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Clinical Significance of Gastrointestinal and Flushing Events in Patients with Multiple Sclerosis Treated with Delayed-Release Dimethyl Fumarate

From the Université Saint Joseph de Beyrouth and Hôtel-Dieu de France Hospital, Beirut, Lebanon (JC, GM); the Neurology Institute, Harley Street Medical Center, Abu Dhabi, United Arab Emirates (JM, BY); the Department of Neurology, Clinical Investigation Centre Neurosciences and Mental Health LR 18SP03, Razi University Hospital–Manouba, Tunis, Tunisia (SM); the Faculty of Medicine of Tunis, University of Tunis El Manar, Tunisia (SM); and the Department of Neurology, Centre Hospitalier de l’Université de Montréal, Montreal, Quebec, Canada (GM). 

Gabrielle Macaron; 1000 St Denis Street, Montreal, QC, Canada, H2X 0C1; email: gabrielle.macaron@umontreal.ca; gabrielle.macaron.med@ssss.gouv.qc.ca

The prevalence of multiple sclerosis (MS) is increasing in the Middle East and North Africa (MENA), in part due to better access to earlier diagnosis. Many MENA countries are now considered to fall in moderate to high MS risk zones. MS in MENA populations occurs at a younger age and is more severe, specifically in North African populations. Large disparities in MS care have been observed among MENA countries. Access to care remains a significant obstacle in countries with low incomes, active wars, and a large number of refugees. The MENA MS population could serve as participants in the evaluation of several genetic, epigenetic, and environmental risk factors for MS. Indeed, low vitamin D levels due to reduced sun exposure in hijab-wearing women might explain the striking rising prevalence in Iran after the Islamic revolution, and the prevention of MS with vitamin D could be evaluated in this community. Moreover, because immigration is part of the history of MENA populations, it can serve as an archetype for the study of the impact of immigration on MS risk and severity. Unfortunately, MENA populations are underrepresented in clinical trials, limiting our understanding of this group. However, with the creation of the Middle East and North Africa Committee for Treatment and Research in Multiple Sclerosis and the emergence of highly specialized MS centers in several countries, better access to care and collaborative research efforts are expanding.

Jad Costa, MD, reports no conflicts of interest. Joelle Massouh, MSCN, has received honoraria for lectures and advisory boards from AbbVie, Biogen, Biologix, Janssen, Lundbeck, Merck, Novartis, Roche, and Sanofi. Saloua Mrabet, MD, received a Middle East and North Africa Committee for Treatment and Research in Multiple Sclerosis clinical fellowship grant in 2020. Bassem Yamout, MD, received lecture honoraria from Bayer, Biogen, Genpharm, Genzyme, Merck-Serono, and Novartis; research grants from Bayer, Biogen, Merck-Serono, Novartis, and Pfizer; and advisory board honoraria from Bayer, Biogen, Genpharm, Genzyme, Merck-Serono, and Novartis. Gabrielle Macaron, MD, received an Innovations in Well- Being Award from the National Multiple Sclerosis Society/International Progressive Multiple Sclerosis Alliance (grant #PA-2304-41062) (2024-2025). She has been on advisory boards for Genentech-Roche, Merck/EMD Serono, and Novartis, and has participated in educational programs for Biogen, Johns Hopkins e-Literature review, MedEdge, 

Several genetic and environmental risk factors for multiple sclerosis (MS) have been identified, such as human leukocyte antigen (HLA) complex (particularly with HLA-DRB1*15:01

), reduced sun exposure and low vitamin D,

 Other environmental risk factors include smoking, obesity, diet, and microbiome.

 Although the prevalence of MS varies along a geographic gradient, MS prevalence has increased in every world region in the past 2 decades. According to the Atlas of MS data,

the global MS prevalence increased from 29.26 to 43.95 per 100,000 people between 2013 and 2020, with the highest MS prevalence recorded in North America (approximately 300 per 100,000) and European countries (142.8 per 100,000), and the lowest in Western Pacific regions (4.79 per 100,000). A rapid increase in the female-to-male ratio has also been observed over the past century, supporting an interaction of sex and environmental factors on the development of MS in women.

 Genetic, epigenetic, and environmental factor interaction is complex, but explains the differences in MS risk, phenotype, and severity across different populations. Phenotypic differences between predominant ethnic categories in the United States and Europe have been studied, but unfortunately, the Arab population of individuals with MS in the Middle East and North Africa (MENA) has received little research interest. The clinical and demographic aspects of MS in the MENA region are, therefore, less characterized. The aim of this narrative review is to highlight epidemiological and phenotypic characteristics of MS in the MENA region, discuss the main challenges in accessing care, and highlight research questions relevant to the MENA population.

Epidemiological Particularities of MS in the MENA Region 

Middle Eastern populations have heterogeneous ethnic origins mixed with Western (Anatolian, Levantine) and Eastern (Iranian, Caucasian) ancestry, with a relatively homogeneous racial background and a common Arabic language.

 It is of note that genetic differences between different populations of the same race might sometimes be greater than between different races. North Africans, natively Berbers, have received genetic contributions from their Middle Eastern, European, and sub-Saharan/African ancestry.

 The MENA region is located at a latitude of 12° to 42° and a longitude of 35° to 54°.

 Based on epidemiological studies prior to 2000, the MENA region was considered to be in the low-moderate MS prevalence zone, with rates ranging between 3 and 20 cases per 100,000 persons.

 However, consistent with the rising incidence and prevalence rates worldwide, a similar increase has been seen in the MENA region. This may be due to advances in MS diagnosis because of, among other factors, increased access to MRIs and specialized MS centers, and/or earlier diagnosis with revised diagnostic criteria, which have been validated in MENA populations.

However, aging of the general population and increased urbanization (implying less sun exposure and increased obesity, stress, and smoking) might also contribute to an increase in MS incidence.

 The most recent reported MS prevalence rates in different MENA countries are shown in the 

MS prevalence is highly variable, with the lowest rates reported in Libya (data from 1985), Oman, and Iraq, and the highest rates in Iran, with a 2017 prevalence of 148 per 100,000.

 Familial MS is particularly prevalent in Iran.

 Interestingly, the MS incidence in Iran has been steadily increasing since 1990, faster than the rise in other MENA and Western European countries.

 Lebanon has also seen increasing prevalence. In 2018, the prevalence was 62.9 per 100,000 people, placing Lebanon in the category of moderate to high risk for MS.

 Similarly, the 2019 crude prevalence rate in the West Bank of Palestine was 51.9 per 100,000, with an overall increase between 2010 and 2019.

 In Kuwait, the crude 2018 prevalence was 105 per 100,000, an increase of 1.6 times compared with 2013.

 In Saudi Arabia, the 2018 prevalence was 40.4 per 100,000, and 62 per 100,000 when accounting for Saudi nationals only.

 In Tunisia, the 2020 prevalence was 58.3 per 100,000 vs 20.2 per 100,000 in 2000.

 In Oman, the 2021 prevalence estimate was 15.9 per 100,000, significantly higher than previously reported (< 5 per 100,000).

 A similar increase was seen in Iraq (11.7 per 100,000).

 However, the latter estimates were based on hospital registries, which are less reliable than national registries. Little is known about the prevalence and incidence of MS in several Arab countries, including Algeria and Syria.

Phenotypic Particularities of MS in the MENA Region

Clinical MS onset tends to occur at an earlier age in MENA patients, most commonly 25 to 29 years of age.

 In an epidemiological meta-analysis carried out in 2015, the mean age at onset was 28.5 years, ranging from 25 years in Kuwait to 32 years in Iran and Saudi Arabia.

 Similarly, in 2020, Yamout et al reported a mean age at onset of 27.8 years across several MENA countries, with 60% manifesting before age 30 and 17% before age 20.

 In comparison, the mean age at onset in predominantly White populations from European and North American studies was 32 to 34 years of age.

An earlier age of onset in North African descendants living in France compared with White French residents was also observed.

According to the Middle East and North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) registry, the presenting symptoms were optic or spinal in two-thirds of cases. MS onset was relapsing in 96% and progressive in only 3.2% of cases.

 The clinical presentation, severity, and disability progression vary widely. In North Africa, people with MS tend to have more severe disease, more incomplete recovery after first relapse, and more rapidly progressing disability, despite earlier onset and often equal access to care when compared with European cohorts.

 This has been consistently observed in MS registries from Algeria, Tunisia, and Morocco.

 In other countries, such as Lebanon, Egypt, Kuwait, Oman, Saudi Arabia, Iran, and the United Arab Emirates, a milder phenotype is observed, comparable to the MS population in Western countries, at least based on the large MSBase registry.

 However, symptoms are reportedly more severe and time to secondary progression (SPMS) is shorter in Muslim and Druze Arabs when compared with Christian Arabs in the region. This further emphasizes the importance of genetic factors, as religion is a relatively fixed heritage in the region.30 SPMS risk seems higher in Oman, Iran, and Tunisia, according to a large (> 50,000 patients) worldwide MSBase study, even after taking into account disability, relapse rate, national prevalence, government health expenditure, and time on moderate- to high-efficacy disease-modifying therapies (DMTs).

 Of note, Canada was among the countries with the highest SPMS risk. However, there was no association between MENA ethnicities and risk of SPMS in this study. The prevalence of primary progressive MS appears to be the highest in Saudi Arabia.

 Studies addressing biologic and radiologic biomarkers of MS in the MENA region are still missing from the current literature. Serum and cerebral spinal fluid neurofilament light chains and central vein sign test results seem to be comparable to Western cohorts in 2 studies from Tunisia and Egypt.

Access to MS care, especially DMTs, varies widely across MENA countries. Between 2009 and 2018, platform injectable therapies were the most commonly used DMTs in Egypt, Iran, and Turkey (53%-86%), whereas oral DMTs and monoclonal antibodies were most commonly used in Kuwait, Lebanon, and the United Arab Emirates (59%-87%).

 Specifically, fingolimod was the most widely accessible oral DMT in almost all MENA countries.

 Access to DMTs for patients with SPMS was limited to a few countries such as Kuwait and Egypt. Consistent with the global increase in prescribing high-efficacy DMTs, a similar trend was observed across the MENA region but at a slower rate. These differences may be attributable to variabilities in gross domestic product per capita, as countries with higher income have better access to newer (and more expensive) treatments.

In addition to inequities in socioeconomic status, political unrest, wars, and refugee crises have further widened the gap among countries. The most recent data based on the Atlas of MS indicate widespread use of off-label DMTs such as azathioprine, mycophenolate mofetil, and rituximab.

 The disparities are further highlighted when considering the case of Sudan, for example, which has no access to any approved DMTs and no access to off-label, high-efficacy DMTs. In 40% of MENA countries (but no Gulf countries), new DMTs are either not registered or not fully reimbursed by governments, and the high cost of treatment is the most significant barrier to care.

 Other barriers include substantial co-payments (coverage by national health system or insurance), lack of MRI access, and paucity of MS specialists, all of which can equally impede care. Indeed, significant difficulties for consistent DMT access due to supply and reimbursement concerns were observed in 56% of MENA countries, specifically in low-income countries and those experiencing political unrest.

Displacement, which has long been an outcome of war and conflicts in the MENA region, has resulted in a sizable number of refugees in countries such as Jordan and Lebanon, posing an unparalleled burden on their health care systems. As of 2023, Lebanon, a country of 4.5 million Lebanese citizens, is hosting 1.5 million Syrians and 300,000 Palestinians refugees, 90% of whom live in extreme poverty, according to the United Nations High Commissioner of Refugees. These 2 groups make up 40% of the population, making Lebanon the country with the highest number of refugees per capita worldwide. DMT access is limited for refugees, with sporadic supply of interferons from the Syrian Ministry of Health (requiring possibly unsafe travel to Syria) and from the United Nations Relief and Works Agency for Palestine Refugees in the Near East. Host governments are also unable to carry the cost of DMTs for refugees. To improve access, key MS centers in Lebanon have secured funds from various entities to offer first-line rituximab free of charge to refugees.

 This is in a country where 61.7% of Lebanese people with MS reported an interruption in or inability to access DMTs, with a significant impact on their quality of life.

In spite of these struggles, optimism prevails with the establishment of multidisciplinary collaborative MS centers of excellence in several countries to refine MS management in the MENA region.

 Another positive step is the addition of 3 DMTs (glatiramer acetate, cladribine, rituximab) on the World Health Organization Essential Medicines List; this is a significant milestone for people with MS across the globe, but it does not necessarily imply real-world feasibility in countries with socioeconomic challenges and political instability.

Founded in 2012, MENACTRIMS aims to improve MS care and research efforts among MENA MS specialists. Its founding led to an increase in the number of specialized MS centers and a rising interest in participation in clinical trials.

 The MENACTRIMS registry, a regional MSBase substudy, was created through a collaborative effort in 2016.

 Other noteworthy endeavors include the publication of the MENACTRIMS treatment guidelines

; the development of criteria and evaluation processes for certification of MS centers; the organization of the annual MENACTRIMS congress and associated workshops and educational forums; and the availability of annual research grants, fellowship grants, and internships for physiotherapists in European MS centers. In collaboration with the International Organization of Multiple Sclerosis Nurses and the Consortium of Multiple Sclerosis Centers, annual MS certification exams for MS nurses and other MS specialists have also been offered, leading to an increased the number of certified health care providers in the MENA region.

Contemporary Topics Relevant to the MENA Region 

Vitamin D deficiency during childhood and adolescence is a risk factor for MS.

The majority of Arab countries are predominantly Muslim, and women wearing the hijab or niqab is a common practice that leads to less sun exposure and, consequently, lower vitamin D levels. This has been observed in several countries. A recent study evaluating low vitamin D levels in Palestinian young adults showed that the majority of men had sufficient/optimal levels vs only 7% of women (of whom 98% wear the hijab).

 After the Iranian revolution of 1979, all Iranian women were legally required to wear the hijab and loose-fitting clothes covering their arms and legs. Between 1989 and 2006, Iran recorded an 8.3-fold increase in the incidence of MS with an increasing female predominance.

 It is highly likely that this substantial and rapid rise may be due to genetic changes and may be linked to reduced sun exposure and associated low vitamin D levels.

 Early vitamin D repletion as a primary prevention strategy may be considered in the hijab-wearing population, but its effectiveness in reducing MS incidence requires further investigation.

The MENA population could serve as an archetype for the study of immigration and the understanding of the pathophysiological bases of MS, particularly the interplay among genetic, epigenetic, and environmental factors on MS risk and phenotype. Several environmental factors for MS are similarly observed between MENA and Western countries.

 Although results are heterogeneous across studies, it is generally accepted that immigration from high- to low-risk regions reduces MS risk if relocation occurs before individuals are 15 years of age.

 Genetic factors may also have a determining role in the occurrence and phenotype of the disease. Seyman et al evaluated MS characteristics in patients of MENA descent residing in the Canadian province of Ontario.

 These patients displayed higher disease severity and greater disability progression despite similar annualized relapse rates and new/enlarging T2 lesions over time when compared with MS patients of European descent.

 Sidhom et al compared disability progression in first- and second-generation North Africans living in France with those living in Tunisia, and with White patients born and living in France.

 Second-generation North African patients had the most severe disease despite no difference in access to care, delay in diagnosis, or use of higher efficacy DMTs.

 In fact, they were more likely to be diagnosed early and treated with high-efficacy DMTs compared with other groups, probably secondary to their more severe phenotype at disease onset. North Africans living in Tunisia had less severe disease compared with those living in France, which highlights the impact of environmental factors. These immigration studies have substantial potential to inform on the importance of epigenetics and environmental factors associated with MS pathogenesis, risk, and prognosis.

According to a large 2018 retrospective study using data from the MENACTRIMS registry, almost half of people with MS in the MENA region were treated with interferon beta. Fingolimod was the most prescribed oral DMT (14.9%), followed by dimethyl-fumarate (4.8%). Natalizumab was used in 8.5% of patients, whereas CD20-targeted therapies were used in nearly 6% of patients.

 Of note, cladribine was recently recommended as a first-line agent in the treatment of moderately to highly active disease in the MENACTRIMS 2023 consensus for treatment of relapsing-remitting MS.

 Although cladribine is a good therapeutic option in countries with poor access to infusion centers and few resources, the extent of its use in the MENA region is not sufficiently reported.

 Evidence-based data on the effectiveness and tolerability of these DMTs in the MENA population are lacking because randomized controlled trials predominantly recruit White patients, and, when enrolled in trials, patients of Lebanese, Egyptian, and other MENA ancestry are often classified as White. Indeed, the 1997 US Census defined a White person as “a person having origins in any of the original peoples of Europe, the Middle East, or North Africa.”

 Extrapolating from other studies evaluating DMT effectiveness in different groups, known racial and ethnic disparities in treatment response are observed. For instance, Black people have a poorer DMT response compared with White people. Despite similar DMT exposure, Black people had a higher risk of disability progression and more frequent treatment-related adverse events compared with White people and Hispanic people.

 The choice of DMT may also be influenced by race and ethnicity. In the above-mentioned study comparing disease severity among North Africans with MS living in France and Tunisia to that among White patients, earlier treatment with higher-efficacy DMTs did not alter the likelihood of having more severe disease in those with North African ancestry.

Recent supporting evidence points toward a decreased SPMS risk with earlier high-efficacy treatment,

hence, this approach should be considered in populations at risk for severe disease course, such as those in North Africa in particular, until better effectiveness data is available.

As MS prevalence rises in the MENA region, there is significant variability in disease severity due to disparities in access to treatment and diverse socioeconomic, genetic, and environmental factors across the region. A lack of comprehensive MS registries across all countries limits the applicability of the observed data to the MENA region as a whole. Moreover, variations in health care systems and the structure of epidemiological research across different countries may contribute to substantial confounders. It is possible, for instance, that patients with severe presentations are predominantly referred to specialized centers reporting these studies, causing a selection bias. Collaborative efforts in the region are pivotal to enhance standards of care and research to address these challenges, as well as the inclusion of patients from diverse ethnicities and races in randomized controlled trials.

Multiple Sclerosis in the Middle East and North Africa: Perspectives and Challenges

 To access the article and evaluation online, go to 

 The target audience for this activity is physicians, advanced practice clinicians, nursing professionals, social workers, rehabilitation professionals, and other health care providers involved in the management of patients with multiple sclerosis (MS).

Describe the feasibility and potential effects of dance to improve functional, psychosocial, and participation outcomes in people with MS.

Explain the limitations of current evidence for dance on functional and psychosocial outcomes in persons with MS in order to better inform patient recommendations.

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

This activity was planned by and for the health care team, and learners will receive 1.0 Interprofessional Continuing Education credit for learning and change.

 The CMSC designates this journal-based activity for a maximum of 1.0 

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

 The CMSC designates this enduring material for 1.0 contact hour of nursing continuing professional development (none in the area of pharmacology).

 This activity is awarded 1.0 CE credits.

 As a Jointly Accredited Organization, the CMSC is approved to offer social work continuing education by the Association of Social Work Boards Approved Continuing Education program. Organizations, not individual courses, are approved under this program. Regulatory boards are the final authority on courses accepted for continuing education credit. Social workers completing this course receive 1.0 general continuing education credits.

 It is the policy of the Consortium of Multiple Sclerosis Centers to mitigate all relevant financial disclosures from planners, faculty, and other persons that can affect the content of this CE activity. For this activity, all relevant disclosures have been mitigated.

, has served as physician planner for this activity. He has disclosed no relevant financial relationships. 

, has disclosed no relevant financial relationships. Authors 

Emily Davis, BA; Amy Webster, MSc; Bethany Whiteside, PhD; and Lorna Paul, PhD,

 have disclosed no relevant financial relationships.

, CMSC, and Intellisphere, LLC who are in a position to influence content have disclosed no relevant financial relationships. 

 CMSC continuing education director, has served as a planner and reviewer for this activity. She has disclosed no relevant financial relationships.

Release Date: July 1, 2023. Valid for credit through July 1, 2024.

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

(3) Complete the evaluation, which is available at 

Statements of Credit are awarded upon successful completion of the evaluation. 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 Intellisphere, LLC 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 Intellisphere, LLC.

 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.

Evidence of the benefits of dance for people with Parkinson disease is well established, but only recently has dance been investigated for people with multiple sclerosis (MS). The purpose of this review was to identify and evaluate the feasibility and effectiveness of dance interventions to improve functional, psychosocial, and participation outcomes in people with MS.

Eight databases and gray literature sources were searched from inception to March 2022. Quantitative, mixed-methods, and qualitative studies evaluating dance interventions for adults with MS were included. Included studies were critically appraised using the Mixed Methods Appraisal Tool, and results were analyzed through a parallel-results convergent synthesis.

Thirteen studies were included, with a total of 174 participants. Various dance genres were investigated, and only 1 mild adverse event was reported. Four to 12 weeks of twice-weekly, 60-minute dance sessions were feasible in those with mild to moderate relapsing-remitting MS. Positive effects were identified mainly in motor outcomes, with qualitative themes indicating psychological and social benefits.

A variety of dance interventions are likely feasible and potentially beneficial for people with mild to moderate relapsing-remitting MS, but studies were generally of low-moderate quality. High-quality studies are needed to determine the effectiveness of dance interventions for people with MS, including those with progressive forms of MS and higher levels of disability.

 The authors declare no conflicts of interest.

 Ms Davis is funded by a scholarship from the Thouron Award. Ms Webster is funded by the Multiple Sclerosis (MS) Society, UK (grant 115).

 A part of this review was presented as a poster at the Annual Conference of the International Association for Dance Medicine and Science; October 28-31, 2022; Limerick, Ireland.

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system characterized by neurodegeneration leading to a variety of symptoms and, often, disability.

 A growing number of disease-modifying therapies are available that can help reduce relapse rates and disability severity; however, disease-modifying therapies do not target the multifaceted symptoms of MS or the psychological, emotional, and social consequences of living with an unpredictable degenerative condition.

 Nonpharmacologic and lifestyle interventions are safe and effective for ameliorating common symptoms and improving quality of life for people with MS.

 Exercise training, physical activity, cognitive behavioral therapy, and mindfulness-based interventions have been shown to support physical and emotional wellness in people with MS, an identified priority among the MS community.

Extensive research evidences the benefits of exercise for a range of physical functioning outcomes,

 but there is a low rate of adequate physical activity among people with MS.

 Although a variety of personal and contextual barriers limit their exercise participation, personalized exercise suited to the needs, abilities, goals, and interests of people with MS could help to overcome these barriers.

 Mindfulness-based movement practices such as tai chi and yoga have been investigated as alternative, attractive exercise forms for people with MS that may provide physical and psychosocial benefits owing to their movement and meditative components.

 Dance is another potentially attractive form of physical activity that generally incorporates types of exercise recommended for people with MS (eg, aerobics, balance, coordination, stretching

) into an enjoyable and emotionally, socially, and artistically enriching experience.

Dance is the synchronization of movement to rhythm, most often characterized by genre, function, or context.

 Because dance can be delivered in a variety of forms across different settings and easily tailored to different abilities, it has been characterized as an accessible and adaptable activity.

 Dance interventions have been found to be equally and occasionally more effective than other exercise forms for improving a range of physical health outcomes, including musculoskeletal functions such as mobility and balance.

 Several psychosocial benefits have also been reported from dance interventions, including improvements in stress levels, depressive symptoms, and anxiety

 and positive psychological constructs such as well-being, coping strategies, and self-esteem.

Research shows that dance yields a variety of physical and psychosocial benefits in populations with other chronic neurologic conditions, such as dementia and Parkinson disease (PD).

 Dance has been especially widely investigated in the context of rehabilitation for PD,

 with several systematic reviews demonstrating the effectiveness of dance for improving motor impairments.

 Given the benefits of dance for PD and the extensive research on the benefits of exercise for MS, there has been a growing practical and research interest in the use of dance for people with MS.

 Literature reviews have been conducted on therapeutic arts for MS

 and music-based therapeutic approaches for MS

; however, to our knowledge, there has yet to be a systematic literature review concerning only dance interventions for people with MS. Therefore, the aim of this study was to systematically review the evidence on the feasibility and effectiveness of dance for improving functional, psychosocial, and participation outcomes in people with MS.

The method of this systematic review was developed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline.

 The review protocol was registered on the PROSPERO database.

Searches were performed from inception through March 2022 in MEDLINE, the Allied and Complementary Medicine Database, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science, Scopus, ProQuest Central Health & Medical Collection, and ProQuest Nursing & Allied Health Database. The search strategy was adapted for use in each database (

, available online at IJMSC.org). Key terms were built around 2 domains, dance and MS. Due to the anticipated dearth of studies in this area, the database search was complemented by a gray literature search of reference lists of included studies, Conference Proceedings Citation Index, ProQuest Dissertations & Theses Database, Science Citation Index, and Google Scholar (citation searching of included studies). Experts from organizations with publicized community-based dance for MS programs were also contacted to identify evidence that may not appear in academic databases.

Articles were included if they met the following eligibility criteria: (1) included adults with a diagnosis of MS (formal or self-report), and, if included alongside other clinical populations, data on adults with MS had to be extractable; (2) evaluated an intervention defined as dance or characterized by purposefully selected, rhythmic movement sequences

; and (3) assessed any outcome related to the body function, activity, or participation domains in the World Health Organization’s International Classification of Functioning, Disability, and Health

 or psychosocial aspects such as self-efficacy, well-being, or quality of life. There were no restrictions on the study design or publication period. Gray literature (ie, evaluation reports, unpublished studies, theses) was eligible for inclusion in line with the stance of a recent systematic review on dance for health across the life span

 to allow for all available evidence on the topic to be included.

 Studies were excluded if they were reviews or opinion articles, not full texts, or not available in English or Spanish.

All database and gray literature search results were entered into Covidence systematic review software (Version 2156; Veritas Health Innovation [available at 

 and duplicates were removed. Two independent reviewers (E.D. and A.W.) screened the titles and abstracts against the selection criteria and then screened full texts of the remaining articles for eligibility. Any disagreements were resolved through discussion among the reviewers or consultation with a third reviewer (L.P.).

Quality was assessed using the McGill University Mixed Methods Appraisal Tool (MMAT),

 which was selected to account for the heterogeneity of the study designs. Quality assessment was completed independently by 2 reviewers (E.D. and A.W.), and any disagreements were resolved through consensus in consultation with a third reviewer (L.P.). No studies were excluded based on the result of the quality assessment.

One reviewer (E.D.) extracted the relevant data from eligible studies using a standardized data extraction table. Data extracted included study details, study design, participant information, intervention characteristics, data collection methods/outcomes, and main findings. Qualitative data such as participant quotes and author interpretations were extracted as individual data.

A parallel-results convergent synthesis was conducted: quantitative and qualitative data were analyzed and presented separately, and the integration of the results occurred in the interpretation of the findings.

 The quantitative and qualitative data were analyzed using narrative synthesis following the Economic and Social Research Council Guidance on Conducting Narrative Synthesis.

 Qualitative data were further synthesized using a thematic analysis process adapted from Thomas and Harden,

 in which results were coded line-by-line according to content and meaning, and the resulting codes were organized into descriptive themes and, subsequently, analytical themes. Due to the inclusion of quasi-experimental studies and the heterogeneity of the included quantitative study designs and outcome measures, meta-analysis was not appropriate.

Through the search of the 8 selected databases, 734 studies were identified (

). After duplicates were removed, 491 studies were screened for relevance. After title and abstract screening, 462 studies were excluded. The remaining 29 studies were retrieved and screened for eligibility; 19 were excluded . An additional 5 records were identified by contacting experts (n = 4) and by citation searching via Google Scholar (n = 1). Four reports were retrieved, and 3 full texts met the eligibility criteria. In total, 13 studies were accepted for inclusion in the review. Seven studies were conducted in the United States, and the other 6 studies were conducted in Spain, Belgium, Scotland, Canada, and Brazil.

Ten of the included studies used quantitative methods: 1 was a proof-of-concept randomized controlled trial (RCT) with 3 trial arms (ie, movement-to-music, adapted yoga, waitlist control)

; 2 quasi-experimental studies compared dance with visual arts

; 3 were uncontrolled, before-and-after studies

; and 3 were descriptive studies (ie, 1 program evaluation

). Two studies used mixed methods (ie, master’s thesis

). One case study used only qualitative methods.

Across the 13 studies, 174 participants with MS were included, 81 in 1 study.

 All other studies had small sample sizes, with 4 studies each including only 1 person with MS.

 with 95% of participants having relapsing-remitting MS. Across validated and subjective measures of disability status, assessments ranged from no disability to bilateral support (score, 0-6) on the Patient-Determined Disease Steps scale

 with most participants having a mild to moderate disability. Disease duration was reported in 6 studies,

 Most studies had limited reporting of other sample characteristics (eg, ethnicity, educational level, socioeconomic status, previous dance experience).

Intervention types ranged from clinical dance therapy

 Only 2 studies implemented the same intervention type, targeted ballet training.

 Two studies investigated partnered dance styles, salsa

 Dance-based exercise was also instructed in 2 studies, Jazzercise

 Spanish dance combined with physiotherapy,

 choreography-based dancing showcased in a public performance,

 were investigated by 1 study each. Only 1 intervention was delivered remotely

; most interventions were delivered in a group in a community setting such as fitness facilities.

; the median intervention length was 10 weeks. The average session duration was 71.9 minutes, with 6 interventions delivering hour-long sessions.

 Eight interventions delivered sessions twice weekly.

 Only 1 study reported the intensity of the intervention as light to moderate exercise intensity using ratings of perceived exertion and ambulatory heart rate.

 Other studies detailed the relative intensities and purposes of the session’s components (eg, the target fitness, motor, or cognitive domain) and durations of components.

 Some studies also described the intervention’s progression, such as incorporating new dance steps

 or progressively increasing the difficulty of dance sequences over the course of the sessions.

When reported, dropouts from the dance intervention ranged from 0

Eva Havrdova, MD

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