This is Episode Four of “Autoimmune Disease: Pieces of the Picture.” Dr. Ana Felix talks with Dr. Ron Falk about multiple sclerosis (MS), the different forms of the disease, getting an MRI, and issues related to treatment. Dr. Felix is an Assistant Professor of Medicine in the Division of General Medicine and Clinical Epidemiology at UNC.
“We walk the journey with the patient. When we cannot cure, we can still be at their side. It’s truly a long-term relationship between the physician and the patient.”
– Ana Felix, MD, MBBCh
Ron Falk, MD: Hello, and welcome to the Chair’s Corner from the Department of Medicine at the University of North Carolina.
This is a series where we are exploring topics related to autoimmune disease, to help patients and their loved ones understand and manage their condition. Today, we will talk about multiple sclerosis, also known as MS. We welcome Dr. Ana Felix who is an expert neurologist in the Division of General Medicine. She sees patients at UNC who have MS and a variety of other neurological conditions. Welcome, Ana Felix.
Ana Felix, MD: Thank you so much.
Different forms of multiple sclerosis
Falk: What is multiple sclerosis? What does that word really mean? It strikes fear in everybody.
Felix: You’re right, it really does strike fear. Multiple sclerosis is a neurological disorder that is related to a dysfunction of the immune system, that affects about 400,000 Americans. We don’t know exactly why people develop MS, but we do know that the immune system is integrally involved in the development of the disease. People with MS may never have symptoms after their first experience with symptoms, or may progress to have significant disability. Those are the reasons that people fear the diagnosis.
Falk: As in many autoimmune diseases, there are individuals who do remarkably well, and it’s almost as if the immune system manages to heal itself and the disease is limited in time. It’s almost a one-shot disease – it happens and doesn’t happen again, but yet, many other patients have relapsing and remitting disease, and others a much more progressive course.
Felix: That’s right. Some patients will have what we call a “clinically isolated syndrome,” where they have one episode that may never recur again, other patients will have repeated episodes, some of which will improve completely, some will leave them with a little bit of neurological impairment, and over time those patients may progress. Then there’s about 10 percent of patients who develop a much more severe form of the disease, where, from diagnosis, they progressively worsen over time.
Falk: Can you predict, for somebody with new-onset of disease, if they’re going to be in the lucky group that have a one shot clinically isolated disease process?
Felix: That’s a great question. We do not currently have a good way to predict which patients are going to progress and which will not. The rule of thumb is that about 20 percent of patients who have a single episode or clinically isolated syndrome, may develop MS over time. That data has led us to treat clinically isolated syndrome aggressively, with the medications that we use to treat MS, to prevent progression of clinically isolated syndrome into multiple sclerosis.
Falk: There are then different forms of MS, or there might almost be under the rubric of the term multiple sclerosis – there are people who have milder disease, there are people who have relapsing disease, then progressive disease. Do the clinical symptoms-do what patients feel- are they different from these different scenarios, or are they similar?
Felix: That’s another great question. Unfortunately, there’s no way clinically to know which syndrome the patient will fit into, and a lot of times this diagnosis of either clinically isolated syndrome, relapsing-remitting, or primary progressive disease, is made retrospectively – looking at the patient and looking back on the history. The symptoms can be very much the same. For example, somebody may develop visual loss in one eye, or what we call optic neuritis. That can be a single episode, never recur again, with complete improvement, it can be a single episode with some impairment, and then the patient develops other symptoms, typically involving other parts of the brain and the spinal cord. Or, that can develop into other forms of MS and MS-like conditions that are progressive.
Falk: There is this concept in MS that the disease is separated in time – different events over time and in space, different parts of the body. Is that helpful in figuring out if somebody early on in the course of disease has MS?
Felix: That is in fact how we define MS. So MS has always been defined by episodes of neurological dysfunction that involve different parts of the central nervous system. Then patients have to have more than one episode. So a single episode does not equal MS. However, with the advent of MRI or magnetic resonance imaging, we now have the ability to look at patients’ brains and spinal cords and assess whether they may have had a previous event that perhaps they didn’t even realize they had. So MRI helps us find the dissemination or the separate episodes over time. Somebody presenting with a new set of symptoms, for example optic neuritis, who on MRI has evidence that they’ve had prior events in their brain, the diagnosis can then be made.
Concerns that new patients might have
Falk: Patients who have newly-diagnosed disease are concerned of course about all the nasty sorts of things that can occur – if you go on the web, you immediately jump to the progressive forms. You don’t have as much discussion about less concerning diagnosis. What questions do patients have for you? What are their early and most worrisome concerns?
Felix: Most patients are concerned that they won’t be able to work anymore, that they won’t be able to walk anymore, that they may be blind or completely disabled. And for that reason, the diagnosis is very challenging. As we already mentioned, very few patients proceed to have that kind of devastation in the short term—while it is true that patients with relapsing-remitting MS, if they have recurrent episodes, may not recover completely from each episode. Over time, each time they have an episode of dysfunction, be it that they lost vision or perhaps they had some difficulty with walking, or some numbness or weakness, over time, if they don’t recover completely they may have cumulative dysfunction that impairs their ability to function. So patients fear that perhaps more than anything at all.
Falk: Is that concern something that makes it so patients don’t want to see a neurologist? In other words, don’t want to be seen early? There are wonderful new drugs that help patients with MS. What are the blocks or the barriers for patients wanting to be seen by neurologists?
Felix: As a neurologist I find that most patients I meet are eager to meet with me at that point in time. However, the journey towards a neurologist sometimes takes various forms. In addition to that, there are many people who have symptoms similar to the symptoms that one sees in MS, like numbness, like fatigue, who don’t have MS.
So neurologists spend a lot of time trying to tease out which of these patients truly have MS, as opposed to which of the patients believe they may have MS when in fact there’s no evidence that they have it. The barriers to seeking neurological care currently include some difficulty in the number of neurologists available to see patients quickly, and then the number of patients who have symptoms that may not be MS that take up a lot of time and a lot of assessment.
Falk: So what you’re suggesting is, is that somebody who’s worried about a neurological process, “I have numbness. I have tingling. I can’t feel my toe as well as I used to,” may have and probably has a completely different entity than multiple sclerosis. It’s really again this process of having multiple episodes with different parts of the body that should clue a patient in who hasn’t been seen, that perhaps they need neurologic attention.
Felix: Correct, and simple disorders like carpal tunnel syndrome which may cause your hands to go numb can be distinguished from multiple sclerosis that can also make your hands go numb, typically by a neurologist.
Getting an MRI
Falk: The magnetic resonance image or MRI, has been instrumental in helping neurology figure out whether someone has prior white spots or abnormalities in the central nervous system. Are there problems or dangers with MRI’s?
Felix: MRI has been a very safe procedure for most patients. There are some barriers to getting an MRI. For example, patients who have metallic implants cannot go in an MRI machine. And CAT scans, which are the other alternative we have to MRI are just not as good at detecting these white matter spots.
In addition to that, MRI as an experience is very claustrophobic. It’s very common for patients, even those who’ve never known themselves to be claustrophobic, to truly struggle in the machine. The test can take up to an hour, it makes loud noises, and can make people feel dizzy and just very uncomfortable. Sometimes we need to use sedation to help patients relax for the procedure. It’s absolutely crucial during an MRI of the brain in particular and the spinal cord, that patients lie absolutely still. So you can imagine that lying absolutely still for an hour when you’re terrified and feeling uncomfortable is not easy.
Falk: Yes, so sedation or an anxiety drug is really very, very useful, and perhaps listening to some music that you really enjoy is helpful as well. It’s a difficult experience for some, and others sleep right through it and have no problems at all.
Treatment of multiple sclerosis
Fortunately, there are wonderful new drugs in the treatment of multiple sclerosis. Tell us about the treatment options.
Felix: The treatment options have truly expanded. Up until 1993, we had steroids, and we still use steroids. So we sort of separate treatment of MS into “How do we treat the patient who comes in with brand new symptoms?” – we still use steroids. But in 1993 a new group of drugs called interferons became available for patients. Those were available until 2010, so between 1993 and 2010 we were essentially stuck with these injectable forms of medication that make people feel like they have a flu-like illness and pretty uncomfortable. But they’re still truly the mainstay of the drugs that we use in MS, along with another injectable form called glatiramer acetate, which is not an interferon, but falls in that category of the basic drugs we use. Then in 2010 the first pill became available to treat MS called fingolimod, and since then we’ve had a bit of an explosion of available opportunities for treatment, both with pills but also with injectables. This includes injections patients can give themselves, as well as injections that we give in the clinic called infusions, and patients typically will receive that at different points in time, depending on which medication they’re receiving.
Falk: In general, though, those drugs are aimed at altering component parts of the immune system. As an advantage of over an era where prednisone or other steroids, as you mentioned, broadly are anti-inflammatory drugs that inhibit multiple component parts of the immune system and have a much higher risk of side effects.
Felix: That’s right, and so we typically do not use steroids long-term. They’re truly just used for the acute episodes. It’s not clear that they help patients over the long term, but they do seem to help patients recover faster from their episode, so we still use those. They typically are infusions that we administer for three to five days. Then the patient continues with the medication that they take on a regular basis.
The side effects of the medications, and the newer medications in particular that we have, have also presented challenges. So none of these medications are without their challenges, but it does allow us a greater armamentarium of medications to offer patients, depending on whether they’re mostly concerned about safety, whether they’re mostly concerned about convenience, or mostly concerned about efficacy of the treatment, and each patient’s treatment is somewhat adjusted to their individual needs.
Falk: So the patient is in the driver’s seat, to a certain extent, in helping figure out what kind of medication works best for them in intervals that seem to keep them in remission.
Felix: You’re right, and this is one of the conditions where patient-centeredness is crucial to treating patients. The doctor and the patient, and the team and the patient, become a unit that together move forward to prevent the patient from having disability over time. One of the objectives of meeting with a patient is turning the patient into an expert on their disease and the treatments that are available to them, so that they can be empowered to make decisions that are appropriate for themselves.
Falk: The business of empowering patients to help in the treatment approach, and even what kind of treatment, is critically important, because if a drug is not working well, it really is incumbent upon the patient to say, “Hey, wait a minute, doc, you have me on this drug, it’s supposed to help and it’s not helping me. As a matter of fact, it’s making me feel ill. Help.” What’s the next step?
Felix: That’s a great question, so patients do have to be empowered, but in addition, neurologists have to see these patients on a fairly regular basis. One way that patients know the treatment isn’t working is that they just feel bad, or they have ongoing episodes of neurological dysfunction. Another way is that we typically will repeat the MRI once a year, at least early on in the treatment, because as we talked about earlier, you may have abnormalities on an MRI with no symptoms whatsoever.
If the patient is not getting the benefit of the treatment, then we have to explore these other options. For example, if they’re taking interferon—which is very convenient, they take it once a week, they’ve managed their side effects very well and can function beautifully, and they have more disease, that could be because the drug’s not working or they’ve developed antibodies. Then we talk about oral agents or some of the other infusion available drugs. There are novel therapies that are coming up, even as we speak, that are being evaluated by the FDA. So I anticipate that in the coming years, we’ll have even more options.
Falk: As in other autoimmune diseases, the concept that a drug that may have been working for a while, stopping working, is not unexpected. Is that right?
Felix: That’s exactly right, and we don’t always know why. With the interferons, there are antibodies that we can sometimes measure that tell us that the patient has essentially become immune to that treatment, and other options have to be looked at. The beauty of the treatment for MS and having all these different options, is that each treatment attacks the immune system dysfunction at a different level, so as more drugs have become available for other immune diseases, we have also borrowed them sometimes, particularly for patients with very severe forms of MS where the drugs we have available don’t work. We do reserve those drugs for very severe cases, but the good news is we have a much larger toolbox than we’ve ever had before.
Falk: Lots of vines in the therapeutic jungle. Can one start using the word “cure”of multiple sclerosis, or are you really aiming for “remission on therapy”?
Felix: That’s a great question – we do not have a cure. We are looking at remission, and remission defined as the patient not having any more symptoms, or new exacerbations as we call them. In addition to no MRI evidence for progression of disease, and those are equally important, because patients may not have symptoms and yet the MRI may show that there are areas of having ongoing demyelination, or active disease.
Falk: If the MRI shows stability, if the patient feels well, do you stop therapy?
Felix: Currently we don’t stop therapy. That’s probably the hardest thing for patients. So a young woman who’s been on injectables that they’ve been taking every day for years, who feels great, and never have another episode, they’re five years in and have young children, the fact that they have to continue taking the medicine every day as an injection is very challenging. That has been addressed by modifying the types of injectables we have, making them able to be around longer, so you can give yourself the injection fewer times, but it still presents a big challenge. I will add that an oral agent is no different—the fact that you have to take a pill every day when you feel no worse is very hard to continue.
Falk: There are risks associated with all of these medicines, so it’s a risk-benefit ratio. How do you talk to patients and say- “The benefit of staying on a drug, even though you feel great, you’re doing well, is worth the risk”-?
Felix: That is really truly one of the ways that we have to develop relationships with patients, where we have to have an ongoing conversation and the patient has to become an expert in understanding their disease. MS over time, if untreated, or if patients have another relapse, may have devastating consequences. The brain and the central nervous system—the term that we use to describe that is, it’s all about terrain, it’s like real estate. So if you have a very small abnormality, and a very crucial part of your brain or central nervous system, spinal cord, you may be completely devastated. The idea that even one episode can leave you with significant disability is the conversation we have that balances out the risks of the medication.
Current research and difficult questions to answer
Falk: An area of research that’s occurring in other kinds of autoimmune diseases are biomarkers for relapse, and even biomarkers for remission. If you had a biomarker for remission, I know I’m in remission because a biomarker really proves that it is, that would permit this stopping of medication. Those biomarkers in MS – where is the research at this time?
Felix: That research is ongoing. It’s not been as exciting as we’d hoped – the results have not been as great as we’d like, but it’s coming. I will add that as we’ve learned so much more about other autoimmune diseases, that has impacted the research in MS. So we have a greater toolkit, again, in the research arena to help us understand both what causes MS, because we don’t quite know what triggers that initial episode. But also how we might impact as such because we have a marker to tell us whether the patient will either have another relapse or not, or whether they will be the kind of patient who will develop progressive disease or not.
Falk: Patients always ask me the following three questions: What caused my disease? What will make it go away? and What will prevent it from coming back? How do you answer those questions for somebody with MS?
Felix: That is very difficult for most neurological diseases, because the truth is, we don’t know the answer to all of those. What I typically tell patients is that they didn’t do it to themselves—there was nothing that they did, their family did, and nothing they could have done to prevent it. And try to share as much information as I can with them so that they understand that, and understand that we walk the journey with the patient. When we cannot cure, we can still be at their side. We believe when they call us and tell us they’re feeling worse, we change treatment accordingly, we offer the most cutting-edge options that the patient has access to, and we are an advocate for the patient. That is a little different to the original goals which would ideally be, never make it come back again.
Falk: The concept that patients didn’t cause the disease themselves, and that you don’t know what makes the disease come and go, is a really critical message. If you did know what caused the disease to relapse and remit, then modern medicine would have figured out a medicine or a tool to prevent relapses and remission. If we could answer those critical questions, we’d have solved a lot of these diseases.
The other important point that you’ve made is the patients do best if the patient and the physician share the same degree of neurosis—that there really is a need for an interaction on a regular basis for patient and their provider, and rely on constant communication.
Felix: That’s right, it’s truly a long-term relationship between the physician—typically a neurologist—and the patient. It’s probably one of the more rewarding components of being a neurologist, because you get to know patients so well, and you know when they’re not feeling good.
There are things, however, that will empower patients to feel better, and that are known to make patients feel worse. Those include stress, for example, exercise, tobacco use—those are not unique to MS, but if the patient is struggling with habits that may be causing them harm, we have opportunities to at least help them overcome those, if they choose to. So they’re just as important as if we’re talking about heart disease.
Falk: Where would you suggest patients turn on the web for trusted and real information about their disease?
Felix: The National MS Society has a wonderful web site and has been an extremely important partner in collectively being an advocate for patients and what they need, and communicating all research updates in a very effective way both with patients and physicians. The National MS Society is an excellent web site that has information for patients about current treatments, alternative and complementary treatments, where to find an MS expert in their region, and if they’re relocating how to find a new neurologist. All of those can be found with just a click on their web site.
Falk: Thank you, Dr. Felix, and thanks to our listeners for tuning in. If you enjoy this series, you can subscribe to the Chair’s Corner on iTunes or like us on FaceBook so you’ll know when we post our next episode. Thanks so much for listening.
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