Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial.

BACKGROUND: Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings. METHODS: Participants were randomised to: 'CR plus EX', 'CR plus sham EX (EX-S)', 'EX plus sham CR (CR-S)' and 'CR-S plus EX-S' and attended 12-week intervention. All subjects performed physical/cognitive assessments at baseline, week 12 and 6 months post intervention (month 9). All MRI substudy participants underwent volumetric MRI and fMRI (Go-NoGo task). RESULTS: 104 PMS enrolled at four sites participated in the CogEx MRI substudy; 84 (81%) had valid volumetric MRI and valid fMRI. Week 12/month 9 cognitive performances did not differ among interventions; however, 25-62% of the patients showed Symbol Digit Modalities Test improvements. Normalised cortical grey matter volume (NcGMV) changes at week 12 versus baseline were heterogeneous among interventions (p=0.05); this was mainly driven by increased NcGMV in 'CR plus EX-S' (p=0.02). Groups performing CR (ie, 'CR plus EX' and 'CR plus EX-S') exhibited increased NcGMV over time, especially in the frontal (p=0.01), parietal (p=0.04) and temporal (p=0.04) lobes, while those performing CR-S exhibited NcGMV decrease (p=0.008). In CR groups, increased NcGMV (r=0.36, p=0.01) at week 12 versus baseline correlated with increased California Verbal Learning Test (CVLT)-II scores. 'CR plus EX-S' patients exhibited Go-NoGo activity increase (p<0.05, corrected) at week 12 versus baseline in bilateral insula. CONCLUSIONS: In PMS, CR modulated grey matter (GM) volume and insular activity. The association of GM and CVLT-II changes suggests GM plasticity contributes to cognitive improvements. TRIAL REGISTRATION NUMBER: NCT03679468.

Is High-Intensity Interval Training More Effective Than Moderate Continuous Training in Rehabilitation of Multiple Sclerosis: A Comprehensive Systematic Review and Meta-analysis.

OBJECTIVES: The present study aimed to conduct meta-analysis to determine whether the high intensity interval training (HIIT) protocol is more beneficial in improving outcome measures compared to moderate continuous training (MCT) in people with multiple sclerosis (PwMS). It also aimed to systematically review the exercise protocols differences. DATA SOURCES: A search strategy, locating HIIT in PwMS, was executed in six databases, PubMed, EMBASE, Web of Science, Central Cochrane, Pedro, and Ovid MEDLine. STUDY SELECTION: Randomized control trials of HIIT utilizing cycle ergometer or recumbent stepper as exercise modalities were included in analysis. Intervention arms should include at least two intervention arms, including HIIT in one arm, and MCT in the other group. DATA EXTRACTION: Data extracted from each study includes the following items: basic details of the study (such as author, date of publication, location, and study design), participant characteristics (sample size, mean age, sex, mean disease duration, and extended disability status scale), specifications of the HITT protocol (exercise modality, session duration, number of intervals/session, interval intensity, recovery intensity, recovery interval, and adverse effect), as well as primary outcomes at baseline and post-intervention (cardiorespiratory fitness, fatigue, body composition, cognitive functions, and blood biomarkers). DATA SYNTHESIS: 22 studies included in the systematic review, 11 were included in random effects model pooled analysis. There was a significant effect in favor of HIIT for VO2max of cardiorespiratory functions compared to MCT (ES=0.45 95%, CI [0.14, 0.76], P=.004), and for memory domain of cognitive functions (ES=0.34 95% CI [0.05, 0.63], P=.02). Statistical significance was not achieved for the other variables. CONCLUSION: HIIT and MCT yield similar results in terms of fatigue, body composition, cognitive functions, and blood biomarkers. However, VO2max of cardiorespiratory functions and memory domain of cognitive functions were in favor of HIIT protocol.

High-intensity interval training is feasible, credible and clinically effective in the early subacute stroke stage in the low-income country of Benin.

High-intensity interval training (HIIT) has been shown to benefit stroke patients when implemented three months post-stroke. This study examined HIIT's feasibility and clinical effectiveness in the early post-stroke stage in Benin. This was a prospective interventional study comprising an HIIT programme executed on a recumbent bike, three times/week, 20-30 min/session for 6 weeks, added to a conventional physiotherapy. The primary outcomes were feasibility, credibility and expectancy assessed with credibility and expectancy questionnaire. A maximal exercise test, 6-min walking test (6MWT), 10-m walking test (10mWT), Berg balance scale (BBS) and five repetitions sit-to-stand test (5 R-STS) were performed before and after the training programme. Ten outpatients, with a median age [P25-P75]: 63.5[56.7-71.2] years; time since stroke: 15.0[9.7-21.0] days, started and completed all training sessions without serious adverse events. High scores were observed on the Credibility subscale at admission (27.0[25.7-27.0]), which remained so after intervention (26.5[25.7-27.0]). Expectancy subscale scores were high at admission (25.5[24.0-27.0]) and post-training (25.5[24.5-27.0]). Peak workload (p < 0.001), BBS (p < 0.001), 6MWT (p < 0.001), 10mWT (p < 0.001) and 5 R-STS (p = 0.004) were all improved. HIIT is feasible and safe in the early subacute post-stroke stage and is perceived by patients as highly credible, meeting their expectations of recovery.

Intermediate outcomes for clinical trials of multiple sclerosis rehabilitation interventions: Conceptual and practical considerations.

BACKGROUND: Rehabilitation is an essential health care service and a critical component of comprehensive multiple sclerosis (MS) care. OBJECTIVE: As part of a 2-day meeting hosted by the International Advisory Committee on Clinical Trials in MS in December 2022, a panel initiated a discussion on the conceptual and practical issues related to selecting intermediate outcomes for clinical trials of MS rehabilitation interventions. RESULTS: The overarching goal of rehabilitation - optimal functioning - was acknowledged as a complex biopsychosocial phenomenon that varies with patient priorities and environmental context. This complexity means that multiple causal pathways and potential intermediate outcomes must be carefully considered during the design of clinical trials in MS rehabilitation that aim to improve functioning. In addition, practical issues must be considered such as psychometric properties of outcome measures, measure type, and characteristics of the target population, including severity of dysfunction. CONCLUSION: This article uses the International Classification of Functioning, Disability and Health as a foundation for determining relevant intermediate outcomes for clinical trials of MS rehabilitation interventions.

The MoxFo initiative - outcomes: Outcome measures in studies of exercise training in multiple sclerosis; scoping review of reviews and classification according to the ICF framework.

BACKGROUND: The number of published studies of exercise training in multiple sclerosis (MS) has grown exponentially with increasing numbers of outcomes capturing exercise effects. This has complicated the selection of relevant indicators and interpretation of intervention effects. OBJECTIVES: The Outcomes subgroup of the MoXFo initiative aimed to (1) identify outcome measures and biomarkers in studies of exercise training in MS; (2) systematically map retrieved outcomes to International Classification of Functioning, Disability and Health (ICF) categories; (3) identify gaps where relevant ICF categories have been omitted. METHODS: Electronic databases and registers were searched from 2010 to July 2020 to identify systematic reviews or meta-analyses of controlled trials of exercise training on any outcome in MS. Retrieved outcomes/biomarkers were mapped to the corresponding ICF category. RESULTS: Eighty-one review articles reporting 235 different outcomes were included. The outcomes corresponded to 15 chapters and 45 categories within the ICF. Outcomes mapped primarily to body function (30 categories) and activities and participation (9 categories) components. Few outcomes mapped to body structures (2 categories) or environmental factors (1 category). CONCLUSION: This sets the stage to develop a resource for researchers/clinicians that will aid in the selection of appropriate outcomes/biomarkers when examining exercise effects in MS.

Improving the efficiency of clinical trials in multiple sclerosis.

BACKGROUND: Phase 3 clinical trials for disease-modifying therapies in relapsing-remitting multiple sclerosis (RRMS) have utilized a limited number of conventional designs with a high degree of success. However, these designs limit the types of questions that can be addressed, and the time and cost required. Moreover, trials involving people with progressive multiple sclerosis (MS) have been less successful. OBJECTIVE: The objective of this paper is to discuss complex innovative trial designs, intermediate and composite outcomes and to improve the efficiency of trial design in MS and broaden questions that can be addressed, particularly as applied to progressive MS. METHODS: We held an international workshop with experts in clinical trial design. RESULTS: Recommendations include increasing the use of complex innovative designs, developing biomarkers to enrich progressive MS trial populations, prioritize intermediate outcomes for further development that target therapeutic mechanisms of action other than peripherally mediated inflammation, investigate acceptability to people with MS of data linkage for studying long-term outcomes of clinical trials, use Bayesian designs to potentially reduce sample sizes required for pediatric trials, and provide sustained funding for platform trials and registries that can support pragmatic trials. CONCLUSION: Novel trial designs and further development of intermediate outcomes may improve clinical trial efficiency in MS and address novel therapeutic questions.

Physiotherapy practices in acute and sub-acute stroke in a low resource country: A prospective observational study in Benin.

BACKGROUND AND OBJECTIVE: Physiotherapy is highly recommended for early recovery from stroke. This study aimed to document physiotherapy practices for people with acute and early sub-acute stroke in Benin. METHODS: In this prospective observational study, physiotherapists working with acute stroke people documented the content of their treatment from six hospitals in Benin during the first session, at 2-week, and 1-month post-stroke with a standardized physiotherapy documentation form. We used the motricity index (MI) and trunk control test (TCT) to assess impairments, and the 10-meter walk test (10mWT), functional independence measure (FIM), walking, stair climbing, and dressing upper body subscales were used for activity limitations. RESULTS: Fifteen physiotherapists (60 % male, mean±SD age=31.3±5.8 years) recorded treatment sessions for 77 stroke participants (53.2 % male, mean±SD age=57.7±12.5 years). Physiotherapists focused on conventional physiotherapy approaches, including musculoskeletal (67 % of pre-functional activity time) and neuromuscular (53 % of sitting activity time) interventions. A significant difference was found between the therapy time delivered for people with mild, moderate, and severe stroke (p < 0.001). The MI (p= 0.033) and TCT (p= 0.002) measures showed significant improvement at 2-week and 1-month (p< 0.001) post-stroke, while 10mWT, FIM walking, stair climbing, and dressing upper body items significantly increased at 1-month (p< 0.001) but not at 2-week post-stroke. CONCLUSION: Physiotherapists working with acute stroke patients in Benin mainly use conventional neuromuscular and musculoskeletal interventions. In contrast, aerobic exercises were rarely employed regardless of stroke severity. Furthermore, our findings showed that the volume of physiotherapy sessions varied by stroke severity.

Clinical perspective on pain in multiple sclerosis.

Pain is an important and frequent symptom in multiple sclerosis (MS), which leads to a low quality of life, increased disability level, and lack of employment and mental health. Recently, studies have shown increased interest in pain in MS and there is a growing evidence of its prevalence. However, the literature suffers from lack of experimental studies focusing on pain reduction. This topical review summarizes the current knowledge about pain in MS with its definitions, assessments, treatments and rehabilitation within a holistic perspective.

Application of step and beat alignment approaches and its effect on gait in progressive multiple sclerosis with severe cerebellar ataxia: A proof of concept case study.

BACKGROUND: In a case report of a progressive multiple sclerosis with cerebellar impairments, we reported that synchronisation of steps to beats was possible only at -12% of usual walking cadence during 1 minute of walking. OBJECTIVES AND METHODS: Here, we investigate the effect of synchronisation using two different alignment approaches on the patient's gait pattern over 2 minutes of walking, compared to walking in silence. RESULTS AND CONCLUSION: This proof of concept showed that the adaptive approach was successful resulting in an improved gait pattern compared to the other conditions, providing preliminary evidence to support a full-scale intervention study.

The relationship between processing speed and verbal and non-verbal new learning and memory in progressive multiple sclerosis.

OBJECTIVE: Processing speed (PS) deficits are the most common cognitive deficits in multiple sclerosis (MS), followed by learning and memory deficits, and are often an early cognitive problem. It has been argued that impaired PS is a primary consequence of MS, which in turn decreases learning. The current analysis examined the association between PS and learning in a large cohort of individuals with progressive MS. METHODS: Baseline data from a randomized clinical trial on rehabilitation taking place at 11 centers across North America and Europe were analyzed. Participants included 275 individuals with clinically definite progressive MS (primary, secondary) consented into the trial. RESULTS: Symbol Digit Modalities Test (SDMT) significantly correlated with California Verbal Learning Test-II (CVLT-II) (r = 0.21, p = 0.0003) and Brief Visuospatial Memory Test-Revised (BVMT-R) (r = 0.516, p < 0.0001). Receiver operating characteristic (ROC) analysis of the SDMT z score to distinguish between impaired and non-impaired CVLT-II performance demonstrated an area under the curve (AUC) of 0.61 (95% confidence interval (CI): 0.55-0.68) and a threshold of -1.62. ROC analysis between SDMT and BVMT-R resulted in an AUC of 0.77 (95% CI: 0.71-0.83) and threshold of -1.75 for the SDMT z score to predict impaired BVMT-R. CONCLUSION: Results indicate little ability beyond chance to predict CVLT-II from SDMT (61%), albeit statistically significant. In contrast, there was a 77% chance that the model could distinguish between impaired and non-impaired BVMT-R. Several potential explanations are discussed.

Cardiorespiratory fitness and free-living physical activity are not associated with cognition in persons with progressive multiple sclerosis: Baseline analyses from the CogEx study.

BACKGROUND: Aerobic exercise training (physical activity for improving cardiorespiratory fitness) represents a promising approach for managing cognitive impairment in multiple sclerosis (MS). However, there is limited evidence that levels of physical activity and fitness are associated with cognition in progressive MS. OBJECTIVE: We examined associations among cardiorespiratory fitness, moderate-to-vigorous physical activity (MVPA), and cognitive performance in a large, international progressive MS sample. METHODS: Two hundred forty European and North American persons with progressive MS underwent cardiorespiratory fitness measurement on a recumbent stepper, wore an ActiGraph GT3X + accelerometer for 7 days for measuring MVPA, and underwent the Brief International Cognitive Assessment in MS. RESULTS: Cardiorespiratory fitness was not significantly correlated with Symbol Digit Modalities Test (SDMT; r = -0.01; r = -0.04), California Verbal Learning Test-II (CVLT-II; r = 0.05; r = 0.05), or Brief Visuospatial Memory Test-Revised (BVMT-R; r = -0.14; r = -0.14) z-scores controlling for age, sex, and education. MVPA and SDMT (r = 0.05), CVLT-II (r = -0.07), and BVMT-R (r = 0.01) z-scores were not significantly correlated. CONCLUSION: Cardiorespiratory fitness and MVPA were not associated with cognition in this large progressive MS sample, yet these outcomes represent critical manipulation checks for documenting the success of the CogEx trial. This highlights the importance of examining other exercise-related mechanisms-of-action for improving cognition in progressive MS.

Differential effects and discriminative validity of motor and cognitive tasks varying in difficulty on cognitive-motor interference in persons with multiple sclerosis.

BACKGROUND: Cognitive-motor interference (CMI) has been well recognized in persons with multiple sclerosis (pwMS); however, there are limited data on effects of task difficulty. OBJECTIVE: Examine (1) the effects of motor and cognitive tasks varying in difficulty on the magnitude of CMI and (2) the discriminative validity of CMI between pwMS and healthy controls (HC). METHODS: Nine cognitive-motor dual-task (DT) conditions (combinations of three cognitive and three walking tasks) were examined. Outcome measures were DT-performance and dual-task cost (DTC) of gait parameters and correct answers. Task differences and overall group-effects were analysed by mixed model analysis, plus the Wilcoxon signed-rank tests or multivariate analysis of variances (MANOVAs), respectively. RESULTS: Task effects were examined in 82 pwMS (Expanded Disability Status Scale (EDSS): 3.3 ± 1.0) and discriminative validity in a subsample (35 pwMS and 33 HC). Motor-DTC and DT-performance were affected by difficulty of both the cognitive task (p < 0.001) and the walking condition (p ⩽ 0.002), while cognitive-DTC only varied between cognitive tasks with a large difference in difficulty (p ⩽ 0.005) and not between walking conditions (p ⩾ 0.125). None of the DTCs differed between groups. CONCLUSION: CMI, and especially motor performance, is affected by difficulty of the DT. Although pwMS performed worse on the tasks than HC, none of the DT-conditions showed a discriminative DTC.

Prioritizing progressive MS rehabilitation research: A call from the International Progressive MS Alliance.

BACKGROUND: People with multiple sclerosis (MS) experience myriad symptoms that negatively affect their quality of life. Despite significant progress in rehabilitation strategies for people living with relapsing-remitting MS (RRMS), the development of similar strategies for people with progressive MS has received little attention. OBJECTIVE: To highlight key symptoms of importance to people with progressive MS and stimulate the design and implementation of high-quality studies focused on symptom management and rehabilitation. METHODS: A group of international research experts, representatives from industry, and people affected by progressive MS was convened by the International Progressive MS Alliance to devise research priorities for addressing symptoms in progressive MS. RESULTS: Based on information from the MS community, we outline a rationale for highlighting four symptoms of particular interest: fatigue, mobility and upper extremity impairment, pain, and cognitive impairment. Factors such as depression, resilience, comorbidities, and psychosocial support are described, as they affect treatment efficacy. CONCLUSIONS: This coordinated call to action-to the research community to prioritize investigation of effective symptom management strategies, and to funders to support them-is an important step in addressing gaps in rehabilitation research for people affected by progressive MS.

Test-retest reliability of static and dynamic motor fatigability protocols using grip and pinch strength in typically developing children.

Upper limb motor fatigability is an important debilitating factor for activities of daily living in clinical pediatric populations. However, the reliability of fatigability protocols in these populations is currently unknown. Therefore, the current study investigates test-retest reliability of a static and dynamic motor fatigability protocol for grip and pinch strength in typically developing children (TDC). Eighty-nine TDC (35 boys, 54 girls; mean age 10 years 11 months) used a grip and pinch dynamometer for static (sustained) and dynamic (repeated) contractions during 30s. For static motor fatigability (SFI), mean (Fmean) and SD (Fvar) of force were calculated, and for dynamic motor fatigability, F mean and number of peaks (Npeaks) were calculated. Intraclass correlation coefficients (ICC) were calculated. ICCs of F mean in static and dynamic motor fatigability were high (ICC: 0.94-0.96 and 0.91-0.98). ICCs were moderate to high for F var (ICC: 0.67-0.85). The SFI showed moderate ICCs (ICC: 0.69-0.77). ICCs were moderate to high for N peaks (ICC: 0.78-0.91).Conclusion: The results suggest that static and dynamic motor fatigability in for grip and pinch can be used reliably in TD children aged 6-18 years. What is Known: •Psychometric properties of motor fatigability protocols using grip and pinch in children are lacking. •Motor fatigability in grip and pinch is an important debilitating symptom in multiple neurologic populations. What is New: •Static fatigability can be investigated using a 30-s maximum sustained grip strength protocol in children. •Dynamic fatigability can be investigated using a 30-s maximum repeated grip strength protocol in children.

Cognitive-motor Interference in Individuals With a Neurologic Disorder: A Systematic Review of Neural Correlates.

BACKGROUND: Performing a cognitive task and a motor task simultaneously is an everyday act that can lead to decreased performance on both tasks. OBJECTIVE: To provide insight into the neural correlates associated with cognitive-motor dual tasking in individuals with a neurologic disorder. METHOD: We searched the PubMed and Web of Science databases for studies that had been published up to January 16th, 2019. Studies investigating the neural correlates of cognitive-motor dual task performance in individuals with a variety of neurologic disorders were included, independently from whether the study included healthy controls. Clinical and imaging data were abstracted for the comparison between single tasks and a dual task in the individuals with a neurologic disorder and for the comparison between the healthy controls and the individuals with a neurologic disorder. RESULTS: Eighteen studies met the inclusion criteria. Study populations included individuals with Parkinson disease, multiple sclerosis, mild cognitive impairment, Alzheimer disease, traumatic brain injury, and stroke. Neuroimaging types used to study the neural correlates of cognitive-motor dual tasking during upper limb or gait tasks included fMRI, functional near-infrared spectroscopy, EEG, and PET. CONCLUSION: Despite large heterogeneity in study methodologies, some recurrent patterns were noted. Particularly, in neurologic patients, an already higher brain activation during single tasks was seen compared with healthy controls, perhaps compromising the patients' ability to further adapt brain activation with increasing load during dual tasking and resulting in reduced behavioral dual task performance.

European evidence-based recommendations for clinical assessment of upper limb in neurorehabilitation (CAULIN): data synthesis from systematic reviews, clinical practice guidelines and expert consensus.

BACKGROUND: Technology-supported rehabilitation can help alleviate the increasing need for cost-effective rehabilitation of neurological conditions, but use in clinical practice remains limited. Agreement on a core set of reliable, valid and accessible outcome measures to assess rehabilitation outcomes is needed to generate strong evidence about effectiveness of rehabilitation approaches, including technologies. This paper collates and synthesizes a core set from multiple sources; combining existing evidence, clinical practice guidelines and expert consensus into European recommendations for Clinical Assessment of Upper Limb In Neurorehabilitation (CAULIN). METHODS: Data from systematic reviews, clinical practice guidelines and expert consensus (Delphi methodology) were systematically extracted and synthesized using strength of evidence rating criteria, in addition to recommendations on assessment procedures. Three sets were defined: a core set: strong evidence for validity, reliability, responsiveness and clinical utility AND recommended by at least two sources; an extended set: strong evidence OR recommended by at least two sources and a supplementary set: some evidence OR recommended by at least one of the sources. RESULTS: In total, 12 measures (with primary focus on stroke) were included, encompassing body function and activity level of the International Classification of Functioning and Health. The core set recommended for clinical practice and research: Fugl-Meyer Assessment of Upper Extremity (FMA-UE) and Action Research Arm Test (ARAT); the extended set recommended for clinical practice and/or clinical research: kinematic measures, Box and Block Test (BBT), Chedoke Arm Hand Activity Inventory (CAHAI), Wolf Motor Function Test (WMFT), Nine Hole Peg Test (NHPT) and ABILHAND; the supplementary set recommended for research or specific occasions: Motricity Index (MI); Chedoke-McMaster Stroke Assessment (CMSA), Stroke Rehabilitation Assessment Movement (STREAM), Frenchay Arm Test (FAT), Motor Assessment Scale (MAS) and body-worn movement sensors. Assessments should be conducted at pre-defined regular intervals by trained personnel. Global measures should be applied within 24 h of hospital admission and upper limb specific measures within 1 week. CONCLUSIONS: The CAULIN recommendations for outcome measures and assessment procedures provide a clear, simple, evidence-based three-level structure for upper limb assessment in neurological rehabilitation. Widespread adoption and sustained use will improve quality of clinical practice and facilitate meta-analysis, critical for the advancement of technology-supported neurorehabilitation.

Advances in physical rehabilitation of multiple sclerosis.

PURPOSE OF REVIEW: Multiple sclerosis (MS) is a neurological disorder that heavily affects quality of life (QoL) and demands a multidisciplinary therapeutic approach. This includes multiple protocols and techniques of physical rehabilitation, ranging from conventional exercise paradigms to noninvasive brain stimulation (NIBS). Recently, studies showing the clinical efficacy of physical rehabilitation have remarkably increased, suggesting its disease-modifying potential. RECENT FINDINGS: Studies in animal models of MS have shown that physical exercise ameliorates the main disease pathological hallmarks, acting as a pro-myelinating and immunomodulatory therapy. NIBS techniques have been successfully applied to treat pain and urinary symptoms and lower limb function and spasticity, especially in combination with physical rehabilitation. Physical rehabilitation is reported to be well tolerated and effective in improving muscle function and fitness even in more disabled patients, and to enhance balance, walking and upper limb functional movements. Moreover, the dual motor--cognitive task performance can be improved by combined training protocols. SUMMARY: The literature here reviewed indicates the importance of clinical and preclinical research in addressing the impact of neurorehabilitation on MS disability, highlighting the need of further studies to reach a more comprehensive understanding of the mechanisms involved, the best combination of techniques and the proper timing of application.

Day-to-day reliability, agreement and discriminative validity of measuring walking-related performance fatigability in persons with multiple sclerosis.

BACKGROUND: Day-to-day reliability and cut-off values to detect abnormal walking fatigability (WF) remain to be investigated in persons with multiple sclerosis (pwMS). METHODS: In all, 49 pwMS (mean Expanded Disability Status Scale (EDSS) ± standard deviation (SD): 3.3 ± 1.9) and 28 matched healthy controls (HC) performed the six-minute walking test (6MWT) on two different days to determine day-to-day reliability (intraclass correlation coefficient (ICC)) and limits of agreement (LOA) for five different equations of WF. OBJECTIVE: To examine day-to-day reliability, agreement and discriminative validity for measuring WF. RESULTS AND CONCLUSION: WF expressed as the ratio between the first and sixth minute had the best day-to-day reliability (ICC's range of 0.76-0.95 and 0.60-0.86, respectively) in both pwMS and HC, while LOA were 15% and 7%, respectively. Ecological validity and clinical importance should be further investigated.

A pilot study of the effects of running training on visuospatial memory in MS: A stronger functional embedding of the hippocampus in the default-mode network?

BACKGROUND/OBJECTIVE: Endurance exercise can improve memory function in persons with multiple sclerosis (pwMS), but the effects on hippocampal functioning are currently unknown. We investigated the effects of a running intervention on memory and hippocampal functional connectivity in pwMS. METHODS/RESULTS: Memory and resting-state functional magnetic resonance imaging (fMRI) data were collected in a running intervention (n = 15) and waitlist group (n = 14). Visuospatial memory improvement was correlated to increased connectivity between the hippocampus and the default-mode network (DMN) in the intervention group only. CONCLUSION: As a result of endurance exercise, improvements in visuospatial memory may be mediated by a stronger functional embedding of the hippocampus in the DMN.

Moving exercise research in multiple sclerosis forward (the MoXFo initiative): Developing consensus statements for research.

Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleotropic effects. There is an exponential increase in the quantity of research on exercise in MS, yet a number of barriers associated with study content and quality hamper rapid progress in the field. To address these barriers and accelerate discovery, a new international partnership of MS-related experts in exercise has emerged with the goal of advancing the research agenda. As a first step, the expert panel met in May 2018 and identified the most urgent areas for moving the field forward, and discussed the framework for such a process. This led to identification of five themes, namely "Definitions and terminology," "Study methodology," "Reporting and outcomes," "Adherence to exercise," and "Mechanisms of action." Based on the identified themes, five expert groups have been formed, that will further (a) outline the challenges per theme and (b) provide recommendations for moving forward. We aim to involve and collaborate with people with MS/MS organizations (e.g. Multiple Sclerosis International Federation (MSIF) and European Multiple Sclerosis Platform (EMSP)) in all of these five themes. The generation of this thematic framework with multi-expert perspectives can bolster the quality and scope of exercise studies in MS that may ultimately improve the daily lives of people with MS.