Ardra Shephard: I'm Ardra Shephard and this is Tripping on Air, a place to talk shit about what it's like to have MS. Normally I like to make everything about me, but MS also affects the people we love. So, weighing in from the partner perspective is Alex Hajjar, my friend whose wife also has MS. Join us monthly as we dish about everything from symptoms to stigma. If you have MS or you love someone who does, we want to connect with you. Ever wondered why your MS seems to be getting worse even though you're not having any relapses? Your MRI is stable, but you feel anything but? Maybe eight or nine years ago, I started to notice that after about 45 minutes on the treadmill, I'd suddenly start tripping. It didn't matter how hard I concentrated, I couldn't keep my toe from catching on the belt. I was on a highly effective medication, my MRI was stable, my legs were always strong when the doctor examined them. A six-minute timed walk would've backed up the theory that I was doing well. I had no new or enhancing lesions, but I knew my MS was getting worse and I wasn't sure I was being taken seriously. As it turned out, my MS was getting worse. The time it took for me to start tripping on the treadmill went insidiously from 45 minutes to 30 to 20 and eventually my progression became obvious. In recent years, I started hearing more and more about smoldering MS. It seemed to describe what I was going through. My MS was worsening even though I wasn't having relapses. I felt relieved to have the words to describe what was happening to me, even if, in my experience, smoldering MS sounds way sexier than it is. Our guest today is Dr. Jiwon Oh. She's the medical director at Toronto's Barlow MS Center. Dr. Oh is here to help us understand what exactly smoldering MS is and to give us the inside scoop on the scientific and treatment advancements we can expect to help manage progressive MS in 2024 and beyond. Dr. Oh, welcome to the show. We're so happy to have you here. What's the deal? What is smoldering MS and how does it compare to some of the more traditional ways we categorize MS? Dr. Jiwon Oh: Thanks, Ardra and Alex, for having me. I'm really delighted to be here. Smoldering MS, Ardra, like you really nicely described, is something that I think people living with MS have kind of known about and have thought about and described for a long time. But there hasn't been as much focus on the clinical manifestations of smoldering MS in the past and it's for a few reasons. First of all, from a clinical standpoint, as neurologists, we use many tools in the clinic to try to measure how an individual patient's disability level is. But let's be real, the tools that we use are far from perfect. Ardra, I know when you're in clinic you see us pull out the reflux hammer and the tuning fork and all of these things have a role and they're good for different reasons. And we even do tests like the 25-foot timed walk, which are supposed to be a little bit more quantitative, but it's pretty clear that the tools that we use, while they're good for certain things like say identifying that there are neurological abnormalities in a person, in a chronic disease like MS that lasts decades if not a lifetime, they're actually not able to very clearly detect disease worsening. And so in these settings, we're recognizing how imperfect the tools that we have are. We're constantly searching for new MRI measures or new blood tests that may help us monitor this more accurately, but don't yet have anything. And so ultimately we need to be using additional, say, questionnaires or other clinical tests that will help us identify that people clearly are very slowly getting worsening, sorry, worsening, but our tools aren't detecting them. So, from a clinical standpoint, exactly what you've described is what smoldering MS is. It's this slowly, grumbling, progressive worsening of symptoms that our typical traditional tests cannot detect. And in the field, why there's such a focus on this, is because smoldering MS is now rearing its ugly head more and more because in the last few years we have access to what we think are highly effective treatments that can control relapses really well. But when we do that, what we're seeing now is people don't have relapses yet they have these symptoms that are slowly worsening over time. Ardra Shephard: I think that's something. Was that a really big surprise to the medical community that these highly effective medications don't stop progression? Dr. Jiwon Oh: It was in a way. And this is an illustration of how as we make these amazing scientific advances, then additional questions crop up. Because even 10 years ago, the general thinking in the field was that the major driver of disability worsening in people with MS is what we think of as relapse biology. So, these are the relapses that we see, these are the new MRI lesions that we can identify on clinical MRIs. So, the thinking was that if we're able to get rid of relapse biology, most people with MS will be completely stable. But that's not the case. And then all of these studies started emerging in the last five years showing that smoldering disease worsening happens even in the very earliest stages of MS, because we used to think that this was only something that we saw in progressive disease and in later stages. So, it was a surprise, Ardra, just because I think the field knew that smoldering MS was a thing and it's really what we generally call progression in MS. I just don't think people recognized how early it happens and how common it is. And then when you talk to people with MS, there's these recent huge surveys that have asked people in different countries, thousands of people living with MS, and this is something that people with MS are like, "Yes, yes, this is something I see," exactly like what you're saying. Ardra Shephard: It's been super validating, frustrating at the same time, but just validating to be like, "Yeah, we're being taken seriously." Sorry, Alex. Alex Hajjar: No, nothing. I was just going to say that parlays really well into the question that I had actually, which is, is the understanding of smoldering MS something that's new and it sounds like maybe the understanding is, but maybe the concept itself isn't? But are most neurologists on board with the concept or are some still coming around? I ask this because as a partner of somebody with MS, I worry that some patients may feel dismissed by their doctors and that there's a risk that they'll be further misunderstood or just not taken seriously by their partners or friends or family. And it seems like there's a lot of people saying that their MS is getting worse, but the doctor tells them they're just doing okay. Dr. Jiwon Oh: Really great question, Alex. And I would say that the field is really recognizing now how important this is and from the very beginning of the disease. And so I would say in people who do a lot of research or who are at large academic centers focusing exclusively on MS, this is a concept that most people are embracing with open arms and really devoting resources to understanding. But because the traditional mentality is so entrenched, it may not have percolated as much into the community as we would like. And so, we're starting to do that though just because there's... And this gets to the second part of what you asked me earlier, Ardra. There's many trials of investigational treatments right now that specifically have the potential to target aspects of smoldering MS. And so because of this, I think there's a lot, the message is getting out, but say in somebody who takes care of a number of people with MS and also takes care of people with stroke and Parkinson's disease and all of these other things, it may not be a concept that's as familiar. Only because, again, the field has, in the last five years, really been focusing on this and it's emerging as something that is extremely relevant and maybe even the greatest unmet need that we have clinically and scientifically. Alex Hajjar: That's interesting. I guess, with these newer therapies maybe a question I could ask is, knowing that the drugs don't stop progression, can you clarify why patients need to stay on their meds? Because I find that some may say like, "Oh, I have an easier time without them." Dr. Jiwon Oh: I should emphasize that all of this is not to say that the relapse disease biology and controlling that is not important. I would say that that is essential in MS care as well. It's just that in the last 25 years there have been now over 20 different treatments available, many of them that are really, really good at almost getting rid of all of relapse disease biology. So, because we can do that, and this is to say that if we cannot control relapses, then absolutely people will accumulate disability and relentlessly. This is evidenced by all of the longer term natural history studies that took place in the years before treatments for MS were widely available. So, if you look at some of the statistics in older studies, and obviously it's always difficult to compare older studies from 50 years ago to what's happening now. But when you look at these general disability times that people reported at the time, so in some studies in people with MS at 10 years, almost everybody would require at least a cane to walk. And that's really different now. And that's because we have a ton of treatments that are really good at controlling relapse disease biology. But now that we're able to do that, what's emerging is smoldering disease that we're not that good at controlling at all, in fact. And that's why it's becoming so important. So, people absolutely should stay on their treatments because controlling relapses is very, very important. And by relapses I don't mean just clinical relapses, because again, MRI disease activity helps us to detect relapse disease biology as well. But now that we're able to do that much better than we did 25 years ago, we now need to focus on this smoldering aspect of disease pathology. And the other thing I wanted to emphasize is that one of the challenges we have is that MS is so variable, like in someone who's presenting at the age of 25, the way individuals' disease course progresses is so different. And so, in some people, controlling that relapse disease biology, if you do it early enough, may actually help them to actually not even have smoldering disease. And that was the hope many years ago. But in other people, they have more smoldering disease biology, than relapse disease biology. So, in these people, these are the individuals where we really hope to get treatments that can really target the smoldering component. And this is all to say that everybody has different balances of how much relapse disease biology and smoldering disease biology they have. So, it makes sense that we treat with what we have available. So, right now it's excellent drugs for relapse disease biology and hopefully in the next few years we'll actually have drugs that can control the smoldering component, which is present in most people with MS, but not everybody. Ardra Shephard: That's really important clarification. Thank you for that. I want to go back to patient reported outcomes in determining smoldering MS. You mentioned some of the tools that we currently use in clinic. I always think whenever that safety pin is opened and dragged across my flesh that maybe I should have gone to med school, it doesn't seem that hard. I know that's an oversimplification, but we don't have the tools maybe yet, but what is coming? Because by the time my progression showed up on a 25-foot walk test or even a six-minute timed walk, I was noticing these changes years before then. So, I guess the question is about how dependent are we on patient reported outcomes and what are some of the tools, that if we don't have them yet, may be coming? What kinds of biomarkers, how are we going to measure and investigate this? Dr. Jiwon Oh: In a nutshell, and I'll go into a bit more detail about this, ultimately I think it's going to be hard to find one measure that captures everything, because MS is so complicated and the neurological system is so complicated that it's unrealistic for us to think that there's going to be one magic blood test like they have in, say, diabetes where you're measuring blood sugars. You know what I mean? And so it's a very different disease. And so, the bottom line is, in the end I think there's going to be probably a number of useful measures that we combine to try to better monitor disease processes in people. In terms of patient reported outcomes, I think they're very important. I don't think there's yet a clear consensus in the field as to which kind of scales are most important. But in general, I would say the symptoms that are much more useful to have reported by patients are things like fatigue, things like quality of life, even things like bladder function and mood and all of these things, are things that should be collected through patient reported outcome measures. And right now, unfortunately in the clinic setting, because we don't have a clear consensus as to which questionnaires are most useful, they're not routinely done. But I do envision in the future that this will likely become a part of clinical care and it's not necessarily something that even needs to be done in the clinic. If we have the right apps or electronic survey systems, we might be able to have people actually fill these out before they come to their clinic visit. I think also digital tools have a lot of potential. I think our lives are inextricably bound to our smartphones. And so in the end, I think there's going to be probably useful MS apps that we can use to help collect some of this information and even do simple tests, like manual dexterity tests, vision tests, even cognitive tests just on your smartphone. Again, there's no consensus about which app is most useful, but even at the Barlow, we're about to launch two studies where we're looking at some of these smartphone digital apps. So hopefully, there will be ones that emerge as being very useful in the near future. And then I think imaging measures. There's a few MRI measures. One of them is called paramagnetic rim lesions that are thought to be able to image smoldering chronic active lesions in the brain. And so, this is something that the field is looking at as potentially very interesting, similar to the way that we currently use regular clinical MRIs and we look for new MRI lesions based on specific sequences that we have. Maybe we'll be able to look for chronic active lesions in the future, which are thought to be a major driver of smoldering disease biology. And then there's different blood tests that look at different measures, including Neurofilament-light chain and GFAP, amongst many others, that people are evaluating to see if they're useful for monitoring a smoldering disease. So in the end, I think it's going to be a combination of measures. And so, you might ask me what I do now. And so in the end, I think patients always know best because, Ardra, you are the one that lives with MS every day, day in and day out. And when you tell me that you feel like your symptoms are getting worse, and you gave a few examples like you used to be able to walk for longer periods without feeling like your toe was catching, things like that. I have patients tell me that they used to be able to walk from Union all the way to their workplace building without resting, but now they need to stop and sit on one of those benches in the underground path for a minute or two before they move on. So to me, that's very good evidence of disease worsening. And every tool that I would use in the clinic would not be able to detect that. I have patients tell me, who used to be avid hikers, they used to be able to hike for 10 kilometers without stopping and now they can only do five. So, these are all examples of patients reporting to me symptoms that I wouldn't be able to elicit in the clinic, yet to me that is clear evidence of smoldering disease. Ardra Shephard: I think it's also true though that for many of us there are worsening symptoms that we don't necessarily notice or attribute to MS. It's interesting to me how many comments I will see from somebody on the blog or the pod when I've talked about a specific symptom and they will say, "Oh, I didn't even know that that was a symptom of MS. I thought it was aging," or this or that. We're talking about how do we measure this? Is it even that important? If we know it's there in different manifestations, obviously we have to treat different symptoms, but knowing it's there, the next phase is what are we going to do about it? And so, if you could talk about, first, maybe what scientific, medical, what we can look forward to or be hopeful about in terms of medical advancements and then about the lifestyle choices and impacts that we can make to help mitigate some of the symptoms of smoldering MS. Dr. Jiwon Oh: I think it's important, first, as you said, Ardra, that we identify that this is happening. And right now, because we don't have any clear treatments that can decrease smoldering MS, it may not be as necessary to continue to monitor it. But the reason we keep searching for clear measures that allow us to monitor smoldering MS is because there's many experimental therapies being tested, that the hope is that they will decrease how smoldering MS is progressing or fix it or get rid of it altogether. And so, that's why we need measures in clinical trials, but also eventually when there are treatments that can decrease smoldering MS, we need to be able to monitor how effective they are. And so, that's why. Number one right now, I think it's still important to identify that it's happening, but also because hopefully we'll have treatments and then we need to be able to monitor it so that we can tailor appropriate treatments for people. What do we have to look forward to? Well, first of all, as we talked about, this is a real focus in the field right now. And so hopefully, in the next number of years, we'll have treatments available that can decrease the rate of smoldering MS, maybe even get rid of it. And so, there are certain experimental therapies right now that are being tested in clinical trials. The closest ones to having phase three, so these are the large clinical trials reported, are a class of molecule called the BTK Inhibitors. BTK stands for Bruton's tyrosine kinase and that's a certain type of enzyme in the body and it's actually expressed in many parts of the body. But the reason we're so excited about this molecule in the field of MS, and actually many other inflammatory diseases, is because we know that it's a key molecule that's involved in B-cell development, but also in the development of these cells called microglia, which are in the brain, and we know that are a major driver of smoldering MS disease processes. And so the bottom line is, this is a class of molecule that, maybe for the first time, can, first of all, we know B-cells play a major role in relapse disease biology. So, early trials are showing that it very clearly helps to decrease relapse disease biology. But the interesting thing is these molecules also very easily get into the brain, and then at least in early lab studies and animal studies, they not only get into the brain, but they actually decrease these activated pathologic microglia that we know are a major component of smoldering disease. So, why are we so excited about this? Because maybe for the first time, this is a molecule that can actually decrease smoldering disease processes in people with MS. And so those trials are, yeah. Ardra Shephard: This sounds super exciting. When can I get some BTK inhibitors? Dr. Jiwon Oh: So the first progressive MS clinical trial of tolebrutinib, which is one of the BTK inhibitors, will be reported later this year. So, really excited about it. Keeping my fingers and toes crossed, because again, the early data look good and this molecule, tolebrutinib, specifically is being studied in progressive MS, both non relapsing secondary progressive MS, as well as primary progressive MS. And there's many other BTK molecules being studied right now. It's probably the only time in the MS drug development time when over five of these are being actively studied in phase three clinical trials right now. So, exciting. The only thing is, the first BTK inhibitor, which was evobrutinib, this was a molecule that was studied exclusively in relapsing MS clinical trials. Everybody expected there to be a clear effect in these trials because evobrutinib was studied versus teriflunomide. But we were all really disappointed in December to learn that those phase three clinical trials were negative, even though the phase two clinical trials very clearly showed an effect on relapse disease biology. So, I sometimes worry a little bit when we put so much hope into something, but then I think having hope is so important. So, I'm just keeping my fingers and toes crossed for the results of the tolebrutinib clinical trials. It's being studied in both relapsing MS as well as two separate trials for progressive MS, and we'll actually have the results of both the relapsing MS and the secondary progressive MS clinical trials sometime in 2024. Alex Hajjar: Well, so am I, to be honest. Ardra Shephard: Fingers and toes crossed, indeed. Yeah. Alex Hajjar: I think when it comes to something like just the name, smoldering MS, it sounds like a campfire. And smoldering campfire, I'm not an outdoorsy person, but that's just where my brain goes. But a smoldering campfire can lead to a full-blown forest fire according to some bears. So, how much damage can smoldering MS actually do? Is it really just a slow burn or can it lead to relapses? Dr. Jiwon Oh: I really like the analogies that you're making, Alex, and I think the goal of using the term smoldering was actually related to that slow burn of a campfire. People think of relapse disease biology as the big flames, so the acute inflammation that can be very hot and aggressive and extremely destructive. And we actually, because we don't know, it's very difficult for us to evaluate MS at the point when it starts, it's really difficult to know if relapse disease biology actually drives smoldering disease or vice versa, or whether it's both of them happening at the same time. And it probably is that it is still thought that the initial start of MS is related to relapse disease biology, but very quickly that incites the smoldering disease and then it becomes this vicious cycle of events. The smoldering component, as long as you are able to control the relapse disease biology component, you may not get the huge forest fires. However, that smoldering burn can be extremely destructive, because it's confined within the brain and the spinal cord. And it looks like with the relapse disease biology, when you're able to quell the fire, that part goes away. It's just that this slow burn keeps going and can be, really, extremely destructive. So, both of them are relevant. Ardra Shephard: I feel like that leads to my, this is maybe the most important question I have personally. Does smoldering MS ever burn out and actually stabilize or does it just smolder until there's essentially nothing functionally left? It just maybe takes a different amount of time. Does that make sense? Dr. Jiwon Oh: Yes, it does. And again, I think an essential question that we don't have an answer to, just because... I talked a lot about, we talk about smoldering MS as kind of this umbrella term that encompasses many different pathophysiologic processes, and one of them I talked about was chronic active lesions. And that's where the term smoldering comes from, because in acute lesions that form related to relapse biology, we know that some of those lesions just become inactive after that acute flame is put out. But some of them go on to become these smoldering lesions, and that's where there's this rim of activated microglia around the lesion and there's this slow burn. So, it slowly increases over time and causes more and more damage. So that's one component of smoldering disease biology, we think a dominant component that we can actually, potentially image. But there is probably many, many, many other things that we don't yet quite understand. And then one of the complexities of this, Ardra, is that there's all of these effects of getting older as well related to smoldering disease. Meaning that, as people get older, we know that regardless of whether you have MS or not, people's brains shrink over time. And so, there's all of these effects of aging that we think are probably compounded by additional effects of smoldering disease. And so in the end, probably smoldering disease is not like this huge forest fire, to go back to that analogy, Alex, that can suddenly ravage everything over time. But together, when you compound things with the effects of aging, likely neurodegenerative processes accelerate over time if the smoldering component is not kept in check. Ardra Shephard: I say it all the time, that MS has me aging in dog ears. I think it's literally true. Dr. Jiwon Oh: Yeah. And these are all things that we're trying to understand more. There's now a huge focus in the field in managing MS in older people, just because there was so much focus initially on as people are diagnosed and getting people on the right treatment. Yet, it's clear that in any patient population, it depends on who you talk to, what you mean by older. But we typically refer to as people get over the age of 50, things are very different than when they were in their 20s and you're trying to start different treatments, like side effects of medications or treatment. There are all of these different processes of aging in women, who are the majority of people living with MS. Menopause is a huge part where we don't quite understand how the processes of hormonal changes interact with the processes of inflammation related to MS. So really, really complicated. Ardra Shephard: There's still so much to learn. It sounds maybe like while we wait for treatments, a lot of the strategies to help mitigate smoldering MS are the same kind of strategies that you would employ to mitigate the facts of aging in general. Is that true? Dr. Jiwon Oh: Absolutely. I always say in clinic, "While we're waiting for treatments to become available that can actually target smoldering MS, in the meantime, the best things you can do is maintain a healthy lifestyle." And so I say, in general, what's good for your general neurological health, so all of these things like sleeping well, eating well, a Mediterranean diet has been shown in many, many different disease states to be really healthy. And not even in disease states, in just normal aging, it's such a healthy target. And then keeping your mind and your body active, and these are all the things that regardless of whether you have a chronic disease or not, it's amazing for me to see sometimes at the age of 60, the different trajectories that people's general health takes. And this is based on just decades of habits. And so, all of these healthy living principles, regular exercise, having a great social network, keeping your mind active and interested, all of these things are essential for maintaining brain health, particularly as you get older. Ardra Shephard: I love these tips because these are things that are within our control while we wait for science to catch up. Alex Hajjar: Yeah. Dr. Jiwon Oh: Absolutely. Alex Hajjar: These are so encouraging actually, because I think in our experience, we try to use game apps, but they are, mind game sounds weird, but puzzle games and things like that and try to go outside for walks and I'm Mediterranean by heritage, so we eat a Mediterranean diet and things like that. So, it sounds like just keep doing what you're doing, I guess, until there's actual more intense medical intervention for, maybe not intense, but stuff that actually targets smoldering MS specifically. Dr. Jiwon Oh: Yes. Alex Hajjar: So yeah, it's all stuff we can actually do at home, which is nice to hear. Dr. Jiwon Oh: Absolutely. And it's not just good for MS, it's good for your heart, it's good for preventing Alzheimer's and Parkinson's all of these things. Ardra Shephard: Always remember you can get more than one thing at a time. Dr. Jiwon Oh: That's not what I'm trying to say, Ardra, but you're right. Ardra Shephard: No, I think that when we have MS, we do tend to blame everything on MS, but you do have to look after your whole body, right? Dr. Jiwon Oh: Absolutely. And there's a ton of literature on the effect of comorbidities on MS. So, if you have uncontrolled high blood pressure and diabetes and cholesterol and smoking and all of these things, they actually make MS a lot worse. And again, it's not just MS, they generally make your general health a lot worse. So, these are all things to keep in mind. Alex Hajjar: I just have maybe one quick question about, because, I guess, people who live with MS have more susceptibility to infection. And I'm just saying that because Ardra and I have talked about being germophobes on the show, do comorbidities or just general infections like flus or anything like that play a bigger part if smoldering MS is more prominent in someone? Dr. Jiwon Oh: I think many people with MS, because they are on immunosuppressant or immunomodulatory therapies, that's why there's a slightly higher risk of infection. So I think always, especially during cold and flu season, good to be vigilant and use common sense. We do know that when people have a systemic illness like the flu or COVID or a very bad cold, your body kind of revs up your immune system because it's trying to fight an infection. And so, there's actually a term for this, we call it pseudo relapse, where people when they're very feverish and your body is mounting the systemic immune response, and sometimes you can see this after a vaccine as well, just because your body revs up the immune system, people will often notice that neurological problems that they had in the past that may not be as apparent on a day-to-day basis, they'll suddenly notice that they worsen. So this is, we think, a component of smoldering MS. Probably the more smoldering MS people have in those settings, you can notice a lot more symptom worsening. And so, that's why we do recommend a flu shot every year just because when you get the flu, it's just not nice at all and you're out for many days and it actually really makes MS symptoms a lot worse. Ardra Shephard: This is such great information, so much to unpack. MS is a constant learning curve for patients and anyone who has a stake in MS. Can you leave us, Dr. Oh, with something? I know we talked about BTK inhibitors, but what can we be really optimistic about in terms of MS care in 2024? What's coming soon and what's sort of maybe in the medium term that we haven't talked about? Dr. Jiwon Oh: I think for the past decade, there's been a real focus in the field on progressive MS and progression in MS, and this all links to smoldering MS. And so, I think there's a real effort, and I think in MS, we're lucky because the world really works together in the field to try to push the field forward. Really, there's been concerted efforts from MS societies around the world, major academic institutions, clinicians and scientists and patients all coming together to try to solve this puzzle of smoldering MS and progression in MS. So, not only are there therapies potentially that may become available, and again, really keeping my fingers and toes crossed, but we also, because we recognize this as a field, I think there's a lot of focus right now on trying to identify tools to monitor this better, trying to identify lifestyle modifications that can make things better. And little things, like trying to identify the right patient reported outcome measures that every clinic should be using. What are the cognitive measures that every clinic should be using? So, all of these things. I think the future is bright. It always takes time for change to happen quickly, and hopefully there's additional therapies even outside of the BTK inhibitors that will be tested in the coming years that will make even more of a difference. But the bottom line is, I think the field as a whole, because there's such a recognition of the importance of this, will be moving forward in great strides in the years to come. So, this has to do with not just therapies, but just general clinical care, monitoring, principles about how to manage MS on a day-to-day basis. So, I think overall, it's really good news. Alex Hajjar: It sounds really great that the whole community is embracing it, I guess, and making it a more prominent issue and so there will be a better understanding in the future, I guess. Ardra Shephard: We all have the same goal. Dr. Jiwon Oh: Yes. Ardra Shephard: Yeah. Dr. Oh, thank you for sharing your expertise with us and for the important research and work you are doing at the Barlow MS Center here in Toronto. What gets measured gets managed. If you're concerned about smoldering MS, talk to your doctor. Treatments have come a long way, but those of us experiencing MS progression can feel frustrated that treatments haven't come far enough. Take comfort in knowing that the best minds in MS research are working hard to figure out how to stop disability from accruing and that in the meantime, a number of lifestyle modifications can help slow the burn of smoldering MS. Exercise, sleep, good nutrition, strong social networks, and stopping smoking are actions we can take to encourage best possible outcomes. Thanks for tuning in Trippers. May all your smoldering be limited to smoky eyes and suggestive looks. If you enjoyed this episode, like, comment, share, we'd love to hear about your experience with smoldering MS in the comments. Thanks for listening to Tripping on Air. Don't forget to visit us at trippingonair.com