The Puzzle of Progression

The Puzzle of Progression

Episode 198 – Podcast Transcript

[(0:24)] Stephanie: Welcome to the Can Do MS Podcast. I’m your host, Stephanie Buxhoeveden. I live with MS and I’m also a clinician and MS researcher. Today, we’re joined by Lisa Fox, a physician’s assistant at Johns Hopkins University Hospital, who brings years of clinical experience and firsthand insight into advances in MS research. Hi, Lisa. I’m so excited to talk to you today.

[(0:45)] Lisa: Good to see you again, Stephanie. Thank you for having me today to talk about MS and progression on this podcast.

[(0:50)] Stephanie: Yeah, it’s a really important topic and especially because for decades, we’ve used the terms relapsing, remitting, secondary progressive, primary progressive, and the categories were helpful, but as you and I both know, really failed to tell the whole story. So my question to you first is what’s changed and why are we here talking about this right now at this moment?

[(1:15)] Lisa: I know, it’s- it’s the evolution of MS, I feel. It’s- it’s very exciting that we’re starting to see deeper than just the standard progression and relapses. We’re now starting to understand MS a bit better, in my opinion, and we’re starting to see that MS is more than just the functional, the gait. We know that there’s cognition. We know the fatigue, but we aren’t able to really kind of show, uh, people and show how to put that on paper in research studies. We’re able to expand that a little bit more and understand progression a bit more because how often do you hear in clinical practice, Lisa, I feel like I’m progressing, but my MS- MRIs are- MRIs are stable. And I’m like, I hear you. It’s a blessing your MRIs are stable, but I also respect that you’re progressing and your cognition or your fatigue or your balance. And to be able to explain that in words and have the FDA and, um, research kind of keep up with how patients are feeling, it’s so important. And it also is cool because they’re being heard in that respect. So we’re able to evolve with the understanding of science as we evolve in understanding the disease state better.

[(2:28)] Stephanie: Yeah, I think that’s exactly it, is our understanding of the science of MS is in a place it wasn’t 10 years ago. And I think people don’t appreciate this, but neurology is one of the newest fields of medicine. And we didn’t have even an MRI that could detect an MS lesion until the late 80s, which I know nowadays, when you say you’re born in 19, whatever, you’re a dinosaur, but, you know, the- the MRI- first MRI that could detect an MS lesion was developed after I was born within our lifetime.

[(3:02)] Lisa: It’s crazy, yeah.

[(3:04)] Stephanie: So technology and neurology and this whole field has a lot of catching up to do when- when you compare it to things like cardiology and oncology. Um, and I think that’s really, to me, like we were at this inflection point where the science is catching up and a lot of those, well, we don’t know, we don’t know what causes it, we don’t know why people are progressing. We’re starting to answer those questions, which is really cool.

[(3:28)] Lisa: First of all, you’re not a dinosaur and you’re not old because I was born- born in the 90s. [Laughter] Um, but- nah, I was born in the 70s, but the 1900s, right?

[(3:35)] Stephanie: 1900s, yeah.

[(3:36)] Lisa: Yeah, exactly. Um, but I also agree. I mean, MS, we started having our first MS medication in the 80s. So it’s- it’s crazy how far we’ve come in truly such a short period of time.

[(3:49)] Stephanie: Yeah. And another thing we’ve done extremely well in the not so distant past is get these disease modifying therapies that target the inflammatory piece of MS. And so I think it’s fair to say that we’re really good at preventing and reducing relapses, but that doesn’t mean we’ve automatically stopped all progression, right?

[(4:11)] Lisa: Right. Exactly. I mean, it’s a blessing we’re not adding further disability. Um, I was telling my patients that it’s- it’s cool that we’re able to really kind of stop relapses from occurring. Um, we’ve done a very good job of that. Um, but the next step is to stop the progression as we’re talking about today.

[(4:28)] Stephanie: Yeah. And I think that was maybe one of the moments that really showed us that progression is a significant factor in everybody, because once we got so good that it became, I feel like it was rare that I was giving steroids for a true MS relapse, yet most of my patients are still getting worse. And so when we essentially got, I won’t say solve, but close to solving the problem of relapses and shutting those relapses down, and we still saw people getting worse, we started to appreciate that progression happens and they’re both happening simultaneously. And it’s not a phenomenon strictly reserved for somebody with secondary progressive MS. You can have relapsing MS and still have progression. And so brings us to this buzzword. There’s so many buzzwords right now. I’m sure people listening have heard smoldering MS. Um, but the term that we’re going to focus on today is PIRA, and that stands for progression independent of relapse activity. That sounds ominous. So how do you explain PIRA in clinic?

[(5:38)] Lisa: So let me just repeat the definition just because it is complex, right? Um, it’s progression, um, irregardless or despite relapse activity. So we understand that MRIs can show active lesions and patients can have active new symptoms. And we- we kind of classify that as a relapse, right? You’re having new neurological symptoms. You’re having a new MRI activity. But what if you have activity, um, you have neurological symptoms despite all that. So that’s kind of the definition of what we’re seeing is progression, um, yeah, independent of the relapses. And that is kind of the new, um, understanding of MS. And I think it’s cool that we’re starting to talk about it because it’s more the silent MS symptoms that are becoming more, um, evident to our MS patients. Um, not to get you wrong that it still causes balance and things that we’re able to measure specifically in the clinic. But it’s- it gives patients that validity that they’re being heard in that regard, as I said earlier.

Um, and it’s neat because we’re able to understand the depth of the MS. We know that in MS we’re looking at the MRI specifically, but now we’re able to go deeper into the central nervous system and we’re evolving with that. We know that the new MS criteria for diagnostic purposes has evolved because we’re now looking at the back of the eyes called this retinal nerve layer- uh, fiber layer that is allowing us to measure a little bit deeper for MS patients to understand what this progression means and to validate their feelings and these symptoms that they see on a daily basis. But we haven’t been able to give them a number, if you may. And we haven’t been able to say, hey, I understand you’re tired, but there’s nothing to measure outside of you telling me that. So now understanding these newer updates in the, um, MS criteria with like the back of the nerve, giving them a little bit of understanding a bit more, and also some new biomarkers that are coming out to help us understanding central nervous system inflammation, it’s allowing us to e- evolve as we’ve talked about. And this progression of independent relapses kind of explains to the patient of what they’re feeling and trying to put it in a numerical value or understanding, um, on a daily basis to let researchers and let us diagnose patients sooner. It- it- it’s- it’s just- it’s the evolution of MS. So, yeah.

[(8:00)] Stephanie: Yeah. And it’s validating what I have personally felt, you know, seeing that report, your MRI is stable yet again. And on one hand, it’s a relief because I don’t want new lesions. But on the other hand, it’s frustrating because I was walking easier last year or typing easier last year, or I wasn’t getting fatigued at 3 p.m. So these are these intangible things that don’t necessarily have scores or tests. And we’re getting there. We’re getting new biomarkers, as you mentioned. But to make this really tangible for people listening right now, how do they tell if this is a relapse or if they’re having gradual progression?

[(8:49)] Lisa: So I like to explain to my patients in MS, we have these cells that have been affected from the multiple sclerosis, like the coating on the nerve gets inflamed and it causes this, as you know, demyelination or this impairment of the nerve coating. And when that happens, the cells don’t get the communication well, so we get these MS lesions. And in our brain, in our spinal cord, we have all these healthy cells that haven’t been touched, right? But in MS, the lesions I’ve had, the MS lesions are being held by the healthy cells. So the healthy cells are holding the MS lesions hand. And when that healthy cell becomes tired, such as like heat, hormones, dehydration, infection, oh, you had a fun boys or girls weekend, oh, you didn’t sleep well, your 2 year old kept you up all night. Those are external stressors that take the energy from the healthy cell and say, hey, come help me. And then all of a sudden your MS lesion cries out, no, don’t forget about me. And then your right eye’s gone wonky, right? Your right leg’s not as fluid as it used to be. Um, your fatigue is increasing.

And then as you recover from that external stress, let’s say your fever resolves, um, you hydrate, uh, you sleep well, you feel better and you go back to your baseline. That to me is what I call a pseudo exacerbation or old neurological symptoms becoming more alert to you. And you’re- they’re talking to you, saying, take care of me. And that is not true progression, right? That is more, your old MS lesions crying out for a little bit of time and then coming down. Now let’s say you’re eating well, you’re hydrating well, you’re taking care of yourself, you’re exercising, um, you’ve really managed kind of a work life balance with family and work, etc., and you’re still noticing slow up and down pattern, but losing a little bit of ground over a period of time, that to me is central nervous progression. And to me, that tells me, hey, we need to think about where our patient is. Are they on- are they doing everything they possibly can? Are we controlling these external stressors as best we’re able to and concomitant medical conditions? Are we overlooking like a B12 deficiency or a thyroid disorder? So you have to think a little bit outside the books for these individuals. But if everything seems to be, no, they’re doing really well, they’re doing the best they can, they’ve really taken care of themselves, and they’re still showing progression, then you think maybe there is a more central nervous system component to it. And we need to think about where this patient is and their disease state, what medications they’re on, how can we slow this progression down as best we’re able to?

[(11:30)] Stephanie: Yeah. And I think all of those things are- they’re so nuanced and they’re so important. We’re going to take a quick break for a word from our sponsors. And when we come back, we’re going to walk through that a little bit closer.

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[(12:12)] Stephanie: Welcome back. So when we left off, we were talking about how nuanced it is to tell the difference between a relapse, a pseudo relapse, progression. Um, and I imagine, I don’t have to imagine, I’ve been in the room with people in these conversations where we’re shifting to saying MS is one disease. Uh, and I’ve seen two very different reactions from people. I’ve seen someone who I know lives with relapsing MS say, are you telling me I have progressive MS? And this fear response. And then you have people like me who have lived with the disease for over a decade and who has felt firsthand being dismissed because an MRI is stable, feel validated and say, I’ve- this is what I’ve been trying to tell you this whole time. So I think there are these two very different responses and I think both are valid and completely normal and- and understandable. And as we’re entering into this next era of MS, where we’re talking about it as a continuum or a spectrum and you’re no longer relapsing, remitting, we’re progressive. Um, how do you help your patients navigate the emotional, psychosocial side of that?

[(13:35)] Lisa: Yeah. I tell my patients, MS is a snowflake. Um, I know there’s some conversations about one disease, but I think every MS patient is completely unique in themselves because every patient has different MS symptoms, different MS lesion load, different family support system, different coping techniques. And you really, as a patient, I encourage you, um, as your provider, you challenge us to say, hey, I don’t feel as well as I used to. And- and this is why, and really be a voice for yourself because we’re evolving in the MS and we’re starting to understand deeper beyond just the true relapses. We’re now, as we’re talking about- talking about the progression and what that means, what is the central nervous system, deeper inflammation that’s going on, um, in one of your- um, in your brain and in your spinal cord, and we’re evolving past MRIs in that respect.

Uh, but I really want you as a patient to talk about your symptoms because you will be heard and we are understanding that better in the community, um, and as providers so that we can move and make that progression as little as possible as we age and as we experience different stressors in our life. So I challenge you to be unique in yourself, like a snowflake and be a voice for yourself so we can hear every individual differently and cater towards you. Um, and right now we’re working on that progression. And I know we’ll talk about some remyelination in the near future in this podcast, but we’re getting there. We’ve come a long way in 40 some years, right? Um, and we’re going to make that ga- those gains. But right now I’m excited that we’re able to talk about progression and hear you and understanding this non-relapsing versus relapses and not feeling as well with progression in terms of, um, um, on a daily basis. But I think we’re- just be keeping pro advocates, um, for yourself.

[(15:31)] Stephanie: Yeah. And I think you said a lot of very important things, but one that hit home for me is I sort of had a mindset that progression’s inevitable and that it was always sort of lurking and- over my shoulder. Um, but what I’ve come to appreciate is, it is variable for each individual, but also for yourself at different times in your life. And you alluded to some of these things where, yes, our medications maybe don’t address this progressive side of MS as well as they do the relapses and the inflammation, but there is- there are things we can do if you are seeing progression, right?

[(16:13)] Lisa: Yes. So yeah, no, it’s- it’s because we’re talking about it more and you can hear the word smoldering, we can hear progression, we can hear, oh, I’m entering secondary progressive or I’m non-relapsing progressive. There’s so many different terminologies starting to really kind of, as you said, buzzwords, but it’s how you feel. And- and I tell my patients that if we are preventing any new lesions from occurring, any new relapses, active relapses, new symptoms, we’re still ahead of the game. So we’re still not adding anything one, because if all of a sudden we add on a new optic neuritis or we add on a new foot drop or bowel bladder issues, that will just make it so much harder. So that’s a blessing to an extent as with much as we can, we say anything in MS, right? Um, it’s hard, but not adding anything on is kind of where we are with MS medications. Now it’s how to treat those old symptoms to cope. I had a patient the other day in the office and she was with her cane. And then she switched over to the rollator because she was really tired halfway through the walk to her- to the office. And she was fine after a few steps. She’s like, oh, I’m more steady. You could just see her shoulders relaxed. And I looked at her and I said, I respect that the cane is less of a stigma than the rollator.

However, look at your energy level, look at your body language, look how light you feel because you walked the last half to the office with so much ease and you have little children. I’m like, take that energy, preserve it on those days that you can with a rollator so you can be there for them. And we kind of worked through coping techniques to preserve that energy for her. And just to see the- the, okay, I can do this, even though I’m not ready to move to the rollator, she realized she can do it for the fatigue improvement. It made a huge difference. And again, it comes down to the patients and their prog- everybody’s different and how they’re going to cope with where they are in their life. But, um, we’re working on ways that we can hopefully slow down that progression so it’s not so much, um, in our face all the time. But again, we’re being heard and we’re understanding that our patients are being heard, and we are personally as providers, understanding it even better for them and for you.

[(18:27)] Stephanie: Yeah, 100%. Rehab is everything. And, you know, we’re all changing and aging and going through different things, becoming parents, working, retiring. Maybe you develop another medical condition that piles on. Um, so just because rehab or an exercise program did or did not work in the past, I’m always an advocate for trying it again or revisiting or starting from scratch or reinventing that lifestyle change. Because as you’ve stressed, exercise, sleep, diet, these are all ways that in addition to our medications, we can preserve our brain, preserve our health, preserve our energy and help us, as you said, in that example with using the rollator, work around our symptoms so that we can do more and just reach into our toolkit for those [inaudible].

[(19:26)] Lisa: A100%. Uh, that toolkit’s critical. Um, and every patient needs- the- they might think of it differently, some might not think of it like that, but, uh, it’s definitely there; that toolkit, uh, incorporates partners and family members and devices along those lines. You’re exactly right.

[(19:44)] Stephanie: Yeah. I just got back from a- a big MS conference, um, and they were talking about, you know, even though these high efficacy therapies, these really highly effective medications that we now have for MS, the earlier you use them, the longer you can go without progression. Do you see that in practice, that- that early use?

[(20:10)] Lisa: I do personally. I- I- and I- well, there’s a huge MS study, MS treat that’s looking at that too, um, in terms of DMT treatments. Um, DMT is being disease modifying treatments for MS. Um, so we are- there is a huge study in that respect as well going on, as well as multiple. But over at Hopkins, we are looking at that. But I tell my patients, the less injury to the brain and spinal cord, the less symptoms ultimately, right? So if we can keep as many healthy cells as healthy as possible, then ultimately, hopefully we have less symptoms to be bothersome as we age or have the MS ages as well. So I actually am a strong advocate of treating MS early and slowing down any new progression because once you- once you get a lesion, I can’t reverse it. Or I, we can’t reverse it, right? Um, so preventing that I think is the very, very, uh, first point of preventing any new disability and accumulation of disability.

[(21:12)] Stephanie: Yeah. That- and that brings me a lot of hope, knowing that this generation of people being diagnosed with MS have these wonderful treatments available to them. They can get diagnosed faster with that criteria we were talking about, get access to these medications. It’s easier from an insurance and access standpoint to get them on early effective treatment. And there’s a- there’s a lot to be hopeful and excited about. It’s almost hard to narrow it down. But…

[(21:43)] Lisa: Oh, so much.

[(21:44)] Stephanie: …but I think I’d love to pick your brain just for a few minutes about whether we’re getting closer to really being able to detect and quantify that progression that we were talking about, and whether we will see therapies that eventually address this neurodegeneration.

[(22:03)] Lisa: So if you asked me that 6 months ago, I would have been like, hmm, having a haul in a little bit, but we have things in the works, right? Now, fast forward 6 months into February here. Um, I think we’re- we’re on the tip of the iceberg just because we have this new biomarker, which is called serum neurofilament light, right? Uh, yeah, it’s- it’s not the cleanest test overall because it measures inflammation in the central nervous system, and it can be falsely elevated migraines. And I say people went sledding on the ice we received here in Maryland or like a rollercoaster, right? It can be elevated. But it gives us an understanding of some inflammation that is not able to be picked up on MRI. And it kind of may correlate from what we’ve seen so far with neurological progression or some symptoms of patients in there and they’re- and it validates them. Um, so concomitant medical conditions, I see elevation in my patients that I’ve been testing. So all- other autoimmunities do send to have a higher level, but it’s- we’re just starting to understand this and it’s exciting. Um, it’s not, again, it’s still so new and it’s out there in the general public to be used, but we’re still understanding it. But you’re right, it is- it gives a lot of peace of mind, like there might be a blood test. So it’s very exciting that there’s actually a way to measure, uh, through the blood, what might be going on in the central nervous system. And as I said, it’s still- we’re learning about it, but it’s available. And we’re- patients that have come into the office and saying, I just feel like I’m progressing. I’m not doing well. My- my right leg’s not working as well and- and I’ve been eating and drinking and I’m like, well, let’s test your levels. And if it’s elevated, it gives them like, oh, I’m- this is actually really happening. And if it’s not, I’m like, well, let’s look at everything else and let’s go through how you’re doing otherwise. So again, I think where we are in a mess and yes, as hard as progression is, and it’s- it’s allowing patients to be like, I can talk about it more and I need to talk about it more to my providers so that we can continue to do research and we can continue to support, um, the future and continue to improve our patients’ symptoms.

[(24:22)] Stephanie: I think biomarkers are key. Ways to measure things are key. We’re getting newer and cooler, even MRI metrics. I know you’re doing a lot of that work at Hopkins. Um, do you think there’s a in which one day somebody will be on a disease modifying therapy and also on another medication that helps remyelinate or protect the nerves against damage?

[(24:48)] Lisa: So, yeah, no, I think again, we’ve- uh, Peter Calabrese once said that it took him 30 years to just get into the relapsing drugs and understanding relapsing, remitting MS and how to stop relapses. Now he’s on the end of his next 30 years. So we’re right there for remyelination. Um, so I- I do believe we are right there. And we, um, I was talking to Dr. Scott Newsom the other day, and he’s hoping to start doing some remyelinating studies at Hopkins. So it’s- it’s tangible. It’s definitely coming. And I do feel research is moving in that right direction. I- and I feel, um, everybody’s ready for this. And I do feel it will be a concomitant kind of component of it. I don’t think we’re gonna have a sole remyelination drug without a rela- like a stopping relapses in my personal opinion, but I could totally be wrong. Um, but I do feel we are turning the edge in that respect.

[(25:44)] Stephanie: Yeah. And I feel the whole field right now is laser focused. This is the biggest need, and the biggest gap is stopping progression and the holy grail of reversing it, should that ever come to fruition. But to see the whole scientific and medical community focused on this aspect of MS and the amount of funding and research and work going on, again, I just came back from a conference. So I- I’m chasing the high of- of science and all of the cool things, but there’s a huge movement going on right now. And again, that’s why we’re here talking about this. We understand MS better. And once you understand something, that’s when you can start treating it. And that’s when you start working towards curing it.

[(26:37)] Lisa: Yeah, very much so. And I do feel that we’ve been talking about kind of the biomarker and the remyelination a little bit, but we’re also evolving in how we treat the central nervous system relapses and reducing. So, uh, some MS medic- medications are evolving too and how we’re looking at the central nervous system to regret- even like, demyelination a bit more. So in addition to the, um, kind of sequestering some inflammation. So it’s, yeah, it’s- it’s exciting to see what we’re going to come up with in the next 10 years, for sure. I think we’re going to see changes.

[(27:13)] Stephanie: Yeah. Yeah, it is going to be exciting. I’m excited to take the ride with you. And- and I hope we talked about a lot today, but the takeaway is whatever comes out of this reclassification of MS, it’s not suddenly changing your diagnosis. All we’re saying is we understand MS more completely now. And if you’re noticing gradual changes, it matters. There are things you can do, right? If you have a Lisa in your life that you can go to and tell about things that you’re noticing, um, you can start working on individualizing your care and working to be at your best no matter where you are in life and where you are in your MS.

[(27:58)] Lisa: Very well said. I agree, Stephanie. And I think patients, um, I want them to not just say, oh, I’ve had it for 10 years, right? And, uh, I’m secondary progressive and there’s nothing I can do. I completely disagree. I think you can be, um, taking care of- of many different aspects of different parts of your life in different ways to what works the best for you, which is different to every individual, but know that the community of providers and researchers are hearing the MS patients and moving forward to be advocates just for you. Um, it’s not easy, um, but they’re going to continue to really work to slow down progression and continue to prevent relapses and ideally one day find, um, something to stop MS.

[(28:43)] Stephanie: Thank you so much, Lisa. This is an exciting conversation. It’s great to have you. And we really appreciate you being here.

[(28:49)] Lisa: Well, thank you. I love- I love talking about it all. And, um, it’s been wonderful talking with you today.

[(28:55)] Stephanie: Thank you for listening to this episode of the Can Do MS Podcast, which was created in collaboration with Novartis. If you liked this episode, please leave us a rating and review on Apple Podcasts or Spotify. We appreciate your feedback. Until next time, be well and have a great day.

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