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Reduction of Relapses in Multiple Sclerosis after Anti-Alpha4 Integrin Antibody (Natalizumab)

Depression is a common comorbidity in patients with multiple sclerosis (MS) and is associated with decreased quality of life. Identifying treatments that aid psychological and physical rehabilitation in patients with MS provides valuable information for interdisciplinary teams.

Seventy-five adults with MS who completed the Patient Health Questionnaire-9 (PHQ-9) and Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health scale during routine physical therapy appointments where the (CAREN) system was used were studied. Data were retrospective and collected via patient-reported outcomes. Group comparisons used 2-sample 

 tests for continuous variables and Fisher exact tests for categorical variables. To examine self-reported depression, mean ± SD baseline scores were computed and stratified by number of CAREN sessions.

Patients with 5 or more sessions seemed to have lower baseline PHQ-9 and PROMIS Mental Health scores; however, no significant differences were found at the univariate level. There were no statistically significant differences in follow-up scores for the outcome measures.

Current research evaluating the rehabilitation of patients with MS using the CAREN system is scarce. This pilot study is important to inform prospective studies exploring use of the CAREN system for psychological rehabilitation. Patients with 5 or more CAREN sessions had lower baseline PHQ-9 scores, which may suggest that mood plays a role in the selection of patients for CAREN system use. This study shows that mood is not affected by the CAREN system. More specific research needs to be completed with a more robust sample.

From the Mellen Center for Multiple Sclerosis (AK, ABS), Department of Qualitative Health Sciences (NRT), and Neurological Institute Center for Outcomes Research and Evaluation (NRT), Cleveland Clinic, Cleveland, OH, USA. 

: Alexa Kane, PsyD, Mellen Center for Multiple Sclerosis, Cleveland Clinic, 9500 Euclid Ave, U-10, Cleveland, OH 44195, USA; 

 The authors declare no conflicts of interest.

 Aspects of this study have been presented in abstract form at the Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC); May 28–June 1, 2019; Seattle, Washington.

Mood disorders are common in patients with multiple sclerosis (MS). The prevalence of depression is approximately 50% depending on the method used and the study population.

 The lifetime prevalence of depression in patients with MS is approximately 3 times higher than that in the general population and exceeds that in other chronic diseases, including other neurologic disorders.

 Current research suggests that the development of depression in patients with MS involves at least 3 mechanisms: (1) psychological reaction to disease, (2) inadequate coping, and (3) lesion burden to the central nervous system and functional changes due to inflammation.

 In addition, there is an understanding that use of MS therapies, corticosteroids, and spasticity medications is associated with high depression.

 Therefore, depression is often considered both a reaction to and a symptom of MS.

The impact of MS on quality of life (QOL) has been well documented in the literature.

 Compared with other chronic illnesses, MS has a greater effect on QOL due to its chronic progressive course.

 The presence of depressive symptoms is one of the most critical predictors of QOL, with depression explaining more variance in QOL than disability status.

In addition, patients often report gait abnormalities among the most distressing consequences of MS, with limited mobility subsequently affecting independence and QOL.

 Research has provided evidence that physical therapy can improve QOL in patients with MS.

 As such, limited mobility is often a contributory factor to mood symptoms, and specifically, depression. It has been suggested that virtual reality, and specifically the Computer Assisted Rehabilitation Environment (CAREN) system, can be an effective adjunct treatment to decrease depression and increase QOL in patients with MS.

The CAREN system is an immersive virtual environment that provides a motivational and effective alternative to traditional rehabilitation for patients with MS.

 The CAREN system is a high-tech medical and research system that allows medical experts to view and analyze balance, locomotion, and coordination in an interactive, controlled environment. With CAREN, rehabilitation experts, orthopedists, occupational therapists, physiotherapists, neurologists, and pediatric, mental health, and research experts collaborate using a multidisciplinary tool. The CAREN system uniquely immerses participants in a multisensory virtual reality experience that allows the registration, evaluation, clinical analysis, and rehabilitation of human balance, including the visual, auditory, vestibular, tactile, and proprioceptive systems of the body. The physical setup of CAREN involves a “6-degrees-of-freedom” motion base topped with force plates or an instrumented treadmill and a real-time motion capture system integrating visual projection and surround sound. The CAREN platform fully immerses the individual into an environment where visuals, the floor (which moves up and down, left and right, and turns), and the sound system combine and react to behavior. The user can easily create a variety of customized virtual environments for research and rehabilitation purposes. The CAREN system is able to provide real-time feedback. In addition, many rehabilitation therapists use the ability of the CAREN system to complete dual tasks during the session, including cognitive dual-tasking or a physical task while also walking. The real-time feedback is a significant benefit that provides instantaneous results for both the therapist and the patient, contributing to the immersive environment of the CAREN system.

Owing to the small number of CAREN systems in use, there has been little scientific evidence of its effectiveness for mood and QOL.

 Virtual reality has been shown to benefit balance impairments, physical activity, and level of functioning.

 The CAREN system may be more motivational in nature compared with traditional physical therapy due to the repetitive nature of traditional rehabilitation.

 Virtual reality, and specifically the CAREN system, may provide psychological advantages to traditional rehabilitation services, such as providing clearer goals, greater task concentration, and clearer immediate feedback.

 Therefore, the CAREN system may be associated with a positive effect on patients’ mood and subsequent QOL while also contributing to effective physical and cognitive rehabilitation.

Identifying treatments that aid in reducing mood symptoms while also increasing functionality in patients with MS could have an important effect on their care. More extensive studies evaluating the ability of systems, such as the CAREN, to treat symptoms associated with MS, including mood symptoms, are needed.

 In addition, the need to examine treatments that positively associate with a reduction in psychiatric symptoms are needed in the MS population. The present study explored the potential psychological benefits of the CAREN system in a subset of the MS population. To our knowledge, this is the first study to examine depression in the context of treatment using the CAREN system in patients diagnosed with MS.

Patients in this historical cohort were chosen for study by retrospective review of medical records. All the patients attended the Cleveland Clinic Mellen Center for Multiple Sclerosis for care between January 1, 2013, and December 31, 2018. Inclusion criteria included age 18 years or older and, due to the pilot nature of the study, at least 1 physical therapy session using the CAREN system. Patients were excluded if they did not complete the Patient Health Questionnaire-9 (PHQ-9)

 and the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health scale before and after the physical therapy appointments using the CAREN system. Use of the PHQ-9 has been determined to be valid in the assessment of depression symptoms in the MS population.

 Approval was obtained by the Cleveland Clinic internal institutional review board and ethics board. The need for informed consent was waived.

Descriptive statistics (eg, means, SDs, medians, inter-quartile ranges, frequencies, percentages) for demographic and clinical variables recorded at baseline were computed for the entire cohort and stratified by number of CAREN sessions (1–4 vs 5 or more). Group comparisons were performed using 2-sample 

 tests for continuous variables and Fisher exact tests for categorical variables.

To examine self-reported depression and QOL in patients with MS using the CAREN system, mean ± SD baseline scores were computed, again for the full cohort and stratified by number of CAREN sessions. Similar tests as mentioned previously herein were performed to determine whether baseline scores varied by group as defined by number of sessions. In addition, we created linear regression models in which the baseline score was the dependent variable. Categorized number of CAREN sessions was the independent variable, and variables found to be statistically significantly associated with group were included as covariates.

To compare pre-post psychological self-report scores after trial of the CAREN system, we created separate linear regression models (one for each score). The last score recorded during the course of treatment was the dependent variable, and the corresponding baseline score was included as a covariate. Again, variables found to be statistically significantly associated with group were included as covariates.

Because this study is exploratory in nature, correction for multiple testing was not performed, but interpretation of the results will be made in light of the number of tests being performed. All computations were performed using R version 3.5.0 (R Core Team),

 < .05 was considered statistically significant.

A total of 75 patients with MS used the CAREN system during the study period and were chosen for study. Patient characteristics for the entire cohort and stratified by number of CAREN sessions are presented in 

, which is published in the online version of this article at IJMSC.org. Mean ± SD patient age was 51.5 ± 14.5 years; 66.7% were women and 68.0% were of White race. Compared with patients with 1 to 4 CAREN sessions, patients who had 5 or more sessions were older (

 = .037), and were more likely to be taking escitalopram oxalate (

 = .038). Although patients with 5 or more CAREN sessions seemed to have better baseline PHQ-9 and PROMIS Mental Health scores, no significant differences were found at the univariate level (

; supplemental materials are available in a PDF at the end of the online article).

Results of linear regression models for baseline scores are presented in 

. After adjusting for age, time since diagnosis, and use of escitalopram oxalate, there were no statistically significant differences in baseline scores for any of the outcomes (PHQ-9, PROMIS Physical, PROMIS Mental Health).

Results of linear regression models for follow-up (ie, posttreatment) scores are also presented in Table 1. After adjusting for age, time since diagnosis, use of escitalopram oxalate, and the corresponding baseline score, there were no statistically significant differences in follow-up scores for any of the outcomes (PHQ-9, PROMIS Physical, PROMIS Mental Health).

Current research evaluating the rehabilitation of patients with MS using the CAREN system is scarce. Although no statistically significant differences were found between or within groups, this pilot study is an important step to inform perspective studies exploring use of the CAREN system and other types of virtual reality for psychological rehabilitation. Previous research suggests that the CAREN system creates a more engaging environment for therapy.

 Given the more engaging environment, it has been suggested that there is a decrease in depression. The current pilot study’s results are unclear regarding this suggestion.

Patients with 5 or more CAREN sessions seem to have a lower baseline PHQ-9 score, which may suggest that mood plays a role in the selection or participation of patients using the CAREN system. More specifically, patients who have lower levels of depression may be selected more frequently to use the CAREN system. A possible explanation for this finding is that patients experiencing less depression may be more likely to volunteer to trial the CAREN system. Recent research has suggested that physical disability has been associated with higher depression in MS.

 Therefore, patients with higher levels of depression may not be able to physically use the CAREN system for physical rehabilitation.

There were multiple limitations to the study given the retrospective methods and limited sample size. The limited sample size likely contributed to the lack of statistically significant associations between the number of CAREN sessions and scores. Given the results and limitations, future prospective studies are needed to evaluate what types of patients would benefit from CAREN-based therapies, including adjunctive treatment of mood symptoms prevalent in the MS population. In addition, a prospective study is warranted to address the previously noted limitations. Capturing mood-related data immediately after a CAREN session is likely a more effective method for assessing the impact of the CAREN system on psychological functioning. Future research should also specifically measure the impact of the CAREN system on reported QOL measurements. Furthermore, future considerations should also include individuals who have not taken an antidepressant in the past 3 months of the study.

Although the investigation of using the CAREN system as an adjunctive intervention for mood is in its infancy, this study provides some context to explore additional ways to provide treatment from an interdisciplinary perspective. The unpredictability of MS may result in significantly greater variability of depression scores from physical therapy session to physical therapy session. Therefore, perhaps the psychological advantages of using the CAREN system may be more related to engagement, joy, or flow as opposed to traditional depression symptoms. Additional investigation as to how the CAREN system can address both physical and psychological rehabilitation should not be deterred by the results of this pilot study. Given the anecdotal evidence of patient report after using the CAREN system, there is likely to be a psychological advantage.

"Virtual reality has been shown to benefit balance impairments, physical activity, and level of functioning.[17] The CAREN system may be more motivational in nature compared with traditional physical therapy due to the repetitive nature of traditional rehabilitation."

Assessment of Computer Assisted Rehabilitation Environment (CAREN) System Use and Mood in Patients With Multiple Sclerosis

One of the celebrations at the 2025 annual meeting of the 

 (CMSC) had Francois Bethoux, MD, at its center. 2024 marked a decade of his service as editor in chief of the 

). At the journal's editorial board meeting, he received a plaque and a round of applause from his colleagues. It proved to be only the first recognition Bethoux would receive as he went on to be recognized as a 

® the next night. To add to the celebrations, the entire 

 team also received the Thumbs Up award from the 

International Organization of Multiple Sclerosis Nurses

As the journal of the CMSC, the mission of 

 is "to promote multidisciplinary cooperation and communication among the global network of MS health care professionals, with the goal of maximizing the quality of life of people affected by MS." It is a free publication for authors, researchers, and all those interested in advancing MS care, charging no publishing, processing or subscription fees.

At its founding in 1998, the journal's first editor in chief was Robert M. Herndon, Sr, MD. He passed the torch to Lael Stone, MD, in 2007. In 2014, she passed the torch to Bethoux, making his current 10 years the longest tenure thus far.

Bethoux is chairman of the Cleveland Clinic Department of Physical Medicine and Rehabilitation and director of Rehabilitation Services at the Cleveland Clinic Mellen Center for Multiple Sclerosis Treatment and Research. He also serves as medical director of the Cleveland Clinic's Arts and Medicine Program.

 sat down with Bethoux to get his perspective on his career path, his involvement with the journal, and his opinion on hot topics in the field of MS care.

Tell me about your journey to medicine. How did you get involved in the field of rehabilitation?

 My brother was in a car accident when he was 5 years old, so I was exposed to the field of rehabilitation pretty early. He had a severe traumatic brain injury and a long rehab journey, and [that experience led me] into medicine. I had an interest in neurology first and wanted to know everything related to the brain. I was passionate about that, but along the way, when I did my rotations, I felt that the neurorehabilitation field was the best fit, following people with chronic neurological disability for a long time and trying to promote function and quality of life. That’s how I ended up in the field of neurorehabilitation.

How old were you when your brother was in his accident?

 I was 8 years old at the time. There’s a whole area of literature on being the sibling of a child with a disability, and I would say [the experience] was very formative for me, and I was grateful. I probably wanted to avoid making the obvious choice and going straight [into the field of neurorehabilitation], but it felt very comfortable.

How did you make the move from France to the United States?

 It was an interesting evolution. I was on an academic track in France, and as a part of that, it’s customary to spend a year abroad. My mentor had a friend in Cleveland, Ohio, at the time that I was ready to spend that year abroad, so I applied for a research fellowship with Metro Health Medical Center and Case Western Reserve University. It was a rehabilitation research fellowship. I did some research on functional electrical stimulation, particularly in people who had had a stroke, and I was interested in the medical scene in Cleveland. I interviewed around and had to go back to France. Then, I received an opportunity to enter an MS [multiple sclerosis] fellowship at the Cleveland Clinic’s Mellen Center for Multiple Sclerosis. And my family was ready to make the move, so I jumped at the opportunity, came back, and never left. That was 27 years ago.

Was that fellowship your first exposure to MS rehab, or had you seen it elsewhere?

 I had seen it in my practice in France, but sporadically, because typically, people with MS [are] not a large percentage of patients in neurorehabilitation. In my area of France, there’s a hospital that specializes in the rehabilitation of people with MS. I knew of that hospital, and I knew colleagues who worked there, but I didn’t directly work there. So when I came to Cleveland, I really had, if you wish, a crash course in MS, MS 101. That fellowship provided me with the neurological background to really understand MS, know how it is managed with medications and MRIs, and understand how to integrate rehab. Generally, the model of rehabilitation is that if you have a severe disease, surgery, or an injury, then your ability to function is limited, so you go through a period of rehabilitation and hopefully reintegrate your environment as close as possible to the level of function you had beforehand, or learn adaptations with equipment, etc. With a chronic disease that, in many people, gets worse over time, the role of rehabilitation wasn’t as obvious. I think now the role of rehab in chronic disease is more understood and accepted. We have examples of rehabilitation in many other chronic conditions, from Parkinson disease to cancer. After the fellowship, I felt prepared to stay on as a rehab physician. At first, I was in the [Mellen] MS center, only seeing people with MS. Then I grew my practice outside of MS but stayed physically tied to the MS center for my clinic, and of course, also great ties and collaborations with the neurologists in the MS center.

How much of your practice now is people with MS?

 I would say my clinical practice is really focused on spasticity management and, being in the MS center, probably 40% of the patients I see have MS, which is pretty high for a physical medicine and rehabilitation practice. Then we also see people with strokes, spinal cord injuries, brain injuries, adults with cerebral palsy, so a wide variety of diagnoses, but a strong core of people with MS. I have also been doing clinical research for the past 20-plus years, and that research is 90% focused on people with MS.

 I’m curious: Is spasticity the same across chronic diseases, or are there particular parts of spasticity that you see in people with MS, stroke, or cerebral palsy?

 At the core, we could say that spasticity is spasticity, no matter what the underlying condition is. However, how it manifests and how we manage it will vary. With MS, spasticity is one piece of the puzzle, one part of the symptoms, and it’s not always bothersome, so it doesn’t always need to be aggressively treated. When it needs to be treated, there are many factors to keep in mind. First is the evolution of the disease. Is the disease progressing quickly or is the person having multiple relapses? Fortunately, it’s less and less the case now with the powerful medications that we have to treat MS. Second, what other symptoms, what other limitations is the person facing? And what has been the evolution of the spasticity over time?

With MS, you have symptoms that fluctuate from day to day, from morning to afternoon, and also over the years, gradually. It is important to keep this in mind when we manage it. I would say it is different. We use the same types of treatments, but how they’re coordinated when they are being prescribed or recommended depends. A big emphasis in MS, as in other conditions, is keeping up with physical activity and exercise. It is amazing what a difference it can make, although it’s hard, right? There are so many barriers to exercise when somebody has MS. Just keeping up with regular physical activity when you have fatigue, depression, difficulty moving, abnormal sensations, pain [is difficult]. It seems that everything is conspiring to not let people with MS be physically active, so it needs to be purposeful, and [the person needs] to be engaged. Some people were athletic before having MS, and so they know how to go about it. Others were not, so they need to be [coached], and we need to pay attention because they can’t just go to the gym or watch any video on the internet and just start doing it. That may lead to them saying, “Well, I really don’t like exercise. It’s not really appropriate for me.” We also have to keep in mind that exercise, physical activity, doesn’t really cause MS relapses or progression of the disease but can cause some symptoms to get worse for up to a few hours or some symptoms to reappear, also for a limited time, and that can be very scary.

, rehabilitation before you need it essentially, as a part of clinical care, realizing that exercise and being physically active helps with the management of the disease and the symptoms. Is that a new thing? Has that always been a part of MS care?

I think that the view that rehabilitation should be involved as early as possible, of course whenever indicated, has led to the development of multidisciplinary MS centers and the idea of comprehensive care of MS, which, as you know, the CMSC [Consortium of Multiple Sclerosis Centers] and 

 are promoting. The idea has been around for a long time. As usual, the devil is in the details of how to implement it. We do have to take into account the cost of care, so we don’t want to systematically involve every professional just because we think it could be useful, but there are so many symptoms of MS where the first line of management is nonpharmacological and can be handled by rehabilitation professionals.

The idea is that these rehabilitation professionals will, say, help the person establish an exercise program, or help them manage their energy over the course of the day, or help the person with MS realize how they can do the same task while expending less energy. That doesn’t necessarily require intensive, prolonged rehabilitation. It might be a few exercise training pointers, and then the person goes home, does it on their own, and then they may touch base again with their rehab professional. It’s initiating a dynamic there to try to change behaviors early, when it’s relatively easy, as opposed to later on in the disease, when it may not be as easy. It is also to empower people with MS to say, “Well, that overwhelming fatigue, that difficulty with my foot and my balance....” You know, we need to acknowledge that, and we need to give people the tools to either work around it or to overcome it, and above all, to keep functioning, have a great quality of life, even though there are some symptoms. Sometimes symptoms and what we call neurological deficits, like a foot drop, that we consider mild can have a significant impact. Someone who’s a young adult, maybe raising children, trying to have a career, sometimes running through airports to catch a plane. Many people say that keeping an active job, for example, while dealing with the consequences of MS isn’t necessarily that simple. Maybe each symptom is mild, but the combination of them is difficult to deal with, especially in the demanding world that we have today, where it seems that we have to go faster and faster and faster.

 Yes, and the literature about MS and employment supports that idea as well, showing that it is difficult to sustain employment after diagnosis.

How did you first hear about the Consortium of Multiple Sclerosis Centers?

I heard about the CMSC very early in my MS fellowship because the Mellen Center at the Cleveland Clinic is very involved with the CMSC and has been for a long time. I think one of the early meetings of the CMSC was held in Cleveland. I submitted abstracts to the CMSC annual meeting, and after attending and networking there, I really became more involved. Before that, I was aware of the CMSC and felt it was a very unique organization, obviously promoting the multidisciplinary care of MS, but also looking into the future and trying to build the workforce to help people with MS. That’s a great mission to have.

 And did your involvement with CMSC lead to your introduction to 

 started as an online-only journal, then became print and online, and now is back to online only. I am very proud of the fact that it remains open access at no cost to authors or those who want to access the research. It is a model that is difficult to follow long term, but the CMSC has been incredibly supportive. Dr Lael Stone, who was a colleague of mine, became the second editor in chief of 

founding editor Dr Robert Herndon, and she started to involve me as a reviewer, and then invited me to join the editorial board. That’s really when I got more intimately acquainted with 

 and all of the contributors, which led to my being comfortable taking on the editor in chief role just a few years ago.…

 Just a short decade ago, right? And how did that come about?

When Dr Stone wanted to transition from her role as editor in chief, there were several candidates who were considered, and there was an interview process. I was chosen, and I was grateful for that, and a little scared, of course, at the same time. It’s a responsibility. Dr Stone had initiated transformative initiatives for the journal, particularly the inclusion of 

 in PubMed Central. I took over about that time, and all of a sudden, we saw the number of submissions skyrocket. Over the course of 2 years, I think they increased to the level we have today. And so, for me, it was exciting to see that transformation [that led to] 

 being cited more and known outside of the relatively small group of the CMSC.

It’s been like a French movie whose title is 

, and the movie is everything but slow and simple. It’s not chaos all the time, but I would say it’s been very eventful. There have been some initiatives that the journal has launched, and there were also changes in the scholarly publication field, and 

 tries to adhere to the highest standards of publication ethics. As Dr Stone said when I became editor, “Well, you’re going to stretch another part of your brain.” I definitely did, and I keep stretching it now. The role forced me out of my comfort zone to attend, say, a meeting on publication ethics and to see what other journals were doing with the changes to open access models or the peer review model and see what seemed to be acceptable or not. And, as the CMSC is a professional organization, it seemed important to me to involve people with MS in some way with our publication, and so that’s also something we’ve been pursuing over time.

 What do you think about the development of research that 

 has published from when you started to today? Have you seen any trends?

I would say that there’s been a welcome evolution. Early on, 

 published a mix of original research and updates on topics that were relevant to the readership. The readership of 

 is composed of many clinicians who are not necessarily in an academic setting yet want to know the latest and greatest about MS care, so publishing these updates was important. We’ve shifted toward publishing more original research and systematic or narrative reviews. These are helpful and more comprehensive and really provide, for example, the state of the art of what it is to manage fatigue and maybe aspects of fatigue management, such as exercise.

I’m also very proud of the fact that we address topics that are not commonly addressed in other journals because they are underrepresented or because the research is considered emerging. The studies remain small, and they derive hypotheses but cannot necessarily provide answers that can be generalized to the entire population of people with MS. Another big focus has been on the caregivers of people with MS, the family members, the friends, the spouses who really help on a day-to-day basis. That evolution, I think, has helped us mature into a journal that is hard to classify. Are we a neurology journal? A nursing journal? Is it a rehabilitation journal or a multidisciplinary care journal? We are unique. We’ve also evolved into being a great supporter of early investigators and trainees who want to publish. To me, it’s a great contribution to the future of MS care and research because we get people very early in their career and support them in publishing, maybe their first manuscript or their early manuscripts, and we address topics, again, that are very relevant to multidisciplinary MS care but are not necessarily very mainstream.

 What has been the biggest challenge for 

A very practical challenge is finding reviewers, and we constantly have a call on our editorial board, on [CMSC] membership, to review the articles so that the authors can get great quality reviews from experts in many, many fields. That’s been a practical challenge. Another challenge, I would say, is the fast pace. The publishing field has intensified over the past few years, which, in a way, is great as we get new research in front of an audience much faster. But it’s very important to note that, at the same time, it collides with the difficulty of finding reviewers or giving authors the time to revise the manuscript. That pace is an ongoing challenge, but I would say it is a good challenge that keeps us on our toes.

 What would you cite as one of the successes of 

I have already listed [becoming] more [known] and the articles being cited [more]. I started seeing 

 research in theses, which is a great success. My personal best is involving people with MS through the cover art. To me, that speaks deeply to the fact that we’re all here for people with MS and their families, to provide them with options, support, and guidance, while also empowering them to be the most important part of the care team. Being able to showcase the art and say a little bit about the artist is thanks to our collaboration with the Multiple Sclerosis Association of America and their wonderful Art Showcases. That’s very dear to my heart because it puts the patient back in the center on the cover of the journal. I know that it keeps me grounded. I have a secret passion for arts and medicine as well. It’s a secret that is not so secret. But it’s very niche, and I feel like any time we can remind people how the arts can be helpful when you’re dealing with a chronic condition, or when you’re taking care of people with chronic conditions, that’s also great, and so that’s why I’m particularly proud of this success.

 In the field of MS research, rehab or otherwise, what has had the most impact in the past 10 years?

It’s a tricky question because so many things have happened. This is going to date me, but when I did my fellowship, we had 3 approved medications for MS, and now it’s hard to count how many. There are so many coming out every year. And then, you know, the goal of the disease-modifying therapies has evolved. We talk about no new disease activity, no evidence of disease activity. We have now also discovered that there can be progression between relapses or progression independent of relapse activity. I feel like there’s so much more that is known about the disease process and also so much more attention to small but significant changes that can impact the person with MS. 

At the same time, there’s been tremendous growth in evidence in the other disciplines involved in the management of MS; the field of exercise and rehabilitation is a great example. More and more technology is available for rehabilitation and directly to patients, but do we have the evidence to show how to use it to get the most benefit? We need research for that. Do we know whether it’s safe? We need research for that, and that has been growing exponentially. We now have a very solid body of evidence that exercise is not harmful when it’s done properly and is helpful in MS. We also have more evidence on all the psychological consequences of MS and how some treatments can help, like cognitive behavioral therapy, which can be applied for many of the consequences of MS. And in the field of caregiver research, [we have more on] caregiver involvement and all the consequences on the caregiver’s health by being involved in giving care, for example. There has also been the development of qualitative research. Quantitative research is important, and it can be done on large samples of people with MS, but qualitative research goes in-depth, trying to understand what [the numbers] really are telling us. What do people feel and experience in their daily lives? What are the themes that can be extracted? I find it fascinating. We’ve also seen [continued] growth of social media and the internet over the past 10 years. We need to understand how people with MS are using social media and how caregivers and health care professionals can use it as well.

So all this knowledge is coming together and coalescing into a model of care, and that model of care, of the comprehensive care of MS, is as relevant, if not more relevant, now than it was before, particularly at a time when we’re trying to use health care dollars wisely. We also have to take into account the fact that not everyone has access to MS care…. Now we have online care. I don’t like to say virtual care because it sounds like you have a virtual doctor talking to a virtual patient, but I’m willing to embrace it. Online care gives access to MS specialists to patients who live in an area where they don’t have access to an MS clinic.

I’m sure I’m missing a lot of important developments that have happened.... I haven’t mentioned basic research. 

 does not publish basic research because that is not our mission, but we’ve seen more and more of that basic research being translated, and that becomes relevant to the clinical care of people with MS. That is great, and, as we all know, people with MS are hungry for this information to know what they can do: For example, when is that research going to come to the clinic? It’s fascinating.

 I hesitate to pick one thing in the next 10 years because I feel like the next decade will also be a very important one for MS research and clinical care developments. But what do you have your eye on? What are you following in MS research?

One thing that I’d like to talk about is the advent of artificial intelligence [AI] and how it can permeate MS clinical care and research. You’re talking to somebody who had a flip phone until a couple of years ago, is not on social media or has very limited access to social media, and has just tinkered with the most easily accessible AI probably a total of 5 times over the past few years. But the health care system I work for is talking about integrating AI into visits so that we can spend more time face to face with our patients instead of typing on the computer, but also to avoid what is sometimes called 

. You know, late in the evening after the kids are in bed, finishing notes because we wanted to spend more time with our patients, and so the consequence was doing overtime to finish the notes. If [AI] delivers on its promise, it will be transformative in the day-to-day experience of caring for people with MS. That’s just one example. Could AI help with reading MRIs? Help with basic decision-making as well to help guide the first steps of decision-making? Help generate hypotheses for research and deal with massive amounts of data? We now have the capacity to collect massive amounts of data and store it, but how do we handle it? AI seems to be a promising [way] to help sift through data and tease out some of the meaningful conclusions, or at least meaningful leads. To me, AI has the potential to permeate every aspect of MS care and research. Of course, it is a little scary. We’ve already seen some of the drawbacks, and we see that AI needs to learn more, but the beauty of AI is that it keeps learning, so I am very interested in seeing [what happens].

 As a journal editor, are you wary of researchers using AI when writing articles?

I’ve lost a few nights’ sleep over this, but just a few because, at some point, I was like, will I be able to tell if somebody used AI to write a scientific article or not? And, I heard teachers say the same thing: Will I be able to tease out if a student has used AI to write their paper from start to finish? Then I started turning the premise around a little bit, saying, “First, we’re going to ask the authors to be upfront about it, to tell us if they used AI to write the paper.” You know, we have the word 

We work on papers from many countries, particularly in countries where MS research is emerging, researchers or clinicians who want to publish don’t necessarily have access to translators, and sometimes that hinders the publication of their manuscripts. If AI could help organize the content and assuage some of the [translation] issues, then that could be a good use of it. As with many new technologies, it’s watchful optimism. That’s kind of my position right now: Ask everybody to be transparent and keep learning because humans can keep learning. It’s not only AI that can keep learning.

 Thank goodness. [We just attended] CMSC 2025 in Phoenix, Arizona. What did you enjoy?

As with each annual meeting of the CMSC that I have attended, it’s the networking. Everybody who attends is passionate and comes to the meeting with a different experience, different expertise, different desires. So literally, the conference is teeming with ideas, and there are some new people in the field that we get to meet in person. Sometimes I’ve interacted with people by email or via online meetings, but then I get to spend time with them, discuss in person. [Over the years,] there have been many opportunities to discuss the embryo of a project. Being able to meet in person, spend time together, that sometimes helps coalesce ideas in a very quick exchange and outline next steps…. That’s really what [I enjoy].

This interview has been edited for clarity.

IJMSC Insights offers a closer look at the latest research and the people behind it from the community of the International Journal of Multiple Sclerosis Care (IJMSC) and the Consortium of Multiple Sclerosis Centers (CMSC).

IJMSC Insights: Francois Bethoux, MD, on 10 Years at IJMSC

 To access the article, post-test, and evaluation online, go to 

 The target audience for this activity is physicians, physician assistants, nursing professionals, speech pathologists, and other health care providers involved in the management of patients with multiple sclerosis (MS).

1) Identify several variables that may place a person with MS at risk of language symptoms.

2) Describe the role of frontline health care providers in management of language and communication symptoms in patients with MS.

In support of improving patient care, this activity has been planned and implemented by the Consortium of Multiple Sclerosis Centers (CMSC) and Delaware Media Group. The CMSC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

 The CMSC designates this journal-based activity for a maximum of 0.75 

™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

 The CMSC designates this enduring material for 0.75 contact hour (none in the area of pharmacology).

, has served as Physician Planner for this activity. He has disclosed relationships with Springer Publishing (royalty), Qr8 (receipt of intellectual property rights/patent holder), Biogen (receipt of intellectual property rights/patent holder, speakers’ bureau), GW Biosciences (consulting fee), MedRhythms (consulting fee, contracted research), Genentech (consulting fee), Helius Medical Technologies (consulting fee), Osmotica (consulting fee), and Adamas Pharmaceuticals (contracted research). 

 has served as Reviewer for this activity. She has disclosed no relevant financial relationships. 

Sarah El-Wahsh, BAppSc (Sp Path) (Hons 1),

 has disclosed no relevant financial relationships. 

 has disclosed founding a start-up unrelated to the topic of this article; to date, the start-up designs apps for delivering speech therapy to children with developmental speech disorders. The peer reviewers for 

 have disclosed no relevant financial relationships. The staff at 

, CMSC, and Delaware Media Group who are in a position to influence content have disclosed no relevant financial relationships. Note: Financial relationships may have changed in the interval between listing these disclosures and publication of the article.

In order to receive CME/CNE credit, participants must:

1) Review the continuing education information, including learning objectives and author disclosures.

3) Complete the post-test and evaluation, which are available at 

Statements of Credit are awarded upon successful completion of the evaluation and the post-test with a passing score of >70%. The post-test may be retaken if necessary. There is no fee to participate in this activity.

 This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. The CMSC and Delaware Media Group do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the CMSC or Delaware Media Group.

 Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health care professionals without first evaluating their patients’ conditions, considering possible contraindications or risks, reviewing any applicable manufacturer’s product information, and comparing any therapeutic approach with the recommendations of other authorities.

Persons with multiple sclerosis (MS) can experience language-related symptoms such as difficulty with word finding, understanding verbal information, and structuring discourse. These symptoms have negative psychological and interpersonal consequences. Studies exploring characteristics of language impairment in MS are limited. The aim of this study was to investigate what symptom-related (eg, fatigue), demographic (eg, age), clinical (eg, MS type), social network, and quality of life (QOL) variables are associated with language impairment in MS.

Participants were recruited internationally to complete an online questionnaire. A forward stepwise regression analysis was run with the dependent variable being a language impairment index from the Communication and Language Assessment questionnaire for persons with Multiple Sclerosis (CLAMS). Nineteen independent variables were entered into the regression.

Two hundred and two participants completed the questionnaire. The CLAMS language impairment score was significantly associated with self-reported cognitive impairment, speech and voice impairment, yes/no response to a binary question on presence of language impairment, group membership and participation, and QOL. The adjusted 

Self-reported language impairment in MS is significantly associated with several symptom-related, social network, and QOL variables. These results provide an early model of language impairment in MS to guide future studies of treatment approaches and causative relationships between variables.

The authors acknowledge with gratitude the persons with MS who participated in this study. Without them, this study would not be possible.

Persons with multiple sclerosis (MS) can experience language-related symptoms. Research studies involving standardized assessments and self-report measures have found that persons with MS can experience difficulty with word finding,

Effective communication is critical for performing daily activities, pursuing goals and hobbies, making and maintaining relationships, participating in health care decisions, having independence, and being involved in the community. Language-related symptoms in MS can have negative psychosocial ramifications, such as frustration, embarrassment, loneliness, and limitations in social and familial relationships.

 In a study on quality of life (QOL), 43% of persons with MS (N = 30) experienced language difficulties that affected their QOL (eg, “It is extremely frustrating. I can’t say what I want to say,” “You feel incompetent”).

 There is growing evidence that language can be affected in MS; however, studies that examine what variables are associated with these symptoms are lacking. This information would inform patient care and future studies investigating the management of language-related symptoms in MS.

Patient-reported outcome measures (PROMs) are tools that gather information about the effects of a condition from the perspective of the individual with the disease without input from an external party.

 These tools are especially useful when exploring variables that are difficult to observe firsthand (eg, fatigue, pain, emotional well-being),

 which are variables of interest in this study. A previous study used PROMs to explore the association between self-reported language impairment in MS and health-related QOL (HRQOL), demographic, and clinical variables.

 This research quantitatively found that self-reported language impairment was associated with lower mental and physical HRQOL. An acknowledged limitation was that self-reported language function was assessed using four questionnaire items. This may be considered a cursory measure of language function. Moreover, the study involved only bivariate analysis to explore potential relationships. Given the potential impact of language-related symptoms on HRQOL, this preliminary study highlights the need to further investigate variables associated with language function in MS using a more comprehensive PROM and more advanced methods of statistical analysis.

The aim of this study was to investigate what self-reported symptom-related, demographic, clinical, social network, and QOL variables are significantly associated with self-reported language impairment in a sample of persons with MS. A data-driven approach was used.

This research was approved by The University of Sydney Human Research Ethics Committee.

To be eligible, participants were required to be 18 years of age or older, report a diagnosis of MS, speak English as their main language (ie, the language spoken most fluently and most often), and report no other history of neurologic deficits. Participants were not required to have a language impairment.

Participants were recruited internationally in response to advertisements placed with MS organizations, neurology and general practitioner clinics, and speech pathology forums, as well as social media platforms. These relevant groups were identified through a Google search. The advertisement informed participants about the study purpose and procedures, and it contained the questionnaire link.

Participants completed a package of self-reported questionnaires covering numerous topics: language-related symptoms, speech and voice symptoms, cognitive functions, fatigue, pain, mobility, hearing, vision, social networks, emotional well-being, and general HRQOL. These topics were selected based on findings from previous research indicating that these variables are pertinent to MS. Participants completed the questionnaire package online using REDCap (Research Electronic Data Capture) software. Submission of a completed questionnaire constituted informed consent. Participants were able to complete the questionnaire in one or multiple sessions to reduce respondent burden. Participants were asked if they used the “save and return later” function to complete the full questionnaire within 1 week.

Participants reported their sex, age, country of residence, highest level of education, employment status, and number of languages spoken. Participants also completed clinical questions pertaining to MS type, disease duration, age at diagnosis, history of childhood communication difficulties, and involvement with speech pathology services.

Language skills were measured using the Communication and Language Assessment questionnaire for persons with Multiple Sclerosis (CLAMS).

 The CLAMS is an 11-item PROM that assesses self-reported language function in MS. Items address a variety of language skills (eg, word finding, clarity, cohesion, specificity, and logicalness of verbal expression). The CLAMS has been validated for persons with MS, and statistical analyses have demonstrated satisfactory internal consistency, test-retest reliability, criterion validity, and no floor or ceiling effects.

Speech and voice skills were measured using the Speech pathology–specific questionnaire for persons with Multiple Sclerosis (SMS).

 The SMS has been validated for persons with MS and has been shown to be psychometrically sound. The five items of the speech and voice component of the SMS were used in this study.

Speech usage was measured using the Levels of Speech Usage scale.

 This is a single-item scale that asks participants to select a category that best reflects their speech demands in everyday living. The five categories are undemanding, intermittent, routine, extensive, and extraordinary use.

Cognitive ability was measured using the five-item version of the Perceived Deficits Questionnaire (PDQ).

 Although performance-based neuropsychological assessment is a well-established measure of cognitive ability, it can be time-consuming and expensive and was impractical for this study given its international online design. The PDQ was designed specifically for persons with MS to evaluate self-reported cognitive skills and is one of the symptom-specific measures in the Multiple Sclerosis Quality of Life Inventory (MSQLI).

Symptoms of MS, including those concerning pain, fatigue, emotional well-being, and mobility, were measured using the 36-item Short Form Health Survey (SF-36).

 The SF-36 is one of the most widely used patient-reported HRQOL measures and is frequently used in MS research.

General QOL was measured using a single-item scale that asks participants to rate their overall QOL on a 10-point visual analogue scale, with anchors of 0 (worst possible QOL) and 10 (best possible QOL). A definition of QOL was provided to participants. This single-item scale is similarly used in the MSQLI.

Social networks were primarily measured using the Stroke Social Network Scale.

 This tool measures social networks across five key domains: children, close relatives, close friends, groups, and satisfaction. Questions pertain to size of networks, frequency of contact, proximity, and satisfaction with frequency of contact. Although this tool is validated for the stroke population, this 22-item questionnaire was used given its underlying conceptual model, ensuring brevity but also ability to capture information across separate social constructs. The SF-36 also yields a social functioning scale and was used as a collateral measure of social networks.

Raw data from REDCap were transferred into SPSS Statistics for Windows, version 26.0 (IBM Corp) for analyses. This study involved a quantitative experimental design using survey methods and a forward stepwise linear regression analysis. The dependent variable was the CLAMS score. Before performing the regression analysis, categorical data were dichotomized. Type of MS was collapsed into two categories: relapsing-remitting MS and chronic progressive MS (secondary progressive MS, primary progressive MS, progressive relapsing MS). Education data were collapsed into two categories: university degree (undergraduate qualification, postgraduate qualification) and no university degree (secondary education, certificate/diploma). Correlations between the CLAMS score and potential independent variables were evaluated using Pearson or Spearman correlation coefficients between continuous variables and point biserial or nonparametric point biserial correlations between continuous and dichotomous variables. These correlational data were used to evaluate statistical significance and to inspect for the possibility of multicollinearity. If two independent variables correlated greater than 0.7 with each other, one of the two independent variables was removed from the regression analysis to avoid multicollinearity.

Self-reported language impairment in MS can be predicted by self-reported cognitive impairment, speech and voice impairment, yes/no response to a binary question on presence of language impairment, group membership and participation, and negative effect on quality of life.

WA Sheremata, MD

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