it. It's not just you bring in a new imaging technology, now the answer's on it. That imaging technology needs to be ready for prime time. It needs to be standardized. An institution or an office needs to purchase it, install it, implement it, train the radiologist to read it. It doesn't just pop up on the screen and say, this is MS.

26:08 It's a technique. It's like art appreciation. You have to learn how to read what is a pearl, what is a central vein sign. I'm afraid that not only are these techniques not available to people making a two-tiered system, some haves and some have nots. It's going to cause new forms of error. People misreading these things, misreading an OCT scan and saying, well, this person has optic neuritis. You can't diagnose optic neuritis with an OCT. So I'm concerned that we're going to not only delay diagnosis because patients are going to wait to try to find a place that has these resources.

26:49 It's going to shunt MS diagnostic workup from everyone, every neurologist, to only the specialized few, which is going to make the wait times longer. We just talked about how people don't have enough time to spend with their patients. The wait times might be months, might become years. So the criteria, as you said up front, intended to expedite, make the diagnosis earlier, sooner, faster. I think it's going to delay it because it's going to make the wait time for people to get to specialists who know how to navigate this criteria longer. It's going to delay the diagnosis it was intended to expedite, and it's going to cause new etiologies of error, new mistakes on top of the old mistakes, but not correct any of them.

27:33 One of the things I wondered about with some of the advanced technologies being promoted as part of the criteria is not only that people might get it wrong. And not only that in community office settings, they're not available. It occurred to me, the community neurologist who reads that and just says, oh, this is not for me. I give up. I give up. I wrote in the paper that general neurologists will be hamstrung. And that's a loaded word, but I think it makes it not for them. And I don't know that that was intentional on the part of the McDonald criteria authors. I just think that they live and breathe that stuff and forget that not everybody can and not everybody does.

28:20 So my thought is, you know, an operating system for a computer, they add features and then they add more features and more features. And after a few years of the development cycle, the thing gets so complicated that it doesn't work very well anymore, slows the whole thing down, doesn't run on your computer anymore. And then the next iteration of that operating system strips out all that stuff. They start over clean, right? A clean, new, fresh operating system, getting rid of all the noise that got added. I would love to see a version two of the McDonald's 2024 criteria, a revision, a cleaned-up version, strips away a lot of the unnecessary things, gets back to basics, cleans it up, makes it doable by anyone.

29:02 And then we can bridge this gap from where we are to where we want to be with new technology. But it's bogged down in a way that I do think is going to cause a lot of people to throw up their hands and say, this disease isn't for me anymore. I don't understand what the MS community wants from me. And I think that does a real disservice to people, especially in under-resourced areas. I think it's going to worsen inequity of how health care is delivered in MS, which we don't need. We sure don't. Well, I feel like we've just been given a masterclass in contemporary issues in MS care. Dr. Steven Krieger, I want to thank you for all you do to improve the lives of people who are living with MS.

29:43 Thank you for sharing your clear-headed thinking so transparently. Thanks for talking with me today. It's my pleasure. And listen, people can disagree with me on this stuff. This is my own perspective on it. And I'm okay to be wrong. I would like to be wrong about this last part. My hope is maybe the uptake will be faster than I realize, and these new MRI sequences will be easier to interpret than I realize, and we'll look back on this and think, ah, Krieger underestimated it. I hope I'm wrong. Well, let's see. That's going to wrap up this episode of Real Talk MS. Real Talk MS is powered by the National MS Society. And you can share this episode of the podcast by letting your friends or family members know that all they have to do is point their web browser at realtalkms.com slash 458.

30:33 You'll find that link in today's show notes, so you can easily copy and paste it right into an email or a text. Next week, our coverage of the Consortium of MS Center's annual meeting continues. You'll meet two experts who are each changing or at least expanding the rules of the game when it comes to MS rehabilitation. You'll hear Dr. Brad Willingham talk about how artificial intelligence can be used as a decision support tool in MS rehabilitation, and Dr. Brian Sandroff discusses whether physical exercise can be used to treat MS-related cognitive issues. I'm John Strum. Thanks for listening. Stay safe and make healthy choices.