#095: Hidden Challenges – Exploring Smoldering MS with Prof. Gavin Giovannoni

Introduction – Who is Prof. Gavin Giovannoni?

Nele von Horsten: Hello Gavin, it’s a pleasure to have you on the podcast today. Before we begin, could you please introduce yourself for those who may not be familiar with you?

Prof. Gavin Giovannoni: Thank you, Nele. I am a neurologist at the Royal London Hospital and a professor at Queen Mary University in London. Originally from South Africa, I focus on research and treatment innovations in multiple sclerosis (MS), aiming to improve patient outcomes.

Understanding Smoldering MS

Let’s talk about Smoldering MS. What is it, and how does it change our understanding of the disease?

Prof. Gavin Giovannoni: I mean, smoldering MS is a term, it’s evolved over the last six to eight years, but it’s a concept to try and capture the part of multiple sclerosis that we’re not measuring using clinical outcomes and MRI. So most people think about multiple sclerosis as having relapses or attacks, and we measure those clinically. And on MRI, we get these new lesions that come and go.

We call that MRI activity. And those two components of multiple sclerosis are what we call the inflammatory component. And we now know that when we actually put people with multiple sclerosis on therapy and we stop them having relapses and stop them having MRI activity, a significant number of them will still get worse. And that’s called PIRA, progression independence of relapse activity, which is what we measure in trials every three months by doing disability scores or whatever. But in addition to that, there’s also evidence of smoldering MS that’s not picked up by our outcome measures in clinical trials. And so the smoldering MS umbrella is to try and capture all the components of worsening MS that’s not detected using our standard outcome measures. And most people with multiple sclerosis are aware of this. You know, they often go to see the neurologists before their sixth or annual follow-up appointments, and they’re told, you know, you’re relapse-free, your MRI is stable, therefore your disease is under control, go away. And most people don’t feel satisfied with that because they know that things may be getting worse. And that’s what we’re trying to capture, that worsening that we’re not measuring with our standard outcome measures. And there’s a whole lot of different processes that are underlying smoldering MS.

What are the underlying mechanisms of Smoldering MS, and why is it so challenging to diagnose?

Prof. Gavin Giovannoni: Yeah so what we think there are quite a few mechanisms. So one of the things is that the inflammation that’s driving MS becomes compartmentalized. It it’s actually happening within the brain and spinal cord and that’s driven by a group of cells called the microglia. They actually derive from white blood cells that go into the brain when the brain’s developing and they produce inflammatory mediators and chemicals that damage you know nerve fibers so that’s what we call the hot microglial component and there are treatments now to try and switch off these microglia. Also with inside the brain and spinal cord of people with ms there are these cells called B-cells and plasma cells these are the cells of the immune system that make antibodies. And we think those antibodies are actually part of what’s driving smoldering MS. They attack the nerve cells and the myelin causing ongoing damage and our current treatments don’t really get into the central nervous system to kill these. So we now have to develop a new class of therapy, or therapies, I should say, that go into the brain to try and scrub the brain clean of these B-cells and plasma cells.

And there is a biomarker when we do lumbar punctures and take the spinal fluid out, and we find these things called oligoclonal bands. These are immunoglobulin bands, and that’s actually a marker of these B-cells and plasma cells making these antibodies. So in the future, we may want to scrub the brain clean and clear the spinal fluid of these oligoclonal bands.

Then there’s persistent demyelination. So we know that MS causes the myelin, the insulation of nerve fibers, to be stripped off. And although some of those nerve fibers can remyelinate, in some people, remyelination doesn’t progress. And so persistent demyelination is another mechanism. So therefore there’s this rationale to create remyelination therapies.

Another component is what we call energy deficit. So when you’re actually conducting down a demyelinated nerve fiber, it takes much more energy to stick the electrical signal down the nerve fiber. And in addition to that, the mitochondria, the little component of the cell that makes energy, is actually not working as well in people that have got inflammation in the brain and spinal cord. And so there’s an energy deficit. So there are potential mechanisms to try and enhance energetics in the brain. And that’s where oxygen therapy and things try and promote mitochondrial function are in. And then there’s also premature aging. We know that what protects us from aging is what we call brain health, how much reserve capacity our brains and spinal cord has. And we know that multiple sclerosis reduces that by causing death of nerve fibers and the axons, your reserve is reduced. So as you get older, you start seeing aging happening earlier. So aging mechanisms come in. And we don’t really have anti-aging treatments at the moment. You know, we have a clue that brain health is important for anti-aging mechanisms, exercise in particular, but there’s things around diet and sleep, preventing what we call comorbidities, people getting high blood pressure, diabetes, all those things that are poor for brain health also play out in people with MS. So this is one of the reasons why it’s very important for people with MS, not only to just focus on MS, but also to focus on general health, because general health is important for the brain and spinal cord. So there’s different components that we think are driving smoldering MS.

What percentage of MS patients are thought to have Smoldering MS, and how can early detection benefit long-term outcomes?

Prof. Gavin Giovannoni: I think it’s important not everybody does have smoldering MS because we do know that some people come to post-mortem, they die in old age, and they’ve got MS on their brains and spinal cord, but they’ve never developed MS in life, never been diagnosed. So whatever’s causing multiple sclerosis, that person’s immune system must clear it. And then there’s some people that end up old age with no disability. So they’ve had MS their whole life, and they don’t get worse.

In retrospect, we call that benign MS, but we don’t like that term because it’s very difficult to predict who’s going to have benign disease. Sothe proportion of people that end up with benign MS was very low in the past because most people ended up with disability. But I think now that we’ve got effective treatments, we begin to see the proportion of people ending up in old age with less disability is increasing. So I do think our treatments are working by preventing relapses and MRI activity, but they’re also having an impact on smoldering disease. And I would be giving you an incorrect figure by giving you a definitive figure. But I would estimate in people with established MS, about 30% to 40% of them now will get to old age without disability. And in the future, we want that to be 80% to 90%. And this is why detecting smoldering MS is important, because there’s going to be a new class of therapies coming out, people will be potentially eligible for that would target smoldering mechanisms. So we’re anticipating in the next 12 months a new class of therapy to come out that will work much better on smoldering MS than the current therapies. So there is an incentive going forward to detect this.

They want to know about this because they’re experiencing it and then they ask the question what can I do about it and so obviously using a disease modifying therapy is one strand but also focusing on all the other things. Being aware of what else you can do to tackle smoldering MS is also an important part of MS management. Rather than put your head in the sand and ignore it, I think it’s much better to confront it and understand what’s going on. Maybe you disagree with me. I know there are some people who don’t want to know about this, but that’s a personal choice. If they don’t want to know they’ve got smoldering MS, then they shouldn’t be told.

Nele von Horsten: Yeah, of course. And it’s everybody’s choice. But my motivation to do that podcast is get people informed so they can do whatever is possible to stay as healthy as possible. And of course, people can decide not to listen to the podcast or other things like going to the dentist, getting your vaccinations, being sporty, living a healthy lifestyle. There are so many little components we can do. And I prefer to choose all the little modules to end up in the 30% to 40% range without disabilities in old age. And I would love to see it happen, that 80% to 90% get old without disabilities in the future. That would be so lovely.

Prof. Gavin Giovannoni: So another thing that people tend to just live with is infections. So we know that people with multiple sclerosis get bladder problems, and they’re much more likely to get recurrent bladder infections. And some of them may get recurrent chest infections because of swallowing problems. And some of them may have inflammation in their gums. We call that periodontal disease. And some people get recurrent sinusitis. But there is also evidence now showing that if you get recurrent systemic infections, that causes smoldering MS to speed up. And, you know, rather than live with your bladder infections, because some people just seem to say, I’ll get a bladder infection every six to eight weeks and I’ll just get antibiotics and that’s fine. Well, I don’t think that is acceptable. You know, there are really good strategies now to prevent people getting urea tract infections and also to prevent themselves getting severe chest infections. So, it’s also engaging with other health care providers to stop infections. It’s another component of treating smoldering or preventing smoldering MS. And I’m always shocked when I get new patients to hear from them how many of them just accept recurrent infections. And I say – you don’t have to live with recurrent infections. There’s a lot we can do. That’s another message to get across.

Why are terms like RRMS, SPMS, and PPMS becoming outdated?

Prof. Gavin Giovannoni: The concept here is how do we define diseases. So when you define diseases in the medical field i’m not talking about psychiatry they do a little bit differently to us because psychiatrists tend to talk about symptoms phenomenology rather than, in medicine we talk about a clinical pathological corridor. So when you usually what we call medical philosophy framework MS is one disease it’s got a clinical phenotype what you see clinically, and it’s got a pathology that goes with that, what you see under the microscope. And when you do the clinical pathological correlate, there isn’t any difference between the different types of MS. They kind of fall into the same spectrum. But what happened was to get drugs licensed for a disease or to help incentivize the pharmaceutical industry, various governments created these things called the Orphan Drug Act. So this is to try and encourage drug companies to develop drugs for diseases that affect small numbers of the population. And the Americans were the first to do this. The FDA, the Food and Drug Administration, put forward an Orphan Drug Act that goes back to I think the late 70s, early 80s.

The Orphan Drug Act defined an orphan disease as a disease that only affected 200,000 or less Americans. Andwhen you actually look at MS, there were more than 200,000 people with MS in America at that time. So what they decided to do, and this is just a business political decision, they decided to actually slice up MS initially into three diseases, relapsing remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS), and then each grouping would have less than 200,000. The reason for doing that is to get interferon licensed with one trial. And that’s how interferon beta got licensed on one trial, because MS was an orphan disease. So it was essentially a fudge. It wasn’t based on biology. It wasn’t based on pathology. And then they added a fourth group called clinically isolated syndrome (CIS) to that. And I think when the diagnostic criteria change, they’ll take asymptomatic MS, radiologically isolated syndrome (RIS), and create another category. So you’ve got these little pigeonholes to define what the disease looks like. And they’re not really different diseases. And the reason why I say this is because you can actually push people from one type to another type. I’ll just give you an example.

Somebody may have relapse-remitting MS, and you put them on a very effective disease-modifying treatment, and you stop them having relapses, and they’re getting worse because of smoldering MS. That’s progressive MS. That’s what we see, worsening independent of relapse activity. And similarly, you can take somebody who’s got primary progressive disease, and if you give them a certain type of immune stimulant, you can actually cause them to have relapses. So you can push people along the spectrum. So I think my interpretation of what we see clinically is you’ve got MS, and the real disease is a smoldering disease. And then what you see from a clinical perspective is the inflammation that occurs from the systemic inflammatory response to the disease, whether you can have relapses on MRI activity. And this analogy doesn’t only apply to MS. It happens in many other diseases. We see this, what we call a clinical phenotype, a spectrum, based on how the immune system responds to what’s causing the disease.

And I think actuallya large proportion of the MS community, research community, are now beginning to accept that MS is one disease, and that putting people into these little pigeonholes is artificial. You know, the reason why this is important is because it has implications for treatments. People think that treatments don’t work in progressive disease. Well, I think that’s wrong. They do work. They just don’t work as well because people with progressive disease are much older and further and more advanced. So you don’t see the treatment effect being that prominent compared to early MS. It’s just a matter of where you are on the course of the disease.

Treatment and Management Approaches

Why should we move beyond the terms RRMS, SPMS, and PPMS when pursuing personalized treatments?

Prof. Gavin Giovannoni: I think what will happen is you’re going to be labeled or people are going to get given a diagnostic label as having multiple sclerosis. And then on top of that, they’re going to ask, do you have any evidence of inflammation, focal inflammation? Are you having relapses or new lesions? And then you’ll have to have that treated with a particular class of disease model, an anti-inflammatory. And then if you’ve got evidence of smoldering disease, you’re going to have therapies that target those smoldering processes. That’s going to open up this new therapeutic era where we’re going to be using combination therapies not just one treatment at the moment. You know treatments are monotherapy you can only take one therapy at a time but I think going forward we’re going to be doing combination therapies to tackle both processes.

What current treatment options are available for Smoldering MS, and how effective are they?

Prof. Gavin Giovannoni: We don’t have any therapies that are licensed specifically for add-on, smoldering MS. There’s a new class of drugs called bruton tyrosine kinase, BTK inhibitors. The first one was only tested in relapsing-remitting disease, and it wasn’t shown to be better thanteriflunomide, a licensed therapy, so it never went forward. But tolibrutinib, which is the second trial, there were three trials to report out, shows that the drug actually works above and goes beyond focal inflammation and actually slows down a smoldering component. So that’s potentially going to get licensed. So somebody who’s on an existing DMT and is getting worse would potentially be eligible for tolibrutinib. But I’m not 100% sure what the European Medicine Agency (EMA) will do. You know, the agencies may have different opinions.

But I see the American FDA has fast-tracked the approval process for tolibrutinib so they probably will get it in the United States earlier than the European community. That will be an option in the next 12 to 18 months and then they areother BTK inhibitors. After that there are two big trials happen. There’s one called fenibrutinib and then there’s one called remibrutinib and there’s one after that as well so that’s that and then in additionthere are other therapies been tested. So there are drugs that are being repurposed from an oncology field that go into the brain. There’s proteasome inhibitors that hopefully will kill the B cells and the plasma cells that make the antibodies.

Cladribine is one of the therapies that are licensed for treating relapsing MS. We have evidence that because it’s a small molecule it does go into the brain, and it does kill B cells and it does reducethe amount of antibody in the brain. So that’s actually a drug that possibly has an effect on small ring component in addition to the inflammatory component in the periphery. So clearly this is new in the field, but there’s going to be treatments where we will target smoldering MS. And then at the same time, people with multiple sclerosis have to engage with the non-MS targets. Like I mentioned to you, and, you know, certain thingsare reallyimportant. I don’t know how aware your audience is of social determinants of health so these are the things that affect you socially that impact on brain health so things like social isolation and loneliness.

These things are really important and there’s preliminary evidence suggesting that people that have got socially isolated or lonely in other words they don’t have enough social interactions their social capital do worse, it’s very well known that, these social determinants have an impact in mental health, particularly, but they also look like they have an impact in MS. So part of our responsibility as healthcare professionals is to try and identify people that have what I would call modifiable social determinants and then use different types of treatments. There’s a thing called social prescribing. Now, I don’t know, in Germany, is social prescribing a big thing or not?

Nele von Horsten: I’m not sure. I mean, I had Anthony Feinstein on the podcast talking about the COGEX study where they found out how important the social component is. But I’m not sure what social description means.

Prof. Gavin Giovannoni: So the example would be if somebody is socially isolated, you could actually see what they like and then you can give them subscriptions to art classes, music lessons. They can join gardening classes, walking clubs. But the important thing about these activities is not so much the activity. It’s the fact that they go and do it as a group and they have interactions with other people and they form friendships and they regrow their social networks. So it’s more about reconnecting people that have become disconnected from their communities. The church, you know, religion is very important. I’m not saying I’m going to promote religion yet, but one of the things about religious groups is they tend to maintain social capital. Because by participating in a religious group, by going to church and involved in religious activities, you are keeping that component of your social determinants healthy. It’s what I call social health. And we can’t underestimate social health. You know, I see it all the time, when people lose motivation, then it impacts on mental health and all those things make things get worse much more quickly.

This why I have this philosophy of marginal gains, trying to fix all the little things adds up to big changes. And that also means looking at social health. So it’s social health, metabolic health, making sure we prevent comorbidities or treat them aggressively, getting people who smoke to stop smoking, getting people who are not eating well to eat healthily and lose weight if they’re overweight. You know, all these little things make a difference. I’ve got examples of people that have lost weight by doing exercise programs and going on certain diets and seeing their disability scores improve, not because their MS has improved, simply because their physical health has improved. You can improve disability by focusing on general health.

Nele von Horsten: Absolutely. And I just had to think of when I was living in Chicago, I did an architectural tour because Chicago has beautiful architecture. And I was invited by the parents of the lady who was doing the architectural tour to join them for Christmas. And of course, it was totally lovely to be together with a family, even though it was not mine. And they did that because they were very much religious and living up to that idea of helping out the others, inviting them, welcoming me into their community. And it was very lovely to join them on Christmas and go with them to the church. And yeah, that can be so important for you and your health and your well-being. I absolutely agree on that.

Prof. Gavin Giovannoni: One of the problems about this component, what I call the non-MS targets, is sometimes they form vicious cycles. So if somebody’s social health deteriorates, they lose their job, they get divorced, they split up with their partner, and they end up alone, then that also feeds into worse mood, depression, that affects their sleep. I mean, the elephant in the room for MS is often missed because you don’t see it. It’s sleep. I mean, sleep hygiene is shocking in the average person with MS. When you do a survey, you find how badly people with multiple sclerosis sleep. Now, there’s a whole lot of reasons why they’re sleeping badly. Often it relates to bladder problems, leg spasms, pain, depression, anxiety, too much alcohol at night, sleeping in the day. There’s a whole lot of reasons why people have poor sleep. And there’s also potentially obstructive sleep apnea, which is quite common in people in MS. And you can’t fix your MS if you’re not sleeping properly. So one of the things, one of the indicators, we should be focusing on is how do we get people with MS to sleep better. And then what happens is you break those vicious cycles. All of a sudden they wake up in the morning feeling refreshed and they don’t feel as fatigued. Their energy levels go up. Their mood improves. Everything improves if you fix sleep,

And I’ve done a few surveys around this. and it’s about 80% of the MS people that have a sleep problem. That’s four out of five. That’s much higher than the general population. The general population, that figures in around about 30%. If you go to people that are in the word of commerce, don’t have a disease, a healthy general population, about a third of them will complain of intimate insomnia, for example. So it’s much, much higher than the general population. So this is something I’ll be interested to know from you. I mean, just is your sleep, would you say, are you satisfied with your sleep hygiene?

Nele von Horsten: Yes. I mean, having a baby is not so easy, but she is sleeping now here when we have the interview. And of course, as I’m breastfeeding, which hopefully will keep her away from many health-related issues, makes my sleep, let’s say, challenging.

But I do then sometimes a 10-minute nap during the day. Normally, I don’t have to do it because I have the hormonesdo to breastfeeding. But normally, I can sleep very well. And I just have issues with sleeping when I have psychological problems where I really am thinking about that problem.

Prof. Gavin Giovannoni: So that’s called rumination anxiety. People worry about things and they ruminate they get these intrusive thoughts at night it’s very common in MS rumination so psychiatrists talk about it’s ruminating so you get this written this intrusive thought. It happens in normal people and there are ways to deal with intrusive thoughts you have to practice mindfulness and if you get quite good at mindfulness you can switch those thoughts off. There’s incredibly good sleep apps now that have been amazing and one of them is actually licensed in the UK by the NHS and it just pays for it. I think the subscription is about 45 pounds I’d say 45 euros a year and it’s cheaper and much healthier for you than taking sedatives and the results are almost as good as sedatives. It works long term as well. So uI urge your listeners if they are having sleep problems to you get them investigated by their MS team. And one of the treatments would be to use the cognitive behavioral therapy for insomnia, and the CBTI is the term they use for that. It involves mindfulness meditation techniques to help you sleep.

Nele von Horsten: Okay, great. Yeah, I was using13, 14 years ago, Progressive muscle relaxation by Jacobsen. Quite popular in Germany and can help a lot.

How can new biomarkers and advanced imaging techniques help?

Prof. Gavin Giovannoni: ASo unfortunately, the current MRI protocols, t hey just really look for new lesions. They don’t really look for the other biomarkers. So this is where we would call advanced imaging techniques come in. They can measure brain volume, for example. And they can show that people with multiple sclerosis may have what we call accelerated brain volume loss. Another term is atrophy. Just to say to your listeners, that happens to normal people as well. So from the age of about 35, it’s downhill, all our brains shrink. It’s part of aging. People with multiple sclerosis seem to have a much faster rate because of the MS on top of aging. There are now algorithms for measuring. Now, this is where people with multiple sclerosis need to be very aware. Very few centers measure brain volume loss. And the reason is it’s not part of the standard reading. The MRIs have to be taken and analyzed in a software program offline. And that takes time and resource.

There are companies now that provide the service, but they have to charge for it. And healthcare payers, insurance companies are often resistant to pay for that. And I suppose at the moment, without treatments to target smoldering MS, knowing if your brain’s shrinking more than it should be is maybe not a good thing unless you have a therapy. What will happen in the future, certain lesions get bigger slowly. So most lesions in MS, whenyou get put on a treatment shrink. But a small number, about 5%, about 1 in 20 lesions, will continue to get bigger slowly. It’s called a slowly expanding lesion. That’s smoldering MS. And those lesions we know are much more destructive and are causing problems so that could potentially be measured in the future.

And then there’s also blood markers. People can measure this protein called neurofilament that is released from damaged nerve fibers. And if you’ve got raised neurofilament levels, it means your MS is active. And that’s over and above. It provides more information than just measuring relapses and neuroactivity. Some centers, our center, for example, has been using neurofilament levels as anaddition. We very rarely make decisions based just on neurofilament level. We use it with the MRI and the clinical to give us a much bigger picture to make a decision on treatment. And there are other biomarkers emerging. There are other proteins that can be detected in the blood that will come in the future to measure smoldering MS.

And then there’s more sensitive clinical tests. Worsening cognition is one of the big components of smoldering MS. And our current clinical scoring systems don’t monitor cognition. So some centers now do thesesix-monthly or 12-monthly cognition tests, and they can pick up worsening cognition. Now, again, some people with MS don’t want to know that their cognition is worsening. Some people just like to adapt and cope with it. But if your cognition is worsening, it may mean that you should be eligible for a better therapy, for example. There’s some recent data that came out at our ECTRIMS meeting from Australia, from MSBASE, which is a big international database registry of patients, showing that even if you are free of inflammatory activity, but you’re getting worse and you switch to a more effective therapy, you do better than staying on the existing therapy. So I think there’s a logic for measuring, using more sensitive clinical outcomes to see if you are worsening because it may nudge you towards a more effective therapy.

Nele von Horsten: And how is it in the UK? In Germany, it’s quite a problem to grt tested. We don’t have enough neuropsychologists to do thatmore advanced testing. I did it once. My brain atrophy is getting checked. NFL levels are checked, all these things. but that is because it’s a university MS center. So, of course, that’s not the normal setting, but we really have issues with the amount of neuropsychologists.

Prof. Gavin Giovannoni: The neuropsychologists have put together these small batteries that can be done without a psychologist. They’re screening tests. They’re not good enough on their own. So there’s one that’s the most commonly used is called the SDMT, the symbol digit modality test. It’s essentially a cognitive reaction time. You have to think about recognizing thesesymbols and then react. And so there’s a well-defined normal range, and there’s a well-defined variability around repeat measurements. And if it changes by more than four points, it’s clinically meaningful. And that doesn’t take too long to do. And these are now automated ones, the online ones, and these ones that have been done on an iPad, for example. But again, it takes time. And, you know, a lot of neurology centers, MS centers, they just don’t have that time or the inclination to do it.

So I don’t know what the solution is to this. My recommendation is for people to self-monitor. There’s a whole lot of things people with MS can do themselves using various apps or online resources, and they can monitor their own worsening and then bring the results to the clinician. But before doing self-monitoring, you need to make sure your healthcare professional is going to respond to that information. You know, I’ve got examples of people, quite obsessive measuring everything, how far they can walk, their walking times, they’re doing their cognition tests and everything. And they take the information to their healthcare professional and they ignore it. That’s not good, that’s very disheartening for the person with the disease.

How important is patient education and shared decision-making?

Prof. Gavin Giovannoni: That’s essential. I mean, I just don’t think you can manage chronic diseases, MS, rheumatoid arthritis, various cancers, without shared decision making. And at the end of the day, it’s a partnership. Nobody should dominate that partnership. It’s very difficult to imagine managing somebody who’s got MS without at least having shared decision making. Particularly the young people, they won’t accept the paternalistic medicine where the doctor knew everything. Most young people who develop MS are very informed about their disease and often know more about their MS than their than their neurologists. I’m not saying more than the MSologists, but they often know more about MS than general neurologists. So this is another thing that people with MS can do is actually train their neurologists about MS. It happens all the time.

Patient Perspectives and Challenges

What challenges do patients with Smoldering MS commonly face, and how can a multidisciplinary team help?

Prof. Gavin Giovannoni: I suppose, I was going to give your audience a hint there are tools available online to help you prepare for your annual or your six-monthly follow-up consultation. If you are self-monitoring and you’re detecting that you’re worsening, you should potentially send your questions or your information to your healthcare team before your appointment. And you should prioritize maybe three things that you want to deal with there and then. Because follow consultations are really quite small usually about 15 minutes and it’s really impossible to get through 10 items in 15 minutes it’s best to get through three items well rather than try 15 and it’s up to you to prioritize those. A lot of them you can actually address yourself using online resources. The ones that you want to approach your neurologists or your MS nurse with are things that potentially require medical investigations and interventions. So it’s actually engaging with the disease, self-monitoring, preparing for consultations, and doing as much online and self-management as possible.

Self-management takes time to get into the right mode. It doesn’t happen in year one, year two. It takes a long time for somebody to feel competent or confident enough to self-manage certain problems. But there’s much you could do yourself.

Let me give you an example. Bladder infections, for example. There are lots of MS patients can do before they get to seeing a urologist or seeing their MSologist about recurrent bladder infections or bladder problems. You can do a lot yourself. Same with constipation.

Same with falls and falls prevention same with bone health, same with exercise there’s lots of stuff you can do yourself without necessarily, hassling your healthcare professional and when you go to them you say this is what I’m doing myself to improve my general health but I need help with X, Y and Z this is what I would like and there’s certain things, you’ve got to get medications for spasticity and nocturnal spasms for example, most of the time And that has to be managed with a prescription of an antispastic drug, for example.

How does Smoldering MS affect quality of life, and how can psychological aspects be addressed?

Prof. Gavin Giovannoni: Well, I think awareness, being activated as a patient, engaged with the disease and not ignoring symptoms, understanding actually is empowering and helps. A small group of people become expert patients. I would imagine now that you’re an expert patient and before you became an expert patient and were very engaged with your management of the disease, you probably felt scared, anxious. And, you know, as you learn about the disease and get more confident about managing, interacting with your healthcare professional, things improve. So that’s one of the reasons I tell people, getting on top of the knowledge around multiple sclerosis will help you in time. People may find it scary, but at some point in time, they’re going to have to face it. They’ve got this disease. There’s no point in, I call it the ostrich syndrome. You put your head in the sand and you want to ignore things, but that doesn’t deal with it. And if you really are super anxious and you can’t deal with the uncertainty that comes with having the disease then you may need professional help and that’s where you would need a therapist. You know, either group therapy or one-on-one, CBT, mindfulness, And there are lots of things you can do to try and address the anxiety associated with having MS.

But there’s also self-help you can do. There are online courses for mindfulness and CBT that some patients find very helpful.

When people actually get on top of that knowledge, they also begin to sort the rest of their lives out. They begin to live much healthier, and they focus on lifestyle and wellness. And that’s the pinnacle when you start to actually think. Now, wellness is a philosophical construct. It’s not just about medical problems. It’s about spiritual, environmental.

How you interact with the wider world. And there’s no doubt in my mind, that people who get to that top level where they’re actually focusing on being well, as well as they can, then things change dramatically. So I would say there are one in 10 people with MS who get to that level, and you can just see that it’s transformational. They come to terms with having the disease. They’re very proactive in managing their disease, and they often become proactive in helping other people, either through education or one-on-one counseling or peer support groups, whatever.

They also transform their lives from a wellness perspective. It’s lovely to see that. But it comes from the position of knowledge. It doesn’t come from being an ostrich with your head in the sand. You have to face the disease. And I think this also happens in other disease areas. You see it in people with various oncology cancers, for example. It’s those people who get on top of the knowledge around their cancer. They often say, I might only have four or five years because I’ve got a terminal cancer, but those four or five years were the best years I lived because I felt that I was, from a philosophical perspective, on top of my disease, and I knew exactly what was going to happen, and I dealt with the uncertainty very well.

Have you learned about a thing called overcoming MS program. Is it popular in Germany, OMS?

Nele von Horsten: I don’t know how popular it is here. You mean the one from Australia, don’t you?

Prof. Gavin Giovannoni: George Jelinek evolved. Now, it’s what I would call theultra-distance version of running of lifestyle and wellness. I don’t buy into the diet because I think the evidence base for the overcoming MS diet is incredibly poor. But the rest of the philosophy in the overcoming MS program makes a lot of sense. It’s focusing on wellness. But again, it’s not an alternative to disease-modifying treatments. It’s complementary. In other words, it should be used in combination with disease-modifying therapy. And a lot of the overcoming MS people who follow the program often think it’s an alternative therapy, but it’s not. So, you know, the important thing is that’s kind of like a good guide to the extreme lifestyle wellness program you can put in place to manage your MS. With the caveat, I think the evidence for the diet is very poor. So I wouldn’t suggest the diet necessarily. But all the other things I would suggest are really common sense, to be honest with you.

Nele von Horsten: The episode before this one was just on the Mediterranean diet, where there is a lot of evidence that it is healthy direction, adding a lot of fruits and vegetables and all that, but not being restrictive, just going into the direction of the Mediterranean diet. Would you agree?

Prof. Gavin Giovannoni: Yeah, I think the evidence-based Mediterranean diets in terms of cardiovascular health and then brain health makes sense. But the other side of the thing now is diets are also very important culturally. You know what I mean? Eating and having meals and having rituals around festivals is a family thing. So if you’re going to go on a diet that restricts your… Interaction with your family and friends because it’s a very strict diet then that’s not the right diet for you you know what i mean so so I think I’ve writtenon my MS Selfie about my philosophy around diets. They have to be culturally respectful for traditions youshouldn’t go as soon as you start eating a diet that stops you having dinner with your family, that’s not good.

Nele von Horsten: Yes, I probably would get divorced if I restrict meat, for example, and I prefer to stay with my husband. He’s a lovely one.

Prof. Gavin Giovannoni: Yes, I mean, the evidence that meat is bad for you is very limited, to be honest with you. And when you actually do the meta-analysis, it’s what is probably bad for you is certain processing, particularly ultra-processed foods and meats. So if you’re going to eat meat, I would say eat, you know, and that’s the other thing about food. You’ve got to be mindful in terms of the environment, you know, and just to give you an example, some of the vegan diets that are out there, they are so ultra-processed. They’re probably very unhealthy for you if you eat the ultra-processed vegan diets. And also, vegan diets, you’ve got to be very mindful of the fact that they are deficient in many things. So you have to then take supplements. So, you know, there’s no – every diet’s got its quirks. I suppose the Mediterranean diet is the one that we like to promote because it’s got this association. I don’t know if you’re aware, though. The Mediterranean diet was actually part of a marketing campaign for all oil companies. But if you don’t eat the Mediterranean diet, I wouldn’t be too worried about that. I think just make sure you cut out or reduce as much as possible ultra-processed food.

Nele von Horsten: No ultra-processed foods, that is really important. And we have a nice app here in Germany. I think it’s available in whole Europe, the Yuka App, where you can scan the barcode and then you get a zero to 100 points for every grocery, mostly food. And I checked for some of the vegetarian or vegan alternatives. And they were like, wow, horrible because all these things were inside. So I prefer to stay with something like hummus, with a few ingredients, not much processed. So eating the meat but not the sausages, for example, is better.

Prof. Gavin Giovannoni: Michael Pollan is a U.S. journalist. Anybody who wants to read his books, they’re really quite good. he writes a lot about food and he would say, even though fermented foods are, you know, like, you know, various breads and that are processed, but they’re not ultra-processed because you know what goes into them, you know. So if you are going to eat, it’s best not to eat ultra-processed bread, but to eat just fermented processed bread. It’s more expensive, and that’s one of the things about healthy eating. It’s actually in the current food environment, it’s actually more expensive to eat healthily simply because the processed food, the ultra-processed foods are cheaper and that’s another that’s another problem is you know when it comes to social determinants if people are on low incomes for example they can’t afford to eat healthy something because the cheapest foods on the market are ultra processed foods.

How can healthcare professionals collaborate with patient advocates and support groups?

Prof. Gavin Giovannoni: I think it’s important that MS patients aren’t guessed. So this has become something I became aware of in the last two years, that often people with multiple sclerosis complain about a certain symptom and they get ignored by their healthcare professionals. So I think it’s really important that healthcare professionals do not gaslight. In other words, do not ignore or play down symptoms of smouldering MS. They should acknowledge it, document it, and just say, this sounds like you’ve got smouldering MS, and then have a narrative. They need a simple story to tell patients what’s happening to them. And I think people in MS will accept that.

There’s obviously a two-way street in terms of educating both healthcare professionals and people with the disease about this concept, and maybe it can happen together. So I think the concept of smoldering MS is well-established in experts, but in the general neurology field, a lot of people might not feel comfortable discussing it, and that’s an education thing. It’ll happen over time, particularly once treatments become available. Once we get the BTK inhibitors there’ll be a lot of education around the drugs and the concepts about why these therapies should work or who’s eligible for them. So there will be a rapid educational rise in knowledge around smoldering MS over time. But, I mean, most healthcare professionals probably realize that.

It’s more to managing MS than, you know, the once or twice a year consultation. There’s a whole lot of stuff that should happen in between.

You know, it’s a continuous process, keeping people up to date on new developments, on, you know, every time they have their therapies. And there’s lots of interactions that can be used intelligently by healthcare professionals and the MS centers to educate patients. So I don’t know what treatment you are on, but, I mean, you may be going up for infusions every few months or six months or whatever. So there are touch points where I think healthcare professionals should educate people with the disease about their disease. And that can be done using peer-to-peer support groups. They work in some hospitals. The people that do the educating is not healthcare professionals, but volunteer people with the disease. It all depends what healthcare system you’re working in and if you’ve got the means to set up these systems.

Quickfire Q&A Session

Complete the sentence: What is MS for you in one sentence?

Prof. Gavin Giovannoni: A complex but manageable disease where knowledge and collaboration are critical.

What development would you like to see in the next five years?

Prof. Gavin Giovannoni: The development of therapies that not only halt disease progression but also promote repair and recovery, coupled with improved diagnostic tools for early and accurate detection of smoldering MS.

Farewell

Gavin, what message of hope would you like to share with people living with MS?

Prof. Gavin Giovannoni: That we’ve identified a component of MS that the MS community is now targeting. So this is smoldering MS. So there’s going to be an area where we’re moving into much more effective therapy. So I think going forward in the future, the majority of people in MS are going to get to old age, not disabled. And I think that’s going to be the real benefit. And then, as I said in the beginning, I do personally think that MS is a curable and preventable disease. And we just have to be brave enough with our upfront treatments to cure the disease. So, you know, a lot of people don’t use the most effective therapies first line. And I think we need a shift in emphasis there. That’s a whole can of worms, you know, how do we get people to use the most effective therapies up front?

Where can interested people learn more about your work?

Prof. Gavin Giovannoni: Yes, I have a thing called MS Selfie. It stands for MS Self Management. Now, there’s a newsletter that’s on Substack. They can register for that. And then there’s a microsite. That’s a curated site for people for self-management. I usually do one or two newsletters a week. And if people follow MS Selfie, I will always give them the best – I always give them research updates on that. I also try not to overload them because a lot of research is derivative. In other words, it’s repetitive. But I will cover all the new highlights and the hot topics on that if they want to. And they don’t have to pay. So there is a paid subscription component to that. They only have to pay if they want to ask me questions that are not related to my newsletters. And the reason why I get them to pay is because I use the money to support the initiative. I’ve got to pay a medical writer and I’ve also got to pay for a web designer and pay for the platform. So if people want to actually subscribe and they can’t afford to pay I give them a free subscription. So you know it’s like give and take. But they only have to pay for access to the question and answer session that people or they may still ask me questions. That’s all.

Nele von Horsten: Fantastic, yes. And I can absolutely recommend that newsletter. I’m a subscriber. And I used your info cards for the DMTs when I was talking about the DMTs because they are really helpful just giving that short overview. Thank you, Gavin, for this insightful discussion. Looking forward to having you on again soon!

Prof. Gavin Giovannoni: Thank you, Nele. Take care!