Patricia K. Coyle, MD, outlines the signs and symptoms of multiple sclerosis, the diagnostic work-up, and the importance of getting an accurate diagnosis.

: Hello and thank you for joining this NeurologyLive® Cure Connections® program entitled “The Multiple Sclerosis Patient Journey.” MS, or multiple sclerosis, is a disease of the central nervous system that affects close to 1 million people in the United States, a number that’s changed just recently, and over 2 million worldwide. While MS is diagnosed most frequently in young to middle aged adults, it can be diagnosed at any age. Symptoms of MS fluctuate and vary from person to person, and it can happen throughout the course of the disease. When I first started working in MS, it was considered untreatable, but today in the 21st century, there are new and numerous approved therapies that can modify the disease course. The MS journey has become one of successful milestones versus one, many years ago, where there was very little hope.

I’m joined tonight by a full cadre of experts in MS. I am your host, June Halper. I’m a certified nurse practitioner and I’ve been specializing in MS since the late 1970s. Today I’m the CEO of the Consortium of MS Centers, an organization that has set a unique model of MS care, comprehensive care. I’m joined today by a full team of people working with me to provide you with education and support:

Dr. Patricia K. Coyle, professor and vice chair of clinical affairs and director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York. That’s pretty long, Dr. Coyle, a big, long title;

Fred Foley. Dr. Frederick Foley and I have worked together for many years, as I have with Dr. Coyle. We have a long history. Dr. Foley is a clinical psychologist practicing at The MS Center at Holy Name Health in Teaneck, New Jersey;

And finally and most importantly, my friend and colleague, Ann Moore, who is going to share the details of her journey with MS, and I’ve known Ann a very long time, and her partner, Kathy Zelles.

We have a journey to get started on, so let’s go. Dr. Coyle, let’s talk about the diagnosis of MS. I remember when we first started in MS, it was a very long and drawn out process, and today things have changed. How is MS diagnosed today in the modern era, and how does it impact patients and families?

: MS is the major acquired disease causing disability in the central nervous system, short of trauma. It’s an increasing disease among women. Close to a million Americans are affected with MS. There is no single diagnostic test. There are formal criteria, they’re called the 2017 Revised McDonald Criteria, which I think everybody should be following. We need to suspect it. The major phenotype form of MS is relapsing MS. That will begin with a fairly acute neurological attack. That’s how 85% to 90% of MS cases begin. The more unusual form is slow worsening or progression from onset, that’s primary progressive MS. I think you start with a suspicion, and I would argue for a very complete work-up.

At Stony Brook, we would do selected blood work. We would take an MRI [magnetic resonance imaging] of their brain and their cervical and thoracic cord down to the conus, the entire central nervous system. We routinely look at cerebral spinal fluid. We’re looking particularly for oligoclonal bands. We want to have an accurate diagnosis because that’s critical for counseling, for following patients, and for getting patients accurately on early treatment. We recognize there is a misdiagnosis rate of MS of 5% to 10%. We do not want to make a mistake.

: What signs and symptoms would you look for? Or what should a person with MS who thinks they might have the disease look for, or is there a wide range and you can’t pin one or two down?

: Well, first of all, relapsing MS typically presents as a clinically isolated syndrome, CIS. That’s a very clear objective neurological syndrome that reflects inflammation and damage to myelin. For example, an optic neuritis, acute inflammation of the optic nerve with loss of vision in one eye, typically with pain, or a transverse myelitis where the focal inflammatory lesion is affecting the spinal cord. And the person may develop numbness from the waist down or even difficulty with walking with numbness on the legs. You can have a brain stem syndrome with acute double vision and limitation in eye movements, or in a young individual, trigeminal neuralgia, tic douloureux, shooting pain the face. There are objective neurologic disturbances that a patient with typical relapsing MS will begin with. 

: Some people will say, “Well, my MRI [magnetic resonance imaging] was positive, and I was diagnosed.” It’s a complicated process to get diagnosed with MS, and from what I’m hearing, MRI alone is not the diagnosis. What you’re saying is there’s a wide range of things that an expert needs to look for.

: Everything begins with a correct diagnosis. It’s critical that someone go to an individual who’s knowledgeable about MS, and has a thorough work-up, in my opinion. That’s very important.

: What is the average age of the diagnosis? Then what’s the range? What’s your youngest?

: Ninety percent of individuals will present between the ages of 15 and 50. This is a young person’s disease, typically late 20s. Pediatric MS onset before age 18 is only about 2% to 4%, 3% to 5%. Most of them are adolescents. It’s very rare to have onset under age 11, that would be less than 1%. Only 10% of MS will begin after age 50. Less than 1% will present after age 60. So it’s really in this 15-to-50 age range that you see most people presenting, a relatively young person’s disease.

: What’s the idea? I know you have an MS center out in Stony Brook. What’s the ideal model of care when somebody has MS with such wide-ranging symptoms and fluctuations?

: I think it really helps if the health care providers be extremely knowledgeable about MS. As is true for neurology in general, there’s increasing data, information, knowledge all the time. If you really don’t focus on it, see a lot of patients, have a particular interest, do reading about it, it’s very hard to keep up on the latest treatments, the latest information, etc. To go to somebody that’s expert, in particular I believe to be in an MS center where you can call on other experts fairly readily. They may not be there that day, but you can refer somebody to a neuro-ophthalmologist that you trust, a urologist that you trust, somebody who is familiar. You have the supporting staff, the nursing staff, the social worker, etc. That’s very helpful.

: I want to thank you all for watching and joining us at this NeurologyLive® Cure Connections®. If you enjoyed this program, please subscribe to the e-newsletter to receive upcoming information about other programs. I’d like to thank you all for the time and for this wonderful opportunity, and hope to see you all again.

Diagnosis of Multiple Sclerosis

Ann Moore, a patient with multiple sclerosis, shares the story of her diagnosis. Kathy Zelles adds her perspective as a care partner.

: I know your journey started a long time ago with MS [multiple sclerosis], Ann, when your mom was alive. I remember I got to meet her, but she was much more advanced in her disease, and she was much older. Were you diagnosed during her lifetime or was it after?

: No, I was diagnosed eight months after she had passed away. I was diagnosed in June of 1989, so needless to say I was a little freaked out because I saw how progressed my mother was and how limited she was in what she could do. I didn’t know at 15, which is the age that I was; I was told the day my father died that she had MS. She had had it for eight years, but she never told me because I was the youngest of the three. My father and my two siblings knew, but I was not told any of this. I saw things, I didn’t know what was going on. I saw things and then I’m diagnosed, and I said, “Oh my goodness, I’m going to end up just like my mother,” and that scared me.

: Did you go to a primary care physician or your regular doctor first?

: I did go to my primary care physician because, I was sitting one day getting my hair permed on a Saturday, and I had my hands crossed. I came home, and I told Kathy I had tingling in my middle finger, my ring finger, and my index finger on my left hand. Being the occupational therapist that she is, she said, “Oh, it must be carpal tunnel” syndrome. I said, “Yes, that sounds reasonable.” Well, as the weeks went on, it progressed, and I’m left hand dominant. It got to the point where the tingling went to numbness, and it worked its way up my arm, and by midafternoon, I felt like I had a tourniquet on me between my elbow and my shoulder, and I was unable to even hold a pen.

I went to my primary care physician, and because a few weeks before I had a sinus infection and bronchitis, I was thinking maybe there’s a swollen lymph node under my armpit. He sent me to a neurologist. I went to a neurologist, I told him my family history, but he was not looking for multiple sclerosis. I forget even what he was looking for. He sent me for an MRI [magnetic resonance imaging], and then called me in my office, and I figured, oh, anybody worth their weight in gold will have me come in to the office and discuss the MRI with me. No. On the rainiest day possible, he called me and said to me, “Miss Moore, I think you have multiple sclerosis, and I’d like you to come in for a lumbar puncture.” I said, “Oh, no, no, no, I’m not having that done. My mother had it done and said it was the worst pain she’s ever experienced.” And he said with this arrogant sneer and laugh, “But I didn’t do your mother’s lumbar puncture.” I said, “You know what, you’re not doing mine either,” and I hung up the phone. That’s when I called you, June, and you said, “Annie, Annie, I’m going to clear the doctor’s schedule, and you’re going to come over tomorrow, and we’re going to take care of this.” And that’s what happened.

: I wish you hadn’t joined the club, but let me tell you it’s been….

: Yeah, right? If I’ve got to be in a club with anybody, you’re a good person to be in a club with.

: Thank you. Kathy, how has this all impacted you and your relationship? I know you’re a professional, you’re an OT [occupational therapist] and probably have a lot of suggestions to make in the management of Ann’s disease.

: That’s what happened. I jump from my professional self to my personal self. We’re both pretty easy going, for the most part. We kind of roll with the punches, so we’ve been lucky in that sense. We haven’t had a lot of crises related to the MS. It’s like a wax and wane. For the most part, we’ve gone on with our lives the best that we could and used a walker here and a wheelchair there for when things get tough. When it’s not, we go on like it’s any other day.

: How’s the journey been on you personally, especially because you’re a rehab professional? It must be frustrating sometimes.

: You know what it was like initially. Who was the patient? Was I the patient, or was she the patient? 

: Because my only reference at that point, I was a brand-new therapist, and the only people I had seen were in the hospital, were very debilitated and that’s all I could see. But the more we explored, once I got over the initial shock of, “Holy moly, I have to change the bathroom, and we’re going to have to open the doors,” the rehab head in me, we settled down and we managed. Since the beginning, once I got over the first shock, I think we’ve been OK. We’re lucky.

: There were bumps in the road, but that’s where Dr. Foley comes in.

: Your journey has been interesting, that’s for sure.

: It really has been because eight months after my mother died, I was diagnosed. I’m thinking, “Oh my God.” Everybody I knew as a young adult in Glen Rock, New Jersey, who had MS, their spouse left them. I said, “Oh my God, Kathy is going to leave me, and I’m going to end up in a wheelchair,” and so I had a pretty hard time for a while in getting through that stage.

Patient’s Journey: Diagnosis of Multiple Sclerosis

Frederick Foley, Ph.D., describes the psychological challenges that patients with multiple sclerosis face.

: Dr. Foley, we’ve been working together for a long time, and when I first met you at the Albert Einstein College of Medicine MS Center, things were quite different. We didn’t have medications. We certainly didn’t have a center in New Jersey. Today the world of MS [multiple sclerosis] has changed and people’s journey has changed, but the psychological impact of MS probably has not. Is that your impression, or have things changed?

: Well, the psychological challenges that patients with MS and their family members face are still the same as they were in the 1970s. There are some better treatments now, which is encouraging, but right from the beginning, adjusting to the diagnosis, adjusting to exacerbations, induces tremendous anxiety in many patients. Patients wonder, “Am I going to get better? What’s going to happen to me?” One of my patients described it as, “Living with the uncertainty of MS is like living with the sword of Damocles dangled over my head by that thin hair that can break at any time.”

Patients need to adjust to these huge changes that MS brings into their lives. Clinically significant depression is very common in MS, so the average person with MS has a 50% to 60% chance of experiencing a severe depression that we call a major depressive episode. In MS, for some reason, there is more depression than in any other central nervous system disease. Likewise, clinically significant anxiety occurs in 60% to 70% of people with MS. These are real problems that, fortunately, we’re getting better at treating. 

Another major psychological symptom with MS is cognitive changes. Cognitive changes occur in 50% to 70% of people with MS, and adjusting and coping with these represents a major challenge to the person with MS and their family members. The cognitive changes that occur frequently aren’t readily observable, since language is frequently preserved. Someone could have very good verbal fluency, but be quite deficient in certain areas of cognition. All of these symptoms represent challenges that are ongoing to the person with MS and their caregivers and family members.

: What modes of therapy do you find helpful in the normal world? We’ll talk about COVID-19 [coronavirus disease 2019] in a few minutes, but do you find group therapy, self-help groups or one-to-one, or does all of the above count?

: All of the above count. Patients frequently become more isolated with MS and lose friendships, and their social circles narrow. We’re social creatures by nature. We need to have social networks, and so reaching out is important to get the support that the person with MS needs. Fortunately, there are better treatments for depression. Antidepressant therapies have been found efficacious, but we find clinically that we really have to push the doses up to the maximum frequently before we’re going to get efficacy in our patients with MS.

Likewise, a type of psychotherapy called cognitive behavioral psychotherapy has been found to significantly improve clinical depression and clinical anxiety in MS. It has been successfully applied now to certain MS symptoms, such as managing fatigue, managing insomnia, and also reducing the distress associated with chronic pain that occurs in MS. These are all relatively new treatments. We’re grateful that we’re continuing to work to find new ones.

: Do you find that comprehensive care, because I remember we used to do a lot of team meetings like every other week, but do you find the team, somebody like Kathy, for example, who’s an OT [occupational therapist], do you find that members of the team help you and enhance your work? And how do you handle that in terms of keeping everybody informed and up to date, including the patient and family?

: I’ve been grateful to be able to work in a comprehensive care center where we educate each other about things that we may not be aware of. For example, the physical therapist has taught me a great deal about physical therapy protocols and physical therapy for fatigue management. The OT has taught me a great deal about adaptations that the patient can utilize to improve their quality of life and their functioning. Of course, the neurologist has taught me a great deal about how to diagnose and treat MS with disease-modifying therapies and symptomatic medicines. And the nurses, the nurses are stalwart.

: I’m glad you said that, Fred, absolutely.

: They have the most contact with patients, so they are absolutely key to having decent comprehensive care. We all learn from each other, and it enhances patient care when we all know what the issues are. 

Psychological Impact of Multiple Sclerosis

Patient and neurologist perspectives on managing the psychological challenges with multiple sclerosis.

: Ann and Kathy, I know you’ve had your personal journey, and I know one of the reasons we’re all together tonight is that you’ve had a professional relationship with Dr. Foley. How has the type of therapy he spoke about just now helped the two of you manage to get over the, as you mentioned, bumps in the road?

: The cognitive behavioral therapy that Dr. Foley does with me has helped me very much. As a matter of fact, I’m utilizing his services right now. We’re doing it virtually on FaceTime. But I’ve got to tell you, every time that I think I’m starting to tank, or things aren’t going well, or I may be frustrating or scaring Kathy, that’s when I go call Fred Foley. And he has made many suggestions. He’s helped me work with my breathing. He’s made tremendous suggestions in how to help me, because I’m one who can beat myself up better than anybody in this world, and I can be an all or nothing person. Dr. Foley has helped me to try and find the middle of the road, the gray area, and he’s very good at that.

: Dr. Coyle, I know you have a comprehensive care center. How do you integrate the more psychological aspect of managing MS [multiple sclerosis] into your work?

: There are three things that I would mention. Number 1 is have a go-to psychiatrist, at least one, possibly two psychiatrists who have an interest in MS who you can refer to or discuss patients with, who have a vested interest in MS. They can be very valuable for teaching for seminars, etc., or for starting patient groups. Secondly, a social worker. There is so much pressure that can be put on an MS individual if they’re having problems with their job, or with their insurance, or with funding, etc. A social worker can be key, who’s knowledgeable, and also knowledgeable about MS. To have identified someone, that is very helpful and we do have someone like that.

Thirdly, our doctoral-level neuropsychologists are a core part of our MS team. We turn to them for cognitive function testing. But a full cognitive function testing also takes into account other symptoms— depression, anxiety. They can make very knowledgeable recommendations about sites and referrals, etc. We find that extraordinarily helpful. At all three of those levels, we have integrated people who have a particular interest in MS to enhance the comprehensive care. 

: Yes, I do agree. Having neuropsychology is essential for many reasons. Cognitive issues and problems are hard to detect, and if they go undetected, people lose their jobs, it has severe consequences for their lives. We can advise them if they’re having cognitive changes to receive rehabilitation for that, to consult employment attorneys, and to negotiate to get reasonable accommodations at work, and also to educate families and partners that there are these cognitive changes that are very real. The person is not doing this on purpose, the changes are a result of the cognitive changes, and it requires an adjustment on everyone’s part.

: We’re so lucky that in our area that we have you, and Dr. Coyle, and the team. But I’m just thinking of course, today in the era of COVID-19 [coronavirus disease 2019], and what we’ve been all dealing with and also people who live in areas that are rural with an MS center maybe hundreds of miles away. Again, that’s tough. We’re very lucky, we’re very lucky to have you and your team. I guess one of my dream things would be some day to be able to have a comprehensive care center in every state, so people would have a resource. I’ll say it over and over again, we’re lucky to have you guys. It’s amazing to have worked with you and to see the work with positive results you both have achieved in your models of care.

I want to thank you all for watching and joining us at this NeurologyLive® Cure Connections®. If you enjoyed this program, please subscribe to the e-newsletter to receive upcoming information about other programs. I’d like to thank you all for the time and for this wonderful opportunity, and hope to see you all again.

Managing Psychological Symptoms of Multiple Sclerosis

An expert neurologist frames the conversation she has with patients who are newly diagnosed with multiple sclerosis about therapy options.

: Dr. Coyle, what is your conversation with a newly diagnosed person? How do you approach that subject, or do you bring other people in to discuss it? I know that you have such a large practice in such a large center. Do you have different strategies or is there a general strategy on disclosing? Not over the phone, I assume.

: No, no. I am a big proponent of treatment and treating early. I am personally engaged in that because, quite frankly, I don’t think anybody can talk to it better than I can. I don’t like to delegate it at all. The conversation is a little bit different for relapsing MS [multiple sclerosis] where we have multiple options versus primary progressive MS where we only have one disease-modifying therapy. If you really think about it, we have 25 distinct medications. I’m counting generics at the current time. That’s unbelievable. You can’t possibly cover that.

I’ve put them into groups or buckets. I talk about the needle injectables, the interferon betas and glatiramer acetate, the nine oral drugs, and the high efficacy monoclonal agents, which are largely intravenous, and one subcutaneous. I will introduce those three groups and I will talk about the pros and cons of each of those groups, and then shared decision making with the individual. We’re going to talk about what are the most important things for them and come up with a recommendation. We’re going to focus on one of those groups and then I will begin to go into details with regard to the individual medications.

I discuss current concepts on efficacy because the efficacy is not the same with our disease-modifying therapy. I also discuss whether this has been flagged as a medication that needs to have special monitoring. Is it immunosuppressive? Are we purely talking about an immunomodulatory drug? We have a discussion about what will need to be monitored and followed because in shared decision making, you need buy in of the individual. They’re the ones that ultimately are taking the medication. And I will make recommendations absolutely because that’s what an expert is supposed to do.

: But we are making a joint decision. I think knowledge is power, knowledge is power, and I am very strong on recommending treatment as early as possible.

: We met earlier today, and we were talking. I was shocked to see one of our throwaway magazines that’s not a medical magazine has advertisements for MS drugs. There’s one of the drugs is actually advertised on TV. How do you overcome something like that where somebody walks in and says, “I saw this in a magazine. It sounds perfect for me. Can I please start this?” 

: Personally, I find it a little bit disconcerting to see advertisements for MS disease-modifying therapies, but that is life. As the expert, I want the patient, there needs to be full flow of communication. They’re going to ask me questions and I’m going to give them my very honest opinion and take on it. I try to be as informed as possible, so I’m never locked into an opinion. I draw an opinion based on the best data, and if new data comes in, then my opinion may change somewhat. But I’ll certainly be very candid when the patients bring up specific agents that they may be interested in.

: I want to thank you all for watching and joining us at this NeurologyLive® Cure Connections®. If you enjoyed this program, please subscribe to the e-newsletter to receive upcoming information about other programs. I’d like to thank you all for the time and I thank you all for this wonderful opportunity and hope to see you all again.

Treatment Options Available for Multiple Sclerosis

A patient shares the treatments she has received for multiple sclerosis.

: Ann, when you first started your journey with MS [multiple sclerosis], were you put on a disease-modifying therapy? I think you mentioned 1989 and we know that was one of the early years before therapy started. I think it was 92, right, Dr. Coyle?

: I was diagnosed in 1989 and I conferred with you and Dr. Geiser, and it was determined that I have MS. But, at that point, they had no therapies out. I have to be honest, I thought for the first 10 years they made an incorrect diagnosis. I was fine. I had nothing wrong with me. No numbness, no tingling, no weakness, no anything. And then 10 years later I’m like, “Oh, something’s not right here.” I was having a, unbeknownst to me, a thoracic exacerbation. I called over to the MS Center, at that point Dr. Cohn was there, went over to see you folks, and you said, “Annie, here are the therapies that are out. I know you; I would suggest that this is the one you go on, but I suggest that you also do some research on your own and see if you concur with me.” I was very happy at your suggestion and for 15 years I was on Copaxone and I thought it was a magnificent drug. I still think it’s a good drug. Just after 15 years it ran its course and I had to switch therapies.

: I know Copaxone had minimal side effects, but the injection every day, how’d you handle that? 

: I went on, when you had the powder and you had to mix it with the solution and rub it between your hands.

: No auto injects or anything like that. Kathy had to do four of the injections because I couldn’t reach them. You know what, needles don’t bother me, so I did not have a problem in doing that. I mean, I do have divots in all seven locations right now and will for the rest of my life, but it’s OK.

: Well, Kathy didn’t seem to mind. Right, Kathy?

: I am on Rituxan. I had been on Rituxan now for a couple years, so, as a matter of fact, I go, I believe it’s in February, that I go for a Rituxan infusion. Yeah, Dr. Williams, the doctor that I go to right now at the International MS Center is very good because he can juggle. As he said, “Ann, I have a lot of cocktails.” I mean, over the years, yeah, I was on, but even before I went on Copaxone, I did IVIG for 10 months. I’ve done Tysabri a couple times. But for the last three or four years it’s been methotrexate injections and Rituxan.

: Dr. Coyle, any comments about Ann’s therapy?

: Well, rituximab [Rituxan] is a chimeric anti-CD20 monoclonal antibody therapy. It is not approved by the Food and Drug Administration (FDA) for MS but clearly has significant off-label use in Sweden. Kaiser Permanente, I understand it’s their go-to MS drug. It’s much cheaper. We have two FDA approved anti-CD20s, in humanized and human for MS, but rituximab is much cheaper. I think it’s a very reasonable alternative, high-efficacy agent, even though it’s never going to be approved for MS.

: Well, it seems like your journey with MS and medications, Ann, has been an interesting one and it seems that.

: Yeah. I am my mother’s daughter. My mother had this, we would have put it on her headstone if we could have, “Can do.” I can do it and that’s how I feel.

: Right, Dr. Coyle, Dr. Foley, right? The New Yorkers …

Patient’s Journey of Therapies for Multiple Sclerosis

Ann Moore shares the quality of life issue of cognitive changes in multiple sclerosis and strategies she uses to manage.

: Speaking of New York and issues unrelated to MS [multiple sclerosis] but certainly related both directly and indirectly, there’s an issue of quality of life. MS, Dr. Foley said it, it’s this sort of Damocles. Some people talk about it as if it’s in the Charlie Brown cartoons with the cloud over your head walking around. It’s something that’s there the rest of your life. What is the most significant quality of life issues that the two of you have faced? And Kathy, speak up. This is your partnership as well as Ann’s. How do you manage them other than getting a word in edgewise from Ann?

: Right? I think for me it’s being flexible and sometimes knowing when to take a step back. Like if I know I’m frustrated or upset, like I’ll come home and I’m like, “Why did you do that? You should have done this.” And then I step back and go, “Well, I didn’t leave her a list, so she didn’t really process.” The cognitive things are actually the hardest thing because you can’t see it, and anybody that knows her doesn’t really notice but I notice. 

: I chase my tail most days, especially now with this flare-up that I’m having. If I don’t write it down and write it down in the order in which I should do it, based upon the time in which I get up when I have the most energy, the plan goes out the window.

: Dr. Foley, I see you nodding your head. Any comment?

: But Ann is talking about a very good strategy to use to help compensate for cognitive changes. We teach people to become more organized. We teach people how to use lists and calendars in ways that are effective. There are also some techniques now for improving verbal learning and memory in MS which we can help patients with. Ann, you’re on board with a good technique there.

Quality of Life Issues:  Cognitive Changes with MS

Many patients describe multiple sclerosis fatigue as their number one symptom. Different types of fatigue are discussed.

: I’m thinking about the impact of fatigue. I know that one of the most prominent features of MS [multiple sclerosis], even early on before someone receives a diagnosis, is fatigue. Dr. Coyle, you find that the diagnosis of MS is sometimes stymied by the fatigue that people can’t figure out where it’s coming from and how it can impact the rest of the body, including cognition?

: It’s very interesting. We now recognize that there’s a prodrome to MS that may take five to 10 years before neurological onset of the disease where there are health care issues not necessarily neurologic at all that are occurring. And there are studies that indicate fatigue, very significant fatigue leading to diagnoses of chronic fatigue, etcetera, may be part of the prodrome in the few years before somebody declares themselves as having MS. I think we recognize fatigue as often the number one symptom of MS, often rated as the worst symptom, reported ultimately in as high as 80% to 90% of individuals with MS. And there are different types of fatigue. There’s primary MS fatigue, and there are secondary types of fatigue. But the interesting thing is that the fatigue is not necessarily associated with obvious visible disability. It’s an invisible symptom, and you can have somebody that looks great and has normal strength and coordination, and yet they may not be able to work because of their profound primary MS fatigue. It is a very significant symptom that can have tremendous impacts on activities of daily living if it interferes with both physical activities and cognitive activities.

: But how do you measure it though? Is there only patient self-reported? Is there a scale? Is there an exam you could do?

: Well, there is no biomarker. It is based on patient-reported outcomes or PROs. There are a number of validated scales that one can use to rate the degree of fatigue. You are depending on the patient reporting it. We don’t have any blood tests that we can do to measure it at this point in time.

: Are there specific disease-modifying therapies that you would avoid because of the side effect or is it just across the board that it doesn’t really matter your decision is going to be on the MS?

: The only class of agents I might be concerned about would be the interferon betas. As a cytokine, sometimes you can see associations with fatigue with various cytokines. But we do not identify DMTs [disease modifying therapies] especially with causing worsening fatigue as a very, very common issue. Generally, that’s not a major factor and the primary MS fatigue we don’t understand. It’s related to various biological issues. It may connect to circuits, to inflammation within the central nervous system, to specific targeted areas being involved. And there may be multiple mechanisms that are involved in primary MS fatigue.

Multiple Sclerosis Fatigue

Negative results of the TRIUMPHANT-MS trial for treatment of fatigue in multiple sclerosis.

: I know when I was logging on to ACTRIMS-ECTRIMS most recently that virtual 2020, there were a couple of studies. One was called TRIUMPHANT-MS trial of methylphenidate, modafinil, and amantadine. I remember Dr. Anne Cross, Lauren Krupp and I, did a study many, many years ago. Can you comment on that? It was kind of interesting.

: TRIUMPHANT was a PCORI-funded study run at Johns Hopkins principally, and the goal was to test three of the top agents that are used to treat fatigue against placebo. And they entered 141 MS [multiple sclerosis] patients and they really did rolling crossover studies where for four weeks they would be on placebo or one of the three agents that you had mentioned with two week washouts. They did this study because the observation had been that the data, the clinical data supporting drugs helping fatigue is really weak. They wanted to take out these three principle agents and formally test them. They used a patient-reported outcome called the Modified Fatigue Impact Scale or MFIS as the outcome. None of these three top treatments for fatigue showed any significant impact on fatigue compared to placebo. It was a bust.

: They failed to show benefit for any of the three drugs. Now, of course, they argued, well, it’s only 141 patients. They did a post hoc analysis and those that had increased daytime sleepiness did show a response to methylphenidate and modafinil. But that’s a post hoc analysis. You can’t count it. It just emphasizes that we use drugs to treat fatigue, it’s only one of a systematic multicentric approach. And I wouldn't be so encouraging about it. I tell my patients there’s a 50% chance, but one on one somebody might really get a benefit from treatment with a drug, medication, but there are other ways to treat fatigue as well.

: I remember when we did the study, God, it’s got to be in the midle 80s with Lauren Krupp, and we did it at Holy Name, we had the same result. It was really nothing outstanding.

I want to thank you all for watching and joining us at this NeurologyLive® Cure Connections®. If you enjoyed this program, please subscribe to the e-newsletter to receive upcoming information about other programs. I’d like to thank you all for the time and I thank you all for this wonderful opportunity and hope to see you all again.

TRIUMPHANT-MS Trial for Multiple Sclerosis

The phase 3 OPTIMUM head-to-head trial of ponesimod compared to terifunomide showed a positive impact on multiple sclerosis fatigue.

: There were other studies presented over at ACTRIMS-ECTRIMS virtually. And there was another study called OPTIMUM which looked at ponesimod and teriflunomide. I’m wondering if there was anything that we need to think about in terms of future treatments.

: This was a very interesting phase 3 trial. Ponesimod is a second-generation S1P [sphingosine 1-phosphate] receptor modulator. It’s a second-generation oral fingolimod. It hits S1P [sphingosine 1-phosphate] receptor 1 principally. They’re trying to get away from the cardiac side effects and the first dose monitoring. It went against oral teriflunomide. It was the first randomized prospective study that looked at two oral agents. It was a 108-week study. The primary outcome was annualized relapse rate. That was significantly better with ponesimod than teriflunomide. 

But the people running the study did something that was pretty surprising. They added, as a secondary outcome, a fatigue measure. Now, that’s unusual. You really don’t see that. They used a new more extensive validated patient-reported outcome for fatigue— the Fatigue Symptom and Impact Questionnaire in Relapsing MS. What they found was that the fatigue as measured by this fairly extensive self-reported outcome remained basically at the exact same level throughout the two years of the study in the ponesimod arm, whereas it significantly increased over time in the teriflunomide arm. There was significantly less change, less development of worsening fatigue with the ponesimod versus the teriflunomide. That was interesting. It was gutsy. It was a secondary outcome. They happened to have won in that regard. It will be very interesting. Ponesimod is in front of the FDA right now. They’ll probably make a decision in the first of order of this upcoming year, and it will be very interesting to see if ponesimod gets approved, what people think about this impact potentially on fatigue.

: It’s interesting because it’s probably one of the first disease-modifying therapies that had an impact. As you said earlier, the interferon betas made people more tired of the side effects, should it be approved? I guess it may fit in to your treatment paradigm as far as you come across somebody with significant fatigue and relapsing MS [multiple sclerosis].

: It will certainly be something to consider. It’s going to be competitive in the S1P [sphingosine 1-phosphate] receptor modulator group— fingolimod, siponimod, ozanimod, and presumably this may be added, ponesimod, absolutely.

: Well, you’ve got one more drug to think about, my goodness. We’ll need a chart like the chart for atomic weights.

: That’s why you need somebody knowledgeable about MS [multiple sclerosis]. I mean, if you’re going to diagnose and treat patients, you need to be familiar with all the treatments.

: Dr. Foley, in listening to all this, any comments about patients’ quality of life? Do you have any feelings about this particular study as it’s starting to evolve? Are you hopeful?

: Just from a clinical standpoint, I’ve seen the impact that the disease-modifying therapies have had on patients’ quality of life. Any time you can slow the progression to disability, that kind of has a counterpart in a quality of life. There are still many challenges of quality of life in MS [multiple sclerosis]. Every study in quality of life in MS show that MS patients have significantly lower quality of life than people without MS [multiple sclerosis]. And that quality of life tends to become lower over time as disability progresses. The challenges that people face to managing their employment status, managing their relationships, managing the MS [multiple sclerosis] symptoms. As Dr. Coyle was saying before, fatigue is a devastating symptom and the primary cause of unemployment in MS [multiple sclerosis], the frontal motor problems. All of these things affect the quality of life that patients and their family members have to continue to struggle with.

OPTIMUM Trial for Multiple Sclerosis

The support of family and friends offers strength to patients with multiple sclerosis.

: Speaking about struggle and the things that we need to keep us going, we all need support networks. Obviously, you and Kathy, Ann, have a very strong relationship and you’ve been through quite a bit together for a very long time, and nothing seems to have broken you apart except maybe a dog barking like in my house. There’s a term that Fred taught me a long time ago about people who bounce well with MS [multiple sclerosis]. I think he defined it as resiliency. In fact, there’s a lot of nursing research going on about the characteristic of resiliency because right now a lot of nurses are going through very difficult times with the COVID [coronavirus disease 2019] and the things that we’re facing. It seems to me that how you have developed this characteristic or did you always have it? Were you always flexible? I just need to know a little bit more about what made you bounce or bounce nicely, yeah.

: There are times where I can be very flexible and then there are times where I can dig my heels in. I’ve had to learn resilience. I’ve had to learn patience with myself. I have the patience of a saint with anybody else in my life but with myself I have no patience at all. As Dr. Coyle and you were just saying about the fatigue, they’ve tried me on Nuvigil and Provigil years ago and the heart palpitations, I thought my heart was going to pop out of my chest. I haven’t been on anything. So I’m willing to, if they’re coming out with some new drugs, I’m willing to give it a shot because right now that’s one of the biggest parts of the exacerbation that I’m having is I get up, I take a shower, and I’m ready to take a nap. I think the quality of my life right now is not, I don’t think, I know it’s not where I’d like it to be and it’s very hard for me to accept it.

: I bet. Kathy, how have you handled this, the ups and downs? You’ve been a stalwart partner. I know you’ve had your other ups and downs of your own personal nature. What’s helped the two of you to come through this so successfully? And I do think you’re a successful partnership, from my perspective.

: Both of our families are actually really supportive. My parents are both in the medical field and still alive, so we often will chit-chat with them and perspective is always a good thing. We have a huge network of friends that almost know what we need before we know. So, if we’re really struggling, there’s always somebody that will fill in the blank. Like I’m still working but Ann’s has not been, and the fatigue is what really, between that and the brain fog, she couldn’t do what she was doing. So that was a huge adjustment. The fatigue is the most frustrating part because you can’t consistently plan a schedule.

: That’s the hardest part for me because I’m a very structured person, and if you’re supposed to do this at 9 o’clock this morning then what are you doing? Your support system, my professional background, I can go back and read things and go, okay, like you have to give her the benefit of the doubt, you have to give her the support. You have to know when to back away a little bit and get your perspective back and make appropriate suggestions.

: What advice would you give other care partners? Certainly, one of the things I saw when I was in practice, and I was in practice for 25 years, is the high rate of divorce and people separating. You probably have been probably at the far end of relationships that stayed together.

: And Dr. Foley knows what I’m talking about.

: That was my biggest fear that Kathy was going to leave me and not until too long ago I still had that fear. It’s due to the help of Fred and through dealing with Kathy and talking to her that I realized that she loves me unconditionally and she’s not going anywhere. But it wasn’t always like that. It was a big, huge fear of mind because that’s what I saw in Glen Rock where I grew up.

: I know there were a lot of those patients. What convinced you that she was going to stay? What gave you the security knowing that you had a strong relationship?

: Talking to Dr. Foley and letting Kathy know. I’m more of a talker than Kathy, so I can beat a dead horse sometimes. I have learned to not beat the dead horse and tell Kathy, “This is what I can use from you. Maybe you can see it this way. Could you view it another way,” because she knows I’m not a slacker.

: And if I don’t do something, there’s a good reason for it. Because we have communicated and a lot more recently in the last many years, I think it’s helped us to stay together.

: She’s a very proactive person as far as her medical care goes, so she’ll reach out. She went for a stint at Kessler for cognitive.

: Rehab which was really helpful because it gave her a lot of tools, and I didn’t have to be the one to tell her. We use the outside, even though I can support it, I don’t feel like I have to do it.

: It’s like teaching your spouse how to play tennis. You don’t want to do it. You’ll never be married at the end of it, so don’t do that with us.

Patient Support Networks for Multiple Sclerosis

Clinicians suggest improved communication between partners and striking an optimistic tone with patients can be encouraging for patients with multiple sclerosis.

: Fred, what advice would you give your patients, although you know Kathy and Ann for a long time. How did you get this thing? I know you were involved for a very long time. What words did you use? What strategies did you use that you think worked and would work with others?

: Well, everyone’s situation is different. Everyone’s relationships are unique, so it’s just important to find out and understand what is the nature of the relationship and what are the strengths and what are the weaknesses, and to kind of develop a strategy to shore up the strengths to improve communication between the partners. If you can do that, I found that if I can help them improve their communication, most of the time they’ll just work things out themselves. That’s a key strategy.

: Dr. Coyle, I know you’re sitting and listening to all this. I know you have hundreds of patients and probably face similar relationship challenges. How do you handle it? I know they probably all look to you for advice and support, but I know you also have nurses and psychologists at your place.

: I think quality of life is very important, and you can start by saying how do you think about being diagnosed with MS. If at all possible, it’s better to be optimistic than to be pessimistic. It’s better to look at the glass half full than the glass empty. Bad things are going to happen to all of us. Bad things are going to happen to good people. If you hear you have MS and you view it as this horrible thing and you dwell on that, that is a negative. That’s not producing a good quality of life.

I try to be very encouraging. I tell my patients, “Our expectation is that you’re going to live a normal life. If you really do the right things, if we treat you appropriately, if you follow a wellness program, if you take care of comorbid conditions, you can live a normal life. We can work together to have you have a normal life because MS has been transformed in the new era.” As disability may develop and as symptoms develop, they can also have very negative impacts on quality of life. Important to communicate, important to recognize, important to try to treat to let the individual know that you’re doing the best you can what are the ways of coping and you really encourage that they have a support system. I have no problem having a family member come in with the patient to sit right there, to be for the whole thing, the whole visit. That’s fine because you’re hearing the patient and their significant other, hear everything that’s being said, be able to ask questions. I think that helps the support system. These are just some of the things that I think you need to be very cognizant of.

Optimistic Outlook in Treating Multiple Sclerosis

Final thoughts from participants on improving quality of life in patients with multiple sclerosis.

: All in all, I think our discussion tonight really shows that there’s a huge amount of promise in MS Final Thoughts: Improving QoL in Multiple Sclerosisdue to disease-modifying therapies, as you said, the three different groups. But also it seems to me, and I guess having been in the field for a long time, knowing you, Dr. Coyle, knowing you, Dr. Foley, and of course, knowing you two people over there, Ann and Kathy, it seems to me that it’s more than just medications. It seems to me that education, that we need to use as much of a tool for each person as much as they can learn and understand, to be very sensitive to somebody’s background, ethno-culturally, people of color, people of different birth and background, that whatever you spoke about tonight was really individualized care. 

As you just said it Dr. Coyle, I think we sort of missed it in our conversation, the whole wellness approach. I think MS [multiple sclerosis] is a disease of the central nervous system, but if you take good care of yourself, you can maintain your heart and your lungs, you can do all the things in your gender that you take care of and work as part of your team. I think to me that’s the most important thing to not have a physician or a clinician, such as Dr. Foley, say you must do this. You’ve got to participate. I think you have to understand, and you have to be involved in the process. We’re reaching the end of our visit. I’d like Dr. Foley to say some closing words, maybe some words of wisdom.

: Well, from a psychological perspective, MS [multiple sclerosis] has presented many, many challenges to persons with MS and their families. Anxiety, depression, adjustment issues, uncertainty, misinterpretation of kind of changing behaviors in patients, all these things represent challenges. Fortunately, we know that many of these psychological challenges and even some of the cognitive problems that patients develop can be treated more successfully today than they could five years ago. We’re very optimistic that we will continue to be able to improve the quality of life for people with MS.

: Ann and Kathy, thank you so much for sharing your story with us. Would you like to say one or two closing remarks to end our very?

: I would say is I would concur with what Dr. Coyle said earlier on. Get on therapy as quickly as you can. I mean, there wasn’t anything out when I was diagnosed but I waited a long time. I’m not saying it was bad, but if I had gotten on it earlier, that I would recommend. Talking often and regularly with your significant other and your close friends, and also, I would suggest seeking out support of people who are in the same boat as you. I go to an MS support group here in West Milford that meets once a month, and I think that’s very, very important to do.

: Just to roll with the punches a little bit. Remember that flexibility is important, and the bottom line is you love each other, make sure you respect everything about the person. I know her really well, so I know when things are bumpy and when they’re not. When they’re not bumpy, do something fun. You have to laugh.

: Absolutely, yeah. Dr. Coyle, thank you so much for spending this time with us and sharing your thoughts. Would you like to say some closing remarks and any words of wisdom before we adjourn?

: Just from a neurological point of view, this is a new era. MS is the poster child for successful development of disease-modifying therapies. Make sure your diagnosis is proper, you’re going to a knowledgeable person, get on early treatment, follow that wellness program, treat comorbid conditions to promote CNS [central nervous system] health, to have the central nervous system age better, open communication. And remember, the bottom line is you want to be happy. If you’re not happy there is something wrong, and you have to fix something, and if you’re not happy in your relationship with your healthcare provider, that has to be fixed. You want to be happy. You should be happy. If you’re not happy there’s something wrong. Act on it.

: Wow, powerful words. I think we have some very powerful messages we shared tonight. I want to thank you all for watching and joining us at this NeurologyLive® Cure Connections®. If you enjoyed this program, please subscribe to the e-newsletter to receive upcoming information about other programs. I’d like to thank you all for the time and I thank you all for this wonderful opportunity and hope to see you all again.

Final Thoughts: Improving QoL in Multiple Sclerosis

The Multiple Sclerosis Patient Journey

A diverse panel including an expert neurologist, psychologist, patient, and care partner give their perspectives on various facets of multiple sclerosis.