MS education: Quality of life with MS [Text on screen: Multiple sclerosis education series April 8, 2021 Spring Into Wellness: A focus on quality of life with MS The Ohio State University Wexner Medical Center] Kristi Epstein, APRN-CNP: Good evening everyone and welcome. We're happy to have you tonight. We'd like to welcome you to our patient education series. Tonight we are doing Spring Into Wellness. This is going to be a focus on quality of life in patients with MS. So I'm Kristi Epstein. I'm the nurse practitioner in the MS Clinic. I'd really like to welcome you to our third session of our virtual education series. [Text on screen: Kristi Epstein, APRN, CNP, CCRN MS Nurse Practitioner] Kristi Epstein, APRN-CNP: This series is for people who are affected by MS. If you're here, you're either living with MS yourself or you care about someone who's living with MS. Whatever your reason for joining us tonight, we're very happy to have you here. We hope this series of webinars will be informative and helpful for you as you manage and flourish in living your daily life with MS. So I'm going to go over a few housekeeping notes for you. First of all, we're going to want you to remain muted, and your cameras will be turned off for the duration of the webinar. This session will be closed captioned and will be recorded for viewing at a later time. As you listen to the presentations, please feel free to type questions you have about what you're listening to into the Q&A box. Just a reminder, please don't disclose any private health information, no personal information, or ask questions about your personal MS diagnosis or treatment. All questions should be general and related to MS and the presentation content. At the end of our session, our experts will answer many questions as possible during the Q&A panel. I will serve as the moderator and a presenter during tonight's conversation. I'm a nurse practitioner specializing in multiple sclerosis. Many of you have met me. I have over 20 years of experience as a nurse, including infusion therapy, critical care oncology, and neurology. Special interests within the MS Clinic include wellness, reproductive issues, clinical research, and of course quality of life. [Text on screen: The Ohio State University Wexner Medical Center Kristi Epstein, APRN, CNP, CCRN, MS Nurse Practitioner Benjamin Segal, MD, MS Program Director, Neurologist Tirisham Gyang, MD, MS Specialist, Neurologist Meena Khan, MD, Sleep Medicine Specialist, Neurologist Brooke Harshbarger, DPT, PT, Physical Therapist Margaret Hansen, PharmD, Pharmacist Robert Fallis, MD, MS Specialist, Neurologist] Kristi Epstein, APRN-CNP: Joining me tonight will be a few members from the MS team here at Ohio State University Wexner Medical Center, including Dr. Tiri Gyang, Dr. Meena Khan, and physical therapist Dr. Brooke Harshbarger. We'll be joined later during our Q&A session by the MS Center director Dr. Benjamin Segal, Dr. Robert Fallis, and our clinical pharmacist Dr. Margaret Hansen. We're going to learn more about each of our experts as we proceed throughout tonight's event. So we're going to start with a poll question, and we'll get that up on the board for you here now. [Text on screen: Poll Question] Kristi Epstein, APRN-CNP: We'll start our session together with a poll question to get ready for our first presentation. So on your screen, you can interact with our poll question by selecting an answer and just click submit. So let's read our first question. What is the most important supplement for MS patients to take? So go ahead and consider those choices there and remember to hit submit. I wanted to add while you're thinking about that that we've had a few technical difficulties today during registration, so we apologize for those difficulties and we're so glad that you could join us. Go ahead and submit, and let's take a look at that answer. So it looks like everybody got that right. Just about 79% say vitamin D. Great job. [Text on screen: Quality of Life in MS Integrating Wellness into Daily Living Kristi Anglin-Epstein APRN CNP CCRN The Ohio State University Department of Neurology Division of Immunology] Kristi Epstein, APRN-CNP: So I have the privilege of kicking off our session this evening with a look at different ways to improve and maintain quality of life in MS. We're going to look at how we integrate wellness into daily living. Next slide. [Text on screen: Objectives. - Identify Quality of Life and Wellness as it pertains to living with chronic disease and Multiple Sclerosis. - Discuss Diet - Discuss Supplements frequently asked about in MS clinic - Multidisciplinary Approach - Quality of Life Visits] Kristi Epstein, APRN-CNP: So things that we're going to go over is we're going to identify what is quality of life and wellness as it pertains to living with chronic disease and multiple sclerosis. Then we're going to discuss some things that I am frequently asked about in clinic, including diet, supplements, and exercise. Then we're going to discuss, what is a quality of life visit and what is a multidisciplinary approach? Next slide, please. [Text on screen: Quality of Life and Wellness - What is Quality of Life (QOL)? - Defined by the World Health Organization as an individual's perception of their position in life in the context of the culture and value systems in which they live, and in relation to their goals, expectations, standards and concerns. - Defined by Britannica as the degree to which an individual is healthy, comfortable and able to participate in or enjoy life events. - Defined by CDC as an individual's or a group's perceived physical and mental health over time. (HRQOL).] Kristi Epstein, APRN-CNP: So quality of life and wellness. What is quality of life? Well, there are some very complex explanations that we could give, but basically it is the degree to which an individual is healthy, comfortable, and able to participate in or enjoy life's events. Next slide. [Text on screen: Domains of Quality of Life. - Physical status & functional abilities. - Social interactions - Religious and/or spiritual status - Economical and/or vocational status & factors - Psychological status & well-being] Kristi Epstein, APRN-CNP: You can see that many things are interrelated in quality of life. So physical status, social interactions, religious, spiritual status, economical factors, and psychological wellbeing. Next slide. [Text on screen: Wellness. - Defined by the World Health Organization as "a state of complete physical, mental and social well being and not merely the absence of disease or infirmity." - Defined by Britannica as "a state of being in good health, both physically and mentally, and of being free of and not at risk for illness." - Defined by CDC as "a state that integrates mental health (mind) and physical (body) resulting in more holistic approaches to disease prevention and health promotion."] Kristi Epstein, APRN-CNP: Wellness. So what exactly is wellness? Wellness is defined as a state of being in good health, both physically, mentally, and of being free of and not at risk for illness. Next slide, please. [Text on screen: Domains of Wellness. - Emotional - Spiritual - Intellectual - Physical - Environmental - Financial - Occupational - Social] Kristi Epstein, APRN-CNP: So there are also many domains involved in wellness, including emotional, spiritual, intellectual, physical, environmental, financial, occupational, and social. So you can see how these things fit together. Not only do you involve things that you're doing in your life, but how you're feeling physically, mentally, intellectually, how it involves work and a lot of things in your life. So we'll talk more about that as we go along. Next slide, please. [Text on screen: What is MS? Multiple Sclerosis is a complex disease process in which an abnormal immune mediated response occurs in the body's immune system, attacking the central nervous system causing focal demyelination, inflammation and varying degrees of neuro-axonal loss that results in neurological dysfunction. It is a chronic disease affecting a demographic from 18-60, with a multifactorial combination of environmental and genetic risk factors. These include gender, ethnicity, latitude, and preventable factors such as obesity, smoking and low vitamin D. Many consider this to be an autoimmune disease, however no specific antigens have been identified in MS.] Kristi Epstein, APRN-CNP: So what is MS? Many of you know multiple sclerosis is a very complex disease process in which an abnormal immune-mediated response occurs in the body's immune system, attacking the central nervous system, causing focal demyelination, inflammation, and varying degrees of neuro-axonal loss. That results in neurological dysfunction. It's a chronic disease affecting a demographic from 18 to 60, and it has multifactorial combination of environmental and genetic risk factors. These include gender, ethnicity, latitude, and preventable factors such as obesity, smoking, and low vitamin D. Many may consider this to be an autoimmune disease, however, no specific antigens have yet been identified in MS. Next slide, please. [Text on screen: Integrating Wellness to Achieve QOL. - Identify Goals - Patient and Provider - Identify areas of deficit in specific domains - Screening tools, diagnostic testing such as EDSS scoring, Fatigue scales, BMI and lab testing - Formulate a plan of integrated, co-directed intervention - Referrals as needed such as Physical Therapy, Cognitive testing, Dietician, Urology, Ophthalmology - Define tools to measure success - Follow up intervals, sequential screenings such as every 3-6 months - Reflect, Refine, Repeat] Kristi Epstein, APRN-CNP: So how do we integrate wellness in order to achieve quality of life? What we need to do is really work together, provider and patient, to formulate a plan of integrated and co-directed intervention. So your provider and you will work together to reach your goals, and we will refer to specialists as needed. Some things that you may be familiar with are physical therapy, cognitive testing, dietitians, urology, neuro-ophthalmology, things of that nature. We'll use tools to measure the success of these interventions and we will always go back and reflect, refine, and repeat until we get it right. Next slide, please. [Text on screen: MSQLI Screening tool NMSS List of Instruments Making up the MSQLI (in order of administration) - Health Status Questionnaire (SF-36) - 36 items - Modified Fatigue Impact Scale (MFIS) - 21 items - MOS Pain Effects Scale (PES) - 6 items - Sexual Satisfaction Scale (SSS) - 5 items - Bladder Control Scale (BLCS) - 4 items - Bowel Control Scale (BWCS) - 5 items - Impact of Visual Impairment Scale (IVIS) - 5 items - Perceived Deficits Questionnaire (PDQ) - 20 items - Mental Health Inventory (MHI) - 18 items - MOS Modified Social Support Survey (MSSS) - 18 items] Kristi Epstein, APRN-CNP: So this is just an example of a screening tool that you might see in the Quality of Life Clinic. This consists of questions that you would answer that give us a scale to measure how you're functioning in some of these areas of your life. Next slide, please. [Text on screen: Can Diet Effect MS? Diet can positively affect the overall health of an individual living with chronic disease. Poor diet, obesity, low vitamin D and smoking can increase the risk of developing MS due to the pro-inflammatory effects of this type of lifestyle. Once the abnormal immune response has started however, there is no evidence to suggest that any diet can reverse this process. Making changes such as eliminating food allergens, eating a healthy balanced diet, smoking cessation, belly fat reduction and vitamin D supplementation can have very significant effects on reducing inflammation. This is important as there is an inflammatory component in MS as previously discussed. Wellness should be approached using evidence based practice, diets and supplements should be based in science, backed by evidence and discussed with your provider. Questions to ask before starting a Diet or Supplement; Is it harmful? Is it cost prohibitive? Is there evidence to support its use?] Kristi Epstein, APRN-CNP: So a lot of people ask me in clinic, and this pertains to wellness and quality of life, what about a diet for MS? Can diet affect MS? So diet, as most of you know, can positively affect the overall health of an individual living with chronic disease. But at this point there is no evidence to suggest that any diet can reverse the process that's going in your immune system. So once the abnormal immune response has started, there is no evidence to suggest that any diet can reverse this process. Making changes such as eliminating food allergens, eating a balanced diet, smoking cessation, belly fat reduction, and vitamin D supplementation can have effects on reducing inflammation, and that's why it's important. So whenever we're considering any diet, we need to think about or supplement asking ourselves three questions. Is it harmful? Is it cost-prohibitive? And is there evidence to support its use? Next slide, please. [Text on screen: What is the best diet? Investigating popular trends. - This is a discussion regarding popular diets, we are not endorsing or recommending any specific diet, please discuss individually with your provider. - Mediterranean Diet: vegetables, fruits, whole grains, beans, nuts and seeds and olive oil. No refined foods, added sugars or processed meats. - Anti-inflammatory Diets: omega 3 fatty acids, long chain fatty acids. - Wahl's Protocol: Dr. Terry Wahls. Physician with SPMS U of Iowa. Increase cellular function and ATP production. Diet and exercise protocol. - Intermittent fasting/Calorie Reduction: Intermittent fasting has recently received a lot of attention as a tool to reduce inflammation. There are some good results in MS trials regarding reduction of inflammatory markers and reduction of adiposity (body fat) which is pro-inflammatory. There are many ways to achieve intermittent fasting results with modified plans, strict 72-hour fasting is not the only method to achieve results. - Individualized Diet: based on food sensitivity testing, allergy testing, elimination diets. Example gluten allergy.] Kristi Epstein, APRN-CNP: So when we talk about diet, there are a lot of popular diets that you may see and you may ask us about. These include the Mediterranean diet, which is otherwise known as a heart-healthy diet, anti-inflammatory diets. You may have heard of Wahl's Protocol, intermittent fasting, and/or things such as MS-specific diet. There are a lot of different ones out in the market. A lot of people ask me about ketosis, keto diet. So I want you to understand that we're not endorsing or recommending any specific diet for MS because there is no specific diet for MS. The best thing that patients can do is eat a healthy diet. We like to go with the approach of developing an individualized diet with our patients. This is based on what food sensitivities you might have, what type of foods that are healthy for you. Next slide, please. [Text on screen: Intermittent Fasting and Gut Microbiome] Kristi Epstein, APRN-CNP: Here's just a little information on intermittent fasting. Intermittent fasting has shown to have some success in autoimmune diseases, but it can be difficult for patients to accomplish. So there are many ways to participate in intermittent fasting without doing strict 72-hour intermittent fasting. These are things that can be discussed in a quality of life visit. Next slide, please. [Text on screen: Individualized Diet. - Balanced diet with RDA of calories from protein, carbohydrates, and fat. Reduce/avoid processed food, added sugar, saturated fats and processed meats. Heart healthy diet. - Food Sensitivity Testing - Blood test, skin test - Elimination Diets - Food Journaling - Gut Microbiome - Pre and Probiotics. Increase anti-inflammatory cytokines and T-regs. Keep tight gut junctions. 8-12 week adherence. - Consulting GI, Dietician when needed - Interpreting results and formulating diet plan based on allergies, BMI and caloric RDA] Kristi Epstein, APRN-CNP: So what does it really mean an individualized diet? So what we're really talking about is a diet that works for you. That means a balanced diet with the recommended daily allowance of calories from protein, carbohydrates, and fat. What we want to do is reduce and avoid processed foods, added sugar, saturated fats, and processed meats, and otherwise follow a heart-healthy diet. If you feel like you have food allergies, you can look into food sensitivity testing. This can be accomplished by doing elimination diets, food journaling. Lots of people do ask me about probiotics. Probiotics work to help keep your gut biome healthy. If you are going to try these out, you want to make sure that you try them for 8 to 12 weeks, and then you talk to your provider if you're going to try these. Next slide, please. [Text on screen: Supplements frequently asked about in MS Clinic. - Vitamin D: Downregulates inflammation in CNS. Check serum levels and prescribe appropriately. Ample evidence in numerous trials. - Alpha Lipoic Acid: Some evidence in reduction of atrophy in progressive MS patients. - Biotin: Recent studies do not support any change in disability. MS SPI, SPI 2 trials. - Turmeric Curcumin: Studies show curcumin exhibits neuroprotective effects in MS through antioxidant, anti-inflammatory, anti-proliferative and anti-differentiation mechanisms. Psoriasis trials. More MSD trials are needed. - Antioxidants: Reduce cellular oxidative stress. Examples; Vitamin C, Vitamin E, Carotenoids. - Pre and Probiotics: Evidence suggests probiotics consumption via gut microbiome changes can have beneficial effects on improving immune/inflammatory response in MS] Kristi Epstein, APRN-CNP: So a lot of people ask me about supplements in clinic, and there have been many trials over the years. I would say that these are probably the top things that I'm asked about in clinic. Vitamin D, as you know, you already answered correctly, is very important because it downregulates inflammation in the central nervous system. Alpha lipoic acid is another thing I'm asked about. Biotin, turmeric curcumin, antioxidants, and probiotics. Next slide, please. [Text on screen: Vitamin D - Hypovitaminosis D is linked to higher disease activity. - Risk factor for development of MS. - Innate immune response promoted and adaptive response muted resulting in reduced cytokine production mediated by Type 1 T helper cells. - Provider will determine recommended daily dosage. - Monitor Serum levels regularly, avoid toxicity.] Kristi Epstein, APRN-CNP: So as we mentioned, vitamin D, low vitamin D is linked to higher disease activity in MS and is a risk factor for developing MS. So your provider will test your vitamin D level and we will monitor those levels regularly, and we will recommend a vitamin D supplementation for you. Next slide, please. [Text on screen: Vitamin D] Kristi Epstein, APRN-CNP: This is just a picture of vitamin D and how it downregulates inflammation in the central nervous system. Next slide. [Text on screen: Biotin. - Biotin is thought to enhance neuronal and oligodendrocyte energy production to improve cellular function, repair or survival. - Biotin augments ATP production and theorized to enhance myelin repair or synthesis. - SP1 SP2 Trials in MS failed to show significant evidence to support use, no change in disability noted with high dose biotin. - High dose biotin can skew important lab results such as thyroid test as it can effect study assay. - No current evidence to support high dose biotin.] Kristi Epstein, APRN-CNP: Biotin. There was a period of time where high-dose biotin was being studied, and I do still encounter some patients who are on high-dose biotin. Recently, it's come to be known that high-dose biotin has not shown to be effective in changing the outcome of disability or outcomes for patients who have MS. In fact, there is no current evidence to support the use of high-dose biotin. If you want to take biotin, you can take normal recommended dosage. Be aware that high-dose biotin can actually skew some important lab results such as thyroid testing. So you want to talk to your provider if you're in any way taking high-dose biotin. Next slide. [Text on screen: Alpha Lipoic Acid. - ALA is thought to limit the transmigration of inflammatory T cells and monocytes into the CNS. - In mouse models with EAE, ALA suppressed the time to development of symptoms and slowed progression of symptoms. - MS trial in SPMS showed some good results in reducing whole brain atrophy. - Reduces oxidative stress. - Frequently used in diabetic neuropathy. - Found in spinach, broccoli and tomatoes. - Current ongoing studies in MS. - No consensus in current evidence to support its use.] Kristi Epstein, APRN-CNP: Alpha lipoic acid is still being studied in MS. There are current ongoing studies. Currently, there is no consensus that gives us evidence to support its use. However, it's likely not harmful. It's being studied. It has been studied in the past in secondary progressive MS and did have some good results in reducing whole-brain atrophy. If you're interested in alpha lipoic acid, you can discuss this with your provider or with me at a quality of life visit. Next slide, please. [Text on screen: Turmeric Curcumin. - Inhibits pro-inflammatory cytokines. - Reduces infiltration of inflammatory cells into the CNS. - Modulates cell cycle regulatory proteins, enzymes, cytokines and transcription factors in CNS-related disorders including MS. - Natural anti-inflammatory. - Bioperine/Black pepper added to Turmeric increases gut bioavailability by prolonging glucuronidation - Take separately from other medications. - Often used in arthritis and skin conditions such as psoriasis. - No current significant evidence to support its use in MS, more studies needed.] Kristi Epstein, APRN-CNP: Turmeric curcumin. A lot of people are taking this. As we know, this is a natural anti-inflammatory. Currently there is no significant evidence to support its use in MS, and there are more studies needed. Again, we need to look at if it's harmful, if it's cost-prohibitive, and if there is any research to back up its use. Next slide, please. [Text on screen: Antioxidants. - Examples Vitamin C, Vitamin E, CoQ10. - Reduce cellular oxidative stress. - Evidence of OS found during active relapses, in active inflammatory lesions and chronic plaques. - Mouse models in EAE demonstrated evidence of OS in the brain. - The brain is more susceptible to OS. - Healthy lifestyle changes such as healthy diet and regular exercise also reduce OS. - Used in combination with DMT.] Kristi Epstein, APRN-CNP: Antioxidants. So examples would include vitamin C, vitamin E, and CoQ10. What antioxidants do is they reduce cellular oxidative stress. Oxidative stress has been found during active relapses and active inflammatory lesions and chronic plaques in MS. So we would never use these instead of a disease-modifying therapy or an MS-specific medication, but we would use supplements such as these in combination with disease-modifying therapy. Again, always discuss things that you want to take or are taking with your provider. Next slide, please. [Text on screen: Multidisciplinary Approach. - The best way to achieve QOL for our patients with chronic disease is to utilize a multidisciplinary approach. - Screening tools completed during QOL visits help identify areas of deficit and help direct referrals to appropriate specialties eg. the MFIS and PHQ-9. The MS QOL54. Screening tools provide a metric to measure outcomes. - Referrals help patients receive the best care for multisystem disease related conditions, and this improves QOL. - Multidisciplinary Clinics: Patients see embedded specialists on the same clinic day for example, sleep, cognitive testing, Physical Therapy, Clinical Pharmacy, Cognitive Talk therapy.] Kristi Epstein, APRN-CNP: So what is the best way to achieve quality of life? So as you know, as patients living with MS and dealing with people who have MS, there are many body systems that are affected. So we need to take a multidisciplinary approach. We use screening tools in our quality of life visits, and those are those scales that I talked about with you, to identify areas of deficits individual to each patient. Then we're building in our clinic a wonderful multidisciplinary clinic, during which patients can come and see embedded specialists during the same clinic visit. For example, you might see a sleep specialist. You might see a talk therapist. You might be able to undergo a consultation with physical therapy or talk with our clinical pharmacist. Next slide, please. [Text on screen: Quality of Life Visit. - Meet with provider and discuss goals. - Review MS/disease progress details and DMT details. - Complete MSQLI screening tool. - Complete other screening and baseline testing, labs, bladder scanning, OCT, BMI. - Discuss recommendations for diet, exercise and supplements. - Referrals to specialists as needed for example, Cognitive Testing, Physical therapy, Assistive Devices, Urology, Clinical Pharmacy, Sleep Clinic. - Regular follow up to assess progress and redirect as needed.] Kristi Epstein, APRN-CNP: So what's in a quality of life visit? Briefly, like we said, you would meet with a provider and discuss your goals as we discussed. We can review MS, the disease process and details about MS and details about your disease-modifying therapy. We would have you complete screening tools so that we can identify where your areas of deficits specifically are. We can do other screening tests such as labs, bladder scans, OCT, which is testing of your vision, and calculate things having to do with diet, exercise, and supplement. During that time, we can identify with this information which subspecialists you may need to see, including physical therapy, a sleep specialist, clinical pharmacist, urology, cognitive testing, things of that nature. We would have regular follow-up so that we can see what your progress is and we can redirect as needed. Next slide, please. [Text on screen: Summary. - Achieving Quality of Life should be an achievable goal and priority in patient care. Focus on treating the disease process and symptoms but also on the whole individual. - Treating the disease and its symptoms only does not treat the whole individual. - Utilizing techniques to achieve wellness can promote QOL. Diet, exercise, mental health, DMT. - Wellness should be approached using evidence based practice, diets and supplements should be based in science, backed by evidence and discussed with your provider. - QOL can be best achieved by taking a multidisciplinary approach to patient care. - Measure outcomes at regular intervals and refine goals and therapies as appropriate. MSQLI tool, feedback from patient and caregivers.] Kristi Epstein, APRN-CNP: So, in summary, patients should absolutely be able to achieve better quality of life. This should be a priority in our patient care. We need to focus on treating the disease process and symptoms, but also on the whole individual. Treating the disease and the symptoms only does not treat the whole individual. So we need to utilize techniques in order to achieve wellness that can promote quality of life. These include diet, exercise, focusing on mental health, as well as disease-modifying therapy. So wellness should really always be approached using evidence-based practice. Diets and supplements should be based in science and backed by evidence. Always discuss with your provider. Quality of life can best be achieved by taking a multidisciplinary approach to patient care, as we discussed. We always need to meet again to measure our outcomes and make sure that we're going in the right direction. This would involve getting feedback from you, the patient, during our patient visits. Next slide, please. [Text on screen: References] Kristi Epstein, APRN-CNP: These are just some references, some great articles. All of these talks will be uploaded to our website once this is complete, so that you can go in and view the detail from these slides. So I thank you for listening, and I invite you to request an appointment in our Quality of Life Clinic so that we can go down this journey together. Thank you so much. [Text on screen: Brooke Harshbarger, DPT, PT Physical Therapist, Outpatient Rehabilitation] Kristi Epstein, APRN-CNP: So our next speaker is going to be Dr. Brooke Harshbarger. She's a physical therapist. She has an interest in working with neurologic patient populations. She's a member of both the brain injury team and the multiple sclerosis team in the outpatient rehab at the Ohio State University Wexner Medical Center. She loves working on research projects, with a recent project in examining and treating individuals with post-concussive disorders. [Text on screen: Poll Question] Kristi Epstein, APRN-CNP: Before Brooke joins us, let's go ahead and do another quick poll question. That's going to come up on the board here. Okay. So exercise is not safe for people with mild to severe mobility, deficits related to multiple sclerosis, true or false? Remember to hit submit so that we can see your answer. Give you a little bit more time here. What do we think? Okay, so everybody got that right. That was an easy one. All right, great. Well, it's going to be my pleasure then to go ahead and introduce Dr. Brooke Harshbarger. [Text on screen: The Ohio State University Wexner Medical Center. Rehab and Exercise for the Person with MS. Brooke Harshbarger PT, DPT April 8, 2021] Brooke Harshbarger, DPT, PT: Hi, I'm Brooke. I'm a physical therapist with OSU at Martha Morehouse. I'm going to be talking to you today about rehab and exercise for people with MS. Next slide. [Text on screen: Exercise and MS. Why is physical activity important? Decreased physical activity: - higher disability score on EDSS - progression of deficits (fatigue, depression, spasticity, cognition) - deconditioning Research: 25% of patients had prematurely retired from work due to MS. - Greatest effects on employment status: impaired mobility, pain, gait disturbances, and cognitive impairments. Increased physical activity: - Improved flexibility, muscle endurance, bone density, muscle strength, quality of life, balance, aerobic capacity, mood, mobility/functional abilities - Reduced fatigue, pain] Brooke Harshbarger, DPT, PT: So when we talk about wellness as a whole related to MS, it's crucial to talk about exercise, because physical activity can have a big impact on the symptoms that you live with day-to-day. So research has shown that if you have less physical activity, your symptoms can become worse, and you start noticing you're more limited by depression, spasticity, fatigue, or thinking difficulties which we call cognition. On the other hand, if you increase your physical activities, you can notice improvements in those same things, as well as flexibility, strength, balance, your mood, and you might have reduced fatigue or pain levels. So your abilities related to all of these different symptoms or health factors can have an impact on what you feel you're able to participate in day-to-day. Research shows that 25% or one in four patients had to prematurely retire from work due to MS, with the biggest factors being difficulty moving around, high pain levels, gait or walking problems, and thinking problems. Next slide. [Text on screen: Exercise and MS, Research. - Research supports exercise benefits for individuals with mild to severe mobility deficits related to MS. - No increased risk of exacerbation or relapse. - Physical and occupational therapy have had positive impacts on physical function, cognition and other neuropsychological symptoms in MS patients.] Brooke Harshbarger, DPT, PT: So no matter your current abilities, research shows you can still gain benefits from being active, whether you have mild or severe mobility issues related to MS. The good news is there's no risk of exacerbation or worsening symptoms and there's no risk of an MS-related relapse. Rehab is also a great way to get more physical activity as research shows that physical therapy and occupational therapy have positive effects on your thinking, your mood, and your physical abilities. So in conclusion here, the research has demonstrated a variety of benefits for all individuals with MS, which can directly impact how easy it is and how often you participate in day-to-day tasks. Next slide. [Text on screen: Rehabilitation, how do I know if physical rehabilitation is appropriate for me? - Difficulty tolerating exercise. - Loss of balance or falls. - Difficulty completing daily tasks (ADLs, walking, using stairs. - Symptom management. - Unable to perform activities in the same way or in the same amount of time.] Brooke Harshbarger, DPT, PT: So, like I said, PT and OT can be a helpful resource to initiate an exercise program or to get more physically active. So you may benefit from meeting with a therapist if you currently have difficulty tolerating exercise, if you have safety concerns related to loss of balance or falling, if you have difficulty completing your daily tasks, which we call ADLs. Also difficulty with walking or using stairs, if you need help managing your symptoms, or if you're unable to perform activities in the same way or in the same amount of time. Next slide. [Text on screen: Rehabilitation, the rehab team. - Physical Therapy - Occupational Therapy - Speech-language Pathology (Speech Therapy) - Neuropsychology - Rehab Psychology - Vocational Rehab] Brooke Harshbarger, DPT, PT: So here's a glimpse at the various rehab team members that you may benefit from working with. All of the different disciplines listed on this slide are all part of the MS team here at OSU. So some of the big ones that people with MS see primarily are physical and occupational therapy. So the difference between those two is that physical therapy is more focused on walking, using stairs, balance, and leg strengthening while occupational therapy focuses on the activities of daily living, like cooking, using the bathroom, bathing, or feeding yourself. They also focus on upper body strength and grip strength. You can also complete vision therapy with them. So, ultimately, if you're not sure what therapy is best for you, talk to your doctor about it and they can get you a referral to the right type of therapy. Rehab is all about individualized goals and creating individualized plans to reach those goals. So we'd like to prioritize what's important to you. Next slide. [Text on screen: Rehabilitation, adapting exercises. Body weight supported training with a harness. - Over-ground or treadmill. Aquatic therapy - Provides body weight support. - Decreased risk of falling. - Improved tolerance to exercise (cold pool) Electrical stimulation - Assisted muscle contraction. - Combined with traditional exercise (cycling, walking, resistance training] Brooke Harshbarger, DPT, PT: So from a PT perspective, it can be beneficial to adapt exercises, either to meet you at your current level or to maximize your benefits of exercising while reducing fatigue that's common in people with MS. Exercising while reducing fatigue that's common in people with MS. So one option is body weight support training using a harness system. You can use those overground or over a treadmill. Aquatic or pool therapy also provides body weight support, but it has the added benefit of decreasing the risk of falling while exercising and it can improve your tolerance to exercise if you're exercising in a cold pool. And then finally, we use electrical stimulation to assist your muscles contracting when you're exercising. This is never used alone as the benefit still comes from actually participating in the exercise. Rather, it's used to supplement, used to supplement traditional exercise. It can be combined with cycling, walking, or any type of strengthening program. Next slide. [Text on screen: Getting started, exercise guidelines. Exercise Type: Flexibility Training - Potential Benefits: Decrease spasticity, prevent contractures - Modes: Traditional stretching, yoga, Pilates, pool - Frequency: Daily to prn, Before/after exercise. Exercise Type: Resistance Training - Potential Benefits: Reduced fatigue, improved walking, improved task performance - Modes: Body weight resistance, free weights, machines, resistance bands - Frequency: 2-3x/week Exercise Type: Endurance Training - Potential Benefits: Reduced fatigue, improved recovery from exertion, improved walking abilities - Modes: Swimming, stationary bike, walking, NuStep, arm bike - Frequency: 3-4x/week, 20-30 minutes Exercise Type: Balance Training - Potential Benefits: Decrease falls - Modes: Sitting balance, standing balance, pool, yoga - Frequency: "it depends"] Brooke Harshbarger, DPT, PT: So whether you're looking to start an exercise program or beef up your current routine, you want to consider what type of exercise you're participating in. So there's not one best type of exercise. They all serve their purpose and provide different types of benefits. So there's flexibility training, which you might have heard as stretching, resistance training, which means strengthening, endurance training, which is cardio, and then balance training. So there's potential benefits of each listed here, but this list is not all-inclusive and there's a lot of crossover between the benefits of each. There's different modes or methods of participating in each type of exercise listed here. And I just want to highlight if you tried a type of cardio or tried a type of stretching that you weren't engaged in or just didn't like, you have other options out there so keep looking. And then in that last column, there's MS specific frequencies from research for each type of exercise. And so if you have balance problems, there's a big old, it depends there because it depends on what your balance is like for how often you need to work on your balance. So this might be something that you consider as individuals with MS have a higher risk of having a balance problem. So it can be overwhelming to look at this slide and think, how am I going to fit all of these different types of exercise into my day-to-day schedule? So an example of a weekly exercise routine could be performing endurance or cardio training every other day, like Monday, Wednesday, Friday, and then doing your strength training on those off days, like upper body strengthening on Tuesday and lower body strengthening on Thursday. Next slide. [Text on screen: Getting started, examples of general exercise. Aquatics. - Pool temperature should not exceed 84 F for people with MS. - Studies show improvements in walking speed and dynamic balance. Pilates. - Exercises based on whole-body movement - Emphasizes body alignment and stabilizing core muscles during movement - RCT: improvement in walking distance and speed after two 50-min sessions/week for 12 weeks] Brooke Harshbarger, DPT, PT: So there's ways to achieve multiple goals with one exercise type, especially with more general exercise programs like aquatics or Pilates. So aquatic or pool exercise can be done alone or in a group at an exercise class, which is often broken up into a focus based on your goals such as a strengthening class or a pool walking class for more cardio focus. If you do choose the exercise in a pool, it's important to note that the pool degrees should not be above 84 degrees Fahrenheit. That's because of the tendency for heat sensitivity in people with MS. So studies show if you participate in pool exercise, you could see improvements in your walking speed or your balance. So Pilates is another form of general exercise that includes whole body movements with a focus on how your body is aligned and stabilizing your core muscles while moving. A high quality research study called a randomized controlled trial demonstrated improvement in walking distance and walking speed after two 50 minute sessions a week for 12 weeks. Something I want to highlight with that is that was after three months of participation. And so what we see in exercise outside of the clinic and in the clinic is that you have to stick with it to see the benefits that I talked about earlier. Don't give up because you haven't seen any changes after a few weeks. Next slide. [Text on screen: Getting started, examples of general exercise. Seated exercise. - ChairFit with Nancy - https://www.youtube.com/channel/UCCAFFLNiOjqR5FXtuH8ySxA Yoga. - Traditional vs adapted. - Focus: Balance, flexibility, core strength - Virtual vs in-person.] Brooke Harshbarger, DPT, PT: Two other forms of more general exercise is a seated exercise program or doing yoga. So the National MS Society has a great resource called Chair Fit with Nancy, where all types of exercises are performed from a sitting position. So there's a link on this slide directly to those videos or you can go to the National MS Society website. With yoga, you could complete traditional yoga or adapted. Adapted could be sitting yoga stretches or it can be a class that's specific to MS. If you do choose to participate in yoga, you could get benefits from your balance, flexibility, and core strength. And then we have the benefit during COVID times of having virtual classes. So you could follow along with an MS specific class from home. Go ahead and next slide. [Text on screen: Getting Started. Cardio: OSU's 8 Week Walking Program.] Brooke Harshbarger, DPT, PT: Yep. So when you're starting with cardio, it's hard to know how far to start and how to push yourself each time you're going. So this eight week walking program is something that I give patients on their first visit most often. I like this program for a couple different reasons specific to MS. You don't have to start at week one. You can figure out where your current walking distance is or walking time and then start at that amount. It also incorporates rest intervals, which I like for people with MS because of the tendency to get fatigued after a certain distance or a certain amount of time. And this table can also be translated for use with other types of cardio such as swimming or cycling. Next slide. [Text on screen: Getting started, how else can I increase physical activity? - Gardening - Chores - Walking the dog - Cooking - Taking the stairs - Dancing] Brooke Harshbarger, DPT, PT: So don't forget about day-to-day physical activities that you may already be participating in, such as gardening, chores, taking your pet on a walk, cooking, taking the stairs instead of using the elevator or even dancing. [Text on screen: Community Resources. - OSU Adapted Sports program. For more information on OSU Adapted Sports, visit the community calendar: https://teamup.com/ksd5ut3ac3immpgxdg - Franklin Park. Medical provider must complete a referral/registration form. For more information about Franklin Park, visit: http://columbus.gov/recreationandparks/programs/Therapeutic-Recreation/] Brooke Harshbarger, DPT, PT: So it's important to note that if you are completing one or more of those types of exercise, you may feel more fatigued because you're doing multiple different forms of physical activity. The ultimate goal is to get moving as often as you can no matter what type of activity you choose. We're lucky to have a lot of community resources in the greater Columbus area to help you get involved with exercise. OSU has an adapted sports program if you're interested in group or athletic type classes and sports programs. There's a calendar where you can find community events if you want more information on that it's provided on this slide. There's also Franklin Park, which is a no cost gym, which caters to individuals with a medical diagnosis that makes it hard to exercise. So because of that, you have to have a medical provider fill out a registration or a referral form and then you take that with you on your first day to go to that gym. So this can be done by your physician or by a therapist. Next slide. [Text on screen: Community Resources, National MS Society. National MS Society Resources: - Ask an Expert - Educational Videos - Free from Falls program - Relationship Matters program - Webinar Series to learn strategies to live your best life with MS. To access the National MS Society calendar of virtual events, click here or visit https://www.nationalmssociety.org/ and go to the Resources & Support tab to find the Calendar of Programs and Events.] Brooke Harshbarger, DPT, PT: So like I've mentioned several times during this presentation, the National MS Society really is a great resource. They have a lot of different programs that are specific to MS, including exercise programs like videos and advice as well as non-exercise programs and information such as Ask an Expert or their Relationship Matters program. To access the National MS Society calendar of events you can click on that link or go to the nationalmssociety.org website, go to their resources and support tab and then go to their calendar of programs and events. Next slide. [Text on screen: National MS Society, exercise tips. - Stay hydrated, cold water will help keep your body temperature low - Exercise in a cool room and if outside, exercise at cooler times during the day - Remember to stretch afterward - No pain no gain should not be your mantra - Start low and go slow - Prioritize safety to reduce risk of injury - Consult a medical professional before starting a new exercise routine] Brooke Harshbarger, DPT, PT: So lastly, I want to leave you with some general exercise tips. It's always important to hydrate before, during, and after exercise for many reasons, but related to MS, it will help keep your body temperature low. On that same topic of heat sensitivity, exercising in a cool room, or if you want to exercise outside exercise at a cooler time of the day to help monitor that heat sensitivity. Like we talked about, remember to just stretch before and especially afterwards. And no pain, no gain should not be your mantra. Instead, make your mantra start low and go slow. Always prioritize safety to reduce risk of injury during exercise. And remember, you can consult a medical professional before starting a new exercise routine. Next slide. [Text on screen: Special considerations and precautions to take. - Fatigue: Schedule resistance training on non-endurance training days. - Spasticity: Consider foot and/or hand straps with cycling. Use machines instead of free weights. - Heat intolerance and reduced sweating response: Adequate hydration, keep room temperature below 20 and 22 C. Using of cooling fans and precooling. Plan exercise in the morning when body temperature is at the lowest. - Cognitive deficits: Follow written instructions/diagrams. Exercise tasks should be initially performed with minimal resistance. May require additional supervision during exercise to ensure safety. - Lack of coordination: Consider upright or recumbent arm/leg cycling to ensure balance and safety. - Sensory loss and balance problems: Perform exercises in a seated position; use machines or elastic bands instead of free weights. - Higher energy cost of walking: Adjust workloads to maintain target heart rate and check heart rate regularly. - Daily variations in symptoms: May need exercise supervision, make daily modifications to exercise. - Urinary incontinence/urgency: Adequate hydration, and schedule exercise in close proximity to restrooms. - Symptom exacerbation: Discontinue exercises and speak to a provider (PT, physician). Resume exercise program once symptoms are stable and medically ready.] Brooke Harshbarger, DPT, PT: So I'm not going to read to you this very wordy slide, but I did want to provide this to you as a resource to look at and maybe consult your doctor or your physical therapist with because a lot of these special considerations listed on the left are things that people with MS deal with that can make it hard to exercise. So you can look through this list and maybe take some of these precautions that are mentioned on the right or bring this up at one of your next doctor's visits. And that was all. Thank you. [Text on screen: Resources] [Text on screen: Meena Khan, MD Sleep Medicine Specialist, Neurologist] Kristi Epstein, APRN-CNP: Brooke, thank you so much. That was a great presentation and so inspiring. Hopefully it'll get us all started with a little exercise. So along with physical activity, as we all know, it's really important to make sure we're getting enough rest. So that's what our next presenter is going to talk to us about. It is my distinct pleasure to go ahead and introduce Dr. Meena Khan. She's an associate professor of clinical medicine at the Ohio State University in Wexner Medical Center. And she completed medical school as well as her neurology residency and sleep medicine fellowship at Ohio State University. She's a true Buckeye. Currently, she's the program director for the sleep medicine fellowship program and is the co-director of the annual OSU Sleep Symposium. Her clinical interests are neuromodulation for sleep disordered breathing and sleep disordered breathing in neuromuscular disease. Dr. Khan has a couple of cool questions for you to consider before she speaks. So let's check those out. [Text on screen: Poll Question] Kristi Epstein, APRN-CNP: It's going to pop up here? So select the best answer. How many hours of sleep do you think you need a night? Let's see what everyone thinks. Don't forget to hit submit so that we can see what your answers are. Okay. And so it looks like we had some mixed response, but the majority of you said seven to eight hours of night. All right. And then the next poll question. How many hours of sleep do you feel that you get per night? So go ahead and put down what you feel is the number of hours that you might get during a night's sleep. Remember to hit submit. Give you another second or two here and let's see. So people aren't sleeping all that well it looks like. So it looks like we need to hear what Dr. Khan has to say. So I look forward to hearing what her tips are and welcome Dr. Khan. [Text on screen: Tips for better sleep. Meena Khan MD 4/8/21] Meena Khan, MD: Thank you. It's a pleasure to join you guys this evening. [Text on screen: Objectives. -How our brains sleep - What you can do to obtain good sleep] Meena Khan, MD: So what I want to do is just talk to you guys about generally how do we sleep and what are some things that you can do or we can all do in general to try to obtain good sleep. Next slide. [Text on screen: Two Process Model of Sleep. Two primary driving forces for sleep. - Circadian drive: Biological sleep clock in the hypothalamus of the brain. Homeostatic drive for sleep. - Sleep debt one accrues the longer they are awake.] Meena Khan, MD: So basically how we sleep depends on two things. So we have what's called a circadian or a sleep drive. So we all have a sleep or a biological sleep clock in our brain in an area of the brain called the hypothalamus. And so this basically drives natural times where we feel alert and natural times where we feel sleepy. So if you notice there's a time of day where you always hit the wall, there's a time of day where you always get a second wind or pretty consistently, it probably has something to do with this biological sleep clock that we all have. And the other thing that determines how we sleep is something called sleep drive. So the longer we're awake, the more need for sleep that we have. Next slide. [Text on screen: Circadian clock. "Biological sleep clock" in the brain - set to 24.2 hours. Zeitgebers: Light, eating, activity, social cues.] Meena Khan, MD: So in terms of this biological sleep clock, basically our alertness increases in the morning and kind of has a steady increase. And then afternoon time it takes a dip. So that's why we typically get sleepy after lunch. In some cultures, they take a nap, so that's a natural dip in our alertness. If you're having sleeping problems or sleep disorders, this dip might hit you a little stronger than somebody else where maybe you feel like you have to take a nap, you can't really stay awake. And then you get a second wind later in the afternoon where you feel more alert and then sometime in the nighttime your alertness drops off. And usually the dip of our alertness is anywhere between two to 6:00 A.M. for most of us. And so usually that's the lowest that our alertness level is going to be. And so where this can give people trouble is if they're working nights, they may struggle staying awake during that last part of their shift or driving home. The other interesting thing about our sleep clock is that it's actually a little over 24 hours long, meaning when they put people in dark environments without any environmental cues, the tendency is to go to bed later and get up later every day. And so for somebody who may not have a lot of structure to their day, don't have any set times they get in and out of bed or certain places that they have to be every day, and they sleep whenever they want. Sometimes they'll say, "I'm going to bed later and later and later." And then they'll come in when they're not falling asleep until 6:00 AM. And what's happening is they're actually going with their natural sleep clock. There are these things, what we call zeitgebers or things that we can do to entrain our schedule, our sleep clock to the 24 hour schedule that we have. And light is the strongest thing. So our brains are designed that it should be bright light when we're awake and it should be dark when we're sleeping. And the more that we stick to that, the more our brain will entrain or get trained to sleep the schedule that we want. The other things are our eating schedule, our activities, and our social cues. So having some structure of a time you get up and start your day, things that you do during the day, a time that you wind down, a time that you go to sleep, the more routinized you are with those things, the better your sleep is going to be. Next slide. [Text on screen: Homeostatic drive for sleep: Amount of sleep debt a person incurs throughout the day.] Meena Khan, MD: The other thing is our driver, our need for sleep. So the longer we're awake, we actually build up a chemical called adenosine, and the higher that level is, the more sleepy we are. Caffeine actually works as an adenosine blocker. That's how it promotes wakefulness. So things like sleeping in late, taking naps can blunt the sleep drive. And so you may not be as sleepy as you would like to be at night when you want to go to bed if you haven't built enough of this sleep drive or the sleep need by having enough time awake during the day. Next slide please. [Text on screen: Ideal time for sleep] Meena Khan, MD: Ideally, our ideal time to sleep is when our circadian or our sleep clock alertness level is low and our sleep drive is high. And if we can get those things to sync up, that's the ideal time to sleep. Next slide please. [Text on screen: Difficulty sleeping] Meena Khan, MD: So what typically happens is when people have difficulty sleeping, it's when they're going to bed when they're not sleeping. So they'll say, "Well, I feel like I should get into bed at 9:30 because that's when my partner gets into bed, or that's when my family gets into bed, but I'm not really sleepy at 9:30 and I don't really fall asleep until midnight." And then they get frustrated because they're laying there for two or three hours unable to sleep. But the problem is they're trying to sleep at a time when their body just isn't sleepy enough to sleep. The other thing that can give someone trouble sleeping is if they're not building their sleep drives. So they're getting out of bed late, they're taking naps. Sometimes people if they don't fall asleep until two or 3:00 AM they'll feel like, "Okay. Well, I'm finally sleeping, so I'm going to stay in bed until noon." But then what that does is it messes their sleep up for the next night. Next slide. [Text on screen: How can we obtain good sleep?] Meena Khan, MD: So how can we obtain good sleep? What can we do to sync up our circadian or our sleep clock with our sleep drive so that we can sleep well? [Text on screen: Entrain your circadian sleep clock. - Bright light when awake - Dark during sleep time] Meena Khan, MD: So one of the biggest things you can do if you want to train your sleep clock is to make sure that your light dark exposure is optimal. So when you get up in the morning, you want to expose yourself to bright light. Open up your shades, open up your windows, get outside if you can, as much bright light as you can. In the wintertime when it's dark, if you can get a bright light box, sometimes you can get them pretty reasonably off Amazon. Get those bright lights on and be in bright light for most of the day. And then in the evening, nighttime, you make it dimmer and it should be dark when you're trying to sleep. If for some reason you can't sleep in pitch black, then maybe a nightlight would be okay. But you definitely don't want to have huge sources of light, and this includes environmental light. Depending on where you live, you may have a lot of street light. And so getting dark curtains, blackout shades, getting shades for your eyes, that can all help in training or training your sleep clock that this is the time I want to be awake and this is the time I want to be asleep. If you're in dim light all the time, so you're in dim light all day, maybe it's a little bit more dim or darker at night, your brain may not be getting the clues it needs about when you want to be awake and when you want to be asleep. So the bigger the difference between your daytime light and your nighttime darkness, the better your brain is going to get trained for wake and sleep. Next slide. [Text on screen: Build your sleep drive. - Out of bed the same time every day. - Avoid prolonged rest or sleep during the day. - Be engaged and active during the day within your abilities.] Meena Khan, MD: And then building your sleep drive. So the best way to do this is to get out of bed the same time every morning. And we can vary within 30 to 60 minutes, but you definitely don't want to get up at 7:00 A.M. one morning and noon the next day. You want to try to make it pretty consistent. Avoid prolonged resting during the day. Sometimes you have to rest. Sometimes your body needs a break, sometimes your brain needs a break. But maybe try to keep these breaks to 20, maybe 30 minutes once or twice a day, as opposed to laying down for two to three hours in one block in the middle of the day if you can. And then being engaged in activity during the day. So it's really nice to hear in the previous talk about what are some of the physical activities that you can do that's safe for you. And talking to your doctor and talking to your physical therapist about what are the things that you can do to be active that's safe for you. Because the more active engaged you are during the day, the better you're going to sleep at night. Next slide. [Text on screen: Train your brain for sleep. - Bed is for sleep only. - Go to bed only when sleepy. - Get out of bedroom if can't sleep. - Avoid sleeping in other areas. - Same wake time every morning.] Meena Khan, MD: The other thing is you want to train your brain that your bed is for sleep. Sometimes when we can't sleep, we end up doing things like watching TV, looking at our phone, checking our email, checking our social media. I'm up, I might as well go do the dishes or something like that to pass the time. Well, all of those things are going to be counterproductive to sleep. So some things that you can do to train your brain that this is my sleep environment, this is my sleep time, one is that the bed is for sleep only. So we say the bed should be for sleep and intimacy. Everything else should be somewhere else. You want your brain to psychologically think of your bed with sleep. It's going to think that better or quicker if all you do is sleep in your bed. So for example, when you look at your bathtub, you probably just think of taking a bath or a shower. You don't think about going there and sleeping. You don't think about eating your dinner there because all you do in the bathtub is take a bath or a shower. So whether we know it or not, our brain is making these connections. And so if we want our brains to sleep better, then we want it to associate a certain place with sleep. And so that's the best way to do it. The other thing is don't sleep in other environments. So don't sleep in your bed and then go sleep on the couch, then go sleep in the guest room. Your brain doesn't have one place where it sleeps that it makes that association. So it's best to just sleep in one space every time that you have a sleep period. Only go to bed when you're sleepy. So if you go to bed and you're not really sleepy ... And sometimes it's difficult to tell. But sleepy I would say is when you feel like your eyes are closing and you're going to doze off as opposed to being tired where, yeah, I'll lay there, but I'm not really falling asleep, I'm just laying there. The longer that you're in bed awake, the more frustrated you're going to be about your sleep. And then your brain also isn't making these great connections. So only go to bed when you're sleepy. That way you don't have a whole lot of time laying there awake. And if you can't sleep, go ahead and get out of the bedroom. Now, I don't tell people you have to get out of the bedroom. If you're okay laying there and tossing and turning a little bit and see if you can go back to sleep, that's okay. But if you're getting frustrated and you feel like you have to do something, then just get out of your bed and ideally out of your bedroom, but definitely out of your bed and do it in a different space. And if you have to do something, I would do something boring. So checking email, checking social media, playing games, doing crossword puzzles, these are not boring activities. If your brain is already having trouble sleeping, doing something you're engaged in will not make it sleepier. So it's best to avoid electronics because electronics tend to be engaging and the light, even if you have those blue light shields on, it still can affect your sleep. Your brain's already having trouble settling down. You don't want to make it harder for it. So we say if you want to read, read a physical book or a magazine in something you're not interested in. This is the last thing you want to do. This is the last thing you want to read. Think about the days when you were in school and the most boring subject that you had. That's what you want to be doing. You don't want to be doing things you're interested in. Avoid sleeping in other areas, which we covered. And then the same wake time every morning again to build your sleep drive, but also for your brain to associate 7:00 A.M. it's time to get up for the day. And the more consistently you start your day at 7:00 A.M. the more your brain is going to make that association. Next slide. [Text on screen: Sleep Hygiene. Caffeine: - 200-300mg caffeine deter sleep - Half life of caffeine: 5-6hrs - 8 ounces of coffee: 95mg caffeine - 8 ounces of McDonald's coffee: 72mg - 8 ounces black tea: 47mg - 8 ounces of Starbucks coffee: 180mg caffeine - Mountain Dew, 12 ounce: 55mg caffeine - Coca-Cola 12 ounce: 46 mg caffeine] Meena Khan, MD: So just some things about what we call sleep hygiene or good sleep habits. A lot of times when people have trouble sleeping, they read about all these things on the internet anyway, and a lot of times people are doing these things, but they still have trouble sleeping. But I just wanted to make sure to go over a couple of things that I think sometimes people underestimate. So caffeine. Caffeine has a half-life of five to six hours. So what that means. It has a half-life of five to six hours. So what that means is it takes five to six hours for your body to process half of the caffeine it's drinking. So it takes 10 to 12 hours for it to fully process that caffeine getting out of your system. So if you're drinking soda, coffee, tea at 5:00 or 6:00 at night, it's probably still in your system when you're trying to go to bed. So it's best to stop these at least 10 to 12 hours before you go to sleep. And there can be various amounts of caffeine in different things. So an eight-ounce cup of coffee from McDonald's has about half the caffeine as an eight-ounce cup of coffee from Starbucks. So there can be a lot of variety in how much caffeine is in the products we're drinking. But generally what we ask people is about 10 to 12 hours before you want to go to bed, to cut out your caffeine. Next slide. [Text on screen: Sleep Hygiene. Nicotine. - Stimulant: cause CNS arousal - Smokers believe it has a calming effect Alcohol. - Disrupts sleep architecture, decreases REM sleep. - Takes 1 hr to metabolize 1 unit of alcohol. - 6 ounces of wine: 2 units; 8.5 ounces: 3 units of alcohol. - 1 pint of beer: 2 units. - 1 shot of liquor: 1 unit] Meena Khan, MD: So nicotine. A lot of times smoking makes people feel like they're getting relaxed. It helps them sometimes with their anxiety, and that's why sometimes quitting smoking becomes difficult when people are in stressful situations. But nicotine is a stimulant, and studies show that people who smoke have more sleep issues than people who don't. So if you are someone who's using nicotine, avoiding using it at night is going to help your sleep. Alcohol is something else that can disrupt sleep. So drinking alcohol may help you fall asleep, but it actually fragments your sleep the second half of the night. So it causes you to keep waking up from sleep the second half of the night, and it decreases your sleep quality. It decreases your REM or your dream sleep. So if alcohol is something that you drink with dinner sometimes, or even if it's something you drink with dinner every night, we would just say try to limit it to one drink and finish it four or five hours before bedtime. It takes about one hour to metabolize one unit of alcohol, and a six-ounce glass of wine would have two units. So at least two hours to metabolize that. And then with every drink you add, it's more and more time to metabolize that. So it can affect your sleep, it can affect the quality, and it can cause you to wake up quite frequently. Next slide. [Text on screen: Sleep Hygiene. Exercise: Activity helps promote sleep - exercise at anytime] Meena Khan, MD: So exercise. So as we heard in the previous talk, there's a lot of ways to try to incorporate activity and exercise into your program. And if you're able to do that safely, that is going to help your sleep. It doesn't matter what time of day you do it, it doesn't matter when you do it. Any activity at any time is going to really help with your sleep. Next slide. [Text on screen: Timing of sleep medication] Meena Khan, MD: I just want to say one brief thing about sleep medications. I could probably give another 20-minute talk on sleep medications. There are no medications that are like, "Oh, if you use this medication, it's guaranteed to work." And sleep medications in general are a short-term fix. So typically the story is, if someone gets a sleep medicine that works, it works for a little while, but then it loses effectiveness and they have to go up on the dose, they have to switch the meds. And then years go by, and they've been on multiple medications and they still have trouble sleeping. Or if there's somebody where, yeah, the sleep medicine really works, they can't sleep without it. So really those behavioral things that we discussed before, those sleep tips we talked about, those are the best ways to try to optimize your sleep. But if you're somebody who, maybe you have anxiety, you have trouble relaxing, your mind is always going, you're doing all of these sleep tips, you have a consistent time in and out of bed, but you're still having trouble, and you talk with your primary care or your sleep medicine provider and they say maybe you can try a sleep medicine, you just want to make sure that you're taking it and doing it with the behavioral therapy. So if all you do is take a sleep medicine and don't do some behavioral changes to help your sleep, you may notice that the medicine isn't going to help or it's going to be short-lived. So you want to take it when you're sleepy. You want to take it when you think that your body is ready to go to sleep, to just help take the edge off so you can get to sleep. If you're taking the medication when you're not sleepy or tired, then it's probably not doing anything. So if you take your medicine at 9:00 PM but you don't fall asleep till midnight or 1:00, the medicine probably had nothing to do with you falling asleep, that was probably when your body was ready to sleep. So just some things to think about. Next slide. [Text on screen: If you have trouble sleeping: CBT-i coach] Meena Khan, MD: So lastly, if you are having trouble sleeping and you feel like you need some guidance, maybe you feel like, "I'm doing all these things that you're saying, but I still can't sleep," there is this. It's a free application if you have a smartphone. It's called CBT-i Coach. So you can go to the Apple Store or Google Play and get this and you can download it, and it's going to walk you through sleep scheduling, relaxation techniques, some of the tips that we discussed in this talk, and really work in an individualized plan with you to help you sleep better. So this has been helpful for patients who are motivated and really want to do some behavioral changes to help their sleep. Next slide, and that's it. Thank you. [Text on screen: Thank You. www.wexnermedical.osu.edu] Kristi Epstein, APRN-CNP: Thank you so much, Dr. Khan. What a wonderful presentation. And Dr. Khan is a great example of one of the embedded specialists that you could see in our Quality of Life clinic, as well as Dr. Harshbarger. So thank you for that great talk and those wonderful tips. [Text on screen: Tirisham Gyang, MD MS Specialist, Neurologist] Kristi Epstein, APRN-CNP: So what I'm going to do is move on now, and I'm going to introduce Dr. Tiri Gyang, and many of you may have met her at this point. She is a neurologist specializing in the treatment of MS, demyelinating diseases, and autoimmune disorders of the central nervous system. She's at the Ohio State University College of Medicine, where she is the program director of the Multiple Sclerosis Fellowship. She's currently the site principal investigator for the MS clinical trial here at OSU. She's collaborating with other disciplines to build the multidisciplinary clinics in neurorheumatology and neurosarcoidosis. She believes in providing customized, comprehensive, and interdisciplinary care, giving patients the tools they need to thrive and maintain their quality of life. She's a National Multiple Sclerosis Society scholar as well as being a member of the American Academy of Neurology. So let's welcome Dr. Gyang. She's going to give us a great update about current research in our MS Center at the Ohio State University Wexner Medical Center. Dr. Gyang? [Text on screen: Research Updates. Tirisham Gyang, MD April 8th 2021] Tirisham Gyang, MD: Thank you, Kristi, and what wonderful lectures we've had about sleep and diet and exercise. I've learned so much from these presentations. I just have a very short presentation on the current research that we're doing right now at Ohio State University. Next slide. [Text on screen: Current research at OSU. Clinical trials: phase 3 - RRMS study of BTK inhibitor - PPMS study of BTK inhibitor COVID19 vaccine study in MS Lab (translational) research: - Repair pathways in MS - The impact of aging in MS - Immune response to DMTs] Tirisham Gyang, MD: So I'm going to be talking about a few phase three trials that we have that are about to start enrolling very soon. And I'm going to explain what we're testing and what patients we're looking for. And I'm sure a lot of you're aware we have a COVID vaccine study in MS that I'm going to be talking about. And then finally, I'll talk a little bit about some lab research, more translational research that's happening, looking at ways to repair pathways in MS, aging in MS, and looking at biomarkers for disease modifying therapy response in MS. So we're talking about a few of these studies in the next few minutes. Next slide, please. [Text on screen: Stages of Clinical Trials - Preclinical: Several years. - Phase 1: Months. - Phase 2: Months to years. - Phase 3: Years to decades. - Phase 4: Ongoing] Tirisham Gyang, MD: So I just have this diagram to show us how things go from being discovered in the lab all the way to the point where they go out in the market. So the preclinical research is when the study is still in the lab. And we have a few, I'm going to talk about a few studies that are still in that stage here. That usually takes a few years before an idea in the lab actually becomes something that we could test in human beings. And then we have a few phases of clinical trials. So we have phase one, phase two, phase three. Phase three trial is usually the big trial that goes to the FDA, and the FDA uses that to determine if a medication or a procedure or a therapy is effective enough to treat that disorder. And I'm going to talk about a few phase three trials that we're working on here. And then phase four is out of the market. When the drug is in the market in the population, there are trials that can still be done. Next slide, please. [Text on screen: Current MS DMTs - Interferon Beta: Rebif, Betaseron, Avonex, Plegridy - Glatiramer Acetate: Copaxone, Glatopa - Teriflunomide: Aubagio - Fumarates: Tecfidera (DMF), Vumerity, Bafietram - S1P1 modulators: Fingolimod, Siponimod, Ozanimod - B cell depleting therapies: Ocrelizumab, Rituximab, Ofatumumab - Natalizumab: Tysabri - Others: Alemtuzumab, Cladribine] Tirisham Gyang, MD: I'm sure you're all aware, these are the current disease modifying therapies for MS. With each of these therapies, the step process of development happens with each of these therapies. So it goes through the preclinical phase. There's a phase one, phase two, phase three before it is approved to be used for MS. And so if you think about any drug that you are on, a lot of people had to go through the trials and had to go through research to get that approved and certified for treatment in MS. Next slide. [Text on screen: BTK inhibitors in RRMS and PPMS. Bruton's tyrosine kinase (BTK) inhibitor - BTK-i - BTK is an enzyme found inside certain immune cells: B cells; Myeloid cells, macrophage and granulocytes; Microglial cells in the central nervous system - Blocking BTK may have therapeutics benefits in: Certain types of malignances - leukemia, lymphoma; Graft vs host disease - transplant patients; Autoimmune diseases] Tirisham Gyang, MD: So the few trials that we're working on right now are both phase three trials. And there's a specific compound, it's called a BTK inhibitor, that is being explored in both relapsing MS and progressive MS, primary progressive MS. So what actually is this compound, or what is this drug? So the BTK inhibitor, it inhibits a specific enzyme. The enzyme is called Bruton's tyrosine kinase. And this enzyme is present in different types of immune cells. So for instance, we find it in B cells, in myeloid cells, and more interestingly, we find it in certain immune cells that are within the brain and within the spinal cord. These are called microglial cells. And what we are learning, that blocking this enzyme, inhibiting this enzyme, has some benefits. For instance, it is used in some leukemias or lymphomas, so we know we could use it for malignancies. It's also used in graft versus host disease. So patients that have a transplant that need to be on an immune suppressive drug to prevent a rejection of the organ that they received, some of these drugs are used for disorders like that. And then more recently there's a lot of exploration for these drugs to be used in autoimmune diseases, MS being one of them. And we'll talk a little bit about how there could be a lot of advantages for using this drug in MS. Next slide, please. [Text on screen: BTK-i in RRMS and PPMS. Potential advantages of BTK-i in MS: - Effects on both adaptive and innate immune cells - Ability to penetrate the blood brain barrier - Direct effect on microglia cells in the CNS - May have neuroprotective effects - Potential benefit in both relapsing and progressive MS Preliminary studies: - EAE - BTK-i effectively treats experimental mouse model of MS - RRMS - BTK-i vs. placebo - 12 weeks. - 85% relative reduction in new gadolinium-enhancing lesions - 89% relative reduction in new or enlarging T2 lesions (secondary outcome)] Tirisham Gyang, MD: So what are the potential advantages of this BTK inhibitor in MS? So a lot of the MS treatments usually target what we call the adaptive immune system or the adaptive immune cells. However, we talked about different cell types that this enzyme is found in. And so the advantage is that it can affect not just the adaptive immune cells, but also what we call innate immune cells. Another big advantage is that this drug actually gets into the brain. So some MS drugs actually just affect the immune cells outside of the brain, so they affect your blood cells, and that translates into preventing inflammation in MS. But this unique compound or this unique drug actually penetrates into the brain. And as we said, it has direct impact on certain immune cells that are found in the central nervous system. These are called microglial cells. And so in addition to having anti-inflammatory properties, we think it could also have a neuroprotective effect. So helping to preserve brain volume, helping to protect brain volume, right with... it's working in the brain. And we are looking at this for both relapsing and progressive MS phenotypes. Now, there have been a few preliminary studies of this drug. We have an animal model of MS called EAE, and it was found that using this BTK inhibitor was effective in stopping the animal model of MS. So we use mice for experiments to see how different compounds can help to reduce inflammation or stop the process of inflammation in MS. And interestingly, this was effective, these drugs. Now, there have been studies in relapsing MS, and I have the reports for one of the studies where a BTK inhibitor was compared to placebo, and there was a significant reduction in the amount of enhancing lesions in the brain and new lesions in the brain. I'm sure a lot of you are aware that we look at your brain MRI whenever we're treating MS. So there may be potential. These preliminary studies tell us that there may be a potential use for these compounds with relapsing remitting MS. Next slide, please. [Text on screen: Phase 3 BTK inhibitor (BTK-i) in MS. RRMS: - BTK-i 60mg daily vs Teriflunomide 14mg daily - Primary end point - annualized relapse rate PPMS: - BTK-i 60mg daily vs. placebo - Primary end point - time to onset of 6-month confirmed disability progression] Tirisham Gyang, MD: And so we have two studies we're about to launch. The one is a BTK inhibitor in relapsing remitting MS, and it's going to be compared to an active control, which is teriflunomide, or Aubagio. And we are looking primarily at the annualized relapse rates. So that's what the study is going to be measuring. And then we're also looking at it in primary progressive MS. And in primary progressive MS we're comparing it to placebo, and we're going to be looking at the confirmed disability progression over six months. That's the primary outcome. So we are very soon about to start enrolling patients for these studies, and you can reach out to us if you're interested in more information about them. Next slide, please. [Text on screen: COVID19 vaccine in MS study. - Questions the study will help to answer: Does MS affect the response to the COVID vaccine? Are there DMTs that affect the response to the COVID vaccine? - Currently enrolling patients MS and healthy controls - Blood testing prior to and after COVID vaccination - Unique assay to test for COVID19 neutralizing antibodies] Tirisham Gyang, MD: Now, in a different study, we're also working on the COVID vaccine study in MS. We talked about this with the last few presentation events that we did. The big question here is, does MS affect how an individual responds to the COVID vaccine? The COVID vaccine, there's a few new vaccines, MRNA vaccines, that have never been used in massive scale before this. And so the question is, is MS going to affect how people respond to the vaccine? And then the second question is, are there specific disease modifying drugs that a patient is on that will impact the way that they respond to a vaccine? So these are the major questions we're trying to answer with the study. We are currently enrolling. If you are interested, the next slide is going to give us some information about how to contact us. And basically what we're doing is we have an investigator here at OSU that has developed a very unique assay to look for COVID-19 antibodies, neutralizing antibodies, and we will be testing for those antibodies before you get the COVID vaccine and after you get the COVID vaccine. And there are a few people that we're going to follow longitudinally after that. Next slide, please. [Text on screen: Contact information. Misty Green: - 614-293-6486 - Misty.green@osumc.edu Contact your provider: - mychart Neurology clinic - 614-293-4969] Tirisham Gyang, MD: So this is just some contact information if you want to hear more about the study. That's the flyer for the study. But if you want to hear more, there's a phone number, there's an email, or you can reach out to your neurology doctor, your MS doctor on MyChart to find out if this is something that you could be a part of. Next slide, please. [Text on screen: Dr. Segal - Lab research. Interrogation of repair pathways in MS. - Investigating the potential of novel white blood subsets. - Suppress destructive inflammation. - induce remyelination/nerve fiber regeneration in mouse models of MS. Isolating cell subsets from human umbilical cord blood and testing their neuroprotective and pro-regenerative properties. Goal: To ultimately develop drugs that reverse damage and restore lost neurological functions in people with MS.] Tirisham Gyang, MD: And just a few more minutes, I'm going to talk about some lab research that's going on. We talked about preclinical research that usually happens before it gets out to be tested in people. So in Dr. Segal's lab, there's a few interesting projects that are going on. I think one of the most interesting aspects of MS right now is, how do we repair damage that has been done due to MS? All the drugs we have help to prevent future damage or future relapses, but then how do we fix the damage that has been done? So there's a lot of research that's going on in Dr. Segal's lab that's trying to answer that question. One of the studies has shown us a very unique or a new type of white blood cell that we didn't know about before that may have neuroprotective properties. It may help to prevent destructive inflammation and it may help to induce remyelination. The remyelination is what helps us to repair those broken pathways that have happened in MS. Also, they're also looking at human umbilical cord blood to test for neuroprotective properties. And this is really, really interesting. Hopefully, the goal is, can we find a way to reverse the damage that has been done, and can people that are disabled regain function that they have lost? So far we don't have medications that are great at reversing disability. All the medications, all the disease modifying therapies prevent more damage from being done. So this is a potential interest of, we may have something in the future that could help us regain lost function. Next slide. [Text on screen: Dr. Segal - Lab research. Impact of aging on MS: - insights into new approaches for the treatment of established progressive MS. - strategies to block the transition from relapsing to progressive disease. - Goal: To increase our understanding of how changes in the body that normally occur during aging interact with the pathogenic pathways in MS to drive the transition from a relapsing to a progressive disease course. In depth analysis of immune responses in relapsing and progressive MS pre and post-initiation of DMT: - analysis of plasma, PBMCs, CSF, CSF cells - Goal: To discover biomarkers predictive of responsiveness to individual DMTs, or that reflect disease activity, and to elucidate new therapeutic targets.] Tirisham Gyang, MD: So a few other things that are happening in the lab. Other studies are looking at the impact of aging in MS. So with the natural or normal process of aging, how does that interact with the progression of MS in individuals that have MS? So there's a few studies looking at that. There's studies looking at how to block the transition from relapsing MS to progressive MS. So some people start with relapsing remitting MS and get to what we call secondary progressive MS. That typically happens over time, and we're all getting older over time. And so how can we block that transition and how can we prevent that disability that progresses gradually in a patient with relapsing MS? And in other very interesting studies, looking at biomarkers. Biomarkers to figure out, how well is a medication working? I'm sure we all know that a lot of times we try MS medications, there's no way to know, how is one medication better than another in an individual patient? So there is some research in trying to figure out, could we have biomarkers that tell us how well an individual will respond to a disease modifying therapy? And that's going to help us in deciding what's the best therapy for a specific patient. Next slide. [Text on screen: Thank You. www.wexnermedical.osu.edu] Tirisham Gyang, MD: I think this is the last slide. So thank you very much for listening, and if you have any questions about research participation, definitely let us know about it and we'll be happy to answer those questions. I'll hand this over back to Kristi. Kristi Epstein, APRN-CNP: Thank you so much, Dr. Gyang. That was very, very enlightening, and it's always very exciting to see what's happening in the lab and hear about the studies that we're doing here at the Ohio State University. So we've reached that period of the night where we're going to address our questions. It's time for the Q&A panel. [Text on screen: Benjamin Segal, MD MS Program Director, Neurologist] Kristi Epstein, APRN-CNP: So I would like to welcome the chair of our Department of Neurology and the director of the Multiple Sclerosis Center at the Ohio State University, Dr. Benjamin Segal. [Text on screen: Robert Fallis, MD MS Specialist, Neurologist Kristi Epstein, APRN-CNP: Also welcoming MS specialist Dr. Robert Fallis. [Text on screen: Margaret Hansen, PharmD Pharmacist] Kristi Epstein, APRN-CNP: And our MS clinical team pharmacist, Dr. Margaret Hansen. Benjamin Segal: Well, thank you, Kristi. This has been a wonderful series of talks, and I myself have learned a lot. And now let's learn some more, because we've had some interesting questions that have been posted. So I think I will answer the first question. And that is, "In MS, what percentage of phase three trials drug?" Well, historically, and this is for all phase three trials, about 40% of drugs are eventually approved. Now, for drugs that are entering phase two trials, that's the step before the phase three trials, only about 12% of the drugs actually are used in clinic following FDA approval. So, many drugs that we test early on and have no experience with... to be effective in the phase three trials. But once they pass the earlier, smaller human trial, which is the phase two, there's a higher success rate. Okay, next question I'm going to pose to Dr. Fallis. And that is, "What is considered a relapse?" Robert Fallis, MD: So a relapse has a couple of different definitions. One definition is something that a person with MS may just find that they have a new change in their arm or their leg. They just have a new change in how their body behaves. That is what we call a clinical relapse. Since MRI scans were invented, there also are relapses that your doctor can see on the MRI scan. You may not be aware of those relapses, but in fact those are really considered relapses. So relapses generally are followed by periods of recovery. Maybe not 100% recovery, but there is going to be some recovery in most cases. Benjamin Segal, MD: Okay. Thank you, Dr. Fallis. The next question I think would be most appropriately addressed based on today's talks by Dr. Brooke Harshbarger, and that is, should MS patients avoid going into a hot tub or sauna? Brooke Harshbarger, DPT, PT: I wouldn't necessarily say you have to avoid that, but you have to pay attention to how your body responds to that. I would say blanket statement, it might not be a good idea just because there is a really high tendency, at least with the people that I see and from research, that people with MS are sensitive to heat. So you just have to keep that in mind when you're making the choices that you make, such as what was recommended about sleep. If you know that there's higher chance of sleep problems and you have to take control of that and address it as necessary. And so it's highly dependent on how your body responds to it, but just take it into consideration that your body may not respond well to it. Benjamin Segal, MD: Okay, great answer. A related question is, if a person with heat sensitivity shouldn't overheat, is working out still effective if you don't work up a sweat? I'll redirect that to you, Brooke. Brooke Harshbarger, DPT, PT: Yes, absolutely. You don't have to work up a sweat in order to work out and know that it was beneficial. When you're doing chores or gardening, you're not necessarily working up a sweat unless it's a hot day and you're still getting those benefits from contracting and relaxing your muscles over and over again. So if you do the stairs three times throughout the day, you're getting benefits from contracting and relaxing your quads and your glutes without necessarily breaking a sweat because you're breaking up that exercise throughout the day. So it might be more beneficial to not break a sweat and to break up exercise, that way. You don't have to break a sweat. Benjamin Segal, MD: Okay. Thank you. Okay, another question involves a therapy that has been used at a number of different centers, and that has been subjected to recent trials. And that is HSCT, which stands for hematopoietic stem cell therapy, which is long term, but what it involves is, treating someone with chemotherapies to basically wipe out their immune system and then reconstituting the immune system with bone marrow cells. So bone marrow cells are where all immune cells develop, and with this therapy you remove immature very young white blood cells from the bone marrow and then treat patients with chemotherapy, which will wipe out the immune system. And once that's done, you replace the cells which have been eliminated with these new cells. And the idea is that MS is believed to be driven by abnormal inflammation in the brain and spinal cord, and you are re-educating the immune system, replenishing the body with a new immune system that maybe won't cause this abnormal inflammation. That's the idea behind it. So the question is, is that something that we consider using? Maybe we could also talk a little bit about the results of those trials and when someone might consider HSCT or hematopoietic stem cell therapy. So I'll ask Dr. Gyang for her thoughts on HSCT. Tirisham Gyang, MD: Sure. So there have been a few trials that have looked at this type of therapy for patients with MS. Typically, these trials have looked at patients with very, very highly aggressive inflammatory MS. So basically you're thinking about someone that has multiple relapses, a lot of inflammation. When we get an MRI, there's a lot of inflammation going on, and the results have actually been very good. I think there's a Canadian trial that has followed these patients over a very long time, and a lot of them just had very, very good results with this type of therapy, but it's not something that is for everyone. So it's a very, very aggressive type of therapy. I know from some of the early trials, there was at least one death during the process of immune ablation because we are completely wiping out that immune profile. And so there's a risk for infections and other things happening during that time and then the stem cells are reinjected or the bone marrow cells are reinjected after that. So there's a few trials I'm aware of that are going on now in some centers that are comparing HSCT with infusion therapies, Eculizumab or Tysabri. These trials are comparing how, is there additional benefit to doing such an aggressive therapy versus doing a standard infusion therapy that's usually very effective in MS. So I think there is a lot of potential. We may find out more information after this trial is done. I see in the comment it's saying in other countries, people are going to other countries to get it. So far in the US, it's not an FDA approved therapy for MS until we get the trials out and the FDA makes a decision on it. It's in experimental phase right now, but the results we have from the trials that have been done has shown very good promise in patients with highly active or highly inflammatory MS. There's not a lot of studies that have looked at this for primary progressive MS or progressive MS phenotypes. And a lot of times I get that question of, if you have primary progressive MS, if it's in a progressive phase, would this type of therapy be helpful? I don't know that we have the evidence to support that yet. Benjamin Segal, MD: Thank you Dr. Gyang, and I'd like to add to that. I know of at least one trial in progressive MS, HSCT and it failed. So it's probably, I think you're correct. It's more for patients with relapsing remitting disease or maybe progressive MS with superimposed relapses or a lot of inflammation as seen on the MRI scan. The other thing is, I remember I'm a little bit older than Dr. Gyang or maybe a lot older, and in the very early trials, it was actually a fairly high mortality rate. I think up to 10% of patients in some of the early trials died because the chemotherapy is quite potent and toxic. Now, they modified the protocol and the mortality rates are much less. In the most recent trials that I'm aware of, there have been no mortalities, but it is a very extreme treatment and usually reserved for people who are failing other therapies. So thank you. Robert Fallis, MD: Dr. Segal, could I ask you to just elaborate one more point on so-called stem cell tourism? Benjamin Segal, MD: Sure. And maybe Dr. Fallis, you'd like also to comment on this. When people talk about stem cells, sometimes they mean one thing and sometimes another. So a stem cell is simply a very immature cell that can develop into a mature cell that normally would be present in an adult. And when we talk about hematopoietic stem cells, these are immune stem cells. The reason, the treatment for HSCT is really the toxic, the chemotherapies that wipe out supposedly the bad immune system. So you could replenish it with a new immune system. Hematopoietic stem cell therapy is not meant to replace damaged cells in the nervous system like the damaged cells that produce the myelin or the damaged nerve cells or nerve fibers. Now, other people, of course, are interested in trying to replace the damaged nerve cells, the damaged myelin producing cells with new cells using a different type of stem cell that has been tried in animal models and there's some promise but we are far from being ready to use that in human successfully and there have been no trials that have even come close to being ready for application in the clinic. Now, there are private clinics in different countries that offer stem cell therapy that is meant to replace the damaged nerve cells and myelin producing cells. None of that is proven. In fact, we have a lot of evidence that it doesn't work and sometimes it can be dangerous. I, myself, had a patient who went to another country for such a stem cell therapy. She had some cells injected in her spinal fluid and she ended up getting a meningitis and dying. There have been other cases where some other stem cells meant to replace the damaged stem cells have been injected in the spinal cord of patients and have actually led to tumor growths. So those maybe in the future, but not in the immediate future, we will come up with stem cell therapies that actually replace damaged cells, but we're not there yet. And you have to be very cautious with regard to some of these clinics that are not authorized and offering those types of treatments. So Dr Fallis, would you like to expand on that further? Robert Fallis, MD: I don't think I could add anything more. I think that is very well said and I would urge caution to patients thinking about this. Benjamin Segal, MD: Okay, thank you. All right, another question. This one is for Dr. Khan. Dr. Khan, are restless legs normal in MS patients right before bed? Sometimes it's hard to sleep because of leg pain. Any recommendations? Meena Khan, MD: So restless legs is fairly common in general. I'm not sure if it's more common in MS patients, but it is something that can definitely give you trouble sleeping. So one thing you can do is talk to your primary care provider or your MS provider, but look for something called anemia where you have lower hemoglobin. And in particular if you have low iron stores, that can cause restless legs. Some medications can cause restless legs with some antidepressants. Things that can help restless legs, one is avoiding caffeine at night because that can make restless legs worse. Exercise, mild to moderate exercise can help with restless legs. And if none of that is really helping, then maybe seeing a sleep medicine provider can help you. There are medications that can be used if none of those other treatments are really helping you. Benjamin Segal, MD: Okay, thank you. So another question. I guess Misty Green is not on the line, but the question is how do we let you know that we are interested in participating in your studies? So Kristi, would you answer that question? Tirisham Gyang, MD: You're muted. Kristi Epstein, APRN-CNP: Okay. Can you hear me now? Benjamin Segal, MD: Yes. Kristi Epstein, APRN-CNP: Okay. So if you are interested in participating in the study, we do have flyers at all of our clinics that have our contact information. We also have direct contact. You can contact Misty. Her email is also on the flyers. You can contact Dr. Gyang or myself and Misty's email, which can be found on the flyers and is on the slide that Dr. Gyang just presented, is misty.green@osumc.edu and you can find the link on our website and on the slides that we presented tonight. If you have any question, you can call the clinic and they can connect you with us so that we can give you appropriate scheduling information and information about the trial. We're also looking for healthy controls. So anybody who may be interested in participating in the trial who has a spouse that doesn't have MS, or a partner or a friend and they would like to participate in the trial, we do need healthy controls. Benjamin Segal, MD: Thank you, Kristi. And with the healthy controls, I believe you're referring to the COVID-19 vaccine. Kristi Epstein, APRN-CNP: I'm referring to the COVID-19 study. And the other trials that Dr. Gyang was talking about. Once we get into the enrolling process, we will get that information out. Benjamin Segal, MD: Thank you so much. Okay, another question is what percentage of MS patients have primary progressive MS? And I'll just answer that. It's about 15%, 10% to 15%. Okay. Let's see... I'll just throw this out and see if anyone has a response. Is there research on benefits of evening primrose oil with MS? Kristi Epstein, APRN-CNP: I'm not aware of any trials. Anyone else? Margaret Hansen, PharmD: I think there has been one actually randomized controlled trial that's pretty old for evening primrose in MS and it wasn't conclusive of being beneficial. There was maybe some retrospective chart review type studies that had maybe indicated there was some benefit, but when they actually did a randomized controlled trial, there wasn't any different compared to placebo. Benjamin Segal, MD: Thank you, Dr. Hansen. But as long as you're on the video screen now, I'd like to ask you another question. Margaret Hansen, PharmD: Oh. Benjamin Segal, MD: This question involves the effect of age, I think on the efficacy and also the side effect profiles of disease-modifying therapies in general. So the question is, is it recommended to start a disease-modifying therapy at age 65? Margaret Hansen, PharmD: Good question. I mean, I would say we don't have a strong guideline that has a definite rule that no, you don't need to start a disease-modifying therapy at the age of 65. But I guess one of the benefits we can say of age is that the immune system does sort of slow down with age. And so typically we do see that continuing DMT into somebody's 60s, past the age of 65, is often not necessary. But people are different. MS is widely different between people. So that's certainly a decision to be making with your neurologist. Benjamin Segal, MD: Thank you, Dr. Hansen. And I agree with you though. In general, disease-modifying therapies seem to be effective in people who are younger or middle-aged. Everyone's unique and I've had patients who've had inflammatory MS in their 60s, 70s and have required disease-modifying therapy. So related question is if someone's been on disease-modifying therapy for decades, let's say started when they were younger and had relapsing remitting disease and now are in a slowly progressive phase or even plateaued, should they continue the disease-modifying therapy? And that is actually being tested right now in a large trial of discontinuing disease-modifying therapy in older people. I could tell you personally, I have stopped disease-modifying therapies in hundreds of patients in that situation. And then if I do that, I monitor them very closely getting MRI scans frequently and doing exams very frequently. And the vast majority of patients had fared well. Though I could recall two patients who when I stopped their disease modifying therapy, though there were in their 70s and hadn't had a relapse or change on MRI scan for decades, two of them had new lesions, they weren't symptomatic and I had to restart the therapy. So everyone's unique, and this is why it's good to be under close monitoring by an MS specialist when you're making those types of decisions. Okay. Here's a question which I think is up Dr. Gyang's alley. Is it safe for an MS patient who hasn't yet started disease modifying therapy to take the COVID-19 vaccine? Tirisham Gyang, MD: So that's a good question. So very recently, the National MS Society released guidelines for the use of a COVID vaccine in patients with MS. And the general guideline is that both the Moderna, Pfizer and I think more recently the Johnson & Johnson, we feel that these are safe. These vaccines are safe in patients with MS. If you have not yet started a disease modifying therapy and you're in the process of starting a medication, it would be good to discuss with your doctor because there are certain medications that may affect how you respond, we think may affect the way you respond to the vaccine. And so for instance, with some of the infusion therapies like the B-cell depleting therapies as a recommendation that if possible, let's get the vaccine first and wait about four weeks after the last dose of the vaccine before initiating therapy. What are the types of therapies? It may not matter. So I think if you have not yet started a disease modifying therapy and you're up to get the COVID vaccine, just have a discussion with your doctor about, is a medication I'm thinking about potentially going to affect how I respond? Is there benefit in me waiting until I complete both doses of the COVID vaccine before I start this medication? Or in some cases it's not going to matter. So I think it depends on the medication that you are planning on starting in general, from what we understand, these are safe. The vaccines are safe in patients with MS and some disease modifying therapies. There may be a timing factor from when you get the vaccine and when you could start your therapy. Benjamin Segal, MD: Thank you, Dr. Gyang. There's one last question that I'm just going to answer very quickly and that is, are you accepting new MS patients? And yes, we are accepting new MS patients at the Ohio State University and we have changed, we're growing our faculty. Dr. Gyang's here now. And I'm here. Kristi's here as well as Dr. Fallis. We have two new MS doctors who are starting in September. And so we do have availability. And if you're interested in seeing one of the OSU MS specialists, please contact us. So thank you so much. This was a great Q&A session and I'll turn the virtual mic back to Kristi to close the session. [Text on screen: Special thanks to The Ohio State University Wexner Medical Center MS Team for sharing their time and expertise with us today.] Kristi Epstein, APRN-CNP: Thank you everyone for joining us this evening, and I want to welcome you to our next event, which is going to be on July 8th. [Text on screen: Thank you for joining us today. We would love the opportunity care for you. To schedule an appointment, visit wexnermedical.osu.edu/appointments or call 614-482-2076. You will be receiving a survey via email to share your experiences from today's event. We would love to hear your feedback and what you want to learn from our clinical team in future sessions.] Kristi Epstein, APRN-CNP: That'll be our next virtual MS education event. And back to the question that someone had, if you want to make an appointment with us, you can go to our website wexnermedical.osu.edu/appointments or you can call 614-482-2076. If you're an existing patient and you'd like to make an appointment, you can also request an appointment through MyChart. We want to thank you so much for joining us tonight, and after a period of time you'll be able to see these recorded presentations uploaded onto our MS community page at wexnermedical.com. Thank you everyone, and have a good evening. [Text on screen: Multiple Sclerosis Education Series. We look forward to seeing you at the next virtual MS Education Event on July 8, 2021. Visit wexnermedical.osu.edu/MSCommunity to learn more and register.]