Rationale and design of a randomized controlled clinical trial of functional electrical stimulation cycling in persons with severe multiple sclerosis

AbstractBackgroundThis 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/designThis 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).DiscussionThis 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

Associations of functional connectivity and walking performance in multiple sclerosis

Background Persons with multiple sclerosis (MS) often demonstrate impaired walking performance, and neuroimaging methods such as resting state functional connectivity (RSFC) may support a link between central nervous system damage and disruptions in walking. Objectives This study examined associations between RSFC in cortical networks and walking performance in persons with MS. Methods 29 persons with MS underwent 3-T brain magnetic resonance imaging (MRI) and we computed RSFC among 68 Gy matter regions of interest in the brain. Participants completed the Timed 25-foot Walk as a measure of walking performance. We examined associations using partial Pearson product-moment correlation analyses (r), controlling for age. Results There were eight cortical brain regions that were significantly associated with the T25FW, including the left parahippocampal gyrus and transverse temporal gyrus, and the right fusiform gyrus, inferior temporal gyrus, lingual gyrus, pericalcarine cortex, superior temporal gyrus, and transverse temporal gyrus. Conclusions We provide novel evidence that RSFC can be a valuable tool to monitor the motor and non-motor networks impacted in MS that relate to declines in motor impairment. RSFC may identify critical nodes involved in a range of motor tasks such as walking that can be more sensitive to disruption by MS

Objectively Measured Physical Activity Is Associated with Brain Volumetric Measurements in Multiple Sclerosis

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<0.05), NWMV (pr=0.433, p<0.01), hippocampus (pr=0.499, p<0.01), thalamus (pr=0.380, p<0.05), caudate (pr=0.539, p<0.01), putamen (pr=0.369, p<0.05), and pallidum (pr=0.498, p<0.01) volumes, when controlling for sex, age, clinical course of MS, and Expanded Disability Status Scale score. There were no associations between sedentary and light physical activity with MRI outcomes. Conclusion. Our results provide the first evidence that MVPA is associated with volumes of whole brain GM and WM and deep GM structures that are involved in motor and cognitive functions in MS

Primary Results of a Phase-III, Randomized Controlled Trial of the Behavioral Intervention for Increasing Physical Activity in Multiple Sclerosis Project

Background We undertook a phase-III, randomized controlled trial (RCT) that examined the effectiveness of a behavioral intervention based on social cognitive theory (SCT) and delivered through the Internet using e-learning approaches for immediate and sustained increases in physical activity among persons with multiple sclerosis (MS). Method The study followed a parallel group RCT design. Persons with MS (N = 318) were randomized into either behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions. The conditions were administered over a 6-month period by persons who were uninvolved in screening, recruitment, random assignment, and outcome assessment. There was a 6-month follow-up period without access of conditions. We collected outcome data every 6 months over the 12-month period. The primary outcome was device-measured minutes/day of moderate-to-vigorous physical activity (MVPA). The data analysis involved a modified intent-to-treat approach (i.e. those who received the allocated conditions) using a linear mixed model. Results There was a significant group by time interaction on the primary outcome of device-measured minutes/day of MVPA (p \u3c 0.005). MVPA was increased immediately after the 6-month period in the behavioral intervention compared with control, and this difference was sustained over the 6-month follow-up. Conclusion This study provides evidence for the effectiveness of a widely scalable approach for increasing MVPA in persons with MS

Clinical Study Oxygen Cost of Walking in Persons with Multiple Sclerosis: Disability Matters, but Why?

Background. The oxygen cost (O 2 cost) of walking is elevated in persons with MS, particularly as a function of increasing disability status. Objective. The current study examined symptomatic (i.e., fatigue, pain, anxiety, and depression) and gait (i.e., velocity, cadence, and step length) variables that might explain why disability status is associated with O 2 cost of walking in persons with MS. Materials and Methods. 82 participants completed the Patient-Determined Disease Steps, Fatigue Severity Scale, McGill Pain Questionnaire, and Hospital Anxiety and Depression Scale and undertook 2 trials of walking on a GAITRite electronic walkway. Participants then completed a six-minute walk test with concurrent assessment of expired gases for quantifying oxygen consumption and O 2 cost of walking. Results. Disability ( = 0.55) as well as fatigue ( = 0.22), gait velocity ( = −0.62), cadence ( = −0.73), and step length ( = −0.53) were associated with the O 2 cost of walking. Cadence ( = −0.67), but not step length ( = −0.14) or fatigue ( = −0.10), explained the association between disability and the O 2 cost of walking. Conclusions. These results highlight cadence as a target of rehabilitation for increasing metabolic efficiency during walking among those with MS, particularly as a function of worsening disability

Phase-III, Randomized Controlled Trial of the Behavioral Intervention for Increasing Physical Activity in Multiple Sclerosis: Project BIPAMS

Background We propose a phase-III, randomized controlled trial (RCT) that examines the effectiveness of a behavioral intervention based on social cognitive theory (SCT) and delivered through the Internet using e-learning approaches for increasing physical activity and secondary outcomes (e.g., symptoms) in a large sample of people with multiple sclerosis (MS) residing throughout the United States. Methods/design The proposed phase-III trial will use a parallel group, RCT design that examines the effect of a 6-month behavioral intervention for increasing physical activity and secondarily improving mobility, cognition, symptoms, and quality of life (QOL) in persons with MS. The primary outcome is accelerometer-measured moderate-to-vigorous physical activity (MVPA). The secondary outcomes include self-report measures of physical activity, walking impairment, cognition, fatigue, depression, anxiety, pain, sleep quality, and QOL. The tertiary outcomes are mediator variables based on SCT. Participants (N = 280) will be randomized into behavioral intervention (n = 140) or attention and social contact control (n = 140) conditions using computerized random numbers with concealed allocation. The conditions will be administered over 6-months by persons who are uninvolved in screening, recruitment, random assignment, and outcome assessment. There will be a 6-month follow-up without intervention access/content. We will collect primary, secondary, and tertiary outcome data every 6 months over the 12-month period. Data analysis will involve intent-to-treat principles and latent growth modeling (LGM). Discussion The proposed research will provide evidence for the effectiveness of a novel, widely scalable approach for increasing lifestyle physical activity and improving secondary outcomes and QOL in persons with MS

Cardiorespiratory Demand of Acute Voluntary Cycling with Functional Electrical Stimulation in Individuals with Multiple Sclerosis with Severe Mobility Impairment

Background: Exercise training is one strategy for improving cardiorespiratory fitness (CRF) in multiple sclerosis (MS), however, few modalities are accessible for those with severe mobility impairment. Functional electrical stimulation (FES) cycling is one adapted exercise modality with the potential for improving CRF in people with severe MS. Objectives: To characterize the cardiorespiratory response of acute voluntary cycling with FES in people with MS with severe mobility impairment, and to compare this response to passive leg cycling. Methods: Eleven participants with MS that required assistance for ambulation completed a single bout of voluntary cycling with FES or passive leg cycling. Oxygen consumption (VO2), heart rate (HR), work rate (WR), and ratings of perceived exertion (RPE) were recorded throughout the session. Results: For the FES group, mean exercising VO2 was 8.7±1.8ml/kg/min, or 63.5% of VO2peak. Mean HR was 102±9.7 bpm, approximately 76.4% of HRpeak. Mean WR was 27.0±9.2 W, or 57.3% of WRpeak, and median RPE was 13.5 (IQR=5.5). Active cycling with FES was significantly (pThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

A continuum of languishing to flourishing: exploring experiences of psychological resilience in multiple sclerosis family caregivers

Purpose Resilience research in family caregiving in chronic neurological conditions is growing, but multiple sclerosis (MS) caregivers are noticeably absent from this body of work. MS caregivers represent a unique population due to the disease’s early onset, prolonged life expectancy, and heterogeneity. As such, this study aimed to explore MS caregivers’ conceptualizations of resilience, examine MS caregivers’ experiences of resilience development, and determine which assets and resources influence resilience in this role. Methods Twenty-four Canadian MS caregivers were recruited. Semi-structured in-depth interviews were conducted with questions derived from an ecological resilience framework. Data were analysed using reflexive thematic analysis. Results Themes constructed a cyclical resilience model, beginning with encounters with hardship and extending to thriving adjustment. Subthemes included reports of additive challenges, impactful individual and community resources, and multi-level adaptive pathways. Within this cycle, the achievement of healthy adjustment exerted a positive feedback function and informed future responses to lifelong challenges. Conclusions Despite the salience of resilience processes within caregiver testimonies, inadequate resources at societal levels were evident. These findings afford researchers and decision-makers relevant information for designing and implementing resilience-building interventions for MS caregivers that attend to contextual factors and current systemic support deficiencies