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Abstract Exercise training represents a health behavior for the treatment and management of the multi-faceted manifestations of multiple sclerosis (MS). This paper provides a comprehensive overview of evidence from randomized controlled trials (RCTs) regarding benefits, safety, participation, and guidelines for exercise training in MS, based on systematic reviews and meta-analyses. The paper then provides our opinions based on extensive experience regarding challenges for improving and expanding future RCTs that will advance our understanding of exercise training in MS. The comprehensive review of evidence from RCTs indicates that exercise training yields substantial improvements in aerobic and muscle fitness, mobility, fatigue and depression, quality of life, and participation outcomes. There is a non-significant increase in the risk of adverse events or serious adverse events with exercise training compared with control conditions or healthy populations. Rates of adherence and compliance with exercise training (i.e., participation) approximate 80% and 70%, respectively. The current prescriptive guidelines suggest 2–3 days per week of aerobic and resistance exercise training as the minimal dose for safely benefiting from exercise training in MS. We propose 10 important topics as avenues for expanding the body of research and improving its scope for evidence-based practice in MS. Overall, the research on exercise training in MS is strong, but it can get stronger. The expansion and advancement of evidence are critical for moving exercise training into the clinical armamentarium of MS disease treatment and management.

Abstract Multiple sclerosis (MS) is a chronic neurological condition resulting in decreased aerobic capacity (peak VO2). The hemodynamic responses to peak exercise in MS are unknown. Further, it is unknown if the hemodynamic responses are due to disease or fitness. Therefore, the purpose was to compare hemodynamic response to peak exercise between individuals with and without MS, with similar peak VO2. Individuals with MS (n = 21) and CON (n = 21) underwent maximal incremental cycle exercise test to assess peak aerobic capacity (peak VO2). Heart rate, stroke volume, cardiac output, and blood pressure were obtained every other minute of the exercise test. There were no significant group differences in peak VO2. All hemodynamic variables increased similarly from baseline to peak exercise in both MS and CON. There was a significant group by time interaction for HR in individuals with MS (p

Abstract Background Major depressive disorder (MDD) is prevalent, yet sub-optimally treated among persons with multiple sclerosis (MS). We propose that exercise training may be a promising approach for treating depression in persons with MS who have MDD. Our primary hypothesis predicts a reduction in depression severity immediately after an exercise training intervention compared with minimal change in an attention control condition, and the reduction will be maintained during a follow-up period. Methods This study involves a parallel-group, assessor-blinded RCT that examines the effect of a 4-month home-based exercise training intervention on depression severity in a sample of persons with MS who have MDD based on the MINI International Neuropsychiatric Interview. The primary outcomes of depression severity are the Patient Health Questionnaire-9 and Hamilton Depression Rating Scale. Participants (N = 146) will be recruited from within 200 miles of the University of Illinois at Chicago and randomized (1:1) into either a home-based exercise training condition or control condition with concealed allocation. The exercise training and social-contact, attention control (i.e., stretching) conditions will be delivered remotely over a 4-month period and supported through eight, 1:1 Zoom-based behavioral coaching sessions guided by social-cognitive theory and conducted by persons who are uninvolved in screening, recruitment, random assignment, and outcome assessment. We will collect outcome data at 0, 4 and 8 months using treatment-blinded assessors, and data analyses will involve intent-to-treat principles. Discussion If successful, the proposed study will provide the first Class I evidence supporting a home-based exercise training program for treating MDD in persons with MS. This is critical as exercise training would likely have positive secondary effects on symptoms, cognition, and quality of life, and provide a powerful, behavioral approach for managing the many negative outcomes of MDD in MS. The program in the proposed research is accessible and scalable for broad treatment of depression in MS, and provides the potential for integration in the clinical management of MS. Trial registration The trial was registered on September 10, 2021 at clinicaltrials.gov with the identifier NCT05051618. The registration occurred before we initiated recruitment on June 2, 2023

Objective: Population-level monitoring of body composition requires accurate, biologically-relevant, yet feasible methods for estimating percent body fat (%BF). The aim of this study was to develop and cross-validate an equation for %BF from Body Mass Index (BMI), age, and sex among children with intellectual disability (ID). This study further aimed to examine the performance of an existing BMI-based equation (Deurenberg equation) for %BF in children with ID. Method: Participants were 107 children (63 boys; aged 6-15 years) with ID randomly allocated to development (n = 81) and cross-validation (n = 26) samples. Dual-Energy X-Ray Absorptiometry provided the criterion %BF. Results: The model including BMI, age, and sex (0 = male; 1 = female) had a significant goodness-of-fit in determining %BF (p

Objective: To compare physical activity (PA) levels between individuals with femoroacetabular impingement syndrome (FAIS) and uninjured controls and determine correlates of moderate to vigorous physical activity (MVPA). Design: Cross-sectional, comparative study. Setting: University laboratory. Participants: A total number of 25 individuals with FAIS (15 female; age, 31.0±9.2 years; symptom duration, 4.7±7.1 years) and 14 uninjured controls (9 female; age, 28.0±9.1 years) (N=39). Interventions: Not applicable. Main Outcome Measures: All individuals wore an accelerometer around the waist during waking hours for 7 days. We compared demographic, clinical data, and PA levels between groups using independent samples t tests and compared the proportions of those meeting the PA guideline cutoff (150min/wk) using a chi-square test. Additionally, we examined correlates of mean daily MVPA using linear regression in both groups. Results: Individuals with FAIS spent less time in MVPA (controls, 52.1±25.6min/d; FAIS, 26.9±19.1min/d; P=.001) and took fewer steps (controls, 8428±2931 steps/d; FAIS, 6449±2527 steps/d; P=.033) than uninjured controls. A lower proportion of individuals with FAIS met the PA cutoff (40.0%) compared with uninjured controls (78.6%; P=.020). Higher body mass index (BMI) values and lower (worse) Hip Disability and Osteoarthritis Outcome Score (HOOS)–Quality of Life subscale scores were associated with lower mean daily MVPA in those with FAIS (R2=21.2%, P=.021; R2=22.0%, P=.018; respectively) but not in uninjured controls. Conclusions: Individuals with FAIS spent less time in daily MVPA, took fewer daily steps, and met recommended PA guideline cutoffs at lower proportions compared with uninjured controls. Higher BMI and lower HOOS-Quality of Life scores were associated with lower mean daily MVPA. Interventions should be developed for individuals with FAIS to increase PA engagement to potentially lessen the risk of future comorbidities associated with decreased PA and increased BMI.

Background: There has been a growing interest in “Lifestyle Physical Activity” (LPA) among wheelchair users. LPA can be quantified via “pushes” as an outcome metric. This study examined the accuracy and precision of research-grade devices for counting pushes across a series of wheelchair propulsion trials. Methods: Eleven non-disabled, young adults completed 19, 1-minute wheelchair propulsion trials at self-selected speeds with a wheelchair equipped with a SMARTwheel (SW) device while being video recorded. Participants also wore 2 ActiGraph accelerometers, one on the wrist and one on the upper arm. Video footage enabled manual counting of the number of pushes (gold standard). Total pushes were averaged across 16 workloads (3 trials of repeated workloads were excluded) for each device and compared to manually counted pushes. Results: Compared to manually counted pushes, SW demonstrated the greatest accuracy (mean difference [MD] compared to video of 2.3 pushes [4.5% error]) and precision (standard deviation of the mean difference [SDMD]) compared to video of 4 pushes, (Coefficient of Variation [CV] =.04), followed by the upper arm-worn accelerometer (MD of 4.4 pushes [10.4% error] and SDMD of 10, [CV= .06]) and the wrist-worn accelerometer (MD of 12.6 pushes [27.8% error] and SDMD of 13 [CV=.15]). Conclusions: SW demonstrated greater accuracy and precision than ActiGraph accelerometers placed on the upper arm and wrist. The accelerometer placed on the upper arm was more accurate and precise than the accelerometer placed on the wrist. Future investigations should be conducted to identify the source(s) of inaccuracy among wearable push counters.

There is increasing interest in the application of neuroimaging technology in exercise neurorehabilitation research among persons with multiple sclerosis (MS). The inclusion and focus on neuroimaging outcomes in MS exercise training research is critical for establishing a biological basis for improvements in functioning and elevating exercise within the neurologist’s clinical armamentarium alongside disease modifying therapies as an approach for treating the disease and its consequences. Indeed, the inclusion of selective neuroimaging approaches and sensor-based technology among physical activity, mobility, and balance outcomes in such MS research might further allow for detecting specific links between the brain and real-world behavior. This paper provided a scoping review on the application of neuroimaging in exercise training research among persons with MS based on searches conducted in PubMed, Web of Science, and Scopus. We identified 60 studies on neuroimaging-technology-based (primarily MRI, which involved a variety of sequences and approaches) correlates of functions, based on multiple sensor-based measures, which are typically targets for exercise training trials in MS. We further identified 12 randomized controlled trials of exercise training effects on neuroimaging outcomes in MS. Overall, there was a large degree of heterogeneity whereby we could not identify definitive conclusions regarding a consistent neuroimaging biomarker of MS-related dysfunction or singular sensor-based measure, or consistent neural adaptation for exercise training in MS. Nevertheless, the present review provides a first step for better linking correlational and randomized controlled trial research for the development of high-quality exercise training studies on the brain in persons with MS, and this is timely given the substantial interest in exercise as a potential disease-modifying and/or neuroplasticity-inducing behavior in this population.

Abstract Background Cognitive dysfunction affects up to 70% of people with progressive MS (PMS). It can exert a deleterious effect on activities of daily living, employment and relationships. Preliminary evidence suggests that performance can improve with cognitive rehabilitation (CR) and aerobic exercise (EX), but existing data are predominantly from people with relapsing-remitting MS without cognitive impairment. There is therefore a need to investigate whether this is also the case in people with progressive forms of the disease who have objectively identified cognitive impairment. It is hypothesized that CR and EX are effective treatments for people with PMS who have cognitive impairment, in particular processing speed (PS) deficits, and that a combination of these two treatments is more effective than each individual treatment given alone. We further hypothesize that improvements in PS will be associated with modifications of functional and/or structural plasticity within specific brain networks/regions involved in PS measured with advanced MRI techniques. Methods This study is a multisite, randomized, double-blinded, sham controlled clinical trial of CR and aerobic exercise. Three hundred and sixty subjects from 11 sites will be randomly assigned into one of four groups: CR plus aerobic exercise; CR plus sham exercise; CR sham plus aerobic exercise and CR sham plus sham exercise. Subjects will participate in the assigned treatments for 12 weeks, twice a week. All subjects will have a cognitive and physical assessment at baseline, 12 weeks and 24 weeks. In an embedded sub-study, approximately 30% of subjects will undergo structural and functional MRI to investigate the neural mechanisms underlying the behavioral response. The primary outcome is the Symbol Digit Modalities Test (SDMT) measuring PS. Secondary outcome measures include: indices of verbal and non-verbal memory, depression, walking speed and a dual cognitive-motor task and MRI. Discussion The study is being undertaken in 6 countries (11 centres) in multiple languages (English, Italian, Danish, Dutch); with testing material validated and standardized in these languages. The rationale for this approach is to obtain a robustly powered sample size and to demonstrate that these two interventions can be given effectively in multiple countries and in different languages. Trial registration The trial was registered on September 20th 2018 at www.clinicaltrials.gov having identifier NCT03679468 . Registration was performed before recruitment was initiated.

Background: Persons with multiple sclerosis (PwMS) are at increased risk to report poor sleep patterns and lower physical activity indices. To date, data on longitudinal objectively sleep assessment is missing. In the present study, we investigated the pattern of objective sleep and subjective physical activity indices over a period of 13.5 months, under naturalistic conditions.Method: 13.5 months after their first assessment, a total of 16 PwMS (mean age = 49.13 median EDSS score: 5; 11 females) were reassessed on their objective sleep via portable sleep-electroencephalogram (EEG-) devices, along with their subjective sleep patterns (symptoms of insomnia, restless legs syndrome (RLS), and sleep-disordered breathing), physical activity indices, psychological functioning (symptoms of depression, fatigue, daytime sleepiness), and MS-related information (fatigue, EDSS; disease-modifying treatments). While the baseline assessment was performed in a rehabilitation center, the follow-up assessment took place at participants' naturalistic and familiar setting.Results: Statistically, symptoms of depression and fatigue, subjective sleep, and physical activity levels did neither increase, nor decrease over time, although descriptively, both moderate and vigorous physical activity levels decreased, and fatigue and subjective insomnia increased. Time awake after sleep onset statistically significantly decreased, while light sleep duration increased by trend.Conclusions: Among a smaller sample of PwMS, objective sleep in their naturalistic setting remained fairly stable over a mean time lapse of 13.5 months after clinic discharge. Physical activity levels descriptively decreased. The present results are of clinical and practical importance for treatment counseling: PwMS can be reassured that their sleep quality does not deteriorate, once they have left a rehabilitation center. Further, they should be encouraged to keeping their physical activity levels as stable as possible.

Objectives: This study reports on the feasibility of the SitLess with MS trial, an intervention targeting sedentary behavior in individuals with multiple sclerosis (MS). Design: Single group, pre-post intervention design. Setting: Community. Participants: Participants (N=41) with mild to moderate disability from MS. Intervention: The intervention was 15 weeks, with a 7-week follow-up, and included 2 stages: SitLess and MoveMore. During the SitLess stage, participants were encouraged to break up prolonged sitting bouts over a 7-week period, whereas the MoveMore stage promoted increased steps per day and interrupting sitting over a 7-week period. The intervention was delivered through weekly one-on-one coaching sessions via telerehabilitation and an accompanying newsletter based on social-cognitive theory. Activity was monitored throughout the program using a Fitbit. Main Outcome Measures: Process (eg, recruitment) and resource and management (eg, personnel requirements) metrics were assessed, along with efficacy outcomes (eg, effect). Progression criteria were set a priori and were related to safety, fatigue, satisfaction, and attrition. Sedentary behavior, measured using the ActivPal, was reported pre- and postintervention, as well as 7 weeks postintervention. Effect sizes (pre to post, pre to 7 weeks post) were calculated for the sedentary behavior outcomes (eg, time sitting, transitions from sitting to standing, number of long sitting bouts). Experiences with the intervention were explored through an online survey. Results: Forty-one participants enrolled, 39 of whom completed the intervention. All participants but 1 were satisfied with the experience. Pre-post intervention effect sizes for change in total sedentary time, number of transitions from sit to stand, and number of long (>30 min) sedentary bouts were 0.34, 0.02, and 0.39 respectively. All a priori progression criteria were met. Conclusions: The SitLess with MS program, a novel intervention that emphasized and facilitated sitting less and moving more, was feasible and resulted in small changes in sedentary behavior in individuals with MS.

Background: Physical activity interventions have yielded reductions in fatigue and depressive symptoms among persons with multiple sclerosis(MS) who have not been screened for elevated baseline symptoms scores. Purpose: This short communication describes a secondary analysis of data from a previous randomized controlled trial (RCT) and focused on physical activity intervention effects on fatigue and depression among persons with MS who had elevated baseline symptom scores. Method: Of the 76 persons who completed the RCT, 64(84%) had baseline fatigue severity scale(FSS) scores indicating elevated levels of fatigue(n = 30,intervention; n = 34,control), and 26(34%) had baseline hospital anxiety and depression scale, depression(HADS-D) scores indicating elevated depressive symptoms (n = 13,intervention; n = 13,control). The physical activity intervention was delivered over a 6-month period, and the control condition was a 6-month waitlist. The participants completed the FSS and HADS-D as part of baseline and follow-up battery of assessments. Results: There was a statistically significant change in FSS scores favoring the physical activity intervention, and the effect size of 0.73 was larger than reported in a previous meta-analysis of RCTs of physical activity and fatigue in MS of 0.45(95%CI=.22,.68). We observed a statistically significant change in HADS-D scores favoring the physical activity intervention, and the effect size of 1.21 was larger than reported in a previous meta-analysis of RCTs of physical activity and depression in MS of 0.36(95%CI=.18,.54). Conclusion: Such results provide preliminarily support for the application of physical activity interventions for the “treatment” of fatigue and/or depression in MS, pending subsequent confirmatory efficacy or effectiveness trials. Keywords: Physical activity, Multiple sclerosis, Depression, Fatigue

We propose a randomized controlled trial (RCT) examining the feasibility of square-stepping exercise (SSE) delivered as a home-based program for older adults with multiple sclerosis (MS). We will assess feasibility in the four domains of process, resources, management and scientific outcomes. The trial will recruit older adults (aged 60 years and older) with mild-to-moderate MS-related disability who will be randomized into intervention or attention control conditions. Participants will complete assessments before and after completion of the conditions delivered over a 12-week period. Participants in the intervention group will have biweekly meetings with an exercise trainer in the Exercise Neuroscience Research Laboratory and receive verbal and visual instruction on step patterns for the SSE program. Participants will receive a mat for home-based practice of the step patterns, an instruction manual, and a logbook and pedometer for monitoring compliance. Compliance will be further monitored through weekly scheduled Skype calls. This feasibility study will inform future phase II and III RCTs that determine the actual efficacy and effectiveness of a home-based exercise program for older adults with MS. Keywords: Exercise, Feasibility, Home-based, Multiple sclerosis, Older adults

Abstract Background Much research has been undertaken to establish the important benefits of physical activity in persons with multiple sclerosis (MS). There is disagreement regarding the strength of this research, perhaps because the majority of studies on physical activity and its benefits have not undergone initial and systematic feasibility testing. We aim to address the feasibility processes that have been examined within the context of physical activity interventions in MS. Method A systematic scoping review was conducted based on a literature search of five databases to identify feasibility processes described in preliminary studies of physical activity in MS. We read and extracted methodology from each study based on the following feasibility metrics: process (e.g. recruitment), resource (e.g. monetary costs), management (e.g. personnel time requirements) and scientific outcomes (e.g. clinical/participant reported outcome measures). We illustrate the use of the four feasibility metrics within a randomised controlled trial of a home-based exercise intervention in persons with MS. Results Twenty-five studies were identified. Resource feasibility (e.g. time and resources) and scientific outcomes feasibility (e.g. clinical outcomes) methodologies were applied and described in many studies; however, these metrics have not been systematically addressed. Metrics related to process feasibility (e.g. recruitment) and management feasibility (e.g. human and data management) are not well described within the literature. Our case study successfully enabled us to address the four feasibility metrics, and we provide new information on management feasibility (i.e. estimate data completeness and estimate data entry) and scientific outcomes feasibility (i.e. determining data collection materials appropriateness). Conclusion Our review highlights the existing research and provides a case study which assesses important metrics of study feasibility. This review serves as a clarion call for feasibility trials that will substantially strengthen the foundation of research on exercise in MS.

Abstract Background Gait impairments present while dual-tasking in older adults with multiple sclerosis (MS) have been associated with an increased risk of falls. Prior studies have examined prefrontal cortex (PFC) activity using functional near infrared spectroscopy (fNIRS) while dual-tasking in older adults with and without cognitive impairment. While the benefits of partial body weight support (PBWS) on gait have been clearly outlined in the literature, the potential use of PBWS to improve the ability to dual task in older adults with and without MS has not been examined. The aim of this study was to examine the effects of PBWS on the PFC activation while dual-tasking in older adults with and without MS. Methods Ten individuals with MS (mean 56.2 ± 5.1 yrs., 8 females) and 12 healthy older adults (HOA) (mean 63.1 ± 4.4 yrs., 9 females) participated in this study. PFC activation (i.e., oxygenated hemoglobin-HbO2) was measured using fNIRS. Assessments were done under two treadmill walking conditions: no body weight support (NBWS) and PBWS. Under each condition, participants were asked to walk at a comfortable speed (W) or walk and talk (WT). Linear mixed models were used to test for differences between cohorts, conditions, and tasks. Results HbO2 levels differed significantly between task (p

Background: Behavioral interventions based on Social Cognitive Theory (SCT) are efficacious for increasing both objectively-measured and self-reported physical activity in people with multiple sclerosis (MS). Purpose: This study involved a secondary analysis of data focused on SCT constructs as correlates of individual-level changes (i.e., response heterogeneity) following a behavioral intervention. Method: Twenty-two persons with MS who completed a 6-month SCT-based behavioral intervention for increasing physical activity were included in analyses. The intervention consisted of two primary components, namely a dedicated Internet website and one-on-one video chats with a behavioral coach. Outcomes included objectively-measured moderate-vigorous physical activity (MVPA) using Actigraph model GT3X+ accelerometers and self-reported physical activity using the Godin Leisure-Time Exercise Questionnaire (GLTEQ) as well as SCT variables of exercise self-efficacy, barriers self-efficacy, outcome expectations, goal setting and planning and facilitators/impediments. Results: There was individual variability in physical activity change following the intervention. For example, 4/22 participants demonstrated a reduction in MVPA, 1/22 participants had no change, 9/22 participants had less than 0.5 standard deviation (SD) increase in MVPA, and 8/22 participants had an increase in MVPA of more than 0.5 SD. Baseline SCT variables, particularly outcome expectations, goal setting, planning, and barriers self-efficacy, correlated with increased physical activity. Conclusions: This study indicates that SCT variables correlate with the response heterogeneity associated with physical activity behavioral interventions, and this might inform the delivery of interventions consistent with Bandura's stepwise implementation model for optimizing the “fit” of an intervention based on SCT for maximizing treatment efficacy in MS. Keywords: Behavior, Health, Multiple sclerosis, Exercise

There is abundant evidence for the benefits of physical activity (PA) among persons with multiple sclerosis, however only 20% of persons with MS engage in sufficient PA. This cross-sectional study examined features of the built environment, social environment, and individual as hierarchical correlates of PA in persons with MS from a social-cognitive theory (SCT) perspective embedded within a social-ecological model (SEM). Five hundred eighty eight persons with MS completed an online survey between September 2018–January 2019 including: demographics, Patient Determined Disease Steps (PDDS), abbreviated Neighborhood Walkability Scale (NEWS-A), Social Provisions Scale (SPS), Exercise Self-Efficacy Scale (EXSE), and Godin Leisure-Time Exercise Questionnaire (GLTEQ). Correlation analyses were used to examine associations among NEWS-A subscales, SPS, EXSE, PDDS, Employment, Education and GLTEQ. We then conducted hierarchical, linear regression analysis whereby we regressed GLTEQ with PDDS, Education, and Employment (Step 1), NEWS-A subscales (Step 2), SPS (Step 3), and EXSE (Step 4) based on a SEM. Land-use mix diversity, land-use mix access, aesthetics, crime, SPS, EXSE, and PDDS correlated with GLTEQ. PDDS was a significant correlate of GLTEQ in Step 1 (β = −0.37;R2 = 0.15). Aesthetics (β = 0.08) and PDDS (β = −0.33) were significant correlates of GLTEQ in Step 2 (R2 = 0.18). SPS (β = 0.23) and PDDS (β = −0.30) were significant correlates of GLTEQ in Step 3 (R2 = 0.23). The final model in Step 4 identified PDDS (β = −0.11), aesthetics (β = 0.07), SPS (β = 0.09), and EXSE (β = 0.54) as correlates of GLTEQ (R2 = 0.43). Such results may inform the design of multi-level interventions that target environmental and individual correlates of PA consistent with the SEM framework and guided by SCT. Keywords: Multiple sclerosis, Environment, Social environment, Self efficacy, Exercise

Background: This randomized controlled trial (RCT) will examine the efficacy of supervised functional electrical stimulation (FES) cycling on walking performance and physiological function among persons with multiple sclerosis (MS) with severe mobility disability. Methods/design: This RCT will recruit 16 persons with MS that require unilateral or bilateral assistance for ambulation (i.e., Expanded Disability Status Scale (EDSS) score = 6.0–6.5). Participants will be randomized to one of two conditions: supervised FES cycling or passive cycling. The FES cycling condition will involve mild electrical stimulation that will generate an activation pattern that results in cycling the leg ergometer. The passive cycling condition will not provide any electrical stimulation, rather the movement of the pedals will be controlled by the electrical motor. Both conditions will be delivered 3 days/week for the same duration, over 6 months. Primary outcomes will include walking performance assessed as walking speed, endurance, and agility. Secondary outcomes will include physiological function assessed as cardiorespiratory fitness, muscular strength, and balance. Assessments will take place at baseline, mid-point (3-months), and immediately following the intervention (6-months). Discussion: This study will lay the foundation for the design of a future RCT by: (1) providing effect sizes that can be included in a power analysis for optimal sample size estimation; and (2) identifying cardiorespiratory fitness, muscular strength, and balance (i.e., physiological function) as mechanisms for the beneficial effects of FES cycling on walking performance. This trial will provide important information on a novel exercise rehabilitation therapy for managing walking impairment in persons with severe MS.

Objective: Low physical activity and high sedentary behavior levels are major concerns in persons with multiple sclerosis (MS) and these differ depending on the level of mobility disability. However, the manner in which daily activity is accumulated is currently unknown in this population. Methods: A secondary analysis was performed on a combined data set of persons with MS from two previous investigations of physical activity and symptomatic or quality of life outcomes in the United States over a two year period (2007–2009). Mobility disability status was determined using the Patient Determined Disease Steps (PDDS) while activity behavior was objectively monitored using an ActiGraph accelerometer for 7 days. Results: Persons with MS who have mobility disability were involved in sedentary behavior, light and moderate intensity activity for 65%, 34% and 1% of the day, respectively compared to 60%, 37%, and 3%, respectively in those without mobility disability (p

Background: There is little known about cardiorespiratory fitness and its association with volumes of the thalamus, hippocampus, and basal ganglia in multiple sclerosis (MS). Such inquiry is important for identifying a possible behavioral approach (e.g., aerobic exercise training) that might change volumes of deep gray matter (DGM) structures associated with cognitive and motor functions in MS. Purpose: This study examined the association between cardiorespiratory fitness and volumes of the thalamus, hippocampus, and basal ganglia in MS. Method: We enrolled 35 persons with MS who underwent a maximal exercise test for measuring cardiorespiratory fitness as peak oxygen consumption (VO2peak) and brain MRI. Volumes of the thalamus, hippocampus, caudate, putamen, and pallidum were calculated from 3D T1-weighted structural brain images. We examined associations using partial (pr) correlations controlling for demographic and clinical variables. Results: VO2peak was significantly associated with composite scaled volumes of the caudate(pr = .47, p

Background: Multiple sclerosis (MS) is associated with increased risk of cardiovascular disease (CVD) and approximately 25–54% of patients report poor sleep quality. There is evidence from the general population of an association between poor sleep and increased CVD risk, but this is poorly understood in MS. Purpose: This study examined the association between self-reported sleep quality and arterial health in persons with MS. Methods: MS subjects (n = 31) and control subjects (n = 23) were recruited. Control subjects were age and body size matched. All subjects were administered the Pittsburgh Sleep Quality Index (PSQI) to assess self-reported sleep quality. Subjects with a global score >5 were classified as “poor sleepers”. Blood pressure, arterial stiffness, and the forearm blood flow responses following 5-min ischemic occlusion (endothelial function) were measured. Results: Nineteen MS subjects and 5 control subjects were classified as “poor sleepers”. AIx was significantly higher in MS subjects who had poor sleep quality (32.5 ± 8.8 vs 22.0 ± 13.2; P < 0.05). Conclusions: Markers of arterial dysfunction were significantly higher in MS subjects with poor sleep quality compared to those with good sleep quality. This study suggests novel evidence for the association of CVD risk and sleep quality in MS.

Objectives: Cardiovascular disease is a leading cause of death in multiple sclerosis (MS), and recent data showed that subclinical markers of atherosclerosis are higher in MS as well. Prevalence of MS in men is much lower than in women, but their prognosis is much worse. Men with MS also have higher rates of hypertension and diabetes than women with MS. Whether vascular function and structure differs in men than in women with MS, and whether potential sex differences are similar to those in healthy controls, is unknown. Aim: To compare vascular function and structure between men and women in a group with MS and in healthy controls. Methods: After a 10 minute rest in the supine position, resting heart rate (HR) and brachial blood pressure (BP) were collected. Augmentation index (AIX), HR normalized AIX (AIX@HR75) and pulse wave velocity were measured with applanation tonometry. Carotid intima-media thickness (IMT) and beta-stiffness were measured with carotid ultrasound, and Forearm Blood Flow (Baseline, Peak and Area Under the Curve) was measured with strain gauge plethysmography. Data were analyzed with a two-way independent ANOVA for factors group, sex and group*sex. Results: In both groups, men were taller and heavier than the women, had higher SBP, lower AIX and AIX@HR75, larger IMT and higher baseline and peak FBF. Different patterns were observed in the sex differences for AIX and AIX@HR75 (in women similar in MS and controls, in men higher in MS than in controls). Conclusions: People with MS demonstrate a vascular profile consistent with a higher cardiovascular risk compared to controls. Sex differences were similar in subjects with and without MS, except for the significantly higher AIX and AIX@HR75 in men with MS vs male controls, suggesting males with MS may be particularly at risk for cardiovascular disease. Control MS p-values factors # Female (n=21) Male (n=18) Female (n=52) Male (n=18) Group Sex Inter-action Age 49 ± 10 41 ± 9 48 ± 12 48 ± 13 0.228 0.126 0.109 Height (cm) 164 ± 6 177 ± 5 163 ± 7 179 ± 6 0.867

Introduction: Peak prevalence of multiple sclerosis (MS) is approaching 60 years of age, suggesting an aging patient population compared to past reports. Aging is independently associated with increased cardiovascular disease risk. Additionally, arterial function is compromised with aging. Carotid artery stiffness serves as a non-invasive method to quantify aspects of arterial function. As MS patients increase their average lifespan, it is unclear if they may experience differential changes in aspects of carotid artery function compared to their healthy age-matched peers. Objective: To compare carotid artery structure and function between young and older subjects with and without MS. Methods: After 10 minutes of supine rest, 120 subjects (MS=89, Control=31) underwent applanation tonometry and ultrasonography of the carotid artery. Subjects were classified as young or older (

Background. Little is known about physical activity and its association with volumes of whole brain gray matter and white matter and deep gray matter structures in persons with multiple sclerosis (MS). Purpose. This study examined the association between levels of physical activity and brain volumetric measures from magnetic resonance imaging (MRI) in MS. Method. 39 persons with MS wore an accelerometer for a 7-day period and underwent a brain MRI. Normalized GM volume (NGMV), normalized WM volume (NWMV), and deep GM structures were calculated from 3D T1-weighted structural brain images. We conducted partial correlations (pr) controlling for demographic and clinical variables. Results. Moderate-to-vigorous physical activity (MVPA) was significantly associated with NGMV (pr=0.370, p

The accumulation of excess body weight may have important health and disease consequences for persons with multiple sclerosis (MS). This study examined the effect of weight status on mobility using a comprehensive set of mobility outcomes including ambulatory performance (timed 25-foot walk, T25FW; 6-minute walk, 6MW; oxygen cost of walking, Cw; spatiotemporal parameters of gait; self-reported walking impairment, Multiple Sclerosis Walking Scale-12 (MSWS-12); and free-living activity, accelerometry) in 168 ambulatory persons with MS. Mean (SD) BMI was 27.7 (5.1) kg/m2. Of the 168 participants, 31.0% were classified as normal weight (BMI = 18.5–24.9 kg/m2), 36.3% were classified as overweight (BMI = 25.0–29.9 kg/m2), and 32.7% were classified as obese, classes I and II (BMI = 30–39.9 kg/m2). There were no significant differences among BMI groups on T25FW and 6MW, Cw, spatiotemporal gait parameters, MSWS-12, or daily step and movement counts. The prevalence of overweight and obesity in this sample was almost 70%, but there was not a consistent nor significant impact of BMI on outcomes of mobility. The lack of an effect of weight status on mobility emphasizes the need to focus on and identify other factors which may be important targets of ambulatory performance in persons with MS.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease with both clinical and pathological heterogeneity. The complexity of the MS population has offered challenges to the measurement of MS disease progression in therapeutic trials. The current standard clinical outcome measures are relapse rate, Expanded Disability Severity Scale (EDSS), and the MS Functional Composite (MSFC). These measures each have strengths and some weakness. Two additional measures, the six-minute walk and accelerometry, show promise in augmenting current measures. MS therapeutics is a quickly advancing field which requires sensitive clinical outcome measures that can detect small changes in disability that reliably reflect long-term changes in sustained disease progression in a complex population. A single clinical outcome measure of sustained disease progression may remain elusive. Rather, an integration of current and new outcome measures may be most appropriate and utilization of different measures depending on the MS population and stage of the disease may be preferred.

It is recommended that researchers who use mixed modal methods for data collection compare their impact on outcome measures. The purpose of this study was to examine the physical activity and fruit/vegetable consumption behaviors of a multiethnic sample of adults, comparing participants who continued a telephone survey and those who transitioned from a telephone to a web-based survey for a follow-up data collection point. This longitudinal study used a random sample of 700 Hawaii residents (63.3% Female; Mean age=47, SD=17.1). At baseline, participants completed a computer-assisted telephone interview assessing the stage, behavior, and decisional balance of both physical activity and fruit/vegetable consumption. For the three-month follow-up survey, participants were given the option of completing the survey either on the web or by phone. Repeated measures analysis of variance (ANOVA) was computed for related physical activity scales and fruit/vegetable consumption variables to compare the change in response across time between a web group and phone group. For both physical activity and fruit/vegetable consumption, all mode-by-time interactions were significant. The participants who preferred the telephone survey maintained their levels, whereas those who preferred the web survey reported a decrease in each variable. These results suggest that changing the mode of a survey may introduce a systematic bias in data and that researchers should proceed with caution when using mixed modes of data collection.