Chapters Transcript Multiple Sclerosis: Symptoms, Management and the Role of Primary Care Dr. Salim Chahin, MD, MSCE provides a thorough overview of MS and the role that primary care plays in MS. So now for our first presenter, we have Doctor Sham Shaheen. He earned his medical degree at the Mosque University School of Medicine in Syria and then did his neurology residency at the University of Iowa and Iowa City. He then went to the University of Pennsylvania in Philadelphia to complete his Masters of Science and Civil Engineering and his fellowship in multiple sclerosis. Doctor Shaheen is currently an assistant professor of adult neurology and neuroimmunology with the washy physicians. He sees patients at Barnes Jewish Hospital for multiple sclerosis. Nmo and mog. So thank you so much for joining us today. Doctor Shaheen, appreciate it. And I'll let you go ahead and start with your talk. Thank you so much Nicole and I know you looked up all the abbreviations. The one correction, small correction I would make is the master's was in uh masters of Science and clinical epidemiology. Um Just in case someone asks me an engineering question, I won't be able to answer those. Anyway. Thank you so much for the introduction and uh welcome everyone. I'm gonna be speaking. Uh The topic is gonna be overview of M SS uh multiple sclerosis, its symptoms, management and then talk about ways uh to improve collaboration between neurology and primary care when taking care of MS patients. These are my disclosures and uh just reviewing the objectives. We will first uh review what we know about the epidemiology of multiple sclerosis. We will talk about common symptoms, how M SS presents, what are some of the common symptoms? How do we treat the disease itself? But then also focus on how do we address some of the symptoms, the more common symptoms that our patients present with. And again, we can finish by tying things together and talking about how can we work together to deliver better care to our patients. So first, um let's start with epidemiology and I want to briefly mention the immunopathogenesis of MS. So a lot of, you know, the MS is thought to be this inflammatory immune mediated disease, but there's actually, you know, a better way to think about it is that there is two components to MS, there's inflammation and there's neurodegeneration. And there are theories out there about what happens. First, there's a lot of uh theories about how does MS start. Um the most prevailing one is again that it is an immune mediated immune mediated disease of the central nervous system. So we're talking brain and spinal cord and it starts off with inflammation. Why it happens is still the million dollar questions. A lot of work is being done to understand that. But it has to be someone who's genetically susceptible and is exposed to an environmental trigger. And we're gonna cover those in the, in the next few slides. Um and early on in the disease, there's a lot of this inflammation that causes the white matter lesions. We're gonna look at those and that can result in relapses. But once you lose the myelin, which is the direct result of inflammation, the nerve fibers themselves are gonna eventually get damaged and that's gonna lead to more degeneration. And as you see from this figure, early on in most patients, there's a lot of inflammation. So a lot of uh lesions and relapses. But as the disease, as time goes on, there's more of this slow brewing damage, this degeneration. Um we used to think that MS was a T lymphocyte mediated disease. But honestly, there's so many other parts of the immune system that are implicated in the pathogenesis. We now know that B cells play an important role and that targeting B cells has really changed how we treat MS. So who does MS affect the most? It is a leading cause of nontraumatic disability in young adults usually diagnosed between the ages of 2050. It's more common in women than men. The ratio is about 3 to 1. There are pediatric forms of multiple sclerosis, there's juvenile multiple sclerosis and especially in our center where we see a lot of MS patients, we have made diagnoses in people who are older than 50. So it is not restricted to this age range. It's just the most common um age range. You see, you will see it in similarly, in the old days, we used to say this is mainly a disease that affects caucasians, but it does occur in almost all ethnic groups, including African Americans and Hispanics and Latinos. But it is still considered more common among people from a Northern European ancestry. It is interesting that research is suggesting that people of African American and Hispanic heritage may have worse disease outcomes and that's still being exploited as to understand why that occurs. Uh You tend to see more MS cases the further you move away from the equator, we're gonna cover that in the next slide kind of explore why that could be. There was a big study sponsored by the National MS Society done in 2017 that showed that the, the uh the number of people in the United States that have M SS is at least 700,000. And again, this is now, um can't believe it's uh almost seven years old study. So when we say people need to have genetic susceptibility, does this mean MS is a genetic disease? It is not, does this mean there are certain genes or certain locations that are more associated with MS? Maybe there's a few that are maybe more, a little bit more common than others, but there's been over two genetics genetic locations that have been identified to confer an increased risk of developing MS. So it's not really easy. We do not need to do genetic testing for our patients. At this point, it does not inform our management. I think eventually it may um the question we get asked a lot by our patients is if I have the disease, will my family member, will my loved ones, will my kids have the disease? And these numbers are very helpful because I tell my patients the risk in random person off the street, the risk in the general population is about 0.1%. If you have a first degree relative, the risk goes up, but it's only about 3 to 4%. So it it is higher, but it is not very high. In fact, in identical twins, depending on the studies, it's about 25 to 30%. So if one twin gets the disease, that means the other twin has a 25% chance of getting the disease. And the other important number to quote is that up to 90% of people with MS do not have a family member who has the disease. So overall it is not considered a genetic disease and the risk of a first degree relative getting the disease is low. So we talked about these risk factors. Um we talked about the further you you live from the equator. So again, if you're looking at latitudes, the the, the most north and southern latitudes have a higher risk of developing MS. But interestingly, if an individual moves from a lower risk to a higher risk area, they will acquire the risk of the area they move to if they do so before puberty. So this, this then the closer they approach puberty, the the risk seems to be a bit slower. So that's why I kind of wrote it as a said, graded age related fashion. Um Why is that? We think maybe there's a, there's a couple of theories, there's a potential pathogen slash virus theory and maybe the way certain viruses affect people differ depending on where they live. But there's also the sun exposure and the vitamin D theory, there's now been several studies showing a link between low vitamin D and the risk of developing multiple sclerosis. Um The Y could have to do with genetics as much as with sun exposure. We uh used to think up until the last couple of years that there is also potentially a link between low vitamin D and the risk of a more severe disease. More relapses, more MRI changes. There's now been a few negative studies that have not shown that a high vitamin D level of vitamin D supplementation lead to better disease outcomes. So I would say the jury is still out on after diagnosis if vitamin D matters, it is something that we recommend to our patients. We say, you know, we check a level every once in a while. Supplement, don't go too overboard with supplementation. The pathogen slash risk factor that has received the most attention remains the Epstein Barr virus EBV. And a study that came out a couple of years ago now, um again showed that there's an increased prevalence of EBV prior to, to MS diagnosis. So in that study where they followed, I would, millions of people where they, I think this was done in the military, they had blood samples collected from people prior to them developing any medical issues. When you, when they went back and analyzed, almost everyone who eventually developed multiple sclerosis became zero positive to EBV at some point prior to their MS diagnosis. Um as you know, a lot of people have serial positivity to EBV. So it is not the only risk factor. A lot of my patients ask me well, if I've had mono in the past, does that mean I'm gonna get MS? No, most people will not. But it's interesting that it seems to be maybe a quote necessary risk factor for the development of MS. It's still being debated as you know, there are vaccines being studied for EBV. So I think we, our knowledge on this is gonna inform how we treat our patients and potentially how we may be able to prevent MS in the future. Numerous studies have shown that cigarette smoking is also associated with an increased risk of MS and actually with worse disease outcomes, a couple of smaller studies suggest that increased dietary salt intake may be related to developing MS and obesity in adolescence as well. But those are, don't have the same number of samples that some of the other risk factors that we mentioned. So next, we're gonna move on to talk about clinical patterns and common MS symptoms or more typical MS symptoms. I'd like to start by uh reminding everyone that MS remains a clinical diagnosis. We live in an age where people can easily get an MRI for a variety of reasons. And um MRI S can, you know, show abnormalities that can lead down a slippery slope. But we always refocus the conversation when we're meeting someone who is coming with a question of, do I have MS and say MS is a clinical diagnosis? We need to hear a demyelinating story. The patient should come in with symptoms that sound typical for demyelination. That's the medical story suggested by the CNS process. This needs to be corroborated by changes on our exam that fit with what they're complaining of and then we can do additional testing. So obviously, you know, MRI has become a very useful tool. It shows us white matter lesions in the brain and the spine. We do lumbar puncture CS F analysis and that can show us specific markers for inflammation within the spinal fluid that are more commonly seen in people with MS. There isn't a specific test for MS in the spinal fluid. But when we look for something called oligoclonal bands and we like, we call it CS F restricted, meaning we only see them in the spinal fluid but not in the blood. It's seen in 90% of people with MS, but it is not unique or specific to MS. You can see it through a much lesser frequency in other patients. Other conditions, we do blood work up sometimes to rule out other things you can do visual evoked potential, which measures the speed of how long it takes for the nerve signal to travel along the optic nerve. And because the optic nerve is a frequent target of demyelination is slowing down, lots of myelin leads to slow down the slowing down of the nerve signal. And you can capture that on a on a very simple test like the visual evoked credentials. Um We have developed diagnostic criteria over the years for MS. It's been updated several times most recently in 2017. And I think the next newest version is about to come out. I sometimes you will read in radiology reports that this MRI quotes meets mcdonald criteria or meets diagnostic criteria. This is where I'd like to again uh mention a reminder that the criteria are to only be applied for someone who has had typical MS symptoms and they are to help us make a diagnosis and not wait for the second episode because when people present with their first episode, it is not always clear if that's gonna, if they're going to develop into MS or not. So the criteria are not for differential diagnosis, they don't help us tell MS from other conditions, they help us secure an MS diagnosis and someone who's presented already with a typical episode. If you've attended a neurology talk or an MS talk, you or even back in medical school, you have seen a slide that looks like this. These are the clinical patterns of MS first introduced in the nineties. Updated in 2014, all, about 85% of patients will present with a relapsing remitting course. And again, the first episode that they have, you can see it here on the right hand side of this slide is called Clinically isolated Syndrome. It's just the first episode of MS. Most people with clinically isolated syndrome are gonna go on to have another relapse and be quote officially MS diagnosed with MS. And this is this is where we apply those diagnostic criteria. But again, 85% of people are gonna be in this category when they start, they have a relapse and then in between the relapses, they're remitting, they're fine. Sometimes they end up with some accrued disability in between relapses. So it's more of a step wise uh uh change after about 15 years, an average of 15 years. This data is from natural history studies, untreated patients. After about 15 years, patients um will go on to slowly get worse over time and that's progression. So when we say clinical progression, we just mean that every year is worse than a year before they can walk less, their legs are weaker, their cognition is weaker, depending on what their um major symptom is. And so again, the the secondary progressive happens after the relapsing remitting phase. If you follow people long enough, almost everyone should be secondary progressive. It's just that the, when they get there and the slope of their progression varies in between patients. And we believe that treatment slows down this progression and or delays it. So again, the 15 year number is from untreated patients. Now, lastly, 15% of patients will start off with a slow gradual decline. They will never have a frank relapse. They won't be able to tell I've had an episode and I recovered from it, but it actually takes them 2 to 3 years to notice that they have some sort of a neurologic problem. Uh that is getting worse over time. Um And it doesn't matter if they can have superimposed relapses or MRI changes. As long as it starts progressive, we call it primary progressive names slash phenotypes are less important. What is important to me and even to payers regulatory agencies is whether or not I think the patients had a relapse or MRI changes because then I call it, they have a relapsing component which means they still have inflammation, which means I can treat that successfully or are they getting slowly worse over time? Which is the progressive component or both? Some people can still have both. And again, as long as you see, a relapsing component, you can treat them with disease modifying treatment and you can make AAA change or a difference. We mentioned that we want our patients to present with typical symptoms. Um What are some of the typical symptoms? Uh optic neuritis, acute optic neuritis is the number one symptom experienced by people with MS. Usually they present with pain with eye movements and then some unilateral vision change. It's usually central scat toma. Some patients say they feel like they're looking through some sort of a screen could involve that entire vision, but often it's central, the scat toma or the blind spot could be anywhere in their vision. But again, most commonly central, that's why when I'm examining my patient's visual fields on exam and I I tell them, look at my nose. The first thing I ask them is, can you see it clearly before I test their periphery because it's central vision is also affected. Next. Second, most common presentation is transverse myelitis. We call it partial transverse myelitis to distinguish it from other autoimmune things that can affect the spine in these situations because the lesion is not involving the entire segment of the spinal cord. Patients will kind of have a bit of an asymmetric involvement. So they have weakness, usually one leg is worse than the other. They will have some, potentially some sensory changes as well. But again, it's gonna be asymmetric. So one side is gonna be more affected than the other, other typical symptoms. So anything involving the brain stem most commonly double vision. Again, uh for those of you, uh you may remember intranuclear ophthalmia or ino which is a certain uh presentation of double vision involving tracks in the brain stem. We don't need to dwell on that for the purpose of today's talk cerebellar symptoms, anything causing balance issues or ataxia is also common. And then there's two somewhat unique phenomenon to demyelination and to le spinal cord lesions. So learn me phenomenon is the sensation that patients feel of tingling or electric shocks up and down the back and into the shoulders when they flex their neck. And usually this results from the fact that there's a lesion in their cervical spot. So somewhere in their neck and you stretch that they stretch that lesion when they flex their neck and that produces these symptoms. It does, this is does not mean there is not necessarily a relapse, it can happen in previously present lesions. Um And again, it doesn't have to, it's not specific to demyelinating lesions. UTA phenomenon is the fact that MS symptoms get worse when you increase the body temperature for any reason. And this is because conduction along the nerve fiber slows down further when you increase the body temperature. So if you have a nerve fiber that's lost its myelin that the conduction is slower, you can add, if you add heat to that, it's gonna slow further. This is temporary. And frequently we have to remind our patients that this is not harmful. So, my patients ask, well, can I still take warm showers? Yes, absolutely. Some of my patients, if they've had an episode of optic neuritis, their vision will get worse when they're taking a warm shower, they step out, it's back to baseline. So it is not leading to any permanent or more damage, other common symptoms. And we're gonna cover those in more detail later, but I wanted to mention them here is cognitive dysfunction, very common in our patients due to the brain lesions, bladder and bowel involvement is also very common symptoms that I have in Srx. Next to our uh what I call the less specific symptoms, vertigo. As you know, it's a lot of things can cause vertigo, room spinning, sensation, fatigue, very non-specific, but common symptom. And um, we're gonna address fatigue and pain when we talk about treating symptoms. But those are symptoms while there may not be specific for MS or demin, they are common in our patients just briefly. What does an MRI look like. Um, you know, not every white matter lesion is an MS lesion, there are certain uh characteristics for MS lesions. They need to be. Some people say at least five millimeter in size size is somewhat debatable. They have to have a certain orientation around the ventricles as you see here. And this is called Dawson's finger named after the pathologist that first described it, they are perpendicular to the uh ventricle. Um So most common location is again, peri ventricular lesions have to be touching the ventricle. Second, most common is just the cortical lesions have to be touching or very close to the cortex to the surface of the brain. Anything in the brain stem or cerebellum is also common for demyelination. Here's another typical lesion and lastly spinal cord and I choose an example here of someone with very severe spinal cord disease. So they have 123 and maybe even four lesions in their spinal cord. And it is the spinal cord lesions that cause more of the physical and sensory manifestations. And as I mentioned, cerebellar lesions will cause the ataxia. Brain lesions tend to be less symptomatic. But the com the sequela of too many brain lesions can lead to cognitive dysfunction, fatigue and other issues. The correlation there is not perfect though. So we talked about patients presenting with a relapse. We talked about um differentiating relapses for progression. But how do we define a relapse? When do I say that? Yeah, I think my patient had a relapse, relapses start acutely to sub acutely. So it's not as sudden as a stroke but it is within a few hours. Uh it reaches its need year within 24 hours and it has to last at least 24 hours. Realistically, it's gonna last days to weeks. Usually the typical average is like 2 to 4 weeks for a relapse. Um It oftentimes is a new symptom. Technically, could be a previously resolved symptom, but whenever it's not new, it's something that the patient experienced before we start thinking about a pseudo relapse. So again, if you're suspecting a relapse, you can treat with high dose steroids. Do you need to? Probably not because studies have shown that steroids just shorten the relapse, they hasten recovery, they have a less of an impact on long term outcomes. So it depends on how debilitating the symptoms are to the patient and how if they're impacting quality of life pseudo relapse is when someone's symptoms come back due to something stressing the body, usually we say it's things like fever and from an infection, any anything heat, as we mentioned ut phenomenon, any other stressors. And so when a patient says I am having the same symptoms over and over again, I start by doing some labs making sure that, you know, checking their urine, uh talking with them about any new symptoms. And potentially if I'm not convinced we may have to go the route of imaging before we actually consider it and or treat it as a relapse. We treat relapses with steroids but we treat the disease with immuno monetary or immunosuppressive treatments. The treatment landscape for MS has evolved significantly over the years. We have many high efficacy drugs that have been come on the market in the last 5 to 7 years, we now have generics which has kind of changed. Uh a lot of the approach to treatment uh options in MS. And we still have newer and novel mechanisms of action being studied in clinical trials including repair. So I think the next era in MS is going to be we can control the inflammation and the relapses. But we're going to see if we can give the patients something to promote myelin repair, which will hopefully affect long term outcomes. Here's a timeline of when all the different MS treatments were approved and you can kind of see that between 1993 and maybe the late two thousands, there wasn't a lot going on. There were a few drugs introduced, a lot of them are interference kind of the low efficacy drugs. But starting in about 2010, we've had an explosion in the number of approved therapies and it continues through 2023. In 2023 it was mostly generics that were approved, but we've now have over 26 technically 26 treatment options. I'd like to divide the drugs into three categories. You have the what we call the platform injectables. These were the initially approved medications. They tend to be the safest. They're immunomodulatory, they're not immunosuppressants. We have oral options and they are um range between immuno moet to immunosuppression and then the monoclonal. So even though it's an IV bag, there's actually one subcutaneous monoclonal injection that's approved through MS and monoclonals tend to be the most highly efficacious. We will not have time to delve into the um mechanisms of action, but I just listed the um names of the drugs here, these are the injectables and again, the brand and the generics that are available. And here are the um oral therapies. Similarly, we've got, they're mostly kind of grouped in um these four categories, but I have the names on the slides. Again, we won't, we do not have the time to go through all the different options. Monoclone antibodies, there's three B cell depletors, there's natalizumab, which used to be approved for G I indications as well. And there's alantis A which is also I believe has uh other indications B cell depletors have become the mainstay of treatment. Again, we didn't really consider the role of B cell treatments until actually my mentor here at Wash U Doctor Cross about 15 years ago. Now we did the first B cell trial. It was a phase two trial in MS and the outcomes were it was a small trial, small cohort. But the changes on MRI and the changes patients experience was amazing. This led to the development of the first drug and now we have three B cell depleting drugs on the market and they've really changed the trajectory of the disease just to highlight what, what, how do we measure efficacy? We look at how much a drug can reduce the rate of relapses. We're not gonna go through these numbers one by one. But again, initially, the drugs were compared to placebo, but with time, they have to be compared to an active comparator. And you can see that B cell therapies kind of score the best you cannot compare across trials. You cannot compare across drugs. But B cell therapies did really well in reducing the relapse rate compared to active comparators. And in reality these days, when we put a patient on A B cell depleter, we do not expect to see an MRI changes. And we, it's very rare for us to see a relapses if one of my patients on the B cell depleter calls and says, I think I'm having a relapse. My answer is probably not because you're on a B cell depleter and but let's go investigate it. So that's how much of an impact these drugs have had in the last day. They were one, the first one was approved about seven years ago. And it highlights why it is important to put our patients on treatment early. So this is a graph showing you the accumulation of clinical disability over time if you initiate treatment early. And this is irrespective of what drug you choose. Versus if you initiate treatment later, there's a magical 5 to 10 year window. I would say five year window where if you make it, if you affect a change in those five years, you have a long, longer term impact and natural history. So we kind of think about it as there's almost two windows of opportunity first is make sure you treat, make sure you diagnose early and you offer treatment as soon as you can. Um But you have another window of opportunity either if, if you choose a drug that doesn't seem to be working as well as you want to or if you're mistreating early, you've got another window to make a change again within those magical five years. Um The, the every year that I give a talk that's similar to this one and we talk about escalations versus early high efficacy. We have this kind of conversation about, well, there's, there's these two approaches to treatment, what I can share is that every year there's more and more evidence suggesting that starting with a stronger drug from the beginning is the right way to go because it's making an impact on long term outcome. But again, just for the sake of talking about and there's actually a couple of uh very rigorous clinical trials that are comparing these two methods. Escalation means start with one of the lesser efficacious agents, but is safer because there's always a trade off between efficacy and safety. So less immunosuppression and then using that second window of opportunity, if your patient is um not responding as well, we call it breakthrough. Either they have new MRI changes or they have a relapse, then switch them to something stronger. But again, more and more of us are using early high efficacy. We start treatment with a strong high efficacious drug and we're now starting to discuss, when do we deescalated after how many years do we feel safe to maybe take, take it down a notch. Early, high efficacy is not induction. Induction. By definition is you're inducing a change to the immune system. There may be a couple of M MS agents that are considered induction therapies. Alantis, IAB and Clane. And we also have um studies on hematopoietic stem cell transplant as a possible induction therapy. Currently, there's trials looking at the efficacy of this um treatment but it is reserved for people who are failing everything else. Why consider early high efficacy? Again, one is some of our high efficacy drugs have a favorable risk profile. So we feel comfortable enough using them in our patients. Early. I mentioned that there's rigorous trials comparing high efficacy to escalation approaches. But there's been enough observational and cohort studies showing that it makes a difference both for short and long term uh outcomes to start with early high efficacy. What drugs are considered high efficacy. Uh There's some debate, not a lot of debate. Again, most natalizumab is a molecular antibody b cell depleter are monoclonal aab is a monoclonal. So most monoclonals are considered high efficacy drugs. There's a group of oral drugs that is sometimes um is uh considered high efficacy depending on the I guess, depending on the investigator. So again, we talked about studies showing that high efficacy makes a difference. Why do it several scientific rational reasons? One is, as I showed you in that early slide, there's a lot more inflammation earlier in the disease. All of our drugs affect the immune system and target inflammation. So we know that we're gonna get a better treatment response from these drugs if we start them early people when they are earlier in the disease, because they are younger, their bodies can tolerate drugs like B cell depleter is a lot better than if you wait 10 or 15 years. There's um now studies showing that even much early in the disease, if you look in between relapses, people are actually not flat, not stable, but there may be getting suddenly worse in between relapses. And when you do high efficacy, you can actually make a difference on this as well. So you may be not only affecting inflammation but also degeneration if you target the patients earlier in the disease. And again, I kind of share that there's a lot of studies showing long term benefits of high efficacy treatment and there are trials to do so So this is where usually people say so why not just put everyone, why are we having this argument about early high efficacy? It's because of the risks. So half of our visits now seem to be targeted to risk mitigation. Almost all of our drugs require some sort of a risk mitigation, some labs, potentially other things. So you know, this is we are not gonna go through this table and it includes what baseline testing we have to do for the different groups. What monitoring parameters we have to do. Some are per label, some are extra because it's things we know matter to um risk mitigation. Um but it takes a lot to mitigate the risk of the higher efficacy drugs. And this is where the balance between benefits from the drug and risk and making sure that we're closely monitoring our patients. Um notably when you put someone on high efficacy, you wanna make sure they're doing reasonable infections, precautions. We wanna, we stress that it's important for them to stay up to date on their cancer screening. For example, in addition to some of the lab and some of the lab work that we do when we see them. So we covered treating a relapse, we covered disease modifying treatments. We're gonna shift and kind of explore some of the uh common MS symptoms. And then um you know, we're not gonna do a deep dive into the treatment of the different symptoms, but we're gonna touch on. Uh some of the things we can do in our clinics and some of the things primary care providers can do when patients present with some of these symptoms. As I mentioned earlier, fatigue is a non-specific symptom. However, it is the most common symptom reported by MS patients. Up to 85 to 90% of our patients will complain of fatigue at some point during their disease. It is an invisible symptom. It's not the only one cognitive dysfunction is another invisible symptom. People can't really tell. Uh some of my patients say, my friends or coworkers say, well, you don't look like you have MS, right? Because what they're experiencing is a subjective symptom. Often that is not easily measurable, cannot be seen by others. We have a hard time measuring it because it's a patient reported outcome. Um But it is a leading cause for departure from the workforce for our patients. Sorry about that. Um It's important when a patient complains of fatigue to explore whether or not it is secondary to other causes. So make sure you identify contributing factors. I ask about sleep. I ask about mood and depression and we're gonna talk about depression later because there's significant overlap between depression and fatigue. Um And then I also explore, is it physical fatigue or is it more cognitive concentration, fatigue and it's not easy to sometimes tell apart cognitive fatigue from cognitive dysfunction. There's also objective fatigability which is simply put, the patient says, you know what, the longer I walk, it's easiest to give an example of physical fatigability. The longer I walk, the more I feel like my legs are weak and then I have to stop and rest before I can pick up again. And you can technically measure that by just having the patient go a certain distance and then you'll be able to see that they are, you know, your their motor testing is gonna change and then when they rest, you kind of reset that a little bit. So I, whenever I encounter fatigue in my clinic, I ask about things that can cause secondary fatigue. I explore whether it's physical or cognitive. Uh And then I talk about the importance of sleep hygiene. Exercise is actually very important, especially if done early in the day so that it doesn't impact sleep in a negative way. We talk about energy conservation methods, napping in the afternoon. If a patient can afford to nap can kind of reset, tiredness a little bit and then we resort to some pharmacological treatments, nothing works perfectly. Amantadine is a kind of a, it's an old flu drug that is now used to treat certain symptoms of Parkinson's disease, but that we've also used for years to treat MS associated fatigue. It is relatively safe. Very few side effects tolerated. So it's usually my first choice approved by insurance. Uh but if it doesn't work, sometimes it doesn't and it's uh it's almost 5050 for all of these options. Then we move on to stimulants. We tend to prefer agents that are used for like uh s sleep, sleep disorders, shift work disorder. So, uh Modafinil or our modafinil are, are our go to choices. If they're approved by insurance, we'd rather not use things like Ritalin um or similar drugs unless we have to, unless we're kind of running out of options. Walking impairment is the kind of the most visible form of disability that patients can experience and can negatively affect quality of life. It is obviously the leading cause of falls and falls can lead to fractures and that can lead to more disabilities. It's a vicious cycle. So one of our goals is to identify those patients that we feel may benefit from early intervention with rehab therapies. I'm happy to prescribe PT once a year to my patients if they can afford the copay, if their insurance approves it and then you know, make sure that you recognize when and, and, and push them towards using an assistive device because that can limit the falls and, and you can lead to better quality of life down the line. We have a medication called D Fampridine that we use. It's approved to gate impairment in people with MS, it blocks potassium channels. So it improves conduction along the nerve fibers, that's how it works. And it actually improves sometimes improves other symptoms of MS, it also works about 50% of the time and, and the reason is if you've lost the nerve fiber, it doesn't mean it doesn't matter what intervention you do, you're not gonna be able to improve conduction because there's no, the highway is gone. Bladder dysfunction is another symptom that we address almost in every visit with a majority of our patients. There's uh just as a urology refresher, there are three different types of bladder dysfunctions that occur. There are three different types of neurogenic bladder, I'm sorry. Um In our patients, any of them can happen. The most common is possibly the star's dysfunction or the spastic bladder, which results in symptoms of frequency and urgency. This is treated pharmacologically with anticholinergic agents like oxybutynin. You know, there's the tried and true anticholinergic agents. There are newer agents like Megatron and I think there's an, there's another one. Now, um uh they have less anticholinergic side effects. Sometimes they have to be second line to be approved by insurance and then you can do uh Botox in the bladder and also help kind of relax the bladder muscles. So there's less of this bladder spasticity. The second most common um, bladder issue experienced by our patients is this, this scenario is emptying dysfunction. So there's a distin area between the TRS or and distincter muscle. The the TriCor is pushing to MT, but the sphincter doesn't open up and so that leads to accidents. It is uh sometimes treated with alpha adrenergic blockers, but most often it's a urology, referral and intermittent self catheterization may be needed. The most difficult form of bladder dysfunction to treat is the um just urinary retention. You cannot easily treat it with um pharmacological agents. And these patients, this can because urine is left over in the bladder, it can lead to frequent UTIs and the treatment is to catheter and self empty. The bladder. I mentioned cognitive dysfunction as another quote, invisible symptom. This is something that is more common than we thought it was because I think it was under it's under reported by our patients and in previously, was under captured by providers, it can occur very early in the disease process and it affects those domains that are most needed by young or by professionals in general to be able to do their job. So if you imagine a young professional, they have a diagnosis, they're not physically impaired, but they have issues with like processing speed, working memory, executive functioning. So it's being able to multitask during a meeting, being able to kind of handle several things at the same time. Um and it's tough and again, this is this results in um people be not being able to work. So this is a cause of uh disability. It is not easily capturing, we have to do neuropsychological testing, we have to document it and we often have to have conversations with disability insurance companies about the fact that this is real. Um The treatment is difficult. It's oftentimes when we say cognitive rehab, we also do occupational therapy and you wanna make sure you treat any underlying symptoms that may be negatively affecting cognition. And ot just teaches patients uh strategies to navigate around some of these issues. Depression is more common in people with MS than in the general population. It is a greater risk factor for suicide And it also leads to patients being less engaged in treating their disease as well as addressing some of their other symptoms. Depression is is is tough. I feel like our patients don't know who to approach and talk about on their depression. So this is where again, the collaboration between the different uh specialties and the different disciplines is really helpful. We you oftentimes resort to pharmacological agents, but I'm a fan of cognitive behavioral therapy, psychotherapy. If there are therapies available in the patient's area as well. The last two symptoms that I want to cover are spasticity and pain spasticity is due to the fact that MS is a brain and spine disease. So it leads to upper motor neuron signs and symptoms. Patients. It's more often experienced in the legs than in the arms. Patients report cramps and spasms. It's usually worse at night, worse when the patient is laying down. And if it's bad enough, it can actually negatively impact walking because as you know, a little bit of spasticity is useful to counteract the weakness but too much. And then again, it actually affects walking negatively. So patients are taught to stretch. We do physical therapy, we try pharmacological muscle relaxant. So I'm sorry, I don't know why my slides are moving by themselves. And um, you know, worst case scenario you can, you can do Botox. You have to be careful with the Botox. Usually the physical medicine and rehab, uh providers will only do Botox when they know that it's not gonna cause more weakness. And then there's also the idea of inter thal baclofen delivery through a baclofen pump pain is another very common symptom. It's tough. So many things can cause pain in an average patient. So many things can cause pain in an MS patient. You have central pain, which is I feel like it's the one our patients have the hardest time describing when I recognize it. I go for neuropathic pain medicines. You have specific pain syndromes like trigeminal neuralgia, which is pain in the trigeminal nerve distribution on one side of the face, triggered by touching chewing wind. Um This is treated with mainly first line is anti convulsants, uh like carBAMazepine. And it is interestingly, vaginal naia is more common in people with MS. And then you've got because of all the different disabilities that our patients accrue. You've got secondary musculoskeletal pain which is treated with physical therapy and ads and, and, and trying to address the triggers and I would like to end with a few slides discussing how can we work together to deliver better care to our patients. Um Sometimes our patients forget that we are not their primary care doctors. One of the things I say when I meet them for the first time is I say, especially if it's a younger person doesn't have a primary, say, go get a primary care doctor. We need to work together. There's so many things that you're gonna, so many questions that are gonna come up so many symptoms and things we're gonna need help with. So go go get a primary care doctor. Why? Because there are things like when you're too focused on your MS, you might start to forget other age appropriate screenings as you get older and especially if you have mobility issues, you might not be motivated to go see more doctors. So it's important to kind of have someone you check in as a patient about these issues. We mentioned that smoking is um a negative impact on disease outcomes. And so we work together with primary care doctors on smoking cessations. As our patients get older, they're gonna start accruing more comorbidities. And it has been shown that comorbidities like high blood pressure, hyperlipidemia, cardiovascular comorbidities lead to worse MS outcomes. So again, establishing with the primary care and addressing these issues is important, bone health, especially with, with people who have limited mobilities, we tend to give steroidss. Although I think we're using less steroidss than we used to. And it's episodic steroids. It is not chronic steroids, but still this could negatively impact bone health. We talked about the role of vitamin D in MS pathology. We talked about the fact that it may not be as significant for disease outcomes once someone's diagnosed. But again, uh it doesn't have to check in on a vitamin D level every once in a while And skin health, especially in people with mobility issues where we're gonna also cover cancer screening in a second vaccine is a hot topic. Um I think some, the number one question I get from primary providers is what do I do with vaccines? There have been many, many studies looking at whether or not MS is triggered by vaccination and or gets worse following vaccination. And the good news is there is no clear association between vaccination and developing MS and or getting a relapse if you already have MS. So we recommend that our patients get all of their vaccines. Definitely the flu vaccine and I added COVID-19 annually. Remember that if a patient is immunocompromised depending on the year, depending on the CDC guidelines, they may be eligible for a second COVID-19 vaccine, second annual COVID-19 vaccine. Eight weeks later. Um We remind her that if the patient is on an immunosuppressive drug or recently came off an immunosuppressive drug, do not give live attenuated vaccines. Um This is the question that I feel for my patients is what vaccines can I get or can't get? And usually my answer is well, depends on what medicine you're on. The National MS Society has a great resource for vaccine. In fact, they have plenty of great resources for MS patients in general. But there's a very uh up to date section on vaccine that has been obviously garnering a lot of attention since the COVID-19 pandemic. Again, things that we can work together on. Uh In addition to what we mentioned include, uh you might see the patient if you live closer to the patient that we do more often than we do so screened for depression. Ask about problems at work for cognitive dysfunction, mood changes. Uh Pulmonary function can be affected sleep problems, any of the symptoms that can negatively impact quality of life and that can be either triggered by MS or make other MS symptoms worse with us. Putting our patients on um immunosuppressants. I usually tell them, please please stay up to date on your cancer screening when you go meet your primary. Tell them I'm 43. What cancer screenings am I due for? Oftentimes? If you, if you're a man, the answer is wait until you're 45. But skin checks is a, it's a very important cancer screening to do a skin check. It is easy. I tell my patients talk to your primary. I know some primary care providers including mine offer cancer screening themselves some refer to a dermatologist, but it's another or at least remind the patient that, hey, I've ordered all the cancer screening I can, but you have to go see a dermatologist and do your skin checks. I honestly would not ask anyone else to manage the side effects that come from AD MT. But again, recognizing that some of these drugs have different side effects and reaching out to us so we can manage them together. It can help promote better adherence to these medicines. And then, as I mentioned in the previous slide, addressing comorbidities will reduce disability outcomes in people with multiple sclerosis. And with that, I will stop. And I'm happy to take questions. I think we have great. We have about 10 minutes. OK. So there is a question from doctor M would love to hear advice on how not to miss the diagnosis. That's a great question. I would say about 30% of referrals we get are for patients who present with some neurologic symptom and you do a brain MRI and you see white matter lesions. Um and we, you know, we see the patient, we say no, it's not MS this is this is usually the the referral that our patients gonna get frustrated with the most, right? But we tell them that they learn the most from seeing from recognizing not MS as much as from diagnosing MS. So I would say just having a low threshold. Um if a patient is complaining of neurologic symptoms. It may unfortunately, in our area, there's not enough general neurologists to go around because it may warrant at least a visit with a neurologist to do a screening neurologic exam and just see if there's any objective findings corresponding to those symptoms. MRI. S are becoming more widely available. It is easier to get an MRI than ever. So just check, starting with an MRI is also reasonable, recognizing that some of the symptoms do not come from the brain. And so maybe imaging, at least the cervical spine if you have concerns about physical symptoms in the lower extremities. Um and lastly, things to kind of maybe lower your threshold for screening is, don't forget that young patients have MS uh the oftentime the misdiagnosis happens when someone is younger, they go to the er, and they're told that this is due to an anxiety issue. And again, maybe it is a functional neurologic symptom, but I think a young person with the right pattern story pattern deserves to be screened with an MRI. Um because I wouldn't ask you to be able to identify the story about it. I would say just initiate an MRI and then a uh a referral at our center. Fortunately knock on wood, we have enough availability that we, if it's, if it's a question of neurologic symptoms plus abnormal brain, MRI, we're happy to see them and take it from there. Um I'm not seeing any other questions in the Q and A or the chat. But if any of you come up with questions later on, you're welcome to email me and I can get those to Doctor Shaheen and, and get those answered for you. Um So thank you very much, Doctor Shaheen and I'll let you get back on with the rest of your day. Thank you very much. Created by Presenters Salim Chahin, MD, MSCE Associate Professor of Neurology Adult, NeuroimmunologyAssociate Residency Program Co-Director View full profile
