Content

Issues

Research

Permissions

Community Content

Videos and Multimedia

IJMSC Awards

For Authors

Information for Authors

Manuscript Submission

Patient Consent Form

About IJMSC

Aim and Scope

Ethics

Editorial Board

Peer Review

Contact Us

Home

Advertising

IJMSC

1rem

Authors

Occupational Therapy Interventions Addressing Activities of Daily Living and Sleep for People With Multiple Sclerosis: A Systematic Review

The experience with spasticity varies among individuals with multiple sclerosis and spasticity (MSS), as they may not recognize it as spasticity or have the language to describe their symptoms. This can lead to potential delays in diagnosis and treatment.

Symptoms and Emotions Exploration Needed in Multiple Sclerosis Spasticity was an online survey completed by 1177 individuals with MSS in 2021. It sought to capture symptoms of spasticity, variability of symptoms, specific spasticity triggers, and how conversations with physicians were initiated.

The mean age of the cohort was 56.8 years and it was 78% women. Prior to spasticity onset, 65% of respondents felt minimally prepared or unprepared for possibly developing spasticity and were unaware that spasticity manifests as part of MS. Eighty percent experienced spasticity daily, which was variable in severity and duration. Spasticity was triggered by a range of factors and 90% of those surveyed were unable to predict when it would occur or its severity. Day-to-day variability of spasticity prevented 65% of respondents from doing things they wished to do. Sixty percent were confused by their symptoms, not recognizing them as spasticity. Although 91% reported experiencing muscle spasms, only 69% used “muscle spasms” to describe their symptoms. Other descriptors included “muscle tightness,” “stiffness,” “cramping,” and “pain.” After recognizing spasticity, 78% proactively initiated discussions with their physicians, 52% wished they had done so sooner, and 42% delayed the conversation by up to or more than a year.

Results emphasize the variable nature of spasticity and the lack of a common language to describe symptoms, underscoring the importance of education, earlier recognition, and customized treatments tailored to the severity and duration of spasticity symptoms.

From the Andrew C. Carlos Multiple Sclerosis Institute, Shepherd Center, Atlanta, GA (BT); Johns Hopkins University School of Medicine, Baltimore, MD (SDN); Department of Neurology, University of Arizona College of Medicine, Tucson, AZ (BH); Outcomes Insights, Ventura County, CA (SD); Jazz Pharmaceuticals, Inc, Seattle, WA (JP, RC). 

Ben Thrower, MD, Andrew C. Carlos Multiple Sclerosis Institute, Shepherd Center, 2020 Peachtree Road NW, Atlanta, GA, 30309, USA; 

The authors would like to thank all survey participants and those who assisted in the development of the survey. Formatting and editorial assistance was provided to the authors by April Ingram of Outcomes Insights and funded by Jazz Pharmaceuticals, Inc. All authors met the International Committee of Medical Journal Editors authorship criteria and had full access to relevant data. The authors had full editorial control of the data presented and provided final approval of all content.

 Dr Thrower has received consultant fees from Sanofi Genzyme and is a member of the speakers’ bureaus of Bristol Myers Squibb, Genentech, and Horizon Therapeutics. Dr Newsome has received consultant fees for scientific advisory boards from Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Greenwich Biosciences, Horizon Therapeutics, and Novartis; is an advisor for Autobahn Therapeutics; is the study lead primary investigator for a Roche clinical trial; was a clinical adjudication committee member for a MedDay Pharmaceuticals clinical trial; and has received research funding (paid directly to institution) from Biogen, the Department of Defense, Genentech, the National Multiple Sclerosis Society, the Patient-Centered Outcomes Research Institute, Roche, and The Stiff Person Syndrome Research Foundation. Dr Hendin has received research funding and consultant fees for advisory boards from and is a member of the speakers’ bureaus of Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Novartis, and Sanofi Genzyme. Dr Chinnapongse was an employee of Jazz Pharmaceuticals, Inc. Ms Danese has received consultant fees from Jazz Pharmaceuticals, Inc. Ms Patterson was an employee of Jazz Pharmaceuticals, Inc.

 This work was sponsored by Jazz Pharmaceuticals.

 Portions of this work were previously presented as an oral presentation and a poster presentation at the Consortium of Multiple Sclerosis Centers Annual Meeting; June 1-4, 2022; National Harbor, Maryland.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system that can have a highly variable and unpredictable clinical course. It is estimated that 2.8 million people are living with MS globally.

 The overall burden and neurological symptoms of MS can be experienced differently, based on location, size, and number of central nervous system lesions. For those with MS, symptoms can occur concurrently, in various combinations, potentially exacerbating each other, further compounding its unpredictability and management complexity.

Spasticity involves the involuntary stimulus of muscles to contract or shorten and is a complicated, multidimensional symptom, contributing to disability in up to 84% of individuals with MS.

 The muscle contractions that characterize spasticity can occur spontaneously or continuously.

 Generally, spasticity may result in potentially debilitating musculoskeletal issues, including focal or diffuse pain, involuntary shaking, joint stiffness, muscle contractures, and limited range of movement, leading to multiple concurrent symptoms that negatively impact daily functioning and quality of life.

 For those with MS, it has been well documented that spasticity can result in physical disability and mobility issues, profoundly impacting quality of life, functioning, and performing activities of daily living, more so as the disease progresses.

As the experience of spasticity varies among individuals with MSS, the spectrum of its signs and symptoms has made quantifiable assessment challenging. Although clinician-assessed scales do exist, including the pendulum test, Ashworth Scale, modified Ashworth Scale, and the Tardieu and Modified Tardieu Scales, they are not widely used in the clinical setting. Patient-reported measures or scales have also been developed, including the 88-question MS Spasticity Scale and the Numeric Rating Scale for Spasticity. Despite the availability of assessment tools, most often, spasticity is included as a component of the standard MS neurological examination that is briefly documented in the patient’s chart. In addition, individuals with MSS may not recognize the characteristics of spasticity, have the language to describe their symptoms, or feel they are worth speaking to their physician about. All these factors may lead to potential delays in the clinician-patient dialogue resulting in delayed spasticity diagnosis and treatment.

To address this need and better understand the clinician-patient dialogue surrounding spasticity in individuals with MS, we conducted the Symptoms and Emotions Exploration Needed in Multiple Sclerosis Spasticity (SEEN-MSS) survey.

 The aim was to provide a more comprehensive understanding of how individuals with MSS experience and describe their symptoms associated with spasticity, the variability of those symptoms, specific spasticity triggers, and how they initiate conversations with physicians.

Survey methodology, eligibility, and a subset of analyses of SEEN-MSS have been previously published.

 A cross-sectional, observational, online survey, SEEN-MSS was developed by Greenwich Biosciences, now a part of Jazz Pharmaceuticals, Inc, and Scott Newsome, DO, in collaboration with 3 United States–based advocacy organizations for individuals with MS: the Multiple Sclerosis Association of America, the Multiple Sclerosis Foundation, and the National Multiple Sclerosis Society. These organizations assisted with online recruitment of survey participants.

The SEEN-MSS survey was conducted from February 4, 2021, to May 3, 2021. Prior to survey initiation, all materials were reviewed, and a waiver was granted by Advarra, an independent review board. All participants completed an online consent form prior to participating in the survey and all screening and survey details were self-reported.

Continuous variables were summarized as means, medians, and ranges; categorical variables were summarized as frequency distributions and percentages.

During the study period, the SEEN-MSS survey was completed by 1177 adults with MSS. Most participants were White (85%) and female (78%) with a mean age of 56.8 years (SD ± 10.7) (

). Of those who reported their specific MS diagnosis, 70% had been diagnosed with relapsing-remitting MS and 73% were receiving treatment with a disease-modifying therapy. A high proportion (80%) of participants reported that they experience spasticity at least daily, and applying the Numeric Rating Scale for Spasticity score, 18% reported their spasticity as mild, 40% as moderate, and 40% as severe. Eighty-seven percent were receiving treatment for their spasticity, most commonly an oral medication (Table 1). Additional characteristics of survey participants have been previously published.

Survey respondents reported that there was a period of approximately 5 years between MS diagnosis, occurring 16.8 years (mean, SD ± 10.0) prior to taking the survey, and onset of spasticity symptoms, occurring 11.5 years (mean, SD ± 9.7) prior to taking the survey. While 91% reported that they experience muscle spasms, only 69% specifically used the phrase 

). Other commonly used descriptors used by respondents included 

Spasticity does not appear to be a symptom that is immediately recognized by individuals with MS. When asked to look back, 60% reported that they were confused by the symptoms that they were experiencing and 70% recognized that they had been experiencing spasticity symptoms earlier than they had realized. Because specific symptoms may not have been recognized or acknowledged by the individual, this may have contributed to delays in clinician-patient dialogue.

Within the survey, 65% of respondents reported that they were either 

not at all prepared or minimally prepared

 for the possibility of developing spasticity, as their physician had not discussed this likelihood with them.

Following their MS diagnosis, physicians initiated a general discussion on possible MS symptoms with respondents within 3 months (30%), within 3 to 6 months (23%), within 7 to 11 months (4%), and after more than a year (30%). Of those who had had a discussion about spasticity specifically, it was started proactively by 78% of respondents while, for 22%, the physician was the one to initiate the discussion about spasticity. Interestingly, of the total cohort, 13% reported that they have never had a discussion with their physician about the symptoms of MS. Two-thirds (66%) of respondents stated that their physician used the word spasticity while discussing MS symptoms with them.

Although 87% of individuals with MSS had spoken with their physician about spasticity, 52% of those wished they had done so sooner. Among those wishing they had discussed spasticity sooner, 51% stated that it might have provided them with a better understanding of what was happening to their bodies, 48% might have sought treatment for their spasticity symptoms sooner, 34% shared that they may have had a name to explain what they were feeling, and 16% felt that earlier discussion might have given them more trust in their physician’s overall management plan for their MS.

Looking back, the majority of respondents (70%) somewhat agreed or strongly agreed that they were experiencing spasticity symptoms earlier than they originally thought and 60% somewhat agreed or strongly agreed that they were confused by their symptoms because they did not recognize them for what they were.

The survey identified 3 key barriers that prevented an earlier discussion about spasticity between participants and their physicians (

). The most common barrier, noted by more than half (52%) of the individuals, was that they lacked the vocabulary to describe spasticity; they did not know how to describe their symptoms. They also assumed that spasticity was simply a part of their MS and not worthy of mentioning (29%) and, similarly, they made the presumption that their spasticity could not be treated (18%), so again, it was not worth mentioning.

For 80%, spasticity is a once-daily occurrence. For 34%, spasticity is constant, while 40% describe multiple periods of spasticity during each day (Table 1). Spasticity is also variable throughout the day in severity and duration for 70% and from day to day for 63%. They reported that their spasticity is often worse in the evening (31%) and throughout the day (30%), compared with overnight (18%), in the morning (17%), or in the afternoon (4%).

Spasticity is triggered by a range of factors, most commonly fatigue (52%), physical activity (49%), heat (45%), and stress (43%) (

Implications of the Variable Nature of Spasticity

From day to day, 90% reported that they were not able to predict when their spasticity would occur or how severe it would be, and 65% agreed or strongly agreed that the day-to-day variability of their spasticity prevented them from doing things they would like to do.

Depending on how troubling the spasticity symptoms were on a given day, 49.7% shared that they changed the way they used their spasticity treatment by dose or frequency. Twenty-five percent did not believe that their physician understood how many aspects of their lives were impacted by spasticity.

The SEEN-MSS survey reveals that spasticity in MS can have a highly variable presentation in onset, duration, and severity; that it can be triggered by a number of different factors; and that individuals with MSS describe spasticity in many different ways. Findings also highlight a communication disconnect between individuals with MS and physicians. Possible MS symptoms are not always relayed in a timely manner, and spasticity is not always included in that conversation. Individuals with MSS are hesitant to initiate a discussion about spasticity symptoms with physicians because they may be uncertain of the proper language to describe the symptoms they are experiencing; furthermore, they may not recognize these symptoms as spasticity and have doubts about whether they should proactively initiate a discussion about these symptoms with their physician.

Although effective treatments for spasticity in MS do exist, this lack of awareness and recognition of spasticity and delays in the patient-physician dialogue limit the availability of treatment for those individuals with MSS who may benefit. Previous studies have shown that early and effective treatment of MS-related spasticity is important; it minimizes the consequences of spasticity-related symptoms, it improves patients’ quality of life, and it alleviates some of the economic burden on health care systems.

Physicians and individuals with MSS may benefit from using a common language and the survey results underscore the importance of education, which enables earlier recognition, diagnosis, and treatment of spasticity in MS. The patient-clinician dialogue may be improved by the development and use of spasticity symptom trackers and assessments of outcome. Although several questionnaires are currently available, they are not commonly used outside of a clinical research setting. Tools that ask the right questions about potential symptoms and manifestations of spasticity, using easy-to-understand terminology at earlier and regular time points, may open up communication between patients and physicians, although acceptance and application within the clinic setting would be necessary. Additionally, capturing a profile of specific symptoms for each patient, accounting for day-to-day and individual variability of spasticity, may also provide the opportunity for more flexible, customizable management plans.

Due to the inherent nature of survey-related research, the findings presented should be interpreted, while keeping in mind the following limitations. Due to the anonymity of survey responses, verification of reported data is not possible. Although this was a large, inclusive sample with a sufficient base size and representation across subgroups to project findings to the broader population, this is a survey and not a stratified sample; also, a clinician survey was not included. The current survey is also subject to potential sampling bias because it was available online only and administered in English. Thus, it has limited potential to reach certain populations including non-English speakers and those with limited access to the internet. These findings were not reported in comparison to any control group. Although the survey questions used were original in nature, customized to the study objectives, and validated through pretesting, the survey itself was not derived from existing validated instruments.

We acknowledge that patient-driven surveys are subjective in nature; however, they do help provide the patients’ experience, which is essential to understanding where gaps may be in the comprehensive care for individuals with MS. A long-standing patient registry, the North American Research Committee on Multiple Sclerosis registry, has published data from multiple patient surveys that have provided useful information for clinical practice. For future consideration, the inclusion of a clinician survey to assess perceived impact of spasticity on the lives of individuals with MSS also may be beneficial.

Spasticity can be highly variable in its onset, duration, and severity and can be triggered by a number of different factors. Although results from the SEEN-MSS survey have highlighted that the negative impacts of spasticity are wide-reaching across multiple aspects of life and cause substantial burden for individuals with MSS, many people with this disease may lack awareness that spasticity may manifest as part of MS. Individuals with MSS have demonstrated that they have uncertainty about how to describe symptoms and whether they should initiate a discussion with their physician.

Recognition, Description, and Variability of Spasticity in Individuals With Multiple Sclerosis and Potential Barriers to Clinician-Patient Dialogue: Results From SEEN-MSS, a Large-Scale, Self-Reported Survey

Multiple sclerosis (MS) is a chronic, inflammatory, and neurodegenerative condition characterized by the immune system's attack on the myelin sheath, leading to neurological dysfunction. While the prevalence of MS in Africa remains lower than in other regions, it has been rising steadily in recent years, with unique challenges hindering its effective management. These challenges include limited health care resources, inadequate diagnostic tools, financial constraints on accessing disease-modifying therapies, and a lack of trained health care professionals (HCPs). Cultural stigma surrounding MS further complicates patient care and treatment adherence. However, ongoing efforts by patient organizations, international collaborations, and local HCPs are focused on raising awareness, enhancing diagnosis and treatment access, and training HCPs. Future directions include integrating MS into national health policies, expanding education and research initiatives, and improving patient support networks. These efforts are vital in addressing the growing burden of MS in Africa and ensuring equitable access to care.

From the Internal Medicine Department, Ladoke Akintola University of Technology, Ogbomoso, Nigeria. 

Nicholas Aderinto, MD, Internal Medicine Department, PMB 5000, Ladoke Akintola University of Technology, Ogbomoso, Nigeria; 

Multiple sclerosis (MS) is characterized by the immune system's attack on the myelin sheath, leading to inflammation and neuronal damage.

 The global burden of MS is substantial. In 2019, there were 59,345 MS incident cases and 22,439 MS deaths worldwide.

 Despite the relatively low prevalence of MS in Africa compared with other regions, in recent years there has been an increase in reported cases.

 According to the global burden of disease study, in sub-Saharan Africa, the latest estimate of MS cases is approximately 49,000, with approximately 2800 new cases yearly.

The rising number of cases highlights a critical need for effective diagnostic and therapeutic strategies tailored to sub-Saharan Africa.

 However, managing MS in this region presents distinctive challenges, including limited health care resources, inadequate infrastructure, and insufficient disease awareness among health care providers (HCPs) and the general population.

 This editorial explores current practices in MS management across sub-Saharan Africa and highlights the significant challenges that HCPs and patients face.

Despite the challenges encountered by individuals with MS in Africa, ongoing initiatives are aimed at improving the management of the disease. The unique socioeconomic, cultural, and health care systems of various African nations complicate the effective management of MS, leading to disparities in diagnosis, treatment access, and patient support. However, efforts are underway to address these issues and enhance care for those living with MS. Recent studies have focused on providing more accurate estimates of MS prevalence across the continent.

 Accurate epidemiological data is crucial for understanding the scope of MS in Africa, which has historically been underresearched compared with other regions. A 2018 study indicated that the prevalence of MS in South Africa (5-30 cases per 100,000 people) is significantly higher than previously estimated, reflecting both a true increase in cases and improved diagnostic capabilities within the health care system.

 This finding not only highlights the growing recognition of MS as a pressing public health issue in the region but also shows a commitment to advancing MS research. Additionally, these studies have prompted initiatives to train HCPs to recognize and more effectively manage MS.

Current efforts to enhance MS care in Africa emphasize the critical importance of awareness, education, and access to treatment. These elements are vital for addressing the gaps in knowledge and resources that affect the quality of care for individuals with MS. Patient organizations are at the forefront of such advocacy and outreach, offering support, education, and resources to individuals with MS and their families. Multiple Sclerosis South Africa stands out as a leading patient organization in the region, hosting annual MS Awareness Week events, organizing support groups, and advocating for government support.

In addition, organizations such as the Multiple Sclerosis International Federation (MSIF) spearhead collaborative research initiatives. One notable project, the Atlas of MS, compiles global data on MS prevalence and health care resources. As of 2023, the atlas has provided critical insights that have influenced national health policies across various countries, further emphasizing the importance of data-driven approaches in improving MS care.

 Moreover, the data derived from the atlas have been vital in advocating for increased funding and resources dedicated to MS research and care. Armed with data, patient organizations and advocates communicate the pressing needs of individuals living with MS, thereby gaining governmental and institutional support.

While ongoing efforts are being made to improve MS care in Africa, significant disparities in access to diagnostic tools and trained HCPs persist across the continent. This variation leads to considerable inequalities in the care available to patients. Africa remains predominantly rural, with countries such as Niger, Burundi, Rwanda, and Malawi having only 1 in 5 inhabitants living in urban areas.

 Despite the appeal of its megacities, Nigeria hosts the continent's largest rural population, totaling approximately 95 million people, closely followed by Ethiopia with about 85 million. In these rural regions, health care infrastructure is often severely underdeveloped, leading to limited access to diagnostic services and patients frequently experiencing significant delays in receiving accurate diagnoses.

 Studies have demonstrated that MS patients often endure symptoms for years before receiving appropriate medical care.

 A retrospective study conducted in Egypt revealed that approximately 49.3% of MS patients were initially misdiagnosed.

The shortage of trained neurologists further exacerbates these challenges. Africa has an alarming ratio of approximately 0.03 neurologists per 100,000 people, contrasting with Europe's 8.45 neurologists per 100,000.

 Moreover, the uneven distribution of health care resources further complicates matters: Most of the neurologists practice in urban areas, leaving rural areas without resources.

In addition to these diagnostic challenges, the treatment of MS in Africa comes with issues related to accessibility and affordability. The proposed 2024 revised diagnostic criteria for MS necessitate MRI findings as a key component for diagnosis.

 This shift raises important questions regarding the feasibility of implementing these criteria in resource-limited settings, particularly in many African countries where MRI availability is limited. In 2017, Africa had 0.7 MRI scanners per million people, the lowest density among 6 World Health Organization (WHO) regions.

 In several regions of Africa, access to MRI is constrained by factors such as the high cost of the equipment, the scarcity of MRI machines, and the limited number of trained radiologists capable of interpreting MRI results. These challenges are particularly pronounced in rural or underserved areas, where health care infrastructure does not support the widespread use of advanced diagnostic technologies like MRI. As a result, the proposed reliance on MRI in the diagnostic criteria could present significant barriers to accurate and timely MS diagnosis in these regions.

Disease-modifying therapies (DMTs) are essential for managing the progression of MS; however, access to these vital medications remains limited across the continent. A survey conducted by the MSIF revealed that countries like Sudan and Syria lack any approved originator DMTs.

 Among the countries surveyed, interferons were identified as the most widely available low-efficacy DMTs; 3 countries reported having no high-efficacy DMTs approved. Follow-on DMTs were available in only 50% of the countries surveyed, indicating a significant gap in treatment options. Patients are often compelled to rely on generic versions of these medications, which vary in quality and availability. The inconsistency in the supply of generics poses a considerable risk, as fluctuations in medication quality directly affect treatment efficacy and safety.

 Moreover, the high cost of branded and generic DMTs often results in nonadherence, as many patients are forced to forgo necessary treatments due to financial constraints. The annual total costs per patient with MS range from approximately USD $463 to USD $58,616, a significant burden beyond most African patients’ reach, where the combined GDP is roughly USD $3.1 trillion.

 Additionally, cultural stigma and misinformation regarding MS can further complicate care. Many individuals view MS as a form of mental illness and hold misconceptions about its causes and management.

 This stigma deters patients from seeking necessary medical attention and adhering to treatment regimens, ultimately leading to poorer health outcomes.

Integrating MS into national health policies is essential to enhance disease management across Africa. This approach would address the unique challenges people with MS face, align with broader public health goals aimed at improving health care systems and outcomes, and ensure that MS is recognized as a significant public health issue. Given the growing prevalence of MS in Africa, which has been highlighted by recent studies indicating that African countries have higher prevalence rates than previously estimated, this integration would be especially timely. A national health policy framework that includes MS could facilitate better resource allocation for diagnostic tools, treatment options, and HCP training. Countries that have integrated MS into their health policies, such as the United Kingdom's National Health Service, have reported improved patient access to care.

 It would be beneficial for African nations to adopt a similar structured approach to funding health care services to enable improvements in patient care.

Furthermore, implementation of cost-reduction strategies are needed, including government subsidies, generic medication production, and partnerships with international organizations to provide funding or medication donations. Regional collaborations could enable pooled procurement strategies to negotiate lower prices for essential MS medications. Establishing and expanding access to nonpharmacological treatments is also needed. Rehabilitation services, including physical and occupational therapy, should be integrated into public health systems through targeted training programs for HCPs, the establishment of dedicated neurorehabilitation centers, and using telemedicine to extend services to underserved areas. Culturally adapted mental health services should also be developed to address the psychological burden of MS, with a focus on counseling, support groups, and training primary workers to deliver basic mental health care.

With the rising prevalence of MS in the region, it is crucial to equip HCPs with the necessary knowledge and skills to manage the disease effectively. Current training programs often lack a specific focus on MS; consequently, many HCPs are unfamiliar with its symptoms, progression, and treatment options. Specialized training programs focusing on MS should be developed and implemented in medical schools and continuing education initiatives in Africa. Incorporating MS into neurology residency curricula can ensure that future neurologists are well-versed in the latest diagnostic criteria and treatment protocols. Online training modules could provide more accessible resources for HCPs in remote or underserved areas, allowing them to enhance their understanding of MS without requiring extensive travel.

Collaborations with international organizations, such as the MSIF, could play a pivotal role in expanding educational opportunities and facilitate knowledge exchange, offering local HCPs access to global best practices and cutting-edge research. Expanding education and training programs will lead to better diagnostic accuracy, more timely interventions, and improved overall management of MS, which would facilitate early detection and prompt initiation of treatment, both of which are vital for slowing disease progression and enhancing patient quality of life.

Establishing more networks for patients and caregivers is essential to deliver holistic support to individuals in Africa who live with MS, as collaboration facilitates access to critical information, resources, and emotional support, all vital for enhancing patients’ quality of life.

 Support groups, patient advocacy organizations, and community outreach programs empower individuals with MS and their families by creating supportive environments

 and studies have shown that community support enhances treatment adherence and well-being.

 These initiatives can also serve as platforms to raise awareness and educate the public about MS, combating stigma and misinformation. Through these efforts, support networks would be pivotal in improving individual and communal outcomes in managing MS.

Encouraging research focusing on the unique challenges and solutions relevant to the African context is paramount for advancing MS management. There is a significant gap in epidemiological data, treatment outcomes, and disease progression studies specific to African populations. Collaborative research efforts involving local universities, health care institutions, and international organizations can help fill this void. Establishing research networks dedicated to MS can promote data sharing and encourage large-scale studies that reflect the diverse experiences of individuals with MS across the continent. In addition, funding initiatives that support local researchers can stimulate innovative approaches to addressing the specific needs of African patients. Enhancing research capacity in low-resource settings benefits local populations and contributes to the global understanding of MS.

Significant challenges and promising initiatives characterize the management of MS in Africa. As the prevalence of MS continues to rise across the continent, there is a pressing need to adopt approaches that prioritize awareness, education, and equitable access to treatment. Current efforts by patient organizations, HCPs, and international collaborations are essential to foster a supportive environment for individuals living with MS, both in Africa and around the world.

 The author declares that he has no competing interests, financial or otherwise.

Current Practices, Challenges, and Future Directions in Multiple Sclerosis Management in Sub-Saharan Africa 

Physical activity guidelines for multiple sclerosis (MS) were first published in 2013. Physical activity is safe and beneficial in MS, yet it is unclear if physical activity levels are changing in real-world settings.

The primary objective of this study is to determine if the physical activity levels of people with MS are changing. Between September 1, 2014, and February 22, 2022, when people first accessed a provincial MS drugs program in Saskatchewan, Canada, they were invited to complete the Godin Leisure-Time Exercise Questionnaire by mail. Scatter plots of total physical activity (TPA) and health contribution (HC) scores were generated from each person's questionnaire. Multivariable linear regression explored associations and interactions between disease-modifying treatment (DMT), sex, age, age at MS onset, and disease duration on physical activity level.

The response rate was 50.8% (505 responses from 993 requests). Of the respondents, 69.7% were female; the mean age was 42.8 (± 11.5) years; median MS disease duration was 6.0 years (IQR, 2.0-14.0); and 47.4% had prior DMT exposure. There was no significant change in physical activity levels of new registrants over 7 years (regression slopes TPA: 0.71, 

 = .21). Men reported higher physical activity levels than women (TPA: β = 11.95; 

 < .001). There were interactions between age and disease duration on activity scores (TPA: β = 0.03; 

 < .001). DMT exposure was not associated with physical activity.

Physical activity levels of people with MS remained suboptimal for health benefits over a 7-year period. Future research should include how to use physical activity guidelines to impact real-world activity levels.

From the Department of Physical Medicine and Rehabilitation (KBK), the Clinical Research Support Unit, Department of Community Health and Epidemiology (AI, TL, HJL), the School of Rehabilitation Science (SJD), College of Medicine, and the College of Pharmacy and Nutrition (CE), University of Saskatchewan, Saskatoon, Saskatchewan, Canada. 

 Katherine B. Knox, MD, FRCPC, Department of Physical Medicine and Rehabilitation, Saskatoon City Hospital, MS Clinic, Saskatchewan Health Authority, 701 Queen St, Saskatoon, SK, Can S7K0M7; 

The authors thank Walter Hader Sr, MD, FRCPC, PE, for his leadership with the Saskatchewan MS Drugs Research Program from 1997 to 2013. The authors also thank Shirley MacGowan, nurse educator, and Sam David Kodamanchali and Monique Reboe Benjamin for research support.

The authors declare no conflicts of interest.

 This study received funding from the Drug Plan and Extended Benefits Branch of the Saskatchewan Ministry of Health.

Physical activity in people with multiple sclerosis (MS) has been associated with improved function,

 as well as an estimated 27% relative reduction in MS relapse rates,

 Comprehensive MS care recommendations include supporting physical activity, symptom management, rehabilitation, and disease-modifying drug treatments (DMTs).

 The first guidelines for physical activity in MS were published in 2013 for people with mild to moderate disability.

 In 2020, updated guidelines included recommendations for physical activity from earliest onset of MS through advanced MS.

 Exercise in combination with DMTs is an approach proposed to further improve health and disability outcomes in MS.

 DMT recommendations emphasize the importance of early treatment for preventing relapses, controlling the inflammatory aspects of MS, and delaying early disability progression.

 However, high-level, quality evidence concerning the mechanistic effects of physical activity levels over the course of MS is needed.

 Despite recent advocacy and research interest in physical activity,

 there is limited real-world data concerning physical activity levels in people with MS.

The primary objective of this study was to determine if physical activity levels have changed over time among people living with MS who were newly registered with the Saskatchewan MS Drugs Research Program

 between September 1, 2014, and February 22, 2022. The secondary objective was to explore associations and interactions between physical activity and DMT exposure, sex, age, age at MS onset, and MS disease duration.

Saskatchewan has a population of 1.2 million and a high prevalence of MS.

 In Canada, provincial/territorial governments are responsible for health services, including provincial drug plans.

 In 1997, the Saskatchewan MS Drugs Research Program began providing administrative and educational services for DMTs as well as research opportunities. The program implemented a voluntary prospective process to assess self-reported physical activity levels on September 1, 2014.

For this study, physical activity levels were evaluated by a one-time mailed questionnaire that was sent when a person first applied to the Saskatchewan MS Drugs Research Program. All individuals who initiated registration between September 1, 2014, and February 22, 2022, received a questionnaire. The study was approved by the University of Saskatchewan Biomedical Research Ethics Board (BEH 14-86).

During the study period, new program applicants were invited to participate if they had clinically definite MS and were ambulatory. Participants were either on a DMT funded through other sources (ie, private insurance or compassionate industry coverage) or they were DMT naive. Eligible participants were mailed a study invitation letter, a consent form, a Godin Leisure-Time Exercise Questionnaire (GLTEQ), and a self-addressed, postage-paid return envelope. They were encouraged to complete and return the GLTEQ within 1 week of receipt. Participation was voluntary and had no bearing on eligibility for DMT funding coverage through the program. All completed GLTEQs received prior to February 22, 2022, were included in our analysis. Participant demographics and DMT history were extracted from the program application, which includes information about MS history and DMT treatment history.

The GLTEQ is a self-reported, validated measure of physical activity in ambulatory people living with MS.

 It provides an estimate of the metabolic output from physical activity in the proceeding week.

 This study aimed to evaluate the change over time in physical activity levels of new registrants according to the total physical activity (TPA) and health contribution (HC) scores on the GLTEQs. The TPA and HC scores are both derived from the GLTEQ and calculated in arbitrary units according to established methods.

 Higher TPA and HC scores indicate higher levels of physical activity. To complete the GLTEQ, participants fill in the number of self-reported 15-minute bouts of strenuous, moderate, and mild intensity physical activity in the preceding week. The HC score includes only the number of strenuous and moderate 15-minute bouts of physical activity multiplied by their respective metabolic equivalents. The TPA score includes the addition of the bouts of mild intensity physical activity. From the HC score, classification of an individual's activity level for substantial health benefits is defined categorically as either sufficiently active (score ≥ 24 units), moderately active (score of 14-23 units), or insufficiently active (score < 14 units).

Participant demographics included sex, age at MS onset, MS disease duration (defined as time from first MS symptom onset), and age and DMT treatment history at the time of questionnaire completion. Available data for DMT history included drug names with start and stop dates estimated to the nearest month. DMT exposure was divided into 2 broad categories: 

 if a person was currently on or was ever previously on a DMT, or 

 if they were never previously exposed to a DMT at the time of questionnaire completion. Exposure time among those exposed to DMT was the total number of months on any DMT rounded up to the nearest month. An additional 12 months of exposure was added for alemtuzumab and 6 months for ocrelizumab from the date of last dose administration, as these are the respective drug dosing intervals. In addition, DMT exposure history among those exposed was further classified into 1 of the following 4 categories: stopped any prior DMT, currently on a first-line DMT for relapsing-remitting MS, currently on a second-line DMT for relapsing-remitting MS, or on a DMT for primary progressive MS. DMT classification was according to Saskatchewan MS Drugs Program criteria: first-line DMTs (interferon beta 1a, interferon beta 1b, glatiramer acetate, dimethyl fumarate, teriflunomide, or ocrelizumab); second-line DMTs (natalizumab, fingolimod, alemtuzumab, or cladribine), and ocrelizumab for primary progressive MS.

 Participants on second-line DMTs would have had prior exposure to a first-line DMT in order to meet funding eligibility for a second-line DMT through the program.

Survey response rate was the number of completed, returned questionnaires divided by the number of invitations sent. Descriptive analyses characterized the study population. The change in TPA and HC scores over time was explored using scatter plots with fitted linear regression. Since there were fewer than 8 weeks of data collection in 2022, those GLTEQ scores were plotted together with the 2021 calendar year data. Change in the percentage of participants annually who were sufficiently, moderately, or insufficiently active for substantial health benefits were examined using the χ

 test. Univariate, followed by multivariable, linear regression analyses examined the associations between independent variables (demographics and DMT history; 

) and TPA and HC scores. Variables significantly associated with TPA and HC scores in the univariate analysis (

 < .05) were included in the multivariable regression model. Variables with 

 values less than .05 after a stepwise backward elimination were retained in the final multivariable regression model. Collinearity, confounding, and interaction effects among independent variables in the final multivariable model were also explored. Statistical tests were significant at a level of 

 values less than .05 (2-sided α = .05). SAS v9.4 software was used for data analysis.

A total of 993 surveys were sent with a response rate of 50.8% (n = 505). Median MS disease duration was 6.0 years (IQR, 2.0-14.0; Table 1); 37.8% (n = 191) had an MS disease duration of less than 3 years. Men were older in general (44.4 years vs 42.1 years; 

 = .04) and older at MS onset (35.3 years vs 32.7 years, 

 = .01) than women. There were no differences in MS disease duration between the sexes (women: median duration = 7.0 years, IQR, 2.0-14.0 years; men: median duration = 5.0, IQR, 2.0-14.0 years; 

Over approximately 7 years, physical activity levels according the GLTEQ TPA or HC scores improved by a small, nonsignificant amount (

). The TPA scores increased by 0.71 units per year (

 = .26) and the HC scores increased by 0.61 units per year (

 =. 21). There was no significant change over 7 years in the percentage of participants considered sufficiently, moderately, or insufficiently active for substantial health benefits over time (

 = .07), despite the observed fluctuations (

Longer time on DMT (if exposed to DMTs), female sex, older age at time of GLTEQ completion, older age at MS onset, and longer MS disease duration were significantly associated with lower (less active) TPA and HC scores on the univariate analysis (

). There were no significant associations between those naive to DMT versus exposed to DMT with the TPA or HC scores (all 

 values > .05). The small number of participants on DMT for primary progressive MS (n = 5) and those who had discontinued MS drug treatment (n = 48) (Table 1) had lower TPA and HC scores compared with those who were treatment naive in the univariate analysis. However, in the multivariable analysis, none of the DMT independent variables remained significantly associated with physical activity levels (

In the multivariable regression analysis, male sex was independently associated with higher physical activity levels; men scored 12 units higher on the TPA score (95% CI, 7.09-16.80; 

 < .001) and 6.7 units higher on the HC score (95% CI, 2.91-10.40; 

). There were also significant interaction effects for age and MS disease duration on physical activity scores. The interaction indicated that increased disease duration was associated with lower (less active) HC scores for participants below the age of 54 years and lower TPA scores for those below the age of 59 years. Increased disease duration above these ages was associated with higher activity scores.

Given the association with sex, and the interactions between age and MS disease duration and activity scores, we performed additional analyses (χ

 tests and scatter plots with fitted linear regression; data not shown) to determine if participant demographics changed over the 7 plus years when questionnaires were completed. The results indicated that there was no significant change in sex, age, age of MS onset, or MS disease duration over the study period (

Physical activity levels in people with MS newly applying to a provincial DMT program did not significantly increase over a 7-year period. Prior exposure to DMT vs being naive to DMT was not associated with physical activity levels in this sample. Men reported higher physically active levels than women, and there was an interaction between age and MS disease duration. Increased disease duration at younger ages was associated with lower physical activity levels. However, increased disease duration in older individuals was associated with higher activity levels. Overall, the majority of participants were not sufficiently active for substantial health benefits.

People living with MS are known to be less active than controls without MS

 and they may experience barriers to physical activity.

 A 2023 meta-analysis of baseline accelerometer or self-reported physical activity data of people with MS participating in physical activity research suggests activity levels may be improving.

 However, physical activity data from research studies may not accurately reflect real-world physical activity behavior. Of concern is a possible growing division between people already physically active for health benefits and those who are inactive at the general population level.

 Participants included in the present Saskatchewan study were not recruited for exercise research at the time they were invited to complete the GLTEQ. There was no significant sustained change in the proportion of people physically active enough for substantial health benefits from 2014 to early 2022. However, the percentage of people sufficiently active for substantial health benefits ranged from 18% in 2017 to 47% for the last 4 months of 2014. Of interest, the high point in 2014 was 1 year after the publication of the first physical activity guidelines for MS.

 In comparison, a pooled secondary analysis of earlier physical activity accelerometer data from 2005 to 2013 from research studies conducted in the Illinois area reported that, at their baseline 20% of the participants were sufficiently active for substantial health benefits.

Similar to the general population, we found men to be more physically active than women.

 In contrast, a Swedish MS registry study found that men were less physically active than women.

 The people in the registry had a mean age of 52 years (SD, ± 14.5) and men had higher disability levels and greater mobility restrictions than women. These differences likely explain the lower activity levels in men from the Swedish registry.

 In the present study from Saskatchewan, there was less discrepancy in mobility between the sexes since participants were ambulatory.

We also found interaction effects between age and disease duration on physical activity GLTEQ scores: Increased disease duration at younger ages was associated with lower activity levels. However, increased disease duration at older ages (ie, age > 54 for the HC score) was associated with higher activity levels. It is possible that older adults have more time to participate in physical activity compared with younger adults or that those with longer-lived experience with MS may prioritize physical activity. A Canadawide survey found older adults with MS to be more physically active than older adults without MS.

 Another explanation for the increased activity observed in older adults may be the limitations of the GLTEQ as a self-report measure of perceived physical exertion. The GLTEQ may be capturing change in perceived or actual physical exertion levels for the same activity into older age. The age and disease duration of participants in this Saskatchewan study remained stable over the enrollment period; therefore, changes in these demographics over time are unlikely to have influenced the observed interaction effects or the physical activity GLTEQ scores.

Riemenschneider et al suggest that an uninvestigated “window of opportunity” in the earlier stages of MS exists for physical activity research.

 Early intervention with DMT is critical to delay early disability progression in real-world settings.

 A similar window of opportunity may exist to maximize the effects of physical activity on disability outcomes by initiating exercise prior to the occurrence of irreversible degeneration.

 The 2020 physical activity guidelines for MS across the disease course recommend “early evaluation by a physical or occupational therapist or exercise or sport scientist, experienced in MS, to establish an individualized exercise and/or lifestyle physical activity plan.”

 The guidelines provide a recommendation of 150 minutes of exercise or lifestyle physical activity per week. Progress toward these targets “should be gradual, based on the person's abilities, preferences, and safety.”

 Additional advanced aerobic exercise targets are described and supported by increasing evidence for safety, feasibility, and improved functional outcomes for ambulatory people with MS.

 A large proportion of people in our sample, irrespective of their DMT exposure history, were not meeting the minimum recommendations for health benefits. Ploughman et al propose exercise as a primer for central nervous system repair, potentially critical to the success of future remyelinating drug therapies.

 Current DMT decision-making and monitoring involves contact with health care systems. People living with MS want information on exercise from health care providers.

 An unrealized opportunity for earlier support for exercise may be feasible in combination with DMT services.

This study has several limitations. Only 1 physical activity questionnaire from each participant was completed at the point in time when they first applied to the provincial MS drugs program. Future research could include repeated measures to understand how physical activity may be changing at the individual level. While data collection continued without interruption through the COVID-19 pandemic, the pandemic itself may have affected the lack of change in activity levels. The physical activity uptake when the new physical activity guidelines were published in 2020 may also have been influenced by the pandemic.

 Further follow-up of current, real-world physical activity levels is warranted. Only a small number of participants with primary progressive MS were included in this study, as DMTs for primary progressive MS were not available for the majority of the study period. First Nations people and members of the Canadian Armed forces do not use the Saskatchewan MS Drugs Program, as their health care funding falls under federal programs. These individuals, as well as people with more advanced levels of disability, were not included in the present study. Social demographic data and other factors associated with physical activity behavior are also not captured in this study. It is possible that a change in the social or racial demographics occurred over the study period among people contacting the MS drugs program. Future research analyzing physical activity levels in real-world settings should aim to include data on race, ethnicity, and social economic status.

At first contact with a provincial MS drugs program, a majority of people with MS remain insufficiently active for substantial health benefits. However, shortly after the publication of the first MS physical activity guidelines, we observed the highest percentage of people meeting criteria for activity levels sufficient for substantial health benefits. Future research could include exploring how health care systems can help support increased physical activity levels for optimal health outcomes.

Physical Activity in Multiple Sclerosis: Real-World Data From Saskatchewan, Canada

Contributing to the total economic burden of multiple sclerosis (MS) in the United States, the estimated direct medical costs of MS in 2019 were $63.3 billion, with medications accounting for over half of these expenses.

 MS disease-modifying therapy (DMT) costs can limit access, causing patients not to adhere to the medication regimen, which may lead to relapse, progression, disability, hospitalizations, and increased health care costs. Integrated health system specialty pharmacies (HSSPs) provide assistance to patients to alleviate the financial burden of specialty medications. MS center medication access specialists (MAS) obtain assistance for DMTs. This study quantifies the financial assistance obtained for patients with MS receiving medications through an integrated HSSP or infusion center.

Sarah Foidel, OTD, OTR/L, FAOTA

Articles

Latest Updated Articles