[Text on screen: Multiple Sclerosis Education Series. Thank you for joining us today. We will begin shortly. The Ohio State University Wexner Medical Center] [Text on screen: General Housekeeping, all mics and videos are muted, please use the Q&A feature to submit questions, the session is being recorded] Kristi Epstein, APRN, CNP, CCRN: Good evening everyone and welcome. I'm Kristi Epstein, I'm a Nurse Practitioner in the MS division. Many of you already know me. I would like to welcome you to this evening's MS education series webinar. [On screen: list of presenters. - Kristi Epstein, APRN, CNP, CCRN - Iryna Crescenze, MD - Cassie Vietas, DPT, WCS - Ryan Dickerson, PhD - Calli Bellinger - Tirisham Gyang, MD] 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 today, we're so glad to spend the next 90 minutes with you. A few housekeeping notes before we begin. You're going to remain muted and your cameras will be turned off for the duration of the webinar. This session will be closed captioned and recorded for viewing at a later time. Throughout the evening we invite you to type questions you have about the presentations into the Q&A box. Just a reminder: keep those not- keep those private and don't disclose any private information or health details; general questions and not your personal health information. All questions will be generally related to MS and the presentation content. At the end of our session our experts will answer as many questions as possible during our Q&A panel. I'm going to serve as the moderator and presenter for this evening's conversation. I'm a nurse practitioner specializing in multiple sclerosis and many of you already know me. I'm involved in the MS quality of life clinic and my special interests in the MS Clinic include wellness, reproductive issues, and clinical research. I'm really happy to be sharing this evening with some of my favorite colleagues from The Ohio State University Wexner Medical Center MS care team, and I did hear that we may be graced by the presence of our fabulous chairman Dr. Segal, so stay tuned. You're going to learn more about all of our participants over the next hour and a half as we talk about various aspects of life with MS including urinary dysfunction, pelvic floor therapy, and some very exciting research updates. Our team is a collaboration of physicians, scientists, nurse practitioners, and specialists that are committed to providing you with the care and treatment that is unique for you and your needs. Our goal is your comprehensive health care and we will work as a team to help you live your very best quality of life. So next it's going to be my absolute pleasure to introduce our first speaker. Our first speaker is Dr. Crescenze. Dr. Crescenze is a urologist specializing in neurogenic bladder as well as reconstructive urology and urogynecology. She completed her residency at the Cleveland Clinic and fellowship at University of Michigan. Her research is focused on management of newly diagnosed neurogenic bladder problems both in a clinical setting and also in the lab. She is most interested in optimizing the use of the electronic medical record, or EMR, to help patients take charge of their bladder problems in order to prevent infections and hospitalizations related to issues. Please join me in welcoming Dr. Crescenze. Dr. Crescenze. Iryna Crescenze, MD: Hi, everybody. It's really great to be here today and I am going to just go ahead and share my slides and hopefully you enjoy the talks. So today I'll be talking about bladder troubles in MS. As many of you know it is a big driver of quality of life for many of you. My disclosures in terms of scientific disclosures is that I'm an investigator for Medtronic [Inc] who makes one of the sacral neuromodulation devices. [On screen: illustrated cross-section of a bladder showing the sac at the top, trigone in the middle, and urethra at the bottom. The urethra is surrounded by the external and internal urethral sphincters.] So I'll start a little bit by talking about the bladder function. So bladder itself is made up of kind of two major components. One is that it has a sac that holds the urine which is a bladder muscle and then there is a trigone. It's kind of the control center of everything where a lot of the nerve endings end and it's right at the bottom of the bladder. And then there's the urethra where the urine has to pass through. The urethra is surrounded by a sphincter. The sphincter is really what controls the urine coming in and out. [On screen: Illustration grouping the brain and spine into the neurogenic category, and the bladder and voluntary muscles of the pelvic floor and external sphincter into the non neurogenic category.] So when you have MS or a stroke or Parkinson's or spinal cord injury, the bladder doesn't get the signals that it needs from the nervous system and it doesn't coordinate the function of storing urine and emptying urine as it should. As you know in MS that can mean that you may pee frequently, you may lose control of your urine, or you may not pee at all. And that's called a neurogenic bladder problem. It comes in many, many different varieties and sizes; you may have one problem, you may have two, you may have a conglomerate of issues. And really my job here is to help you through the figuring out which problem is the main issue and how we can address it. In MS, there is about three to ten percent of patients who will have bladder problems early on in the disease. And about 75 to 85 percent of patients overall with MS will eventually suffer a bladder problem. The severity of symptoms is correlated with the severity of the MS. And the lesion location really determines the type of bladder problem you will have. [Text on screen: Bladder in MS - 3 to 10% in early disease - 75 to 80% of patients with MS overall - symptom severity correlated with progression of MS - lesion location - determines type of symptoms Footnote: Blok B, et al Neurourol Urodyn 2019, Averbeck MA et al Neurourol Urodyn 2019; Litwiller SE eta al J Ural 1999, Marrie RA et al Neurougol 2007] Again, you can, you may say that I can't pee at all or you may pee too much. Either way this has a significant impact on quality of life for many patients. Now in U.S., about one-third of the population as we get older will suffer from a bladder problem regardless of other diseases. But things like age, obesity, postmenopausal status, bowel dysfunction, pregnancy, vaginal deliveries and the number of children, and in men it's the prostate and the history of a prostate cancer that may have required a surgery; will all contribute to the bladder problems in addition to the MS itself. And there also of course could be diabetes and stroke and other issues that can compound. [Text on screen: Concomitant Risks - Age - Obesity - Post-menopausal status - Bowel dysfunction/chronic constipation - Women: Pregnancy, vaginal delivery, number of children - Men: BPH, post-prostatectomy status - Neurogenic: diabetes, stroke, spinal disease/nerve injury, spinal cord injury] So, screening for urinary symptoms are done usually with Kristi. Kristi does a wonderful job doing this at her clinics. If you see her you will know this. It's often done at the time of the diagnosis of multiple sclerosis, it should be done anytime you have a flare and after the flare. And it should potentially include something called the bladder ultrasound to measure leftover urine in a bladder. And if that number is greater than 150, generally we start thinking and talking about there being a bladder problem. [Text on screen: Screening for urinary symptoms? - At diagnosis - After a flare - Left over during in the bladder after urination (PVR >150 cc)] When is it time to see a urologist? So you should consider seeing a urologist if you're having a lot of recurrent infections, you're not able to empty your bladder, or that post void residual (that bladder ultrasound) is showing some high numbers, you have worsening symptoms, you're leaking and leaking a lot more, and honestly it doesn't ultimately matter how bad the symptoms are but if it is driving you crazy or it's bothering you a lot please come see us because there's things we can do to help. So what are my goals for my patients? Number one is I want to protect your kidneys and minimize infections. Unfortunately with a bladder dysfunction, the leakage or difficulty emptying the bladder, that puts you at risk for several different complications and specifically the infections that could lead to some kidney damage. My other goal is to listen to you and really understand what quality of life you have and how we can make that better for you from urinary standpoint. So I wanted to do a little patient scenario to help kind of bring closer to home. So, meet Lesley. Lesley comes into my office and says she has frequency, urgency, she has "turn-key incontinence" (the moment she puts the key in the door, she has to pee) and she's up "all night" going to the bathroom. She uses four pads per day. She has significant bother with this; she's missing meetings, she's missing work, she's having accidents at work and is having to leave. She drinks about two coffees in the morning and eight bottles of water. She drinks one decaf in the afternoon. And on her exam things are pretty normal. When you come to see a urologist you may fill out some questionnaires, we'll do an exam, we'll check how much is left over in your bladder using a small ultrasound probe called a bladder scanner, we'll check your urine for infection. Sometimes, especially with diminished sensation such as you can have in MS, you may not know you have an infection in fact that's driving a lot of the symptoms. And we may do some safety checks which would include a kidney ultrasound and some blood work to check the levels of creatinine which indicates how the kidney works. For some patients an evaluation with Urology may require what we call advanced bladder testing, some of you may be familiar with it. One advanced bladder test that we can do is called urodynamics. This is the picture on the left. [A patient dressed in a hospital gown sits in a specialized chair next to an IV pole and computer cart. Several thin tubes run from the elevated sterile fluid bag under the patient's hospital gown. Another tube runs from under the patient's gown to an enclosed container for fluid collection.] This study involves us filling your bladder with a tiny little catheter and measuring the pressures and the activity of the bladder muscle itself. That's a really nice way for me to be able to tell: is your bladder safe, what does your bladder think, is it just spastic, it just spasming and that's why you're leaking urine, or is there some issue where the muscle and the bladder are not talking to each other because of the neurologic problem that you have and we need to work on that. Another test we may do is called a cystoscopy. That's more infrequent for patients with neurogenic bladder problems, but that may be done for you if you're having a lot of infections or if you have some blood in the urine. And that's the picture on the right. [A doctor dressed in a gown, surgical cap, gloves, and surgical mask inserts a thin scope into the urethra of a patient who is lying on their back. The doctor views the video output of the scope on a nearby computer monitor.] And that's where we put a small camera scope into the bladder to see the lining of the bladder. So let's talk about treatments for lastly. And really any patient that walks into my office is we're going to start with behavioral modifications. Oftentimes making some changes about how you pee and when you pee can be significant to really give you improvement that you may be looking for. So that may include things like managing your fluids. Certainly if you come in and you say you're drinking a couple pots of coffee a day and you say "you know what, I used to do it when I was 21 and it wasn't a problem" well now it is [laughs] and it is for many people. And it certainly is if you have a neurogenic bladder that's being impacted by MS. So we may need to manage your fluids. We need to set realistic expectations and really drinking 60 to 80 ounces of water a day is what we're going to be talking about. You may want to schedule your urination. I sometimes have patients who just wait and wait and wait and wait and then when they have to go they don't have much time to make it. And so sometimes just something as simple as setting an alarm to go to the bathroom every two to three hours will prevent the majority of leaks. And they could be a really easy nice way to manage your bladder. Constipation. So I always say this, but there's only so much space in your pelvis. There's bones, and the bladder, and the bowel is right in there nicely tightly packed. So if you haven't pooped in a week chances are there's nowhere for your bladder and the urine to go. So you probably will have to go pee very frequently and you may lose control because of the constipation really putting a lot of pressure on that bladder. So managing constipation is a big deal. And it's also a big deal in MS because just like the bladder can be affected by nerve changes and nerve injuries the bowel will be affected by nerve damage as well. The "Knack" maneuver, it's a really nice kind of treatment option that will be part of your physical therapy, or physical therapy itself is a really really great option, we'll have more about that later. But essentially these two things are learning how to use your pelvic floor muscles in order to manage your bladder effectively. So if you feel an urge coming up you may want to use your Kegel muscles to prevent it from becoming an issue. You may want to stop what you're doing squeeze the Kegel muscles and that sometimes is enough to prevent a leak. Now, you have to know how to use your Kegel muscles and that's where the physical therapy is so important in working with a physical therapist especially using something called a biofeedback system where you learn how to actually use those muscles, making sure that you're using the right muscles to really control your urine and control the leaks as much as possible. All right. You know while you're working on that we may want to use an incontinence device. They range from pads to diapers to Depends to some options for men which are penile clamps and little condom catheters which can be quite nice. And there's this new device called the PureWick female external catheter which is kind of like a little suction tampon that will suction the urine out but you are connected to it too. If that doesn't get you where you want to be the next step is medications generally for what we call overactive bladder or leakage that happens most commonly with MS. There's a variety of different medications, they have different side effect profiles. But they're supposed to help you with the overactive bladder, making it to the bathroom on time, having time to find the bathroom and not leaking on your way there, and not going as often. If medications are not effective we generally would have a discussion about what we call third line treatments. The primary, the FDA approved third line treatment for patients with multiple sclerosis and overactive bladder is Botox. It has been approved for neurogenic bladder in 2011, we've been using it for over 10 years with wonderful results. It blocks the nerve endings in the bladder muscle and decreases the bladder spasticity and sensitivity. You have way more control, way less leakage, and overall a significant improvement in quality of life. It is safe in neurogenic bladder and it is safe in MS. It's an office-based procedure [cystoscopy with injection], only takes a few minutes to do and it lasts about six months. For some patients we can go 9 to 12 months. The side effects include urinary tract infections, blood in the urine, and sometimes it works too well and you can't pee. That's only about five to ten percent of the time but we can certainly help you manage through that. The next option for majority of patients with overactive bladder is a posterior tibial nerve stimulator. As you can see here it's an electrical therapy. [A woman sits barefoot in a reclined position with a small device attached via cables to her ankle and the arch of her foot.] It's put it's an electrode that's placed in the next the ankle and it sends an electrical current to the same nerves that go to the bladder and it helps reset your bladder and give you some more control of the urgency and the frequency primarily. It's been shown to be about 70 to 80 percent effective in general population. And it's better than medicine and it's better than placebo in the clinical studies that have been done. [Footnote: El-Senousy et al Egypt J Neurol Psychiatry Neurosurg. 2013; Kabay et al Urology 2016, Krivobrorodov et al Urologiia 2006, Guitynavard et al MS 2021] For patients with MS their response rate isn't as good but it's been shown to be closer to probably around 60, 66 percent. It's a very non-invasive treatment option there's no implant and this is done in the office but it does require frequent trips to the office to do this treatment. [Text on screen: Sacral Neuromodulation - FDA approved study -- 60% of refractory OAB patients had >50% improvement -- Approved for fecal incontinence -- MRI compatible - Limitations -- Battery life - average 10 years -- Rechargeable device is an option -- Worse in progressive disease Footnote: Peters et al Urology 2013.] Next up is a sacral nerve neuromodulation. This is a device that's used for overactive bladder. There's two companies that make it, one's Medtronic, one's Axonics. It is an implant. It's a small device that goes in your buttock and the wire or electrode goes to the nerve that goes to the bladder. It helps reset the bladder, helps, again, helps your brain talk to the bladder to control the urge, the frequency, and the spasms. It's been on a market for quite a long time, as well, similar to Botox. It's FDA approved for overactive bladder and it results in about 60% improvement for most patients. It can also be helpful with fecal incontinence and fecal urgency which is a big, big deal for many patients with neurogenic bowel. And it is now MRI compatible. For many years this device was not MRI compatible, but it is now. So it's now become a very good option for many patients with neurologic disease who need MRIs, specifically our MS population. The limitations of this implant is that the battery life is about 10 years, so eventually you'll need it replaced. There's a rechargeable option as well. And the limitation, the really big limitation of this treatment, even though it's really excellent up front: with MS, as MS progresses, as you may develop another lesion here and there, the communication between the nerves changes and the device may lose efficacy. So MS patients are more likely to fail in the long term because of the changes in the MS disease itself. Which is why it's technically off-label use for a neurogenic bladder. But, again, it's so effective for overactive bladder that we often do use it even if there is a component of a neurologic problem, as long as the MS is stable. It's certainly not a good option for somebody with an active, changing MS disease. [Text on screen: What about difficulty emptying? - Weak bladder? - Enlarged prostate? - Abnormal urethral sphincter opening?] There there is a kind of another component of all of this. So, all these treatments I just discussed are really good to help you control the urge control the leak. But what about not being able to pee? Unfortunately some MS patients, especially those with spinal cord lesions, may have trouble going and that can result in abnormal urethral sphincter opening. Now you may also have an enlarged prostate or a weak bladder. Those things happen to people without neurologic disease. And so part of my job is to figure out which one is it, and to be able to offer you some treatments for that. Again, the InterStim(TM) devices (sacral neuromodulation) is an option for patients who have trouble going. It is not as successful in that role, in that indication, but is still an option. Another option is to learn how to catheterize your bladder or to have a catheter placed, which you know are not as good of an option because it is not a natural urination mechanism. [The sacral neuromodulation device consists of a thin wire (lead) and a small, metal device (neurotmodulator). A Foley catheter is a long, thin tube that is inserted into the bladder through the urethra. The end that is inserted has a small inflatable balloon that, once in place, keeps the catheter from slipping out of the bladder. Urine flows down the catheter to the other end, which connects to a liquid collection bag that can be worn strapped to the user's leg.] There is what I call advanced disease. You know, so, you've tried all these things and either your symptoms are not controlled, or your quality of life is still not where you want it to be, or you don't want to have a catheter. What can we do? Well, there is always reconstructive surgery or urinary diversion. Another thing in advanced disease that I am going to be concentrating on is preventing infections regardless of how we choose to manage the bladder, because infections can lead to worsening MS symptoms. And also preventing wound complications for patients who unfortunately may be bed bound and are leaking a lot, and those are the things that really lead to long-term complications. One thing I wanted to say is that in my clinic I tried to use a new tool that we've developed for both neurogenic bladder and an overactive bladder and it's kind of an electronic care companion. It's essentially an education series, or series of materials, that can help you understand the bladder issues that you're having and how they can be managed. It's integrated into Epic, you will get MyChart notifications when you're signed up for it. It will ask you to fill out some questionnaires to better guide your symptoms and it'll provide some education for you. [Text on screen: Electronic Tools to Help Navigate Bladder Health - Based via MyChart App - Fully Integrated with EPIC - Direct patient to provider communication and feedback - Part of the usual care for neurogenic bladder] There is a little pathway that we just went over which is kind of like "where do we start?" You know, what do we need to work on? We work on behavioral things, and we work on medicines, then we talk about advanced treatment options. And this MyChart care companion can help you kind of go through each step of the pathway to learn more about your bladder. [Text on screen: Your Pathway to Managing Overactive Bladder Map Work with your doctor as you follow your path to managing overactive bladder (OAB). There are many strategies and treatment options to help you on your way. First Visit - Assess your symptoms - Discuss testing options - Learn about OAB and talk about what you expect Step 1: Lifestyle and Behavior Changes - Lifestyle and diet changes - Manage fluids - Pelvic floor exercises - Medicine possible Are you better? Yes - Stop Here You are doing great. Stick with your plan and see your doctor regularly. No - Continue on your path. Step 2: Medicine Talk with doctor about medicine options. Are you better? Yes - Stop Here Stick with your plan, continue your medicine and see your doctor regularly. No - Continue on your path. Adjust Medicine Talk to your doctor about changes to your medicine. Are you better? Yes - Stop Here Stick with your plan, continue your medicine and see your doctor regularly. No - Continue on your path. Step 3: Advanced Therapies - Sacral Nerve Stimulation (SNS) - Botox bladder injections - Percutaneous Tibial Nerve Stimulation (PTNS)] Okay. That's all I have for today there's a lot more I can always talk about but I'm going to go ahead and stop so I don't run out of, over time too much. [Text on screen: Thank you! Iryna.crescenze@osumc.edu Clinic Line: 614-293-8155] Epstein: Thank you so much Dr. Crescenze! We so appreciate that presentation, really wonderful. And I actually had the pleasure of spending some time in clinic with Dr. Crescenze and observed some of the procedures that she discussed and patients did very well. So don't be afraid and reach out, ask us questions if you have any, and make sure to put your questions into the Q&A chat box. And I want to let you know as well that we do have bladder scanners at both our Martha Morehouse location as well as Gahanna. We discuss platter issues and other symptoms in the quality of life clinic in our MS multi-disciplinary clinic. But, as ever, at any patient visit with your provider if you're having bladder difficulties at all please let them know and we'll go ahead and get a bladder scan. So thank you again Dr. Crescenze. We are going to move on for another exciting presentation. It's going to be my pleasure to introduce Cassie Vietas. Our next speaker Dr. Cassie is a pelvic floor physical therapist at the Ohio State Pelvic Health Physical Therapy Clinic and that is located in Gahanna. She treats clients with a range of pelvic floor dysfunction including bowel, and bladder, and sexual dysfunction. She completed her Clinical Doctorate in Physical Therapy at Simmons University in Boston in 2021 and she came to Ohio State for residency in Women's Health Physical Therapy which she completed in 2022. She received her Clinical Specialty in Women's Health in June of 2021. She has a special interest in pelvic health for persons with multiple sclerosis and other neurodegenerative conditions. And we're very excited to hear her presentation today. Dr. Vietas? Cassie Vietas, DPT, WCS, CLT: Thank you so much Kristi. I'm just going to get my presentation up here. Ookay there we go. Alrighty, like Kristi said my name is Cassie and I'm here to talk about pelvic floor PT and its role in treating symptoms of pelvic floor dysfunction in persons with multiple sclerosis. I am so excited to be here. All right so I have no disclosures for this presentation but I do have a map of where we're going to go today. [Text on screen: Objective Map What? > Why? > How? > Where/Who?] So pretty much in this presentation we're going to go over what the pelvic floor is and what systems it affects, why it's important to see a pelvic PT and how the evidence supports coming to a pelvic floor PT and when to come. How pelvic floor PT works, including what a first visit looks like and what further treatments look like as well as where to find a pelvic floor PT whether that be at Ohio State or somewhere near you if you're not near Columbus. So what is the pelvic floor? So the pelvic floor is a collection of muscles that are within the pelvic bowl so pretty much anything that you sit on like a bike seat you can consider that the pelvic floor. They span between the pubic bone to the tailbone and in between our sit bones on each pelvis [female or male]. They help keep us continent by squeezing to hold urine, stool, or gas back as well as relax to allow those things to exit our bodies. They're also vitally important to sexual health, our balance, and our lymphatic system. These muscles are often not talked about in the general population, it's not like everyone's going around telling the health of their pelvic floors between people. But in those with MS the pelvic floor muscles are greatly impacted whether that's due to spasticity or changed in muddled communication between the brain and our pelvis. How that interaction changes might affect your urinary system, your bowels, or sexual function. So that might show up in a lot of different ways. In persons with MS it might be a big, quick onset of urges to urinate, incontinence with urge to urinate or with laughing coughing sneezing, or even just like when you're sitting around. It might be frequent visits to the bathroom, having shyness and a difficult ability to empty. And for bowel movements it might present as really big urges to have a bowel movement, leakage with bowel movements, constipation, really frequent bowel movements, or maybe at the end of the bowel movement you don't feel quite empty. Sexual dysfunction is also very common in those with MS, and might present as a pain with participation in any sexual activity, pain with arousal, or orgasmic changes. Lastly pelvic pain is very common in patients with MS, whether that be pain in the tailbone, abdomen, pain in the front of the pelvis, low back or hips. If you're experiencing any of these symptoms it's not something that you necessarily have to resign yourself to live with long term. We gotta reach out to your doctor and get a referral because there are PTs who are here to help you and are excited. All right, so going into a little bit of the "why," the research behind how this is impactful for people. So, you know, we talked about how pelvic floor symptoms might show up but the research says that between one-third and two-thirds of persons with multiple sclerosis have some sort of pelvic floor dysfunction that moderately or severely affects their quality of life. Lowballing, that means around 41% of patients with MS have bladder dysfunction, 30% have bowel dysfunction, and 41% have sexual dysfunction that impacts their quality of life. More than likely everyone who's listening tonight has at least one of those categories. The research demonstrates that pelvic floor PT has been shown to be highly effective with those who have urinary leakage, urgency, and reducing the number of bathroom trips. It has been shown to reduce the number of events of fecal smearing and incontinence, bloating, and frequency of bowel movements, as well as constipation. It improves sexual satisfaction and decreases pain with intimacy. And overall the research says that pelvic floor PT has helped with the quality of life around these symptoms. So it might not decrease them completely but it allows you to participate in your day-to-day life with a little bit more joy and function. So how does PT work? So every patient is different, so every visit in PT is going to be different and unique to each patient that comes in. The first visit is what I like to call a "get to know you visit." So we'll talk expansively about your pelvic floor symptoms including your bowel, bladder, and sexual health. As well, we'll talk about food intake, water, your participation in exercise, and as well as your MS history. So that might be like, you know, what most recent flare you've had. Or talking about if you've been to PT for balance or strength, what things you worked on so that we don't double dip. Additionally I might also talk with you about your history of bowel and bladder before your diagnosis of MS depending on when that was. Oftentimes that gives me a better understanding of your personal habits that may or may not actually cause your pelvic floor dysfunction to be a symptom of your MS but instead something else altogether. We do a lot of testing and that might be looking at your hip strength, your range of motion, your abdominal strength, your back range of motion, how well you move, your breathing, and your pelvic floor function. Assessing pelvic floor function is a completely unique to each patient within their comfort and their mobility. So sometimes that looks like what's called an internal exam that is done per patient but it also might be a modified exam with fingertips on your tailbone. During this visit we also plan how long we're going to see each other and how many times. Oftentimes I see patients anywhere from 8 to 24 weeks and that's pretty consistent between most pelvic floor PTs. But it really depends on your needs, how many symptoms you've got going on, and how often you can get in. Lastly, as always, PTs send you home with a little homework. So that might be exercises, whether that be pelvic floor exercises like Dr. Crescenze was talking about, lifestyle changes whether that's like you know bowel/bladder changes or habits, and then maybe something like a bladder diary or a bowel log. [Text on screen: What is pelvic floor physical therapy? - Exercise - Breathing - Small diet changes - Balance training - Biofeedback training - Water intake management] Just like there's an array of things that we might talk about at the first treatment, there is an absolute array of treatment for folks who come to PT and what we might be doing with them. The treatment might be focused on strengthening your pelvic muscles, it might be focused on relaxing your pelvic muscles if they're really. We often focus on strengthening your hips and core to help support your pelvic muscles just a little bit better. We might focus on breathing techniques to improve your ability to go to the bathroom, as well as improve your relaxation of your nervous system and improve the motion of the pelvic floor. We might talk about small behavioral changes like changes around diet and water intake as well as how often you visit the bathroom, and the techniques that you might use around going to the bathroom. So something like maybe urge deferral or helping you void completely. More specifically to the pelvic floor oftentimes we do biofeedback training. Dr. Crescenze did a really great job like intro-ing that for me. So biofeedback training is the use of small electrodes that look at the pelvic floor function. So, essentially as you squeeze your pelvic floor or stop the flow of urine and gas that number should go up and increase because your muscles are working harder. As we let go of those muscles we'll see that number go back down. So often I use this as a visual tool for patients. [Computer generated line graph shows a fluctuating line that corresponds to muscle activity.] Our pelvic muscles sit right at the bottom of our abdominal cavity and we can't see them so it's hard for our brains to visualize how those muscles are moving, especially when those muscles are weak or very tense. Oftentimes I might also use different types of biofeedback which is really just using something to tell you what's happening in your body. So that might be sitting on a towel roll or like a yoga ball. It might be self-visualization of what's happening at those muscles. So there's a lot of ways to see the improvement with biofeedback that aren't just the machine if that's not something you're comfortable with. Lastly, oftentimes I am working heavily on balance with persons with multiple sclerosis because with that urgency with bowel movements or urinary function what ends up happening is that our brains can't think about walking or balancing to get to the bathroom and holding our urine. So working on balance and what's called dual task training can often help patients with MS deal with that kind of urge and kind of brain takeover that happens when you get the urge to urinate. While these are common things that we might work on it's not expansive to everything I do during the day. Between all the patients I see and all the things I do I probably could give like a three hour long conversation about this. So everybody's different and everybody gets a different treatment. Which is why I'm talking about where you can find a PT. So here at Ohio State we have 17 pelvic floor therapists located in six different locations all around Columbus. In order to come see us all you need is a referral from your doctor and then you can call in and make an appointment at any of our clinics. But I'm gonna guess that many of you who are listening don't live directly near Columbus. [Text on screen: Where else can I find a pelvic floor PT? Pelvic Rehab Locator: https://pelvicrehab.com Academy of Pelvic Health PD Locator: https://aptapelvichealth.org/ptlocator] So there are two different ways to find a pelvic floor PT there are two different links here. And at the end of this presentation I know that this gets linked into the, like a website and you're able to go in and click from here. But basically you'll click on any of these and you'll type in your zip code and you're able to find pelvic floor PTs near you. And you can even search a little more refined than that. You can type in like "for neurogenic" or "[for] bladder" or you can type in "for urinary function" or "bladder or bowel function," whatever you might be coming in for. And then you're able to see all the PTs that might be treating near you. So I have one more "what?" that we're going to talk about and that is: what can I do right now to start working on my pelvic floor function? So the best thing that you can do to start, and it's the most universal thing that I do, is work on breathing with patients. So the diaphragm and the pelvic floor are in what's called "phase lock movement." So basically, like a piston, when one moves up the other one moves up. You can see this nicely on this diagram I have here. When one goes down the other one goes down. That helps manage the intra-abdominal pressure in our bodies, and we can use it to our advantage to help use our pelvic floor more effectively. [Text on screen: What can I do right now? Breathing exercises! a. Breathe in through your mouth/nose. Let air fill your lungs, and your belly will rise allow your ribs to open. b. Exhale slowly, allowing your belly to go back to resting. c. Try this exercise 3-4 times per day for around 10-20 breaths. This simple exercise will set you up for success when you do start physical therapy with a pelvic health provider. *It should not feel like you are forcing air in OR out. Animation shows the interior of the abdominal cavity. When a breath is taken, the diaphragm and pelvic floor muscles move upward in unison. They descend in unison on the exhale.] So starting today if you want to work on your pelvic floor health, you're going to take 10 to 20 breaths three to four times a day. The goal is that you're breathing in through your mouth or nose, whatever is more comfortable for you, letting the air fill your lungs. Your belly will rise and your rib cage will open. You'll exhale slowly allowing your belly to go back to resting and then you'll try this again over and over for 10 to 20 breaths. And this simple exercise will set you up for success when you do see a pelvic floor physical therapist in the future. And that is all that I have. Thank you so much for allowing me to spend some time here with you today, and I'm so glad that I got to be here! Epstein: Thank you so much Dr. Vietas! What a wonderful presentation, and I'm sure everyone out there like me was just practicing their breathing. Again I want to encourage everyone to go ahead and put your questions that you might have into the Q&A box. And if you feel like you're having any issues with pelvic floor please discuss this with your provider and we're happy to place that referral. And we are going to move on and remember again please put your questions into the Q&A box. So next we're going to change gears a little bit and we're going to talk about some exciting research issue. it's going to be my absolute pleasure to introduce one of our fabulous clinical research coordinators that I work with on a weekly basis in our MS Clinic. We have a lot of trials going on in our MS research group. So we're going to be hearing from Dr. Ryan Dickerson. Ryan is a clinical research coordinator within the Neurology Department's MS Clinical Research Group. He completed his undergraduate and graduate education here at The Ohio State University and he has an extensive research background both in the lab and in the clinical setting. As part of his role as a research coordinator he is involved in both OSU faculty-initiated research trials and industry-sponsored trials. And I can tell you that he has saved me many times when I'm having a glitch with a particular tablet in clinic, Ryan is always there and he's such a positive presence in clinic. So now it is my pleasure to introduce Dr. Ryan Dickerson. Dr. Ryan? Ryan Dickerson, PhD: Well thank you so much for the warm introduction Kristi I really appreciate it. Again my name is Ryan Dickerson I'm one of the clinical research coordinators here. And what I want to talk to everyone today about is just some basics about what clinical research is, what you can expect if you choose to participate in one of our trials, and just give a brief introduction about some of the projects that we have going on in the clinic. So you know starting off right with some definitions. So, what's clinical research? It's a medical research that studies and helps us understand health and disease, but it's always being done in a clinical population. So as opposed to something that's really starting off the bat in the lab, or something that may be using an animal model, this is going to be research conducted in all of you. It really helps physicians and other healthcare providers better understand disease so they can treat and prevent illness more efficiently. Additionally it helps us learn things, basic things, about how the body works, how illnesses develop, and how they progress over time. It gives us more information about new treatments, how much of a particular new drug do we have to administer to get the outcome that we want, are there any side effects that we should be concerned about, does it work? Lastly it gives us some basic understanding about how lifestyle and life circumstances influence disease frequency and healthcare outcomes. [Text on screen: Not all clinical research is the same. Observational Studies: - Participants are not assigned to a test group (drug, device, procedure, etc.), though they may be self-electing to take/use a product. - Identify associations between variables (e.g., drug A and health outcome Y) but cannot prove causation. - Help researchers understand a situation and generate a hypothesis to be tested in a clinical trial - Useful when clinical trials cannot be done (e.g., a study asking people to engage in known high risk behaviors, or long-term disease monitoring) Clinical Trials: - Participants are assigned into test groups, often through a blinded randomization - Often involve administration or use of products that have not yet received FDA approval - Gold standard for proving that a new product or procedure works for the intended outcome - Investigational products are often compared to either a product that is already on the market or a placebo - Participants and investigators are often blinded from knowing which intervention a volunteer receives and from seeing clinical results that could provide insight in to group assignment] Generally speaking clinical research is divided into two general bodies: observational studies and clinical trials. You can subdivide further once you get within those two categories, but just to keep it simple I'll just talk about these two. Observational studies typically will not have participants that are assigned into a test group, and that can be a group that's researching a new drug, a medical device, a particular procedure. But importantly a participant may be choosing to participate in one of these particular things on their own, but it's not us telling them you know "you're going to be in group a or group b." Additionally, observational studies are really useful in understanding associations between variables. That could be something like Tylenol and headaches or anything like that, so a drug and its outcome or a device and its outcome, but it can't really talk much about causation. Additionally, observational studies really they generate a lot of new associations that can then be teased out in clinical trials to better understand them that way. Observational studies are also really useful when a clinical trial just wouldn't be appropriate. So that could be something that's a really long-term observational study that perhaps people are monitored for years and decades, something that's really outside of the scope of what a clinical trial would be able to do. Additionally, it's really useful for high risk things. So it really wouldn't be ethical for us to put people in harm's way, but if someone's choosing to do those things on their own we can monitor how things progress for them as time continues. Switching gears, clinical trials, sort of as opposite side of that, we are going to be randomizing people into different arms of treatment and it's typically done in a blinded fashion where a participant doesn't know if they're taking the investigational drug or if they're taking a placebo or whatever drug it's being compared to. Oftentimes the healthcare providers also don't know those things, so that would be considered a double-blinded trial. And those are really considered the gold standard when pharmaceuticals or other researchers are trying to show things are doing the intended outcomes. Additionally, like I mentioned, that blinding process really can be a little disconcerting for some participants just because they want to get those results, but it's just sort of the nature of how clinical trials are ran, and oftentimes it's a decision that people have to make that they want to perhaps be randomized into a placebo group. So that's something to consider as you're thinking about joining a particular clinical trial. [Text on screen: The 4 Phases in Clinical Trials Phase I: Is the treatment safe? - to determine best and safest dose - to evaluate safety - to identify side effects Phase II: Does the treatment work? - to test effectiveness - to further evaluate safety Phase III: Is the treatment better? - to confirm effectiveness - to monitor side effects - to compare to other treatments FDA Approval Phase IV: What else do we need to know? - to confirm effectiveness - to provide additional information The number of participants increases at each phase.] Throughout the research process clinical trials are broadly divided into four phases depending on how far along in the research process they are. The smaller the phase, typically the lower the number of participants that will be in the trial. So a phase one trial that's really seeking to answer the question "is the treatment safe?" may have you know 50 people, 100 people but it's not going to typically be a huge cohort. Versus we start getting up to phase two trials which are really asking the question "does the treatment work?" Those may be, you know, a couple hundred people. Phase three [is] even larger, basically really trying to establish is the treatment better, is it better than other treatments that are already available on the market, or is it better than doing nothing at all? And typically if all goes well with phases one two and three, then it will be reviewed by the FDA and if it gets approval and people start taking that, you know, as they're prescribed by their clinicians, then we can sort of move into a phase four trial which is going to be the largest number of participants really seeing how that new drug or product is performing in the real world with a whole variety of unique situations that people bring to the table. [Text on screen: Who can participate? Clinical research is conducted according to an Institutional Review Board (IRB) approved research protocol developed by the sponsor or lead investigator that details eligibility criteria, including: - Reason for conducting the study - Inclusion/exclusion criteria - How many participants are needed Example Eligibility: Inclusion criteria - Adults ages 18 to 65 - Diagnosed with progressive MS - No evidence of relapse within 24 months - Ability to walk at least 100 meters Exclusion Criteria: - Any active or uncontrolled autoimmune disease other than MS - Women who are pregnant or may become pregnant - Use of anti-CD 19/20 therapies within the last 12 months (e.g., Ocrevus) - Use of systemic corticosteroids within the last 30 days] So, who can participate? All clinical trials at Ohio State and generally in the United States are going to be, there's some oversight by a body called the institutional review board (the IRB) that is a group of people that are not associated with the study themselves but they really have some oversight to make sure that the research is being conducted in an ethical manner and that research participants are you know being treated properly and not putting in any undue risk. The protocol that the IRB reviews is going to be established by either the sponsor or the lead investigator. Within that document that's where they're going to establish the rationale for the study, they're going to set some inclusion and exclusion criteria, as well as dictate the number of participants that are needed. And that's all sort of done through a statistical manner. So below I sort of entered um sort of a generic inclusion exclusion criteria just so you can get a sense for it. This is one that I sort of made up but it's quite typical of what we may see with some of our industry-sponsored trials. So they're going to set, you know, the type of people that they want to test their drug on, so if it's adults, or if it's a pediatric drug that's going to be tested, they'll specify that, as well if there's a specific diagnosis that they really want to test their drug in. They may say set some other things as far as, you know, relapse frequency or perhaps some mobility things, just because the battery of tests that we're going to be doing will require some of those diagnostics. Typically exclusionary things are added in as ways to control for confounding variables, as well as, you know, trying to mitigate some safety concerns. So that's something we often see with women who are pregnant or who may become pregnant. If there's sort of another drug that's sort of contraindicated with the new investigational product that they're putting forward, oftentimes they'll set that forward so we can just make sure that people are going to have the best experience possible as they're going through and not have any surprises. [Text on screen: Informed Consent Detailed description of study rationale and design - Study duration and visit frequency - What will be asked of you at research visits - Risks and benefits associated with your participation - Data security - Other treatment options - Any costs associated with participation - Principal Investigator (PI) Contact Information Opportunity to ask questions Collect signatures Your participation is completely voluntary and can be stopped at any time without impacting your relationship with your health care team.] So if you decide that, you know, a clinical research project is something that you may be interested in participating in, the first thing that a research coordinator or any of the clinician's research staff that are involved with the trial are going to do is go through an informed consent process with you. And the purpose of that is really to just arm you with all the facts so that you can make the correct choice based off of your needs. Some of the things that we talk about in that informed consent process would be the study duration, how frequently you're going to be coming in to see us, often we're going to give a really comprehensive view of what we're going to be doing during those visits. Like I mentioned sometimes it could be: you're going to be taking a walk around the hallway with us, sometimes we're going to be drawing some blood from you, all that's going to be laid out for you in the informed consent process. Really that sort of leads into the next [part]: really digging deep into what are the risks and potential benefits for your participation with us. I want this to be as transparent as possible whenever I'm going through an informed consent process with someone because this is, you know, really serious stuff. We want to make sure that you are entering into a project willingly knowing all the facts. Oftentimes we'll talk a lot about data security so, you know, is your identity safe while you're participating, how will the sponsor see your data, that's something that we discuss. As well as, you know, what are some other treatment options that are already available on the market if you're weighing the odds between "do I want to partake in something that's investigational" or "do I want to stick with the standard of care?" Additionally we'll go over cost of participation if there are any, if there's any sort of stipend for your participation that would be something that we discuss, as well as making sure you have all of the contact information for the principal investigator who's leading the trial. Importantly, once we go through all that, you would have the opportunity to ask ample questions. If it's something you don't want to make a election about participating or not then, you can always take that document home, review it, talk to your primary care physician, talk to your family. You can always get back to us before you actually say yes or no. Once you do decide to participate we'll just collect some signatures, make sure that you have copies all of all of that for your records. But most importantly even after you sign, you are absolutely welcome to stop participating at any time. Your participation is voluntary and if you do decide to withdraw from the study it won't have any bearing about the quality of care that you receive at Ohio State or your relationship with anyone in your healthcare team. [Text on screen: Example Study Schedule Diagram of schedule Screening period: one MRI Main Treatment Period (Blinded): Maximum of 120 weeks, visits every 12 weeks. Half of volunteers receive a dose of the study drug, the other half receive a placebo. MRIs are conducted every visit. Main analysis occurs. Open Label Extension Period (Optional): 8 years, visits every 24/28 weeks. All volunteers receive a dose of the study drug, MRIs are conducted each visit. How we collect data: - Medical history - Current medications - Vitals - Questionnaires - Lab results. (blood, urine, saliva, CSF, etc.) - MRI images - Functional Assessments - Physical Exams] So this is sort of a typical study schedule, this is for one of our ongoing drug trials right now. It's broadly divided into three categories, the first being a screening period. So within that study protocol, there's going to be a lot of things that we need to make sure that you actually meet all the criteria. So that screening period allows us to just sort of do some of those baseline diagnostics, make sure that, you know, all the boxes are checked and everything's good to go. Once we get that sort of secured, we can move into the main treatment period. So starting that typically if it's going to be a randomized control trial the randomization of it will happen right at the beginning and then you'll be sort of selected into either a treatment arm of an investigational product or of the whatever it's being compared to, be it a placebo or be an existing product that's on the market. This particular trial has visits every 12 weeks but every protocol is a little bit different, I just want to sort of give an introduction of what it may look like. And then some trials may also have the opportunity to continue on an open label extension period where everyone could switch to the product even if they were on the compared arm later. Ways that we collect data during some of our research visits: we'll do a really comprehensive review of your medical history and current medications. We always start off with taking some vitals just so we can keep track of that make sure nothing is changing as we're starting to administer anything. Some different questionnaires about quality of life, satisfaction on the trial, all sorts of things like that, a lot of lab results. So we could be drawing blood, collecting urine, saliva, sometimes cerebral spinal fluid. Again all of those are going to be dictated in the actual protocol that is approved by that IRB. Sometimes we collect imaging data, functional assessments to establish disability and a comprehensive physical exam. So you may be wondering, you know, how would a research visit look different from a typical clinical visit? So again that really depends on what the protocol dictates. So some, you know, more straightforward research protocols, if it's a short data collection that the research is going to do, we can often piggyback that off your existing clinical visits. So those are nice because you don't have to make a special trip out, oftentimes they may only take 20 to 30 minutes extra. But that's something that, you know, is sort of unique to those type of protocols. Other more involved trials may last several hours and typically for those we would prefer to have a unique research visit scheduled with you. And, you know, we can build in if it's a really long day, I know I often like to build in lunch breaks and [laughs] ways that it can be a little more comfortable for participants as they're spending the day with us. Also it's something that's a little unique when you're participating in research trials you often get to interact with a lot of people within the team. So instead of just seeing your typical neurologist you're going to see perhaps several clinicians. You're going to interact with me and some of my other colleagues as research coordinators, some of the folks in the imaging group, you really get a nice comprehensive introduction to everyone on the team. Other things to remember like I mentioned, both you and your physician may be blinded, you may not have access to some of the laboratory results that we are collecting as part of the research trial and that's very normal. It's just part of that blinding process so that we don't introduce any sort of treatment bias that your clinician may sort of make some assumptions about which group you're in or not. Additionally because it is typically going to be long visits, oftentimes we're doing things that are above and beyond what the standard of care would be from a diagnostic standpoint/ And that's totally normal, you should expect that, it's just us making sure that we're collecting all the right data both from a research question as well as sort of a safety standpoint as well. Some of the trials, depending on how the protocol is written and what the sponsors dictated, the really long visits or the multi-day visits, sometimes there is reimbursement available for if you have to spend the night so you can come for two days in a row or if you're not able to secure your own transportation here sometimes we can have like transportation services that can pick you up and drop you off as well. So those are things that you can ask the research coordinators about as they're going through an informed consent process with you and they can give you all those details. [Text on screen: Current Studies Status: Ongoing Enrolling? Yes Type: Clinical Title: A Phase-2b, Double-Blind, Randomized Controlled Trial to Evaluate the Activity and Safety of Inebilizumab in Anti-NMDA Receptor Encephalitis and Assess Biomarkers of Disease(ExTINGUISH) Sponsor: NeuroNEXT Status: Ongoing Enrolling? Yes Type: Observational Title: Markers of Biological Aging in Multiple Sclerosis Sponsor: NIH Status: Ongoing Enrolling? Yes Type: Observational Title: Neuroscience Research Institute Brain Bank and Biorepository (NRI-BBB) Sponsor: OSU Status: Ongoing Enrolling? No Type: Clinical Title: Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Efficacy, Safety, and Tolerability of IMU-838 in Patients with Progressive Multiple Sclerosis (CALLIPER) Sponsor: Immunic Therapeutics Status: Ongoing Enrolling? No Type: Clinical Title: A Phase 3, randomized, double-blind efficacy and safety study comparing SAR442168 to teriflunomide (Aubagio®) in participants with relapsing forms of multiple sclerosis (GEMINI 1) (EFC16033) Sponsor: Sanofi Status: Ongoing Enrolling? No Type: Observational Title: COVID-19 Vaccine Efficacy in MS Patients: The Impact of Disease Modifying Therapies Status: Paused Enrolling? No Type: Clinical Title: EFC16035-A Phase 3, randomized, double-blind, efficacy and safety study comparing SAR442168 to placebo in participants with primary progressive multiple sclerosis (PERSEUS) (ECG16035) Sponsor: Sanofi Status: Upcoming Enrolling? No Type: Observational Title: North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) Sponsor: CMSC] So last here, this is just sort of a quick snapshot of the different trials that we have going on within our group. You can see we have several both critical trials as well as observational trials that are ongoing. At this time we're only really enrolling from an MS standpoint for two observational trials. One's Biomarkers of Biological Aging in Multiple Sclerosis. That one's really aiming to understand how the difference of, how as people age of course we acquire a lot of things that we didn't have when we were younger, and a lot of the tools that were designed to assess sort of disability and MS were designed in a younger group of people. So we want to see both, you know, from a tool standpoint how things are different, but also from like a biological, molecular standpoint. So they may be looking at different DNA markers and things of that nature, really comparing between patients that have MS and patients that don't have MS to better understand as we age what does that mean. We also are participating in the Neuroscience Research Institute Brain Bank and Biorepository. So that's just building a library of samples that are available for researchers to put in a request for and they can really ask a lot of questions from the samples that we bank there. A lot of our other studies that are ongoing, some of them are sort of closes to new people enrolling at this time, but we do have several that are in the planning phases, probably getting started towards the end of this year into next year. Can't really discuss those just quite yet just because they're still in the works, but stay tuned for more information about that and we would really enjoy having more of you participate with us. [Text on screen: Why join a clinical trial or study? By participating, you can: - Learn more about your disease or condition - Feel like you're playing an active role in your health - Help researchers find new ways to prevent or treat disease - Benefit future generations through scientific advances. Major medical breakthroughs could not happen without the generosity of volunteers like you. Credit: National Institutes of Health. (NIH)] And lastly, the last thing that I really wanted to sort of take note of when I'm interacting with a lot of our research patients, a lot of them tell me that they get a lot of empowerment out of participating because they feel like they're taking an active role in both their own care as well as what is going to be up and coming for how people with their same diagnosis are treated in the future. So by participating you can be, you know, that extra piece of the puzzle that may help the way people are being treated in the future. And really all of these breakthroughs and everything that changes our paradigms of how we're treating and understanding things cannot be done without people that volunteer and participate in our trials. [Text on screen: Clinical Research Staff - Kasturi Ganesh Barki - Marina Rodriguez - Ryan Dickerson - Emma Hill Thank you For more information, please contact: MSresearch@osumc.edu or Ryan.Dickerson@osumc.edu Office: 614-688-9162 ] So with that, just a quick thank you all for your attendance, and of course both all of our clinicians and faculty as well as our clinical research staff that I have listed up here. Thank you. Both of these emails MSresearch@osumc.edu is available. If you have any questions or feel free to email or call me, all of my contact information is there below. Thank you so much. Epstein: Thank you so much Ryan, that's wonderful. And I do want to let you know we are also still enrolling for the MS Disease Intervention Program [DIP] and that is a trial looking at a 12-week lifestyle intervention and that is open and we are accepting patients. If you're interested in knowing more about the MS DIP Project you can use that contact information that Dr. Dickerson put up on the screen or ask us about that. Now we're going to make a little um, just to switch over to a different type of research, and we're going to investigate a little bit of what's going on in the basic science research lab. As many of you know, Dr. Benjamin Segal the Chairman of our department has a big research lab over on Main Campus and we are going to hear from a researcher in Dr. Segal's lab. So it's going to be my pleasure to introduce Calli Bellinger. She's a third year graduate student in the Neuroscience graduate program at OSU. And she is part of the Dr. Benjamin Segal Lab. she obtained her Bachelor of Arts in Neuroscience at the University of Virginia in 2019. Her research primarily involves studying the role of myeloid cells, immune cells that function as first responders, in a mouse model of multiple sclerosis. So we look forward to hearing what Calli is going to tell us about some of the exciting basic science research in Dr. Segal's lab. Calli? Calli Bellinger: Thank you for that great introduction. I'm going to set up my slides, there we go. Like she said, this is going to be quite a different talk than what you've heard before, this is going to be heavy on the science. But I, hopefully I can present it to you in a way that is palatable and not too boring. [Text on screen: Immature Neutrophils, A New Ally in MS? Calli Bellinger September 21st, 2023] I'm a third year graduate student in Dr. Benjamin Segal's lab, it's been an absolute pleasure being in his lab and I've learned a lot about MS, and it's been great to hear about all the different clinical aspects of MS that I'm usually more removed from as a research scientist. So today I'm going to be talking about immature neutrophils as a potential therapy in MS. So first, let's go, there we go, let me get my cursor real quick. So first I'd like to start in the basic background information on the brain and some of the damage that occurs during MS. One of the main disruptions in multiple sclerosis is damage to brain cells known as neurons. Neurons send and receive information through electrical signals throughout the body. You can think of neurons more like an electrical wire. You have the wire, which is known as the axon for a neuron, that sends and transmits information as well as the rubber coating, which is the myelin of the neuron. This helps protect the axon as well as helps transmit information in a more conductive manner. When damage occurs to the myelin, or the rubber coating, the electricity, the conduction is lost but also the axon itself can be exposed to other pathogens that can then lead to degradation of the neuron. Now, in all of us we have white blood cells, also known as immune cells, that circulate throughout our bloodstream. Normally immune cells will stay out of the brain because we have this three-layer barrier known as the blood-brain barrier. But in multiple sclerosis what happens is there's a leak in that barrier, an immune cell then can enter into the brain and cause destruction of those axons and myelin I was just talking about. Once those destructive immune cells enter the central nervous system they can interact and then multiply and release damaging factors that cause that destruction and damage to the axon and myelin, which might eventually lead to neuronal death. Naturally we would like to use drugs and therapies that prevent these immune cells from coming in to the CNS or the central nervous system, prevent them from releasing those damaging factors, prevent them from interacting with other immune cells. And in fact we do have drugs that do just that. Ocrevus is one of them that targets an immune cell known as a B cell. We also have Natalizumab which helps prevent immune cells from getting into the central nervous system. Now the problem is that most people with multiple sclerosis already have some form of a nervous system damage by the time of the diagnosis. As the next advancement in MS therapy, at least me, we need to have treatments that actually help reverse that neurological damage and further prevent more damage from occurring. This will lead to my project as I aim on focusing on treating neural damage that has already occurred. Now, I'm going to go through a lot of mouse studies, and I thought it would be great to give some background on a mouse model of multiple sclerosis which maybe not all of you know. It's called Experimental Autoimmune Encephalomyelitis. That is a mouthful so I'm going to refer to it as EAE from now on. Now by no means this is a perfect model for multiple sclerosis, however it does allow us to study similar immune responses that we see in MS. Now EAE relies on injecting immune cells, or those white blood cells I was talking about, that will specifically attack myelin within the mouse. We will then track the disease course of the mouse and we do this through a numerical scoring system, zero being no disease. So normally, how the disease progression goes along, once we progress--once we inject those white blood cells that will attack that myelin, there's no disease and eventually the mouse will onset. Now onset is more of a ascending paralysis, you'll see a limp tail [score of 1], they'll have difficulty righting themselves [score of 2], and as the disease progresses they show a more increased hindlimb weakness [score of 3], and then paralysis [score of 4]. So this indicates that a higher clinical score means a more progressive form, more progression of MS or EAE in this mouse model. [Graph on screen shows the score of the test subject increasing from 0 beginning around day 7 after white blood cells have been injected. The score rises sharply from less than 1 to more than 2 between days 9 and 12. The score then remains between 2.5 and 2 until day 17, where it begins to fall.] Let's go forward, there we go. Now I mentioned in the very beginning this thing called neutrophils, and I haven't talked about it since. Neutrophils are one of the most abundant white blood cells in the human body. About 60% of white blood cells are neutrophils. They are quite short-lived. This is a little bit debatable in the literature, some people say it's six hours, 24 hours, it really depends on the individual as well as the circumstance if there's inflammation or not. They're considered the first responders of the immune system, so they are constantly circulating around the bloodstream surveying for pathogens, looking into tissues. However once an infection happens, these neutrophils will mature and activate, as you see here. They will then go to the site of infection and either engulf the pathogen or start releasing pro-inflammatory factors, so factors that will recruit other immune cells to come in, cause a lot of inflammation, and take care of that infection. Now you might be thinking "why would the cell be good for MS? You don't want to increase the inflammation, that would be bad." However what was really cool was that in Dr. Segal's lab they found that there is an immature version of these neutrophils that can be polarized to act a bit different. So we found that when you um, sorry let me backtrack a little bit. So these are immature neutrophils can be quite protective and reparative in the central nervous system. We used this in a different mouse model, neuronal injury model, known as the optic nerve crush model. And we found that when we introduced these neutrophils we found more nerve repair following the injury site. So this, let's see if you can actually see my cursor... there we go, I think you can see it now. [Text on screen: Polarized, immature neutrophils alter EAE disease course Polarized immature neutrophils: - Neuroregenerative: Promote regenerative of damaged axons (Sas et al. 2020) - Neuroprotective: Prevents the damage of neurons - Immunosuppressive: Disrupts the activation of immune cells A magnified image shows two nerves that have been stained with green dye. One portion of each nerve is thinner than the rest, where they have been crushed with forceps. In the first nerve, this area in particular has very little neon green color. The second nerve shows bright green staining, even though it has also been crushed, after the zimocyn compound was introduced in the area promoting regeneration of the axons.] So normally the optic nerve has a lot of axons running through it. So the optic nerve goes from your brain to your eyes, and when there is no crush, what you'll see is this green, neon-green staining. Normally that's going all the way across down the optic nerve. But when you do an optic nerve crush as indicated by the star, you can see by my cursor, basically we just get forceps and pinch that area, I hope you can appreciate that there is a lack of that neon green staining indicating death and destruction of those axons transversing the optic nerve. However we found that when we introduced this compound called zymosin that helps recruit to these immature neutrophils I've been talking about, you'll see a regeneration of those axons by indicating that neon green shifting across the optic nerve. This was really awesome to see in the optic nerve crush model, but you're probably wondering "what does this--why do we care? This, we were all interested in MS." So we decided to try to take those immature neutrophils and use them in our EAE, our mouse model of multiple sclerosis. Now, while this project is still in its earlier stages, what we found so far are that these neutrophils reduce neuronal damage that we've seen within the eyes of EAE mice. So kind of similar to what you see in multiple sclerosis of optic neuritis, so the degradation of these brain cells or neurons within the eye, we kind of see that same thing in the mouse. And we found that when we introduce these immature neutrophils peripherally, so not even at the eye, we saw a reduction in damage to those neurons, which is really exciting. Another exciting factor is we found them to be immunosuppressive, meaning they helped prevent the proliferation or the multiplication of these immune cells, hopefully dampening that immune response. [Graph showing the clinical scores of two test subjects over a span of 17 days. The control subject begins to rise in score on day 7, reaching a peak score of 2.5 on day 13 and decreasing to a score of 2 by day 17. The subject that received immature neutrophil transfers does not increase in score until day 8, reaching a peak score of 1.5 on day 12 and decreasing to a score of just over 1 by day 17.] Now back to this beautiful graph again. What we did was, we introduced these immature neutrophils during the disease course of EAE. We really wanted to see if this was actually going to impact the clinical score. Are these mice going to not get sick, will they have a delay in onset, will the severity of their sickness decrease? And what we found was that when we transferred these neutrophils, so this is, we have a control mouse with the blue squares, the typical EAE course. But when we introduce those immature neutrophils, indicated by the green triangles, we found that there is actually a delay in onset of the EAE disease course, as well as a decrease in severity. This indicated to us that maybe these neutrophils are acting as a way to inhibit or prevent that proliferation of immune cells, and therefore decreasing inflammation within these mice. Along with the optic nerve data I talked about, with the pro-regenerative, these neurons--these neutrophils look like they're a heavy hitter on two sides. They help prevent inflammation from occurring as well as repairing any damage that has occurred through, by being neuroprotective. So in summary of what we've seen in the mice is that we've seen these immature neutrophils that have been polarized that can release reparative factors as well as prevent the multiplication of immune cells, destructive immune cells, which over time could lead to neuronal repair and protection. Again, you might be wondering, "Oh this is really cool but this is all in mice, why do I care, how can we translate this to humans?" Well, in our lab and actually the biobank repository that's been talked about already, due to patient samples that have been donated, we've been able these immature neutrophils naturally occurring within the bone marrow of patients. And the goal is, this is a hopefully a potential future ally in multiple sclerosis, is that we can take those immature--remove bone marrow cells, isolate out those immature neutrophils, put them into culture, put polarizing factors in (which we've already done in the Segal lab to create that immature, pro-regenerative, neuroprotective, immune suppressive type of cell), and then hopefully in the future we'll be able to then infuse that back to the patient to help repair any damage that has occurred due to MS. This is the goal, we've already started making some steps to looking at actual human cells, and we have great potential for this, so I'm actually really excited. You should look out for Dr. Andrew Jerome's work on this in the future. [Text on screen: Acknowledgments Segal Lab: Benjamin Segal, MD Jeff Atkinson, PhD Stephen Atkins Shuo (Shane) Chen Alexander Efanov Andrew Jerome, PhD Hayley Groover Tom Liu, PhD Yan Wang, PhD Sas Lab: Andrew Sas, MD, PhD Alex Sepeda Harrington Lab: Cole Harrington, MD, PhD The Ohio State University ] I would like to thank my lab Dr. Benjamin Segal, who might be talking I don't know. He's been a great mentor, really has introduced me a lot into multiple sclerosis. Dr. Jeffrey Atkinson as well as Dr. Andrew Jerome, both of which are postdocs that really have helped guide questions that I have during lab and all the technical skills. Dr. Andrew Sas who has helped guide me with the neutrophils, as well as Dr. Cole Harrington who is always a great help in reminding me about all of the MS research that's going on in the oligodendrocytes another really cool research that you should look into. [Text on screen: References (In Order of Reference) McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and Treatment of Multiple Sclerosis:A Review.JAMA.2021;325(8):765–779. doi:10.1001/jama.2020.26858 Rosales C. Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types? Front Physiol. 2018 Feb 20;9:113. doi: 10.3389/fphys.2018.00113. PMID: 29515456; PMCID: PMC5826082. Sas AR, Carbajal KS, Jerome AD, Menon R, Yoon C, Kalinski AL, Giger RJ, Segal BM. A new neutrophil subset promotes CNS neuron survival and axon regeneration. Nat Immunol. 2020 Dec;21(12):1496-1505. doi: 10.1038/s41590-020-00813-0. Epub 2020 Oct 26. PMID: 33106668; PMCID: PMC7677206. Shi, L., Chen, S., Yang, L.et al.The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies.J Hematol Oncol6,74 (2013). https://doi.org/10.1186/1756-8722-6-74 ] And with that that'll be all for me. I hope, I'm excited to hear your questions. Epstein: Thank you so much Calli what a wonderful presentation, such exciting things happening in the Basic Science Research Lab. One of my favorite days of the year is always Neuroscience Day when we get to hear the wonderful presentations by these amazing Basic Science researchers in their lab. So next I'm going to let Dr. Gyang take over for our Q&A panel. Dr. Gyang? Tirisham Gyang, MD: Thank you so much Kristi and what an amazing day. We've just had such wonderful discussions, I have learned a lot, just so much about research about urinary issues in MS, about how pelvic floor therapy can be helpful, you know, if you have MS. So, you know, thank you to all our speakers. I will open the floor to all the speakers, and I see Dr. Sagal is still here. So if you could just pull up your cameras on and we will start the Q&A session right away. Great. So we learned a lot today, and uh I'm just pulling up my Q&A banner, okay there we go. I will probably start with maybe some of the research questions. Oh, we have Dr. Cartwright with us as well. Dr. Cartwright is one of our MS fellows, I'm sure some of you will see her in clinic very soon. So we'll start with some of the research questions and I'll go to Dr. Dickerson. One of the questions says "do you have to be an OSU neurology patient to be involved in a research project?" Dickerson: That's a great question thank you. So typically yes we do like to at least have some sort of established relationship of care to get started with one of our trials. We often use, you know from a medical records standpoint, we do a lot of documentation there and that's helpful for us on our research side but also we do have a lot of our clinicians that are doing a lot of the evaluations here. So, I know just in discussing, you know, with many of the other panelists it's a lot--it's quite helpful to be able to already have some sort of established relationship there in just securing diagnosis and all the other things that are involved with that. So yes, typically we would like you to be involved as a patient in our clinic at Ohio State. Gyang: That is a great answer. You know, I am a principal investigator in a lot of the trials and, you know, before we put you into a research we at least want to see you to confirm that you really have MS, and what type of MS you have, and just get some details so that is absolutely right. Thank you Dr. Dickerson for that answer. I see a lot of questions about the Basic Science research that we talked about and I see Calli here and I see Dr. Segal so I'm gonna turn over some of the questions over to them. I will start with this one: "do any animals naturally develop MS, MS-like disease or conditions, or is EAE the only way for testing MS treatments in animals?" So I will have either Calli or Dr-- Bellinger: I can jump on that one and then Dr. Segal could probably jump on that too. So there are actually multiple, EAE is a broad term for different mouse models in MS. There's quite a few different ways to induce EAE, but to answer the original question on does it naturally occur in mice: normally no. There are some genetic backgrounds that can induce EAE naturally--or sorry, MS-like disease naturally, but in order to study, uh have more constant and more controlled experiments it's easier to induce the disease and keep it all controlled than mice spontaneously developing it. Dr. Segal would you like to add? Benjamin Segal, MD: Yes so um in general throughout most laboratories we, you know, deliberately induce this MS-like disease in animals, most commonly in mice and rats. But it's also been done in guinea pigs, and in non-human primates, for example marmosets which is a um a species of monkey, as well as macaques. There has been described in a particular subset of macaques the occurrence of an MS-like disease that seems to be related to infection with a particular virus, and that arose naturally. And that is being studied at some Laboratories in Oregon. There's also occasionally an MS-like disorder that occurs in dogs, which is rare in sporadic. So there are some rare instances in, as I said, non-human primates and dogs of MS-like disease that have, you know, some similarities to the human disease. But this is very difficult to predict and it's relatively rare so it's difficult to study in the laboratory setting. Gyang: Thank you very much for those answers. And then I will do another quick question in terms of the Basic Sci--because there seems to be a lot of questions and I'm gonna lump these questions into one. So several questions about clinical trials: "Will there be clinical trials with the neutrophil research? Would the neutrophils need to be introduced early in the disease? And what is a timeline for the potential optic nerve repair that you talked about in some of your slides?" So this is more, I mean these are two separate questions, I guess. We're talking about when it's going to be in clinical trials, in actual people. And then maybe a little bit about the timeline on how quickly or the timeline on how the optic nerves get repaired in your research. Bellinger: Okay, I was also answering one about polarized neutrophils that I realized I did not describe well. I'll start with that real quick: it's a blanketed statement of saying a "polarized neutrophil." Basically, you have mature neutrophils: super inflammatory. An immature neutrophil is a little bit more changeable more, malleable. You can push it down a pathway that is not as pro-inflammatory. So when I mean polarized neutrophils, it's providing uh factors that can push it down a more anti-inflammatory, more of a reparative function, instead of more inflammatory-secreting factors that can recruit other cells. For the clinical trial aspect I think Dr. Segal could talk more on that. I could say my opinion: I think it's quite far off. But it is still the, always our goal in research is to get uh anything that we're researching into clinical trials to have therapies to help patients. In terms of the optic nerve crush in the EAE mice, typically what we see in that disease course if you remember, we'll start seeing optic neuritis-like symptoms around peak of that disease. And even when we introduce those neutrophils early on before they even get sick we notice that there is a decrease in the damage. Now it's hard for us to study whether that is because there--those neutrophils are suppressing the inflammation which is reducing the actual initial damage in the eye, or if it's actually helping repair any damage that has already occurred. So, would it need to be introduced at the beginning of MS? I would hope, so I would hope to say no. It's really hard to treat someone with MS before they develop or before they clinically get diagnosed with MS. The great thing about the neutrophils that I potentially see is that they can have some reparative function to damage that has already occurred. I hope that answers your questions, I know Dr. Segal could probably talk more on the clinical aspects. Segal: Okay, thank you Calli. So as Calli mentioned we're still in fairly early stages in that we're testing these um immature neutrophils in the animal model more extensively. But we have identified similar cells, as as Calli alluded to, in bone marrow of of human beings. And we have now developed protocols by which we could stimulate the the uh the bone marrow cells to become even more potent um uh repair cells. So what we're now doing is developing different uh methodologies to expand those cells in a dish and to polarize them after we have a large number of them to see if if we can still uh trigger them to acquire these properties that lead to healing in the nervous system. It's it's difficult to predict how long that's going to take, but we definitely are going to put a lot of effort. The human counterpart was recently discovered in the past six months and right now we're putting a lot of effort into expanding the cells and seeing if we could polarize them in larger numbers. So far we've looked at um bone marrow cells from I believe eight um individuals uh human individuals and all of them we were able to polarize or trigger them to acquire these repair properties. And we could actually, after we trigger them, we could put them in a dish with actually human nerve cells and see that they stimulate the human nerve cells to grow new nerve fibers or or axons. So, you know hopefully we'll be successful and be able to expand them so we have large numbers that could be used therapeutically and then ultimately, you know, uh uh go to clinical trials. But uh, you know, this does take time. It's the time span between an initial discovery and clinical trials in the past would take, you know, five to ten years but that's becoming um uh more and more accelerated, you know, as we get better with clinical trials and designing them. So we do have actually a patent for this therapeutic approach and we're gonna really put a lot of effort into it. So I can't tell you exactly when. Our goal is is to um, you know, develop this and and start some clinical trials. And um just got to get Calli and her colleagues to spend more time in the lab and you know, I gotta crack the whip but um we're working on it. Gyang: That is wonderful to hear. We're gonna move to a slightly different direction, but before we do we have a comment that says "thank you for the information, keep doing this good research to help fix the nerve damage." So that that's just a wonderful comment. Now I'm gonna move to Dr. Vietas. There's a few questions for you, two that I'm going to group, all having to do with pelvic floor therapy. I think one of them asked about "double voiding" so maybe you could talk a little bit about that, and then the second one about breathing exercises. "Would breathing exercises be enough or would PT be needed?" Vietas: So I'll start with the double voiding question. Absolutely, PT is effective for those who double void. So oftentimes what we'll be working on is like relaxing to urinate, as well as um kind of giving your body the cues to urinate. Oftentimes with MS those signals from the center that controls urination in your brain that go down to your bladder are a little bit mixed up, so we kind of help create a super highway of information by creating a routine for you. And that's really individual for each patient. And then for breathing, for some people it can be helpful but it's probably not going to get you exactly where you want to be. Um so I would start with the breathing and then move on to working with the pelvic floor PT if you can find one near you. And that's all. Gyang: Thank you for that answer. I have one quick question for Dr. Dickerson. "Is there any research going on for rare NMOSD, since it used to be under the umbrella for MS but now separate?" So you listed a few different MS trials. There were some for MS, there were some for I think uh NMDA Encephalitis, uh somebody's asking about NMOSD. I'm not aware that we have a trial on that yet, but just tell them how maybe we get information about new trials coming up and you know sometimes we engage with you know different sponsors and researchers to get new trials on board. Dickerson: Yeah, no, thank you. Um so, yeah, as Dr. Gyang alluded, um that's not something we have ongoing right now. But we are you know always entertaining uh new trials. So, typically when um, if we get approached either by a sponsor or, you know, an investigator to participate, it's something that, you know, as a department sort of gets discussed. And uh really trying to establish do we have both the expertise and, you know, enough demand to fulfill the requirements of some of those studies? And we're really careful about it because um a study startup process, you know, it takes quite a bit of time and effort. So I to answer your question I'm not aware of any right now that we are overseeing um but for sure, you know, if there was something that came up, came our way, um that would be something we'd be very interested in learning more about for sure. Gyang: Thank you for that, wonderful. Uh there's a few questions asked about symptoms in MS, maybe I'll have Kristi address some of those. One asks in general about, you know, "what are some of the symptoms the patient with MS may have?" Another one asks "is numbness in the abdomen legs and feet normal with MS?" So just maybe a little bit about the different variety of symptoms MS patients could have. Epstein: Absolutely. As most of you probably know, if you have a disease that impacts your central nervous system, that's really the master computer for your entire body. So you can have a myriad of symptoms that kind of affect every body symptom or system. And one of the things that we do at The Ohio State University, not only in our quality of life clinic, but also in our MS multi-disciplinary symptom management clinic, is we review from head to toe all of those symptoms that you may be experiencing. I love that Calli used the analogy of a lamp cord because [laughs] I use that all the time in clinic. If something is going on with your spinal cord, which is really delivering all those messages from your brain down to all these important parts of your body, it's it's involving sensory changes, your bladder, your bowel, your balance, all kinds of different things. When that covering around the nerves is deranged your light's going to be blinking, right? The message isn't perfect like it's supposed to be. So you're going to get those downstream symptoms. So what we really do is we look at a full review of those symptoms. We do things, like Dr. Crescenze mentioned, we'll maybe get a bladder scan if you're having some urinary symptoms, often our patients will get urgency of the bladder. Our patients will have numbness, tingling, weakness. You can have symptoms in the abdomen, you can have a symptom called Lhermitte's where you might have a sharp or electric type shock feeling if you flex your head. [She demonstrates the motion by dropping her chin to her chest.] So yes, there are many, many symptoms. All of the things that you mentioned are possible if you're a patient living with MS. And it's always important to bring those up at your visit with your doctor so that we can go over them step by step, head to toe, to see what exact symptoms you may be experiencing and what treatment or therapy we might be able to recommend for you. Gyang: Excellent. You know, Kristi runs multiple, multi-disciplinary clinics that, you know, really help to address symptoms in MS and quality of life in MS. So definitely, you know, talk to your doctors to be a part of those clinics. Uh, there's a few questions about how to get to see the pelvic floor therapist: do you need a referral by your neurologist? How, you know, if you want to be seen by uh Dr. Veritas' service how do you get in to see, uh how do we get to, get patients into the pelvic floor therapy? Vietas: So you can get a referral from any of your doctors. And all that it would need to kind of state is what you've got going on, you know, even if that's just "pelvic floor dysfunction." And that's, that's all you need. Then you schedule a visit. Generally there's a wait 'cause there's not enough pelvic floor PTs that exist yet um to make it so that we get in like really soon. Um but like for our clinic it's about a three-month wait to get in to see us, but then once you get in we get a little bit, um we get rolling. Gyang: That is wonderful. So that is something that you could discuss with your doctor for a referral, that's great. This is just a comment, somebody says you know they've been with OSU for nine years and they just want to say that "your continued research and personalized care saved my life, thank you for what you do." We appreciate that comment. Uh there's a lot of other questions that I don't think we're gonna have the time to address. I see one asking about Mavenclad, uh I'm trying to find it. "Does Mavenclad help with MS-related bladder issues?" So Mavenclad is one of the disease modifying treatments. In general, the disease modifying treatments help to control the progression of the disease and may not necessarily help with the specific symptoms that you're dealing with. Uh, there was a question as well about Ocrevus, or maybe a comment about Ocrevus reducing the immunoglobulin levels. Thank you for that comment, that is something that we occasionally would see with Ocrevus. We have two more minutes, so I don't know that we could get to all the questions that are on. I see that some of them have been answered. Unfortunately Dr. Crescenze could not stay till the end, but I see that she has answered, you know, most of the questions that were directed to her. Any final thoughts from any of our researchers or our clinicians that are on board? I thought this was just a wonderful venue to talk about both research and clinical care, and is a good way to put things all together. Kristi any final words, or Dr. Segal? Segal: I would just like to congratulate all the speakers and Kristi for uh being a wonderful host again. And also you Dr. Gyang you know for once again coordinating a great question and answer session. I'd also like to thank everyone who attended for your great questions and for your interest. Gyang: Thank you. Well, I think it's about 7:30 and I don't want to keep us uh too long. Thank you everyone for attending and we will end the session now. All the videos and all the slides would be available on our website so just be aware that you can access any of this information on our website. I'll hand this back to Kristi and thanks everyone. Epstein: Thank you everyone again, so exciting to hear from all the speakers about the amazing basic science research. So thank you everyone for joining us tonight. That is all the time we have, unfortunately, and we will address your questions and get those back to you. We'd also like to invite you to log on to wexnermedical.osu.edu/MSCommunity to learn about updates in our MS program including details about this and future sessions in this virtual education series. Also the doctors will be answering questions that we didn't have time to get to in our Q&A session tonight and we'll post the answers on that webpage in the coming days, along with the presentations and a video from tonight's event. There are a lot of wonderful videos there if you want to have an MS Day and watch a lot of videos we welcome you to do that. Thank you once again to all my wonderful colleagues for sharing their time and expertise with us this evening. Thank you so much for attending. We would love to learn about you and how we can care for you and your MS, or provide you support as a caregiver to someone with MS. You can schedule an appointment with one of our physicians on our website or by calling 614-293-4969. And again we look forward to seeing you very soon thank you and good night. [Text on screen: For post-conference questions or information, visit wexnermedical.osu.edu/MSCommunity. You will be receiving a summary via e-mail to share your experience from today's event. Multiple sclerosis Education Series Thank you for joining us today. The Ohio State University Wexner Medical Center]