MS education: Multiple sclerosis, aging and pregnancy [Text on screen: Multiple sclerosis education series March 23, 2023 The Ohio State University Wexner Medical Center] [Text on screen: Kristi Epstein, APRN, CNP, CCRN MS Nurse Practitioner] Kristi Epstein, APRN-CNP: If you're joining us tonight, you are either a patient who is coping with and managing MS, or you're a caregiver who's taking care of someone who is dealing with MS in their daily life. So we welcome you and we hope that our discussions tonight will be helpful. So throughout our webinar, which is going to last approximately 90 minutes, there will be some things that I'm going to let you know. So I will serve as moderator for tonight's event, and then after our event, we will have a question and answer that will be managed by one of our neurologists, Dr. Harrington. [Text on screen: The Ohio State University Wexner Medical Center Kristi Epstein, APRN, CNP, CCRN, MS Nurse Practitioner Tirisham Gyang, MD, Neurologist Allison Jordan, DO, Neurologist Stephanie Kielb, PhD, Neuropsychologist Yinan Zhang, MD, Neurologist Em Harrington, MD, PhD, Neuroimmunologist] Kristi Epstein, APRN-CNP: So what we're going to do is we're going to put up some housekeeping slides to just let you know how things are going to go throughout the event. First of all, you are 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 and you can view at a later time. All of our previous sessions are available and you can watch them on our webpage. So throughout the evening, what we want you to do is put all of your questions into the Q and A box. That is the function for putting your questions in, and we will address those at the end of our presentation. We have a very wonderful lineup and we're looking forward to all of our presentations. With the question and answer portion, we want to make sure that you don't put any personal information. Just put general questions, and all personal questions, you can reserve those for your providers. So I'm very excited about the people who will be presenting tonight and I will be having the pleasure of introducing everyone. These are our presenters for this evening. We have Dr. Gyang, Dr. Jordan, Dr. Zhang, Dr. Kielb, and Dr. Harrington is going to help us out with the moderation of the Q and A. So the topics that we're going to talk about tonight will include a discussion about MS in pregnancy, mental health issues, aging in MS, and Dr. Gyang is going to cover some very exciting topics from a recent meeting, a research meeting called ACTRIMS, and she will give you some details regarding that. So if you want to get prepared, take some notes and make sure to answer, put your questions in the Q and A box and we will get to those at the end of the presentations. So what we're going to do now is we're going to move on and start with our introductions. [Text on screen: Yinan Zhang, MD Neurologist] Kristi Epstein, APRN-CNP: Our first speaker tonight is going to be Dr. Yinan Zhang, and we are very excited to have him here at the Ohio State University. He's a neurologist and a neuroimmunologist and he is specially trained in multiple sclerosis. He is a wonderful researcher and he has started some new programs and new research here at the Ohio State University, and one of his areas of interest is aging in MS. I feel like this has been an area, and many of you may agree, that has been lacking in quality and in-depth research, and Dr. Zhang has really started some exciting and very forward-thinking research in this area. So he's going to talk to you tonight about aging in MS and he may mention his wonderful trial that we have going on right now. So it is with pleasure that I now introduce Dr. Yinan Zhang. Yinan Zhang, MD: Thank you for the wonderful introduction, Kristi, and good evening everyone. It's a pleasure to have you all join us for the webinar and I'm excited to share some discussion with you guys on the topic of aging in MS. [Text on screen: Aging with MS Yinan Zhang, MD Assistant professor The Ohio State University] [Text on screen: Overview Changes in MS with age Changing in MS symptoms Aging and MS medications] Yinan Zhang, MD: So I'll begin tonight's talk with a few slides overall centered on how MS changes with age and also some of the symptoms that may become more prominent or predominant with aging and more noticeable with aging, and then talk about how aging and MS medications play a role in your care and people with MS. [Text on screen: MS changes with age. With aging, - MS relapses are less likely - New lesions are less likely to appear on MRI However, aging increases the likelihood of developing progressive MS] Yinan Zhang, MD: So to begin with, I want to share this important concept about how MS changes with age. So the biggest things to note when patients with MS are getting older is that there are changes in the immune system and changes in the way the disease behaves. And as people with MS age, they're less likely to have relapses because the immune system in some ways quiets down with age. And as a result, you're also less likely to have new lesions develop on the MRI as well. So for many patients, they may notice that their MRIs stay the same year after year, and earlier on in their earlier years, they tend to have more relapses and this becomes fewer and maybe they haven't had any relapses in the past couple of years or even longer than a decade. It's entirely possible. I share this, a figure here in this slide illustrating what the disease pattern may look like as people with MS get older. And that yellow line initially, it shows these bars representing relapses, and you can see that tends to happen more earlier on in the disease course in what we call the relapsing remitting phase of MS. And as people with MS get older and time goes on, some people may transition to what we call secondary progressive MS. And this is a phase of the disease where patients experience gradual worsening of disability or increasing in the disease burden. And during that time, patients may or may not have relapses, and if they do have relapses, these are few and far between. As you can see in that middle section there, the number of relapses is much fewer than earlier on in the disease course. So one of the things that we know is that aging has a big impact on the risk of developing MS, secondary progressive MS that is, and usually in a person's late 40s and 50s, that's kind of where we see many people transition from relapsing remitting MS to a secondary progressive MS. And this is based off a lot of historical epidemiological data. However, the good news nowadays is that with very effective medication and many treatment options for MS, we're seeing fewer and fewer people with relapsing remitting MS transition to secondary progressive MS, and it's a testament to the beneficial therapies that we have for MS over the years. [Text on screen: My MRI is "stable" but I'm feeling worse... New lesions are less likely to form with age. Disease progression is driven by neurodegeneration, which is not seen on routine MRIs. Are MRIs still needed for older adults with MS? - Yes, new lesions can still develop - But they may be done less frequently] Yinan Zhang, MD: One of the questions that I wanted to address that's really come up with a lot of my patients and people with MS in general is that they ask their question, "Why am I feeling worse when my MRI says everything is stable, when my MRI is unchanged? What does that mean exactly?" So we tend to tell patients, "Oh, your MRI is stable and there's no changes." And what this reflects is that there's no new lesions that have formed since your most recent MRI compared to your previous MRI. However, there are some things that we cannot view on the conventional MRIs, which is the process by which the disease progresses. So by that we mean there are underlying processes driven by neurodegeneration, which we can't really see on the conventional MRIs. So the lesions that we see, meaning these white spots that we see on the MRI, they're driven by what we call focal areas of inflammation, and that is a different process than neurodegeneration, which is the predominant force that drives progressive MS and that drives this progressive increase in disability. So even though an MRI shows no change and the lesions remain the same, it doesn't mean that the patient may not feel any worse and in fact, we just don't have methods on the conventional MRIs. Certainly there are research MRIs that can detect some changes, but in the routine clinical MRIs, we can detect these changes in neurodegeneration on the scan, at least from year to year changes. So for that reason, when the provider tells you that the MRIs were stable and when you see on the report that the MRIs were stable, it just means that we don't see any focal inflammatory activity, but that does not rule out the fact that there can still be underlying changes in the disease leading to progression and neurodegeneration making patients feel like they're acquiring increasing amounts of disability. So if that's the case, people wonder, "Why do we still need to do MRIs, especially my scans are stable over these years?" The answer is that there can still be new lesions that develop despite patients who are entering the progressive phase of the disease or who have been stable with relapsing remitting MS for many years. Even though it's less likely that older adults with MS will develop new lesions, that can still happen, and if there were to be a relapse, meaning actual clinical symptoms from one of these new lesions, with older patients, they may have a harder time recovering from a clinical relapse, whereas the body when it's younger, it's more robust, you more are more able to bounce back. When we get older, that ability is harder. So we still want to protect our patients from having new relapses even as they get older, even as that chance decreases. [Text on screen: Are my symptoms due to age or MS? Muscle strength, balance, sensation, vision, mood, cognition, bowel and bladder function] Yinan Zhang, MD: So with age and having MS, there are many symptoms that may develop or get worse, and it's very common to ask the questions, "Are my symptoms really due to age and MS?" And in many cases it can be hard to tell, but in some cases, there may be some ways at distinguishing some of their features. Muscle strength is one of the most common symptoms that patients complain of when they get older, saying that, "Maybe my legs are feeling weaker and I'm not walking as much or not walking as far as I used to walk." And with age, there can be changes in the muscle itself. We call this term sarcopenia, meaning a loss in muscle mass and a loss in muscle function. But at the same time with MS, your brain is trying to send signals through nerves that are injured and therefore that signal is not reaching to the muscle entirely, so both factors can add on to produce a picture of muscle weakness or a lack of strength. And normally with aging, with the decline in strength, that process is gradual. Same thing with balance, but if you are noticing a sudden change in muscle strength or a transition that's occurring where patients are going from walking to using the cane, the walker, and then the wheelchair, these are more likely due to MS-related changes. And sudden changes, you should definitely let your provider know about so we can look to see whether or not this is a relapse or something else that's making the MS symptoms worse. Other symptoms that can get worse with age. Vision is a common thing, and with age we develop what's called presbyopia or a decrease in our ability to read or look at objects that are closer to us. In MS, there can also be vision loss as well. We often see this in the form of what we call optic neuritis, which is an injury to the optic nerve that sends the signal from your eye to the brain. And in optic neuritis, that vision loss can be rather quickly and it can sometimes be accompanied by pain and is oftentimes involving just one eye, whereas age-related vision loss, it's a more gradual process that can affect both eyes oftentimes. Cognition also happens, declines with aging, and it's part of normal aging, but with MS, even in the beginning, cognitive function can be affected. So one of the things to be mindful is that with memory, it's usually pretty stable, but if memory starts to decline, especially at a more rapid rate, then you need to let your provider know and we need to look into things that may signal another process that could be dementia or something else. And we have our wonderful neuropsychologists who offer cognitive testing for all of our MS patients, and it's very important to establish a baseline of your cognitive function. And that way in the future, if there were to be changes, we can see which areas of cognition have been changed. In MS, that tends to more affect processing speed, meaning kind of how we handle multiple information venues and how we can process new information, but if other more stable forms of memory are affected quickly, then that's something that we should be aware of and let your providers know about. There's bladder and bowel function that can be affected in MS as well. That tends to worsen with age. In age, it tends to affect things like pelvic floor or other areas of structural function, whereas in MS, there tends to be a phenomenon called the neurogenic bladder where the signal from the brain is not reaching the bladder entirely, and the way to distinguish these is to see your urologist, or if you don't have a urologist, we have wonderful urologists at OSU who we can refer you for additional testing to distinguish which particular aspects of the bowel and bladder function may be related to MS or other causes. And there are lifestyle changes that can be done to correct or compensate for these deficits in addition to medications if they are deemed necessary. [Text on screen: Aging with MS Clinic at OSU Multidisciplinary clinic to evaluate and treat overlapping symptoms of aging and MS in older adults with MS over age 60. Patient attend a one-time appointment at Martha Morehouse Outpatient Care lasting four hours. Providers include MS advanced practice provider, physical therapist, MS pharmacist, neuropsychologist, and social worker.] Yinan Zhang, MD: So at OSU, we have a wonderful Aging with MS Clinic that was just launched in February of this year. So it's an entirely new service that offers multidisciplinary evaluation of the older adult with MS. We encourage all patients who are over the age of 60 with MS to attend the clinic. Even if you're not at the age of 60 yet, but you feel like you would benefit from the services, let your provider know because we're not going to turn away anyone who's interested. So this clinic, what it is it's comprised of many specialists from different aspects that provide care to MS. So that includes our MS nurse practitioner, Kristi, it includes our neuropsychologist, it includes our MS pharmacist, our physical therapist, and our social worker, and the clinic happens over the course of an entire morning so when patients show up, they will see all five providers, and we provide a comprehensive geriatric assessment of the older adult with MS to address many of the changes with aging and MS, focusing on symptomatic management, focusing on any social needs or concerns that may arise, focusing on looking at mood and cognition, looking at your medications. If you're not taking an MS medication, we look at your other medications to see if there may be any inappropriate drug interactions or ways we can simplify the list. Many things that can really greatly benefit the older adult with MS, and it is a one-stop shop to get many questions asked and symptoms addressed with our various specialists. So I'll put up some information at the end on how you can obtain a referral to that Aging with MS Clinic. [Text on screen: Aging and MS medications Disease-modifying therapies (DMTs) for MS are effective in decreasing relapses and new lesion formation. DMTs generally work better in younger adults with MS. DMTs have more side effects in older adults with MS. DMTs are overall ineffective in slowing disease progression.] Yinan Zhang, MD: In regards to medications, one of the things that I think patients should be aware is about the change in the effectiveness of medications over the lifespan. So initially, rather, we prescribe medications for MS to treat relapses and to decrease the formation of new lesions on the MRI. So when you're being prescribed a disease-modifying therapy, the goal is to decrease the formation of new lesions and decrease the likelihood of having relapses. But as I mentioned earlier in my slide, as people with MS get older, they're less likely to have new relapses and less likely to have new MRI lesions as well. And at the same time, we know that disease-modifying therapies tend to have more side effects in older adults with MS. And most notably, this can come in the form of infections as older adults are more vulnerable to infections, and also being on disease-modifying therapies for longer amounts of time can increase the risk of infections as well. So with all these things being said, many people may be wondering, "Is it time for me to stop my treatment for MS? And if so, at what age would it be appropriate to do so?" [Text on screen: When can I stop my MS medication? Results of the DISCO-MS study: - Study looked at people with MS over age 55 with no recent relapses or MRI lesions - 6/128 people who stayed on medication had an event (1 relapse, 5 with new MRI lesions) - 16/131 people who went off medication had an event (3 relapses, 13 with new MRI lesions) - No differences in disability progression, patient reported outcomes, cognitive testing or adverse events Decision about potentially stopping disease-modifying therapy for MS depends on many factors and should be discussed with your MS provider] Yinan Zhang, MD: So there was a recently completed study across the United States. It was done at multiple MS centers. It's a very large scale study looking at the safety of discontinuing MS therapies in adults with MS over the age of 55 who are stable, meaning that they in that study have not had any relapses in the past five years, and their MRIs have been stable for the past three years, meaning no new lesions have shown up on their MRIs. And just to summarize some of the results, they randomized the participants of that study to either continuing their current disease-modifying therapy or coming off of their disease-modifying therapy for MS. So in the group who stayed on the medication, the vast majority of them of course stayed well, and six out of the 128 people had an event, meaning either a relapse or new MRI lesions. In the other group, the 131 people who went off the medication, a little bit more, but not a lot more, so 16 out of those people had an event, so three people had relapses and 13 had new MRI lesions. So altogether there really wasn't what we call a statistically significant difference between the two groups, 16 out of 131 versus six out of 128. They're in some ways similar and we can't really say that there was a big difference in between the two groups, and certainly there were no differences in the disability progression or patient-reported outcomes or other cognitive testing results or adverse events that were experienced. So what this study means is that in general, it can be safe to stop medications at an older age in patients with MS who are stable in their disease, meaning that they have not had any recent relapses or MRI lesions for at least five years. But nevertheless, there is still a risk in anyone who is not on a medication for MS, and therefore that decision to potentially stop medications really should be had with your MS provider to talk about when and if it is recommended to come off your medications. [Text on screen: Aging and MS. Dr. Zhang is recruiting for a study of biological age in MS - To see if people with MS age differently than those without MS - To understand the impact of aging on the disease course in MS You may be eligible if you are over 18 years of age and have MS. Participants will undergo a blood draw and participate in neurological exams and neuropsychological assessments. For more information, please email MSResearch@osumc.edu] Yinan Zhang, MD: Lastly, I want to mention that we are conducting a study at OSU to look at the effects of biological aging in people with MS. This is a study that I have been piloting in the past year and we are still enrolling participants. And the reason behind the study is that we know chronological age, which is the number of years that we've been alive, is the biggest risk factor for developing secondary progressive MS, and it's a huge risk factor for driving the progression of disease. But we don't know much about how biological age affects MS. And biological age refers to the underlying cellular, genetic and molecular characteristics by which an individual ages. So you might see that someone is older than their stated age or younger than their stated age, and that in many parts can be attributed to differences in biological aging. So what the study involves is it's a one-year observational study and anyone with MS over the age of 18 could be eligible to enroll. And what the study entails is for those who are interested, we would collect your blood at the beginning of the study to look at these markers of biological aging. And then we just follow you along under your standard of care and see how your biological age is associated with the disease characteristics such as the severity of the disease, how the MRIs are changing, and how your cognition is. So that does require patients to get standard MRIs every year, and it also requires the neuropsychological assessment from our neuropsychologist at baseline and at a year later. And in between, of course, you will follow up with your MS provider at every six month intervals. So if anyone is interested in this study, I encourage you to reach out to our wonderful research coordinators. You can email them at msresearch@osumc, or you can talk to your providers directly and ask them about the study to find out if you are eligible for that. [Text on screen: Resources. OSU Aging with MS clinic - https://wexnermedical.osu.edu/neurological-institute/neurology/neuroclinics - 614-293-4939 National MS Society - https://www.nationalmssociety.org - 800-344-4867 Results of the DISCOMS Study - https://mscenter.org/article/results-of-the-disco-ms-study/] Yinan Zhang, MD: So my final slide I want to share with some resources. So these slides will be available after the talk. So you can look at the link to get a referral for the Aging with MS clinic, or find out more about the DISCOMS study, which is a study that looked at discontinuing disease-modifying therapies in patients. And of course, there's the National MS Society with wonderful information that can be beneficial to you. I appreciate your attention, and I'll turn it over to Kristi, who will introduce the next speaker. Kristi Epstein, APRN-CNP: Thank you so much, Dr. Zhang. What a wonderful presentation. And I know there are going to be a lot of questions associated with that. So again, I would like to encourage everyone to just go ahead and put your questions into the Q&A chat box. We will get to your questions. Any questions that we are not able to address tonight, we will post on our website the answers to those questions. Please keep those questions coming. Put them in the Q&A chat box, in the Q&A box rather. And make sure that they are not personal questions. Keep them very general and we will be happy to answer them. So moving on, we are going to go to the other end of the spectrum, and it's going to be my pleasure to introduce Dr. Allison Jordan, and she's going to be talking to us about pregnancy and MS. This is a very important topic. And I know a lot of you out there are going to have a lot of questions, so we look forward to this presentation. Dr. Jordan is actually a local, born and raised in Columbus. She did go to that school up North, but we will forgive her for that. So we are so excited to have her back, and we are looking forward to her presentation. Her special interest lies in pregnancy and postpartum care for patients with multiple sclerosis. So in just a few minutes, she's going to be joining us and we will have an opportunity to hear her presentation. I would like to encourage you to sit back, again, be prepared to take notes if important information is there for you, and make sure that you put your questions into the Q&A box. And now, it's my pleasure to introduce Dr. Allison Jordan. Dr. Jordan? Allison Jordan, DO: Hi. Thank you so much, Kristi. And hello to everyone listening out there. This talk is going to be a brief overview, but my slides will be available after the talk. [Text on screen: Pregnancy, lactation, and postpartum care Allison Jordan, DO Assistant Professor Neuroimmunology The Ohio State University] [Text on screen: Pregnancy planning - Contraception - Genetics of multiple sclerosis - Infertility and multiple sclerosis] Allison Jordan, DO: All right. First, we'll start with pregnancy planning. [Text on screen: When should I start pregnancy discussion with my multiple sclerosis provider? - At least one year before starting to try to become pregnant.] Allison Jordan, DO: And we recommend to talk to your multiple sclerosis provider at least one year before you want to attempt to become pregnant. But I always encourage early and often conversations with your MS provider about where you are in your pregnancy journey. [Text on screen: What if I don't want to have kids right now? - Any form of contraception is safe for patients with multiple sclerosis] Allison Jordan, DO: So what if I don't want to have kids right now but would consider it in the future? Well, then, I would reassure you that any form of contraception is safe for persons with multiple sclerosis, and you have the power to choose whatever contraception best fits your needs and lifestyle. [Text on screen: Will I pass my multiple sclerosis to my children? Children of one parent with multiple sclerosis: - Male: 0.3-2.1% - Female: 1.1-3.5% Children with both parents having multiple sclerosis - Male: 12.0-32.0% - Female: 12.5-30.4%] Allison Jordan, DO: One question that is brought up frequently in my clinic is, "How likely is it that I will pass on MS to my children?" And the answer is that there is some genetic impact to the development of MS, but this is overall a small part of what causes an individual to go on to develop multiple sclerosis. The genetic impact of multiple sclerosis has been looked at across several studies, all with pretty similar data. And so basically if you have a first-degree relative, a parent, a sibling, or a child who was diagnosed with MS, then you have a lifetime risk of about 3% of developing MS yourself. To break this down a little further, this data that you see here is taken from a larger study done in Canada, which is referenced at the bottom here. And if one parent had multiple sclerosis then the concordance rate or probability that the parent would have a child who would then go on to develop MS, was up to 2% chance if that child was a male at birth, and up to 3.5% chance if that child was a female at birth. And this chance then increases if both parents have MS. And the big takeaway here is that yes, genetics do play a small role in MS, but just because you have MS does not mean that your child is going to go on to develop MS. [Text on screen: Is Multiple Sclerosis associated with infertility? Evidence is conflicting, no clear evidence there is decreased fertility secondary to multiple sclerosis - Recommend referral to fertility treatment if pregnancy is not achieved after 3-6 months of optimal conception attempts] Allison Jordan, DO: Another common question is whether a diagnosis of MS is linked to decreased fertility. And there is conflicting data on this, but overall there isn't clear evidence of decreased fertility in persons with a diagnosis of multiple sclerosis. Having said this, the current recommendation is that you would have a consultation with a fertility expert after attempting to conceive for three to six months as compared to the general population, for which the recommendation is to wait a year. And several things go into this recommendation, including wanting to minimize time off disease-modifying therapy. [Text on screen: What is the risk of relapse during pregnancy and after delivery? Relapses in MS decrease during pregnancy. Relapse rate increases during the first 3-6 months following delivery. - Increased rate of both clinical and radiographic relapse.] Allison Jordan, DO: Moving on to what to expect in pregnancy. So let's talk about risk of relapse during pregnancy. And this figure is taken from the Pregnancy in Multiple Sclerosis study, or PRIMS study. This was the first large study to look at the influence of pregnancy and postpartum delivery on multiple sclerosis relapse rate, and it's still the most cited study on this topic. And looking at this figure here, the average relapse rate drops during pregnancy, most notably in the third trimester, as you can see. The rate of relapse then dramatically increased in the first three months after delivery, then fell to pre-pregnancy relapse risk. Newer studies have shown that this increased risk for relapse includes both clinical relapse as well as what we call radiographic relapse, meaning new lesions found on routine postpartum MRI without any clinical symptoms. [Text on screen: What increases rate of relapse? - If you had an active MRI brain before becoming pregnant. - If you suddenly discontinued either Tysabri or Gilenya (without treatment planning) you were more likely to experience post partum relapse. - This odds of postpartum relapse decreases with exclusive breastfeeding (chestfeeding) for at least 3 months.] Allison Jordan, DO: So what increases this risk of relapse? And most importantly, what can we do to minimize the risk? So you are at risk to relapse in pregnancy and in the postpartum period if you had active disease in 12 months before becoming pregnant, or if you were on the medication Tysabri or natalizumab one of the S1P modulators, for example, Gilenya, and discontinue this medication suddenly before becoming pregnant without having a plan to transition off the medication. And the odds of postpartum relapse have also been shown in several studies to decrease with exclusive breastfeeding or chestfeeding for those first three months. And exclusive breastfeeding, chestfeeding in these studies was breastfeeding or pumping without supplemental formula use. [Text on screen: What happens if I have a relapse while pregnant - MRI imaging safe to undergo while pregnant, avoid contrast dye - We want to try to avoid steroids in the first trimester - High dose steroids can be given in the second or third trimester] Allison Jordan, DO: So what happens if I have a relapse while I'm pregnant? Well first if there is any uncertainty of what's going on, for example, concern that maybe this isn't a relapse, maybe this is just a flare of your symptoms, you can safely get an MRI during pregnancy. We just can't use contrast dye. And this is why before becoming pregnant, we want to make sure we have updated MRI imaging so that you can compare your new study to a very recent MRI study to look for any new lesions. If we're concerned, yes these are definitely new symptoms, this is a true new relapse, then we can safely treat with high dose steroids while pregnant. We do want to avoid steroids in the first trimester if at all possible. This is due for concern for increased risk of cleft palate during the time that the palate is being formed, which is under the first 12 weeks of life. [Text on screen: Pregnancy. - What we can expect in pregnancy. - Disease modifying therapy and pregnancy. - Symptomatic management during pregnancy.] Allison Jordan, DO: Next I want to talk about options available for disease modifying therapy in MS and how we would transition off these medications to become pregnant. And to further clarify the definition of disease-modifying therapy, these are the medications available today that we use to prevent future relapse. [Text on screen: Disease modifying therapies and pregnancy. Self-Injectable therapies. Interferon beta (Avonex, Rebif, Plegrity, etc) - This modification can be used right up until positive pregnancy test (discontinue at positive pregnancy test) - Extensive data on use during early pregnancy Glatiramer acetate (Copaxone) - This medication can be used right up until positive pregnancy test, and during pregnancy - Extensive safety data] Allison Jordan, DO: Let's start with injection based therapies. First we have interferon beta medication. Recommendation is that you can use these medications right up until you get a positive pregnancy test and then discontinue the medication upon a positive pregnancy test. For glatiramer acetate, this is Copaxone and its generic equivalents. This medication like interferon beta has been around for a long time and therefore we have good safety data on the drug. And current recommendation is that this medication is safe both while attempting to become pregnant and through the entire pregnancy if desired. [Text on screen: Disease modifying therapies and pregnancy. Self-Injectable therapies. Ofatumumab (Kesimpta) - Short drug half life (16 days), average total clearance 12 weeks - No adverse effects seen in animals exposed during pregnancy - As of August 2021, no congenital anomalies or malformations have been reported - Recommendation is to stop this medication 3-6 months before attempting to conceive] Allison Jordan, DO: Kesimpta is the newest injectable medication on the market and as would be expected, we have pretty limited information on this drug's safety and pregnancy. To date, there have been no reported congenital malformations in persons who have become pregnant while on the medication. But again, data is limited. And it's recommended to stop this medication three to six months before attempting to become pregnant. Before I move on, I want to touch on the topic of why each drug will have a range for discontinuation. Take Kesimpta for example. So most experts will recommend to stop the medication three months before attempting to become pregnant. And this is because Kesimpta has what we call a short half-life. And half-life is the amount of time that it takes for the drug to reduce in your body by half. This means that for Kesimpta, when you track its half-life, the drug is mostly out of the system by the three-month time period. But the official recommendation from the drug company is to wait six months after discontinuation to attempt to become pregnant. This is how we end up with a range of months, which admittedly can be confusing. [Text on screen: Disease modifying therapies and pregnancy. Oral medications. Teriflunomide (Aubagio) - Known to cause embryofetal toxicity - If you wish to become pregnant, must discontinue the medication and undergo an accelerated drug elimination procedure, check blood levels (must be <0.02mg/L) - Without accelerated drug elimination it takes between 8 months - 2 years to achieve desired blood level - This is recommended for both men and women] Allison Jordan, DO: Moving on to oral medications or medications taken by mouth. First we're going to discuss Aubagio or teriflunomide. This medication is absolutely known to cause fetal toxicity, and so recommendation is to have either a permanent form of birth control while taking the medication if you and your partner no longer desire to have children, so that would be a tubal ligation, hysterectomy, vasectomy, or two forms of birth control, for example, using both condoms and hormonal birth control. I personally don't prescribe this medication to anyone who may desire children in the future, and that includes both men and women because this medication will also affect sperm. And if you are on Aubagio and decide that you do want to have children in the future, recommendation would be to use an accelerated drug elimination, have your blood checked and make sure the medication is completely out of your system. If you do not undergo the accelerated drug elimination, it can take up to two years in some individuals for this drug to completely leave the system. [Text on screen: Disease modifying therapies and pregnancy. Oral medications. Sphingosine-1-phosphate (S1P) receptor modulators (Fingolimod, Siponimod, ozanimod, ponesimod) - This medication has evidence for birth defects in animal studies - Recommend to discontinue the medication at least 2 months prior to attempting to conceive - Possible rebound multiple sclerosis activity after stopping these medications (reported incidence of 4-25%) - Recommend to transition to another DMT rather than sudden stop] Allison Jordan, DO: Moving on to talk about S1P modulators. This is Gilenya, Mayzent, Zeposia, and Ponvory. These medications have data for fetal toxicity or harm to baby in humans. We do not recommend you become pregnant while on this medication. And recommendation would be to stop this medication at least two months prior to attempting to become pregnant. Biggest concern with this medication is possibility for rebound of disease activity after stopping. And to further define what a rebound is. So rebound is reactivation of inflammation of disease activity in the setting of stopping a medication like Gilenya. And sometimes this rebound can be a very severe and in rare cases life-threatening. In the case of Gilenya, rebound or reactivation of disease activity after stopping the medication has been reported anywhere from four to 25% of the time. Timing can occur anywhere from two to four months, which is most common but up to 18 weeks after discontinuation. And due to the concern for rebound, most providers will recommend to transition to another medication before becoming pregnant. For example, I will typically transition to Ocrevus with a plan to discontinue Ocrevus prior to pregnancy. [Text on screen: Disease modifying therapies and pregnancy. Oral medications. Dimethyl Fumarate (Tecfidera and generic) - This medication has no known current evidence for human fetotoxicity - Recommend discontinuation of medication and attempt to conceive - No rebound associated with stopping this medication] Allison Jordan, DO: Moving on to dimethyl fumarate. This includes Tecfidera in its generic forms. And recommendation is to discontinue this medication when you are ready to start to become pregnant. No wait time is needed. [Text on screen: Disease modifying therapies and pregnancy. Oral medications. Cladribine (Mavenclad) - Known to cause fetal harm in animal studies - Recommend two forms of birth control while on medication! - Recommend waiting 6 months after last dose before attempting to conceive - Due to the mechanism of action of this drug, protection against relapse continues after last dose - This medication will drop your white blood cell count, with the lowest counts occurring 2-3 months after treatment. Need to make sure these counts recover before attempting pregnancy] Allison Jordan, DO: Last oral medication is cladribine or Mavenclad. This medication like Aubagio is known to cause fetal harm and so recommendation would be to take two forms of birth control while on this medication. And recommendation to wait four to six months before attempting to become pregnant, I recommend waiting closer to six months and that's because this medication can drop your white blood cell count with the lowest counts occurring two to three months after treatment. And so we really just need to make sure these counts are stable or have completely recovered before we try to become pregnant. [Text on screen: Disease modifying therapies and pregnancy. Infusion medications. B cell depleting agents (Ocrevus/Ocrelizumab, Rituxan/Rituximab) - Recommendation to wait 2-3 months after infusion date to attempt to conceive - B cells still depleted for a total of 6 months (in some individuals this effect may be longer), allowing for continued protection against relapse while attempting to conceive] Allison Jordan, DO: Last group of medications to discuss are infusion type medications. First group of infusions I want to discuss are the B cell depleting agents. So Ocrevus or ocrelizumab, and Rituxan or rituximab. Recommendation is to wait two to three months after last infusion before trying to become pregnant. You can then attempt to become pregnant until your next infusion date, and at that time if you are pregnant, you would not go the next infusion. But if you are not pregnant then you could undergo another infusion, wait the two to three months and then attempt to become pregnant again. [Text on screen: Disease modifying therapies and pregnancy. Infusion medications. Alemtuzumab (Lemtrada) - Recommend to wait 4 months from last infusion before attempting to conceive - Due to the mechanism of action of this drug, protection against relapse continues after last infusion - Development of thyroid related complications are common with this medication - Recommend thyroid studies prior to attempting to conceive and continued monitoring during pregnancy] Allison Jordan, DO: Lemtrada or alemtuzumab is another infusion medication. It's given in cycles. The recommendation to wait four months from last infusion before attempting to become pregnant. My biggest concern with this medication is thyroid dysfunction. It's very common with this infusion. And so recommendation is to obtain thyroid studies before trying to become pregnant if you have taken this medication in the past, and to watch thyroid very closely throughout the entire pregnancy. [Text on screen: Disease modifying therapies and pregnancy. Infusion medications. Natalizumab (Tysabri) - Recommend to wait to attempt to become pregnant 1-3 months after last infusion - High risk for rebound multiple sclerosis activity after stopping infusion - Up to 40% of women will experience rebound relapse - 10-20% risk of significant long-term disability from rebound activity - Please make a plan with your multiple sclerosis provider!] Allison Jordan, DO: Last medication to discuss is natalizumab or Tysabri. Recommendation here is to wait four weeks to three months after last infusion. The problem with just stopping this medication is a very high risk for rebound. And again, rebound is that reactivation of inflammation upon stopping the drug. And it's reported that 40% of women who stop medication and then become pregnant will have a relapse during their pregnancy. And these can be quite severe. 10 to 20% of these women will have significant long-lasting disability. So something to be taken very seriously. So if you're on this medication, please make a plan with your multiple sclerosis provider. I typically, again, will transition to Ocrevus and then transition right back to Tysabri after pregnancy if desired. [Text on screen: Pregnancy. - What we can expect in pregnancy. - Disease modifying therapy and pregnancy. - Symptomatic management during pregnancy.] Allison Jordan, DO: Moving on to symptom management in pregnancy. [Text on screen: Fatigue, Multiple Sclerosis, and Pregnancy - Fatigue is a common symptom of multiple sclerosis, reported by at least 75% of MS patients - Some (off label) medications used to treat fatigue include Modafinil, Ritalin, Adderall, Amantadine - Modafinil should be discontinued prior to pregnancy due to data suggesting increased risk for congenital malformation - Cognitive behavioral therapy - Shown to be as effective in reducing fatigue as compared with modafinil] Allison Jordan, DO: As you all know, fatigue is a big part of multiple sclerosis. There are several drug treatment options for MS-related fatigue. The most studied being modafinil, Adderall, Ritalin, Amantadine, also used as off-label to treat MS-related fatigue. And the problem in pregnancy is that recommendation is to stop these medications before attempting to become pregnant because of the lack of safety data. And modafinil definitely needs to be discontinued due to data suggesting increased risk for congenital malformations. And pregnancy is also a period of time where we know fatigue is likely to increase due to a variety of different reasons. A great option to consider would be cognitive behavioral therapy for MS-related fatigue. And for those of you who have never heard of cognitive behavioral therapy or CBT, it's a talk-based therapy focusing on the relationship between thoughts and emotions and how they affect our life and behaviors. And a new study looking at the difference between modafinil and CBT called COMBO-MS showed that both groups clinically improved reduced fatigue and there was no statistical significance between the modafinil and CBT group, meaning they both work equally well. Based on this study, we could discontinue modafinil in preparation for pregnancy and perform CBT to get those anti-fatigue benefits that will last throughout pregnancy. [Text on screen: Postpartum considerations - Consideration for pelvic floor physical therapy for any worsening urinary symptoms or pain - Monitor post partum depression and anxiety - Consideration of physical or occupational therapy needs] Allison Jordan, DO: Other considerations for the postpartum period include pelvic floor physical therapy, and I recommend this in anyone who has just delivered, but especially for those who have worsening urinary symptoms or pain. And then of course monitor for postpartum depression and anxiety, and consider physical therapy or occupational therapy. This is why I always recommend a six-week follow-up with both your OB-GYN as well as your MS provider so that we can address these issues if they're there and give the appropriate referrals. [Text on screen: Breastfeeding (chestfeeding) Disease modifying therapy and breastfeeding] Allison Jordan, DO: Last topic is breastfeeding or chestfeeding in multiple sclerosis. Main focus will be to discuss disease-modifying medications considered safe to take while breastfeeding. [Text on screen: Reasons to consider breastfeeding (chestfeeding) - Breastfeeding (chestfeeding) decreases risk of postpartum relapse - Decreases risk for type 2 diabetes, postpartum depression, high blood pressure, breast and ovarian cancers for mom - Breastfed (chestfed) babies have a lower risk of infections, SIDS, type 2 diabetes] Allison Jordan, DO: And so whenever I talk about breastfeeding or chestfeeding, I like to start by saying I'm here to give you options. The choice is always yours and whatever you decide to do, you're going to be an amazing parent. Reasons to consider breastfeeding or chestfeeding is decreased risk for relapse in the postpartum period as we mentioned before, but also has great benefits for both mom and baby. [Text on screen: Disease modifying therapies and breastfeeding (chestfeeding) Safe for breastfeeding (data available to confirm safety) - Glatiramer acetate (copaxone) - Interferon beta (Avonex, Rebif, etc)] Allison Jordan, DO: For those of you who want to breastfeed or chestfeed, there are several options for disease-modifying therapy that you can take while breastfeeding. And I'll break these options into medications which we have lots of data confirming safety and medications that we have less data. Glatiramer acetate or Copaxone and our interferon beta medications. These have been studied in breastfeeding, chestfeeding and are recommended compatible. The downside to these medications, glatiramer acetate does take some time to become effective. And so it would not be a great option to prevent relapse in the first three months unless you remained on this medication throughout your entire pregnancy. And interferon beta, the injections are a great option. They're good medications, but they are considered a lower-efficacy therapy. It may not be good fit for somebody who has more aggressive or active multiple sclerosis. [Text on screen: Disease modifying therapies and breastfeeding Probably safe for breastfeeding, (limited data) - Rituximab/Rituxan - Ocrelizumab/Ocrevus - Ofatumumab/Kesimpta - Natalizumab/Tysabri] Allison Jordan, DO: And options available for somebody with more aggressive or highly active MS would be Ocrevus, Rituxan, Kesimpta or Tysabri. These medications are likely compatible for breastfeeding, but admittedly our data is limited. These medications have been shown to pass into breast milk, but at very low levels which are unlikely to impact baby. We have also had several smaller studies looking at babies who are taking milk from mothers on these medications. And these studies have looked at things like baby's white blood cell count, which were not shown to have the impact, but again, very small studies. And Kesimpta as mentioned before or rituximab is new to the market and has not been studied extensively yet. But this medication is very similar to Ocrevus and Rituxan. And with that, I will hand it back over to Kristi. Thank you guys. Kristi Epstein, APRN-CNP: Thank you so much Dr. Jordan, what a wonderful presentation. And I know there are going to be a lot of questions. So once again, go ahead and put those in the Q&A box and we will address those at the end of our presentations. And what a wonderful body of information. And just so everyone knows who's on the visit here, all of your providers are here for you for pregnancy planning and any questions that you may have. So feel free to reach out if you're thinking about starting a family. Next, we're going to move on to our wonderful neuropsychologist, speaking of neuropsychologist, and I'm going to have the pleasure of introducing Dr. Stephanie Kielb. She's wonderful and we work with her all the time in our MS division. She's a graduate of Northwestern University in Chicago, and she actually did her fellowship here with us at the Ohio State University. So she is a wonderful and powerful member of our team, and I feel like we could not function without our wonderful neuropsychologist. She's going to talk with you all tonight about mental health and MS. It is my pleasure now to introduce you, Dr. Kielb. Stephanie Kielb, PhD: Thanks, Kristi. Thanks for that really nice introduction and thanks for having me. I'm happy to be back at one of these education events to talk to you all. If you just give me one second, I'm going to share my slides here. [Text on screen: Mental Health and Multiple Sclerosis Stephanie Kielb, PhD Clinical Neuropsychologist and Assistant Professor The Ohio State University Wexner Medical Center March 23, 2023] Stephanie Kielb, PhD: So tonight I'll be talking about some topics in mental health. [Text on screen: Invisible symptoms in MS Fatigue, Cognitive/memory changes, sleep disruptions, pain, depression symptoms, anxiety symptoms] Stephanie Kielb, PhD: We know that MS is associated with a wide range of physical and neurologic complications. And as a clinical neuropsychologist, I'm really interested in what I consider to be the invisible symptoms in MS. Things like fatigue, changes in thinking, or sleep, or mood, the types of symptoms that may not be readily apparent, or observable to the public, or our co-workers or family members, the people in our lives. These are the types of symptoms that can actually be the most debilitating and have the greatest impact on quality of life. They're also highly interconnected. I think it's probably easy to see a scenario where if you're struggling with significant fatigue that might influence how clearly day-to-day you're thinking, which could cause a lot of stress, which could negatively impact mental health, which could start to disrupt sleep, which could make fatigue worse and stress you out even more and affect mental health even more. So things can get very tangled pretty quickly. And if this image on the screen here were more accurate, we would have a bunch of lines connecting all of these different bubbles here. I think one silver lining when we have multiple symptoms that are highly connected is that oftentimes if we can find some improvement in just one symptom, some of the others can also improve as well as a downstream consequence because things are so highly connected. I'm happy to be here tonight to be able to talk about depression and anxiety because these are treatable conditions and so they can be low-hanging fruit when we think about ways of improving quality of life in MS. [Text on screen: Mental health in MS Systematic review of 58 published studies with total sample size of 87,756 individuals with MS: - 35% with clinically significant depression - 34% with clinically significant anxiety] Stephanie Kielb, PhD: There's been a lot of research in this area. The most recent large-scale review study that I found reported that well over a third of individuals with MS reported clinically significant levels of depression and anxiety. And this is pretty staggering when we compare it to the rates and what we know about the general population. There's been studies showing too, that depression and anxiety in MS are higher than the rates in other chronic health conditions such as epilepsy and some types of cancer. So it's a pretty significant problem here. And so I want to talk about the ways that depression can look. Because lots of times when we think about depression, we think about someone maybe who looks sad or is tearful, but depression can look a lot of different ways. For some of us, it presents more as irritability or being short-tempered. For some of us it looks more like withdrawal, withdrawal from doing things socially or doing things that we at one point enjoyed. For some it's more difficulty getting motivated, maybe we're less productive at work, maybe it's more about the effects that it has on our activity level, or our sleep, or our appetite, or our energy. I just want to make the point that depression can really look a lot of different ways for all of us. [Text on screen: Common symptoms in anxiety Sweating, dizziness, accelerated heart rate, sensation of smothering, trembling, chest pain or discomfort, nausea or abdominal distress, chills or heat sensations, feeling dizzy, unsteady or faint, fear of losing control or dying] Stephanie Kielb, PhD: And so anxiety too can come in a lot of different flavors. So for lots of us, anxiety is all about kind of worry or maybe having a tendency to overthink things, or feel nervous, restless, fearful. But anxiety can also affect our body in a lot of ways. Some of us experience things like sweating, dizziness, nausea, heat sensitivity, discomfort, or chest tightness. And I think it can be kind of sticky when we think about these symptoms in MS, because lots of the common symptoms in depression and anxiety are also really common symptoms in MS. And I think that's something we really want to be mindful of. Because I think it can probably be difficult sometimes if you're experiencing fatigue to understand, "Well, is this MS-related fatigue or is it related to mood?" If we have tightness in our chest, is this the experience of an MS hug or is it related to anxiety? And lots of times the answer to that question is both. That both things are part of the experience and going on. And again, it's that idea of if we can just treat one cause, oftentimes the whole experience will be improved. [Text on screen: Treatment for depression and anxiety Two evidence-based treatment approaches. Medications: - Prescribed by a medical doctor or NP - primary care, neurologist, psychiatrist - Examples: selective serotonin reuptake inhibitors (SSRIs), benzodiazepines Talk therapy: - Facilitated by a clinical psychologist or other licensed mental health provider - Examples: cognitive behavioral therapy (CBT), behavioral activation, acceptance and commitment therapy (ACT) Best in combination] Stephanie Kielb, PhD: And so, as I mentioned, fortunately, we know that we do have really good treatments for depression and anxiety. Research shows that there's two effective treatment approaches and that the best are these two things in combination. The first is medication. So there's many different medications out there on the market that are available to treat both depression and anxiety. And these might be prescribed to you by, or they would be prescribed by either a medical doctor or a nurse practitioner, but they may come from your primary care doctor, sometimes your neurologist, or it can be a psychiatrist who's a medical doctor, specialized in treating mental health conditions. The other evidence-based treatment is one-on-one talk therapy, and this would be facilitated by a clinical psychologist or some other licensed mental health provider, like a clinical social worker or maybe a licensed counselor. And so, evidence-based talk therapies include like cognitive behavioral therapy, as Dr. Jordan mentioned CBT, or other approaches, behavioral activation, acceptance, and commitment therapy. These are all approaches we often use in the clinic at OSU. [Text on screen: Evidence-based talk therapy - Focused on the present moment - Time limited intervention. typical CBT= 12-16 weeks - Focused on building practical skills - Goal-oriented problem solving] Stephanie Kielb, PhD: And so, I just want to spend a couple of minutes talking about the approaches to talk therapy that we typically use in MS clinic because there's a lot of different approaches to talk therapy out there. Some talk therapy is more just general, supportive talk therapy. Some therapists are really interested in childhood and the impacts of things that happened in childhood. I was trained as a cognitive behavioral therapist, which means I'm really interested in during a stressful situation, what are the ways we're thinking about things and how does that impact our emotions or what we're feeling about a given situation? And how do we experience those things in our body? What are the physical sensations that we experience? And then, how do the way that we're thinking and feeling about something, how does that impact our behavior, what we choose to do or not do? And then how does our behavior in turn impact how we're feeling and thinking about things? So a lot of the work I do is really focused on the present moment, real time, what are our patterns of thought and behavior and how does it affect our mood? The interventions that I do are time-limited. So sometimes people who are in more supportive kind of talk therapy may be in therapy for years. But a typical course of CBT is actually only 12 to 16 weeks. And oftentimes in the MS clinic at OSU, I see folks for even shorter, maybe six or eight sessions. And I find that even that is enough time to really build some practical skills, develop some tools that you can use to cope with stress in specific situations. And the work that I do is also really goal-oriented. So I like to, at the beginning of working with someone, establish some pretty clear goals. And then session by session we're sort of problem solving and strategizing about the progress that we're making towards meeting those treatment goals. [Text on screen: Strategies for depression - Depression causes us to withdraw from meaningful activity - Behavioral Activation is a helpful treatment approach - Building motivation through activity - Reconnecting with the things that matter - Strategizing around MS - Emphasizing the importance of self-care] Stephanie Kielb, PhD: I want to mention a couple of specific strategies that we might use to address depression and anxiety. We know that depression at its core, it really causes us to withdraw from the things, the behaviors, the things that we find meaningful in life. It causes isolation and disconnection or deactivation. And so in treatment, one approach that I often use is called behavioral activation. So it's really helping to reconnect folks with getting back to doing the things that are important to them that matter. And lots of times I've had people say, "Well, when I feel better, I'll be more inclined to be more active and do more things." But in this model here, you can see that these arrows, they go all directions. So really it can be helpful to start with the behavior. And so by being more engaged, by getting more active, oftentimes we can build some momentum. And then as a result, that motivation and those productive feelings can come back. But it starts with behavior, oftentimes. In working with folks who have MS, we sort of have to be a little bit more strategic, because oftentimes there are physical limitations. And oftentimes, we can't always do what we once did. And so, it takes some creative thinking and being mindful about what type of activity is practical. But oftentimes, just because we can't do what we once did doesn't mean that we can't do anything. So there are ways of re-engaging. And one thing I really emphasize in my practice is self-care. I think that's a term that gets thrown around a lot now, but I find that when we struggle with our mood, it's often the basic self-care types of things that tend to get lost first. I'm talking sort of simple things like making the bed, putting trash in the trash can, getting up the first time your alarm goes off. These sort of basic things that when our mood's in a good place, we don't really even have to think about. But when there's some element of depression, these things become really hard and they're often the first to go. They're often the types of things that if we can get people back to doing them, they have a lot of really positive impact on mood. We can often also use these self-care types of activities as an early warning sign for depression. So if you find that things that used to come automatic self-care types of things are all of a sudden becoming harder, that might be an indication to you that my mood is not in a great place and I want to seek intervention. And as I mentioned, we have two evidence-based ways of intervention. We have medications and we have one-on-one talk therapy to treat depression. So just some things to keep in mind. [Text on screen: Strategies for anxiety Exploring things that bring calm and relaxation during moments of heightened stress - Reaching out to a supportive person - Listening to music, watching a movie - Walking, stretching, or other physical activity - Meditation or deep breathing exercises Example: "Box Breathing" - Inhale for 4 seconds - Hold for 4 seconds - Exhale for 4 seconds - Do nothing for 4 seconds - Repeat] Stephanie Kielb, PhD: And then, a strategy that we use for helping people with anxiety. Anxiety is something that we can really feel in our body. Lots of us, when we get anxious, maybe we get this tightness in our chest, our breathing gets shallow, our muscles just generally, we kind of tense up. And so, a lot of the work in managing anxiety is thinking about what are some things that we can do to help bring about a state of calm and relaxation during moments of stress? Because again, with all these different things being connected, if we can find a way to relax our body, oftentimes we feel less anxious and then we're less likely to think and behave in ways consistent with the experience of anxiety. And so, those things that bring about a state of relaxation can really vary from person to person. And sometimes it takes playing around a little bit to figure out what works for you. Some people really find a sense of calm from reaching out to someone in their life who they know is supportive, for finding that social connection. Sometimes it's about doing things that appeal to the senses, maybe listening to music or watching a movie, taking a bath. Some people, when they're in a state of stress, their bodies really crave movement. They need to move. And maybe that's taking a walk or engaging in some stretching or more vigorous physical activity or less vigorous physical activity. Some people really benefit from practicing meditation or doing deep breathing exercises as a way of bringing about a state of relaxation. So one example of a pretty simple, straightforward but effective breathing exercise would be like called box breathing, where you simply find a quiet space and either close your eyes or just kind of gaze at the floor, but you're really trying to focus your attention on the breath. You want to inhale for a count of four, hold the breath for a count of four, exhale for a count of four, and then just do nothing for four seconds and then repeat that cycle a couple of times. And so really, really simple. But I think simple breathing exercises like this actually can do two things. The first is that, one, when we focus on our breathing, we're not focused on whatever it is that's causing us anxiety, whatever it is we're worrying about. But we also have data that when we're in a state of anxiety, our sympathetic nervous system is kind of turned on. We go into a fight or flight mode where our attention narrows, our pupils dilates, our heart starts pounding, our breath gets shallow, because really our body is preparing to face some threats. That's a classic stress response. So by practicing some deep breathing exercises, you're really sending a message to the rest of your body that my breath doesn't need to be shallow right now. My pupils don't need to be dilated, my heart doesn't need to be pounding. And so there's some physiologic evidence that by practicing deep breathing, we can really deescalate that biologic fight or flight response in our bodies. So it can be really pretty simple, but pretty powerful I think. [Text on screen: Suicidal ideation. Thoughts, wishes, and preoccupations with death and suicide - Thoughts about not wanting to be alive or being better off dead - Preparing to hurt oneself and/or forming a plan to do so Risk of suicide is 2 times higher in those with MS than general population. 988 Suicide & Crisis Lifeline. We can all help prevent suicide. The Lifeline provides 24/7, free and confidential support for people in distress, prevention and crisis resources for you or your loved ones, and best practices for professionals in the United States. website: www.988lifeline.org For an emergency, call 911] Stephanie Kielb, PhD: Okay. And then, a final thing that I wanted to talk about tonight was suicidal ideation or thoughts about death and about suicide. I think when depression and anxiety symptoms are severe, especially when they've stuck around for a long time, we can start to have feelings of hopelessness. And over time, those hopeless feelings can really start to turn into thoughts. Thoughts about maybe being a burden or not wanting to be alive, or wishing maybe that you weren't here anymore. And then over time, those can even progress to thoughts about ways in which an individual, someone might hurt themselves. And the reason that I mention this is because we have research showing that the risk of suicide in folks who have MS is about twice as high as the general population. So I wanted to be sure to mention it so that you're aware, and to also give out the number for the suicide and crisis lifeline. So their number now is just 988. It was changed recently from a random toll-free number just to 988, which I think makes a lot of sense, but that's a really, really great resource if you find that you're in a place where you're particularly low or feeling that hopelessness. It's a number that you can call 24/7. It's free, it's confidential. You can speak with a counselor just to get that extra support to get through a particularly difficult time. And I give that number out a lot. So you don't have to be actively suicidal to call that number. That's just a really good tool that you can have in your toolkit and number that you can call at any time if you feel like you need extra support. In case of emergency though, of course it's important to call 911. And then, just to close, I wanted to give out a couple of additional resources here that I think are really good. These were shared with me from Dr. Robinson and other psychologists in our group who's really excellent. But these are, and we'll make sure that you get the slides, but these talk, give some more specific resources about mental health in MS that I think can be really valuable. So with that, that's all I had. I appreciate the time and I'd be happy to take questions in the Q&A. But Kristi, I'll give it back to you. Kristi Epstein, APRN-CNP: Excellent. Thank you so much, Dr. Kielb. What a wonderful talk. You always have such great tips and things to tell us, and my mom will be very happy because she always told me the first accomplishment I can have in every day is to make my bed. So you just reinforced that. And I'm definitely going to try box breathing. I feel like there are many, many opportunities where I can use that. So thank you so much for that presentation. Again, I want to encourage everyone to put your questions into the Q&A box, into the Q&A box. We will get to your questions after our presenters have finished their talks tonight. And anything that we aren't able to discuss, we will put those answers on the website on the MS community page. So next, I'm really excited to hear what Dr. Gyang is going to have to say about all the new research and exciting things that are happening from the meeting at ACTRIMS. ACTRIMS is the Annual America's Committee for Treatment and Research in MS. It is a very scientifically rigorous meeting, and there are lots of wonderful researchers out there treating and studying all kinds of things having to do with MS. I have a favorite doctor who always presents out there and talks about a lot of quality of life things. So I am so looking forward to what Dr. Gyang is going to have to tell us. So Dr. Gyang, if you are ready to speak, it's my pleasure to introduce Dr. Gyang. She's been with us for, I think three years now, coming to us from Florida, and she is in charge of our fellowship program. And Dr. Gyang is literally involved in every aspect of the MS division. I don't know how she does everything that she does. She is amazing, and she's a wonderful resource for us here at the Ohio State University. So with that, I will turn over the discussion to Dr. Gyang. Tirisham Gyang, MD: Thank you very much, Kristi, and good evening everyone. I am just going to pull up my slides. [Text on screen: ACTRIMS Forum 2023 - Highlights Tirisham Gyang, MD Em Harrington, MD, PhD] Tirisham Gyang, MD: All right, so it's just really exciting to hear all the wonderful speakers that came ahead. I learned so much just listening to all the presentations. So I'm going to be talking about the recent neurology conference that just took place in February. And helping me put these slides together, Dr. Harrington had a lot of input and I just wanted to put their name and acknowledge them here. [Text on screen: ACTRIMS Forum 2023 - San Diego, CA - February 23-25th - "MS Going Viral" - Almost 2000 attendees] Tirisham Gyang, MD: So the ACTRIMS meeting took place February 23rd to 25th. It was in San Diego. The theme of the meeting this year was MS Going Viral. There were almost 2,000 people that attended from all over the country, from Canada, from other parts of the world. [Text on screen: ACTRIMS: Americas Committee for Treatment and Research in Multiple Sclerosis. - Community of leaders/experts from the United States and Canada - Dedicated to the treatment and research in MS - Focus on knowledge dissemination, education and collaboration among disciplines - Annual Forum for clinicians and researchers to exchange information, debate current issues and discuss advances related to basic research and clinical issues. - Foster the careers of young neurologists/scientists in training who have an interest in multiple sclerosis] Tirisham Gyang, MD: So what exactly is ACTRIMS? We kind of keep saying ACTRIMS. I just want to let everybody know what this is. It stands for America's Committee for Treatment and Research in Multiple Sclerosis, and this is a community of leaders and experts from the United States, from Canada, that have a very key interest in MS research and MS treatment. There's a huge focus on disseminating education, collaborations between different specialists and different researchers. And once a year, there's a big meeting where all the experts, the clinicians, the young doctors come together to talk about MS, exchange ideas, and learn about the most recent research. ACTRIMS also has a very strong arm that helps to motivate young neurologists and young scientists to develop an interest in multiple sclerosis. [Text on screen: OSU at ACTRIMS Planning committee and Board of Directors - Dr. Benjamin Segal Resident summit faculty - Dr. Benjamin Segal (Chair) - Dr. Em Harrington - Dr. Tirisham Gyang] Tirisham Gyang, MD: So how about OSU? How is OSU connected to ACTRIMS? I just wanted to highlight a few things about OSU at ACTRIMS. So our chairman, Dr. Benjamin Segal, is actually one of the board of directors of ACTRIMS. And he has served within the planning committee, has planned multiple of these meetings before. So we have one of our very own in leadership at ACTRIMS. This year, there was a resident summit that was chaired by Dr. Segal. And our OSU doctors, Dr. Harrington and myself, were part of that panel to talk to residents to talk to young investigators about MS and a career in MS. And you can see a picture with some of the OSU doctors talking to the residents. [Text on screen: Meeting highlights - EBV (Epstein Barr Virus) and MS - Diet and MS - New digital tools to monitor MS - Diversity and inclusion in MS research - PBS documentary premier - MS in the Black and African Americans - Resident Summit] Tirisham Gyang, MD: So these are a few of the topics I'm going to cover. EBV and MS was a huge topic this year. Diet and MS, digital tools to monitor MS. Diversity and inclusion in MS research. There was a very interesting documentary that premiered about MS in Black and African-Americans. And then I'll talk a little bit about the resident summit. [Text on screen: EBV (Epstein Barr Virus) and MS Dr. Lawrence Steinman, Stanford University - Epstein Barr Virus (EBV) causes infectious mononucleosis - EBV has been postulated to trigger MS - Prior studies reveal that increased serum antibodies to EBV in ~99.5% of MS patients compared with ~94% of healthy individuals - Multiple studies have identified EBV-infected B cells in the brains of MS patients] Tirisham Gyang, MD: So let's start with the biggest topic that was discussed, EBV and MS. So EBV is a virus. It's Epstein-Barr Virus. There was an article that came out in 2020 talking about the connection between EBV and MS. And one of the authors of one of the editorials, Dr. Lawrence Steinman, presented one of the talks about EBV and MS. So what is EBV? This is a virus that causes infectious mononucleosis. Now, a lot of us, maybe as kids, may have had mono or infectious mononucleosis. And there's a lot of data that's putting together the connection between EBV and MS. And there's a possibility that EBV virus may be a trigger to MS. Prior studies have shown that there's an increased serum antibody level of EBV in patients with MS compared to other patients that do not, or other individuals that do not have MS. So 99.5% of MS patients will have EBV antibodies compared to 94% of healthy individuals. Most people, even if they do not have mono, have been exposed to EBV. So about 94% of healthy people, but in almost all MS patients, almost 100%. And there's multiple studies from the past that have shown that maybe there are some EBV-infected B cells in the brains of MS patients. [Text on screen: Dr. Marianna Cortese from Harvard University Cohort of 10 million young adults in active US military - Blood sample analysis - Over a 20-year period (1993-2013) 955 were diagnosed with MS during service - Risk of MS increased 32-fold after infection with EBV - This risk was not observed with other viruses - Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion - 35 of the 801 MS cases were initially EBV seronegative - 34 became infected with EBV before the onset of MS - EBV seropositivity was nearly universal at the time of MS development - Only one of 801 MS cases being EBV seronegative at the time of MS onset] Tirisham Gyang, MD: And so, there was this study, the main study that was published last year, longitudinal analysis that reveals high prevalence of EBV associated with MS. And I'll talk a little bit about this study. One of the authors of this study was at ACTRIMS, Dr. Marianna Cortese from Harvard University. So this is a very interesting study. They took the samples from 10 million young adults in active military. When people go into the military, there's a lot of data that's collected. So they analyzed blood samples from 10 million people, young individuals in the army over a 20-year period from '99 to 2013. What they found was out of this 10 million people, about 1,000, 955 were diagnosed with MS during active service. And I'll talk a little bit about the analysis that was done. But they found that the risk of MS increased 32 fold after an individual was exposed or infected with EBV. Now, they looked at other viruses and they did not see this trend with other viruses. EBV was the only virus that showed this increased risk of MS after an infection. They also looked at another biomarker called neurofilament light chain that tells us there's a breakdown of our neurons or some cells in the nervous system. And they saw that after an EBV infection, this biomarker increased in the serum of people that developed MS. So just a little bit more details. 35 patients out of the patients that developed MS, were initially EBV negative. 34 of them became infected with EBV before the onset of MS. And EBV positivity was almost universal in all patients that had MS except one, apparently one, only one of those patients did not have a positive EBV status. [Text on screen: How does EBV infection lead to MS? - We do not exactly know. - Possible mechanism: 1. Molecular mimicry 2. B cell transformation 3. EBV infection might cause damage to nerves in the brain and spinal cord 4. Other unknown mechanisms?] Tirisham Gyang, MD: Now, how does this happen? How does EBV lead to MS? And we don't exactly know what happens. There are some theories behind how this could happen and some possible theories. We talk about this concept of molecular mimicry, where the EBV has certain proteins or certain antigens that are similar to some proteins in the nervous system, and they could trigger our immune system that therefore goes into the nervous system to attack it. There's theories about B cell transformation, some theories about the EBV infection itself causing damage to brain or nervous tissue. And then other unknown mechanisms that are not known right now. So there's still a lot of things we do not know. [Text on screen: EBV and MS Nearly everyone is infected with EBV, but only a small fraction develop MS. - It is likely that other factors, such as genetic susceptibility, are important in MS pathogenesis. - Timing of EBV infection may be relevant - higher risk associated with exposure in pre-teen and adolescent years compared to childhood exposure. Debate - (Dr. Peter Calabresi and Dr. Jeffrey Cohen) - Would a vaccine against EBV protect against MS? - Would antivirals that target EBV provide effective therapy to MS patients? - Can the B cells in the nervous system be killed or inactivated with therapeutics?] Tirisham Gyang, MD: And then another concept is almost everyone, by the time we're adults, almost everyone is infected with EBV. Even if they do not have mono, they've been exposed to it and we can see those antibodies in their blood. How come only very few people get MS? Not all adults get MS. Very few people get MS compared to how many people have EBV infection in the past. So a few things could play a role. One thing is some people have a genetic susceptibility to MS. So maybe that's one thing that could lead to some people getting MS and others not. The other thing that was discussed was the timing of the infection may be very important. People that are infected in adolescent ages are more likely to have MS than people that are exposed in childhood. There was a very interesting debate by Dr. Calabrese and Dr. Jeffrey Cohen, about what do we do with this information? Should we vaccinate people against EBV? And this would be people that don't have MS or children. Before that risk develops, should we vaccinate people against EBV to protect from getting MS? That's one thing we could research. Should we develop antivirals that we could use in patients with MS to maybe treat that EBV infection to eliminate the virus? Can we take out these B cells? Sometimes EBVs happen in these B cells. Can we kill them off in an effort to prevent MS from getting worse and causing more damage? So this was a debate. There's no clear consensus on what is right or what is wrong, but you can see that a lot of research is still needed. [Text on screen: "Now that the initial trigger for MS has been identified, perhaps MS could be eradicated." Robinson WH, Steinman L. 2022; 375(6578):264-265] Tirisham Gyang, MD: And this is the last slide about EBV. This is a quote from an article from Dr. Steinman, and he says now that the initial trigger for MS has been identified, perhaps MS could be eradicated. So there's still a lot of research that's needed. Hopefully, we get more information and more data with a lot of the research that's been done. [Text on screen: Diet and MS - Caloric restriction. Dr. Laura Piccio from Washington University St. Louis. Animal model of MS in mice. - Caloric reduction shown to reduce neuroinflammation. Human study in MS patients - randomized study. - Normal diet cs calorie restricted diet 2 days a week. - The 5:2 diet - 500 calories/day, 2 days of the week. Calorie restriction was associated with: - Reduction in weight and body fat percentage. - Faster cognitive processing speeds. - Increase anti-inflammatory molecule levels and altered T cell responses] Tirisham Gyang, MD: So shifting gears a little bit, and I'm kind of looking at time, I want us to have questions at the end, Diet and MS. There was a study from Dr. Piccio at Washington University in St. Louis that looked at calorie restriction. So there was a study that looked at restricting the diets of patients with MS, restricting calories on patients with MS, doing this concept called the 5-2 diet, where two days out of the week they eat just 500 calories, which is just maybe a salad or two salads. This was done because in mice they found that reducing calories could reduce inflammation. And interesting results were that in patients that did this reduced calorie diet, this 5-2 diet, they had reduction in body weight and body fat percentage, they had better cognitive processing speeds, and they had more anti-inflammatory molecules in their blood. It shows us that there's some anti-inflammatory benefits to calorie-restricted diet. This is one of the articles from the speaker that shows us how calorie restriction could cause a lot of potential beneficial effects that could help to reduce inflammation in patients with inflammatory disorders. [Text on screen: New digital tools to monitor MS. Dr. Jennifer Grave, University of California, San Diego. - New innovative tools are needed to monitor the progression of MS in clinics and in clinical trials. - Current measures focus on walking and leg strength and do not adequately capture certain changes like vision, cognition, hand function. Dr. Graves described - A portable device for measuring visual conduction. - A variety of wearable accelerometer devices that can measure direction and speed of movement of the arms and legs. - Apps for measuring hand function. These new innovations are being validated and will be available soon for monitoring of MS patients] Tirisham Gyang, MD: Another talk by Dr. Jennifer Grave from University of California San Diego talked about new innovative tools to monitor MS. Now, a lot of the measures we use right now in monitoring MS are not very good at capturing certain things like vision or cognitive function. They're very good with measuring how a person walks and walking dysfunction, but not very good at capturing other measures. And the thing is if we really want to study progressive MS or how MS progresses over time, we need better tools to be able to monitor MS. So Dr. Grave talked about a device for measuring visual conduction. She talked about a variety of different wearable devices that could help measure how a person is moving, how the arms are functioning. There's a lot of apps for measuring hand function. These tools are still being validated and soon would be available for us to use to monitor MS. [Text on screen: Diversity and inclusion in MS research. Dr. Leorah Freeman from University of Texas at Austin. - Under-representation of minority populations in MS research and clinical trials. - Diverse representation in research is very important in generalizing results from studies. - More studies are needed to understand MS in minority populations. ] Tirisham Gyang, MD: Just a quick word on a presentation by Dr. Freeman from Texas talked about why it is important to have diversity in clinical trials and why it's important to have different types of people represented in our clinical trials. That helps us to generalize the results to people, all people that have MS. [Text on screen: OSU Clinical research/trials. - Phase 3 study - Tolebrutinib in relapsing and progressive MS. - Phase 3 study - Vidofludimus calcium (IMU-838) in secondary and primary progressive MS. - Aging in MS study. - NACRMS registry. - Neurology Research Institute Brain Bank & Biorepository (NRI-BBB) Interested in research - Contact Kasturi Ganesh Barki, clinical research manager. 614-293-6123 Office, msresearch@osumc.edu - Ask your provider. Tirisham Gyang, MD: And just a quick note, these are a few of the studies that we have right now. If you are interested in any kind of research, there's a number, there's an e-mail. We want people to come and just hear about the studies that we have available. [Text on screen: Documentary - MS in Black and African Americans. Documentary Premier Panel discussion: - Two people living with MS - Tyler and Dawn. - Dr. Mitzi Williams, neurologist and MS expert. - Dr. Sophia Woodson, nurse practitioner and MS expert. Full documentary available at https://www.abovems.com] Tirisham Gyang, MD: And last but not the least, I think this is kind of towards the end. We had a documentary premiere about MS in Black and African-Americans. There were two people living with MS that presented, this is available online and you can actually watch it. There were two MS experts, Dr. Williams and Dr. Woodson that talked about this documentary. They were all part of this documentary and it was very, very interesting to see that. So you can go to the website to watch it. [Text on screen: Resident summit. - Over 80 neurology residents (doctors in training) from all over the country including OSU. - Lectures, workshops, career panels, etc. - Chaired by Dr. Benjamin Segal. - OSU Faculty - Dr. Em Harrington and Dr. Tirisham Gyang] Tirisham Gyang, MD: Finally, we had a resident summit where over 80 doctors were present, 80 young doctors, doctors in training, and there were a lot of workshops, lectures, career panels to help them and guide them and mentor them as they decide on a career in MS or as they develop their careers in MS. Dr. Harrington and myself were both on those panels, and this was chaired by Dr. Segal, who's the Chair of Neurology here and one of our MS experts. And this is just a picture of the OSU people that were represented at ACTRIMS just to show you our team in San Diego. So that is the end. Thank you so much for listening and I'm going to hand this back to Kristi. Kristi Epstein, APRN-CNP: Thank you so much, Dr. Gyang. What a wonderful presentation. I love Dr. Laura Piccio. I follow her work very closely, so very exciting. And I believe that now I am going to be turning over the show to Dr. Em Harrington. Em comes to us from UCSF and is a wonderful physician-scientist doing some really important research here at the Ohio State University and is an amazing member of our MS team. So I will now turn it over to you, Dr. Harrington as the moderator for all those wonderful questions. Em Harrington, MD, PhD: Great, thank you, Kristi. If everyone can turn on their videos, I'm going to ask some specific questions. This is going to be very fast 'cause we have a limited time. So Dr. Zhang, I'm first going to ask you a bunch of questions 'cause there were many questions in the chat that came about in aging MS. So the first one is how do you define an older adult? Second question was, should you continue to get MRIs as you age with the fact that you have less relapses over time? And then, and some of these may be pretty long answers, but how is MS managed when DMTs are no longer working? Yinan Zhang, MD: Yeah, so these are great questions. So first off, an older adult, we typically characterize a geriatric patient as over the age of 65, but there's no really strict cutoff, and that's why I use the word older as opposed to define a specific age because some people may have geriatric needs who may be in younger ages and so forth. So there's no clear age cutoff, but in general, 65 years and up is defined as a geriatric adult. Now, in regards to the other question, so for MRIs, why do we still need to get them if there's still no changes and not likely any changes? And the reason is it is still possible, although less likely, for people to have relapses as they get older. So we don't want to miss any potential new disease activity in the brain or any changes that may suggest that there is ongoing disease activity or that the medications for MS are not working as well. Now, one can make an argument that when things are very stable or as people with MS are getting older, certainly we can space out the interval for getting MRIs and it's not unreasonable to go for two years or so between MRI scans, but if it's longer, we'll have to of course talk to your doctor, making sure that this is the appropriate monitoring strategy for you. Now, in regards to I guess the efficacy of disease-modifying therapies with age, so the reason we still treat older adults with MS is that there is always that risk of having a breakthrough relapse. And that can happen in people who are in their seventies, even in their eighties. It's not unheard of to have this happen. The chances are, of course, much lower than say someone in their thirties or forties, but we don't want to risk that happening because when your body gets older, it's more difficult to bounce back from a relapse. The ability to repair the damage, it's not as robust as when someone is younger. So just because the risk is smaller, the effect of the consequences of having a breakthrough activity or a relapse can be much higher and for that reason, we oftentimes encourage treatment, but of course it's not an absolute mandate. Now, in many patients, we do stop disease-modifying therapies after a certain age just based on their personal record and how they're doing. So it's a conversation definitely to be had with your provider. Em Harrington, MD, PhD: Thank you so much. And any questions we don't get to, we will post online with the video. So Dr. Segal, I have a couple questions for you. One was regarding one of your papers, which mentioned chronic active lesions in MS. How does someone know if they have chronic active lesions? And the other question was regarding biomarker testing. Are we considering doing annual biomarker testing, like some of the testing that was described at the ACTRIMS meetings such as testing done by the MSDA or CASA-MS for our patients? Benjamin Segal, MD: Well, thank you for those questions. So chronic active lesions are best revealed by examining the lesions under a microscope. So normally, of course, we wouldn't do that. There are particular MRI techniques we can use, special sequences that are usually done in the setting of research that will identify what are most likely chronic active lesions. But in people with progressive MS or people who are over the age of 55, some of the lesions even that we observe on conventional MRI scan, we can say there's a good chance they're chronic active and potentially, and research studies confirm that with the special MRI techniques. With regard to the other question, in terms of biomarkers, we have laboratory studies going on all the time here at Ohio State. I have my own laboratory, as does Em. Dr. Zhang is doing biomarker studies. And then we have a whole army of scientists, who are looking at MS from different angles and we are doing very cutting-edge analyses of blood, spinal fluid, et cetera. We have all of the machinery and assays to do the types of measurements that were described in all of the studies. And we're further doing really sophisticated immune characterizations of people with MS using spinal fluid and blood to look at individual immune cells and to, for example, determine all of the genes that these cells are expressing so that we can better understand the type of inflammation that causes damage during different stages of MS. So yes, all of those studies are being done and we've developed a large bio-repository and a very intensive system to collect and bank samples. So anyone who is seen at Ohio State is given the opportunity to participate in this bio-repository program and contribute samples for research. Em Harrington, MD, PhD: Thank you. Dr. Jordan, I'm going to direct the next question to you. A patient with MS who has a family member who's trying to get pregnant, should they be worried about any genetic risk factors for either if they were getting pregnant or their family member, was the particular question in this case? Allison Jordan, DO: So I guess the question is would be how likely that parent would pass on multiple sclerosis to their child? Yeah, so as I said in my talk, there is definitely a genetic component to MS, but we think it to be a very small component and so up to about a 4% risk, unless both parents had MS and then the risk would be higher. Em Harrington, MD, PhD: Great, thank you. And then, Dr. Kielb, I have a couple of questions for you. One was about somatic therapies. Is there any evidence for those type of therapies and are they effective? And the second question was how to increase motivation? I think we'd all like to do this. Any recommendations or techniques you have for that? Stephanie Kielb, PhD: Yeah. Well, to answer the question about somatic therapy, I don't know that type of therapy particularly well or the research evidence for it. I mentioned I do cognitive behavioral therapy in my clinic because I think the research evidence we know is strong enough, or strongest for its effectiveness, but that doesn't mean that other approaches to therapy don't work. And I think somatic, the word somatic means body. So anything that's getting us more in touch with our body and the sensations in our body and how that relates to how we're thinking and feeling could only be helpful. But again, I don't know the specific research on that. In regards to motivation, yeah, that can be a tough one. And that's something that I work with folks on a lot when treating depression because oftentimes that's a component of depression or a manifestation is a change in our motivation. And so oftentimes, it's helping to reconnect with simple things. Maybe if we've become much less active than we used to be, if we can just take really small steps, do one thing at a time, do one thing differently today than we did yesterday and give ourselves credit for making those small changes. Oftentimes, we can work up and then once we get a little bit of motivation and we get a little bit more active, it tends to build and things can go in a positive direction from there. Em Harrington, MD, PhD: Thank you so much. And last question for Dr. Gyang. Someone who is interested, do they have EBV or have they been exposed to EBV, what would you recommend someone asking that question and should people be tested? Tirisham Gyang, MD: Yeah, good question. So in the adult population, most people have been exposed to EBV. Not everybody has a symptomatic EBV infection, but at some point, most of us have been exposed to the virus and if we test the blood, we see those antibodies to EBV in up to 94% of adults. Now, we talked about the fact that MS patients, about 99.5% have positive antibodies, so most people have been exposed to EBV. I don't know that it gives us more information or more ways to treat an MS patient if we know that they've been exposed to EBV because almost probably all of them have. And even people without MS, a lot of them have been exposed to that. The big question with the EBV, especially with the vaccines is can we target this vaccine in very young people to prevent them from getting that exposure. And then, in the future maybe we would get more information about what to do. Are there treatments that we could do to people that already have MS and probably have had an EBV exposure before? Right now, we don't have any specific recommendations and I don't think there's any specific guideline that says everybody should be tested because most people are going to be positive for that EBV antibody. Em Harrington, MD, PhD: All right, thank you. I'm going to hit one more question and then we will wrap up with Kristi. So Dr. Zhang, someone asked a question about symptom management meds in older people with MS. Are there any downsides for symptom management meds or long-lasting effects that people should be worried about? Yinan Zhang, MD: So there are many medications that can be used to treat different MS symptoms, and many people continue on them for many years. It depends on certain types of drugs. In general, the thought is that with older age, medications tend to have more pronounced side effects in the elderly patient. And for that reason, it's always better to be on fewer things. There's a term called polypharmacy that's being used to describe a patient on many medications that can have potential harmful interactions. And for these reasons, it's always important to go over your medications with your provider, any questions that you have about medication interactions or safety. And remember, we have a MS pharmacist here as well. So ask your provider about referrals to our MS pharmacist and you can ask them about not only your MS medications, but just medications in general and making sure that they're appropriate for you to continue to take and watch out for interactions. Em Harrington, MD, PhD: Great. Thank you. Kristi, I'm going to turn it over to you. I think we're all out of time and went over time. Thank you. [Text on screen: Thank you for joining us today. For post-conference questions or information, visit wexnermedical.osu.edu/mscommunity. You will be receiving a survey via email to share your experience from today's event.] Kristi Epstein, APRN-CNP: Thank you so much, Dr. Harrington. And I want to thank all of our speakers and our panelists for joining us. [Text on screen: Quality of Life Symposium. Saturday, April 22 9:00am - 3:00pm Fawcett Center Register: go.osu.edu/msqualityoflife] Kristi Epstein, APRN-CNP: And I want to invite you to another very exciting event. Our Quality of Life Clinic is going to have a live in-person, we want to see all of your faces, quality of Life symposium. It's going to be very exciting. It's at the Fawcett Center at the Ohio State University, Saturday, April 22nd. What we're going to do is take a really deep dive into a lot of these things that we've been discussing, including diet, exercise, mindfulness, sleep, mental health, physical therapy, recommended exercise, all kinds of wonderful things, a very, very deep dive into details. So we want you all to join us and in order to register, you can go to go.osu.edu/msqualityoflife to register. Also, you can scan the QR code on the screen, but don't worry, we're going to send out invitations to everyone via MyChart. And for those patients who are not OSU patients, don't worry, you're also invited. The flyer is available through the National MS Society. If you have questions, please reach out and we would love to see you there. It's been a long time since we've been able to do an in-person event and what could be better than quality of life in MS. [Text on screen: Thank you for joining us today. For post-conference questions or information, visit wexnermedical.osu.edu/mscommunity. You will be receiving a survey via email to share your experience from today's event.] Kristi Epstein, APRN-CNP: So I want everyone again to show up and put your questions in the Q&A. If they were not answered, we're going to put those on our website and you can check back probably next week to look for the answers to those questions. If you go to our webpage wexnermedical.osu.edu/mscommunity page, you will see all of our previous patient education events. Those are recorded for your viewing and you will see the answers to the questions that we were not able to get to tonight. [Text on screen: Multiple Sclerosis Education Series. Thank you for joining us today. The Ohio State University Wexner Medical Center] Kristi Epstein, APRN-CNP: Again, I want to thank you all for joining us, and we will look forward to seeing you in the future for another patient education event. Good evening, everyone. Hope to see you soon. Take care.