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Background: Although aerobic training (AT) and resistance training (RT) are recommended after stroke, the optimal dosage of these interventions and their effectiveness on balance, walking capacity, and quality of life (QoL) remain conflicting.Objective: Our study aimed to quantify the effects of different modes, dosages and settings of exercise therapy on balance, walking capacity, and QoL in stroke survivors.Methods: PubMed, CINHAL, and Hinari databases were searched for randomised controlled trials (RCTs) evaluating the effects of AT and RT on balance, walking, and QoL in stroke survivors. The treatment effect was computed by the standard mean differences (SMDs).Results: Twenty-eight trials (n = 1571 participants) were included. Aerobic training and RT interventions were ineffective on balance. Aerobic training interventions were the most effective in improving walking capacity (SMD = 0.37 [0.02, 0.71], p = 0.04). For walking, capacity, a higher dosage (duration ≥ 120 min/week; intensity ≥ 60% heart rate reserve) of AT interventions demonstrated a significantly greater effect (SMD = 0.58 [0.12, 1.04], p = 0.01). Combined AT and RT improved QoL (SMD = 0.56 [0.12, 0.98], p = 0.01). Hospital located rehabilitation setting was effective for improving walking capacity (SMD = 0.57 [0.06, 1.09], p = 0.03) compared with home and/or community and laboratory settings.Conclusions: Our findings showed that neither AT nor RT have a significant effect on balance. However, AT executed in hospital-located settings with a higher dose is a more effective strategy to facilitate walking capacity in chronic stroke. In contrast, combined AT and RT is beneficial for improving QoL.Clinical implications: A high dosage of aerobic exercise, duration ≥ 120 min/week; intensity ≥ 60% heart rate reserve is beneficial for improving walking capacity.

Objective The purpose of this study was to examine the evidence of the efficacy of rehabilitation approaches for improving severe upper limb impairments and disability during acute and early subacute stroke, taking into consideration the dosage of therapy. Methods Randomized controlled trials from PubMed, Web of Science, and Scopus databases were searched by 2 independent researchers. Studies were selected if they involved active rehabilitation interventions that were conducted in the acute stage (7 days–3 months after stroke), with the aim of improving severe upper limb motor impairments and disability. Data were extracted on the basis of the type and effect of rehabilitation interventions and on the dosage (duration, frequency, session length, episode difficulty, and intensity). Study quality was assessed using the Physiotherapy Evidence Database Scale. Results Twenty-three studies (1271 participants) with fair to good methodological quality were included. Only 3 studies were performed in the acute stage. Regardless of the type of intervention, upper limb rehabilitation was found to be beneficial for severe upper limb impairments and disability. Robotic therapy and functional electrical stimulation were identified as the most popular upper limb interventions; however, only a limited number of studies showed their superiority over a dose-matched control intervention for severe upper limb impairments in the subacute stage. A longer rehabilitation session length ( Conclusion Different rehabilitation approaches seem to improve severe upper limb impairments and disability in the subacute stage after stroke; however, they are not distinctly superior to standard care or other interventions provided at the same dosage. Impact Robotic therapy and functional electrical stimulation add variety to rehabilitation programs, but their benefit has not been shown to exceed that of standard care. Further research is necessary to identify the impact of dosage parameters (eg, intensity) on severe upper limb motor impairments and function, especially in the acute stage.

Motor sequence learning in persons with multiple sclerosis (pwMS) and healthy controls (HC) under implicit or explicit learning conditions has not yet been investigated in a stepping task. Given the prevalent cognitive and mobility impairments in pwMS, this is important in order to understand motor learning processes and optimize rehabilitation strategies. Nineteen pwMS (the Expanded Disability Status Scale = 3.4 ± 1.2) and 18 HC performed a modified serial reaction time task by stepping as fast as possible on a stepping tile when it lit up, either with (explicit) or without (implicit) knowledge of the presence of a sequence beforehand. Motor sequence learning was studied by examining response time changes and differences between sequence and random blocks during the learning session (acquisition), 24 h later (retention), and in three dual-task (DT) conditions at baseline and retention (automaticity) using subtracting sevens, verbal fluency, and vigilance as concurrent cognitive DTs. Response times improved and were lower for the sequenced compared with the random blocks at the post- and retention tests (P's < 0.001). Response times during DT conditions improved after learning, but DT cost improved only for the subtracting sevens DT condition. No differences in learning were observed between learning conditions or groups. This study showed motor sequence learning, by acquisition and retention, in a stepping task in pwMS with motor impairments, to a similar degree as HC and regardless of learning conditions. Whether automaticity increased remains unclear.

BACKGROUND: Persons with Multiple Sclerosis (pwMS) frequently experience walking difficulties, often expressed as a slower walking speed during the 6 Minute Walking Test (6MWT). In addition, slower walking speeds are also related to higher levels of perceived exertion. PwMS are also known to have a higher energetic Cost of walking (Cw) and may experience muscle fatigue during prolonged walking. In this study, we aimed to explore changes in Rate of Perceived Exertion (RPE) and the Cw within participants during the 6MWT in pwMS. Additionally, concomitant changes in the mean and variability of gait characteristics and changes in muscle activation describing muscle fatigue were assessed.METHODS: The 6MWT was performed on an instrumented treadmill while three-dimensional motion capture and gas exchange were measured continuously. RPE on the 6-20 borg-scale was questioned directly before and after the 6MWT. Cost of walking was expressed in Joules/kg/m. Muscle fatigue was assessed by increases in Root Median Square (RMdS) and decreases in Median Frequency (MF) of the recorded EMGs. Wilcoxon-Signed Rank test was used to assess a difference in RPE before and after the 6MWT. Linear mixed models, while controlling for walking speed, were used to assess changes in Cw, mean and variability of gait characteristics and RMdS and MF of muscle activation.RESULTS: 28 pwMS (23 females, mean ± standard deviation age 46 ± 10 years, height 1.69 ± 0.08 meter, weight 76 ± 18 kilogram, EDSS 2.7 ± 1.3) were included. Although the RPE increased from 8 to 12, no changes in Cw were found. Walking speed was the only spatiotemporal parameter which increased during the 6MWT and RMdS of the gastrocnemius and tibialis anterior muscles increased. The soleus muscle decreased in MF over time.CONCLUSION: The increases in RPE and walking speed was not accompanied by a change in Cw during the 6MWT which indicates that the perceived exertion was not accompanied by an increased physical exertion. Changes in muscle activation might give an indication for muscle fatigue but were inconclusive. Although the 6MWT reflects daily life walking challenges for pwMS, this test did not show the expected changes in gait parameters in our sample.

BACKGROUND: Frontal cortico-subcortical dysfunction may contribute to fatigue and dual-task impairment of walking and cognition in progressive multiple sclerosis (PMS).PURPOSE: To explore the associations among fatigue, dual-task performance and structural and functional abnormalities of frontal cortico-subcortical network in PMS.METHODS: Brain 3 T structural and functional MRI sequences, Modified Fatigue Impact Scale (MFIS), dual-task motor and cognitive performances were obtained from 57 PMS patients and 10 healthy controls (HC). The associations of thalamic, caudate nucleus and dorsolateral prefrontal cortex (DLPFC) atrophy, microstructural abnormalities of their connections and their resting state effective connectivity (RS-EC) with fatigue and dual-task performance were investigated using random forest.RESULTS: Thirty-seven PMS patients were fatigued (F) (MFIS ≥ 38). Compared to HC, non-fatigued (nF) and F-PMS patients had significantly worse dual-task performance (p ≤ 0.002). Predictors of fatigue (out-of-bag [OOB]-accuracy = 0.754) and its severity (OOB-R2 = 0.247) were higher Expanded Disability Status scale (EDSS) score, lower RS-EC from left-caudate nucleus to left-DLPFC, lower fractional anisotropy between left-caudate nucleus and left-thalamus, higher mean diffusivity between right-caudate nucleus and right-thalamus, and longer disease duration. Microstructural abnormalities in connections among thalami, caudate nuclei and DLPFC, mainly left-lateralized in nF-PMS and more bilateral in F-PMS, higher RS-EC from left-DLPFC to right-DLPFC in nF-PMS and lower RS-EC from left-caudate nucleus to left-DLPFC in F-PMS, higher EDSS score, higher WM lesion volume, and lower cortical volume predicted worse dual-task performances (OOB-R2 from 0.426 to 0.530).CONCLUSIONS: In PMS, structural and functional frontal cortico-subcortical abnormalities contribute to fatigue and worse dual-task performance, with different patterns according to the presence of fatigue.

ObjectiveThe purpose of this study was to investigate the test–retest reliability, measurement error, and interpretability of new motor fatigability outcomes of grip and pinch strength for children with unilateral cerebral palsy (UCP).MethodsMotor fatigability during grip and pinch strength was measured twice (within 48 hours) in both hands of 50 children (mean age = 11 years 2 months; 14, 31, and 5 children with Manual Ability Classification System levels I, II, and III, respectively) using a 30-second static and dynamic maximum exertion protocol. For static motor fatigability, the Static Fatigue Index (SFI) and mean force (Fmean) in the first (Fmean1) and last (Fmean3) 10 seconds were calculated. For dynamic motor fatigability, Fmean1, Fmean3, and the number of peaks in the first and last 10 seconds were calculated.ResultsFor static motor fatigability, the intraclass correlation coefficients (ICCs) were moderate to high for Fmean1 and Fmean3 (0.56–0.88), and the SFI showed low to moderate reliability (ICC = 0.32–0.72). For dynamic motor fatigability, the ICCs were moderate to high for all outcomes (0.54–0.91). The standard error of measurement agreement and the smallest detectable difference agreement were large in all outcomes, except for the SFI in static motor fatigability. Details per age group are provided. In general, younger children (6–11 years old) showed lower reliability than older children (12–18 years old).ConclusionMost outcome measures for static and dynamic motor fatigability of grip and pinch strength show moderate to high reliability in children with UCP, indicating that these tests can be used reliably to investigate the presence of motor fatigability in UCP, especially in older children. Standard error of measurement agreement and smallest detectable difference agreement indicated that these outcome measures should be interpreted with caution when evaluating change.ImpactMost of the proposed outcome measures for static and dynamic motor fatigability of grip and pinch are reliable in children with UCP and can be used for discriminative purposes.

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 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.

Fatigue and walking difficulties are common impairments and activity limitations in persons with multiple sclerosis (PwMS). Walking fatigability (WF) can be measured by a Distance Walked Index and is defined as a decline in walking distance of 10% or more during the six-minute walking test (6MWT). However, the clinical manifestation and perceived symptoms related to fatigability are still not well documented. Forty-nine PwMS [Expanded Disability Status Scale (EDSS)

Given the prevalence of motor and cognitive functions in persons with multiple sclerosis (PwMS), we proposed that the theoretical framework of embodiment could provide a rehabilitation avenue to train these functions as one functional unit. PwMS (n = 31) and age- and gender-matched healthy controls (n = 30) underwent an embodied learning protocol. This involved learning a cognitive sequence while performing it through bodily stepping movement under three feedback conditions (melody, sound, and visual). Cognitive and movement performance was assessed by a delayed recall 15 min after undergoing the embodied learning protocol. Half of participants correctly recalled the sequence in all three conditions, while 70% of healthy controls achieved correct recall within the melody condition. Balance impairment predicted the speed of executing the sequence irrespective of learning, most apparent in the melody condition. Information processing speed predicted the speed of executing the sequence in the melody and sound conditions between participants as well as over time. Those who learned performed the sequence faster in the melody condition only and overall were faster over time. We propose how embodied learning could expand the current context of rehabilitation of cognitive and motor control in PwMS.

Introduction One of the most common and life-altering consequences of Multiple Sclerosis (MS) is walking impairment. The distance, speed, and Gait pattern functions are components of the International Classification of Functioning, Disability, and Health (ICF) and are also predictors of dependency in terms of daily living activities in patients with MS (pwMS). Areas covered This article provides an overview of walking impairment in pwMS, with focus on the assessment of gait and the rehabilitation approaches. Expert opinion The authors recommend that pwMS undergo gait assessment integrating the ICF perspective using validated clinical outcome measures that cover spatiotemporal gait parameters. Moreover, assessment of walking speed with short walking capacity tests such as the timed 25-foot walk (T25FW) or the 10-m walk test (10 MWT) and tests for walking distance with middle distance tests such as the 2-min walk test (2MWT) and the 6-min walk test (6MWT). This review further highlights strategies that may restore walking function including pharmacological symptomatic treatment and non-pharmacological rehabilitation approaches such as exercise and task-specific training providing an appraisal of mobility targeted therapies to be considered when planning multidisciplinary comprehensive-care of pwMS. Finally, new and novel strategies such as motor imagery and rhythmic auditory stimulation have been developed to improve walking speed and distance in pwMS.

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.

Background. In the general population, trajectories of walking capacity is accelerated and nonlinear with advanced age. Whether this is more pronounced in persons with multiple sclerosis (pwMS), along with the prevalence of dismobility (ie, slow gait speed), are currently unknown. Our objective was to investigate trajectories of walking capacity and prevalence of dismobility across the adult life span in pwMS versus healthy controls (HC). Methods. Data on maximal timed 25-foot walk test (T25FWT), 2-minute walk test (2MWT), and 6-minute walk test (6MWT) along with prevalence of dismobility were assembled from 2 RIMS multicenter studies (n = 502 pwMS; age range 21-77 years, 6 age groups: 20-29, 30-39, 40-49, 50-59, 60-69, and 70-79 years). HC data were extracted from studies containing normative reference values (n = 1070-3780 HC). Results. Age trajectories of walking capacity was nonlinear and accelerated in pwMS versus HC. While measures of walking capacity in pwMS were suppressed already early in life, the gap between pwMS and HC significantly widened across the 6 age groups (pwMS performed 64%, 70%, 57%, 59%, 51%, and 37% of HC, respectively). This coincided with high prevalences of dismobility in pwMS across the 6 age groups when using usual gait speed cut-point values

INTRODUCTION: Persons with multiple sclerosis (pwMS) could have an impaired trunk and reduced postural control, which negatively impacts activities of daily living. Evidence is growing to consider the positive effects of trunk training on fall incidence and balance problems. Effects on trunk and upper limb performance is unknown. This systematic review provides an overview of trunk training programs and their effects in MS, specifically focusing on the content of training modalities and the effects on trunk and upper limb performance. EVIDENCE ACQUISITION: Two electronic databases were used: PubMed and Web Of Science (WOS). Intervention studies (with- and without control group) published in English, investigating the effects of active trunk training on trunk and upper limb performance in pwMS, were included. EVIDENCE SYNTHESIS: Sixteen studies met the criteria, investigating different rehabilitation modalities. The included interventions in the review varied between more generic postural interventions such as Pilates (N.=8) and Ai Chi (N.=1), with a focus on abdominal muscle activation, breathing, neutral position and lower extremity movements. Further, specifically developed trunk training programs like GroupCoreDIST/ SIT / CoDuSe (N.=6) and Bobath based trunk training (N.=1) are detected, with the main focus on trunk strengthening and dynamic movements. An overall improvement in trunk performance was reported in several tests on trunk strength, stability and coordination. While the majority of the programs integrated the upper limb, only half of them used upper limb outcome measures to evaluate the effect. Here, overall significant improvements were found for the upper limb. CONCLUSIONS: This systematic review showed that different types of trunk training programs can improve trunk and upper limb function in PwMS. The findings of this review suggest that a focus on trunk training to achieve effects on upper limb is reasonable. Future research is needed to further explore relations and the effect sizes.

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.

High-quality clinical practice guidelines (CPGs) can provide evidence-based recommendations for optimizing care on managing multiple sclerosis (MS). There is currently no review that compiles recommendations of high-quality CPGs to guide decision-making for MS rehabilitation. The aim was to identify evidence-based recommendations in high-quality multidisciplinary English CPGs for rehabilitation in MS. CPGs published in the last 10 years (2009-2019) that described recommendations on rehabilitation were searched in PubMed, Turning Research into Practice database, International Guideline databases, National Guideline databases and websites of MS organizations. Quality assessment of CPGs was conducted by two evaluators using the Appraisal of Guidelines for Research and Evaluation II instrument. Recommendations were classified according to the International Classification of Functioning, Disability and Health (ICF) and the International Classification of Health Intervention (ICHI) and documented in terms of strength of recommendation and level of evidence. Five CPGs satisfied the inclusion criteria. Of 120 recommendations, 38 had a strong level with moderate to low level of evidence, 61 were of weak strength and 18 were formulated by the consensus of experts. Recommendations were categorized into 12 domains and 1 chapter on the body function level, 1 chapter on activity level and 2 domains on external factors. The existing CPGs demonstrated more than 100 evidence level recommendations to be followed at the clinical practice, most in body functions of the ICF. Developing up-to-date CPGs with more focus on activity and participation domains for countries with various healthcare backgrounds may be useful for a best clinical practice.

MOBILE and ENHANCE were similarly designed randomized trials of walking-impaired adults with relapsing-remitting or progressive multiple sclerosis (MS) who received placebo or 10 mg prolonged-release (PR)-fampridine twice daily for 24 weeks. Both studies showed sustained and clinically meaningful improvement in broad measures of walking and balance over 24 weeks of PR-fampridine treatment.To evaluate the functional benefits and safety of PR-fampridineData from the intention-to-treat (ITT) populations of MOBILE and ENHANCE studies were pooled in aIn the ITT population (The pooled analysis of MOBILE and ENHANCE confirms previous evidence that treatment with PR-fampridine results in clinically meaningful improvements in walking, mobility and balance, self-reported physical impact of MS, and quality of life and is effective across a broad range of PwMS.

Background: Walking fatigability is prevalent in MS and can be measured by a percentage distance decline during a 6-min walking test. Walking is characterized by an accurate and consistent interlimb antiphase coordination pattern. A decline in coordination each minute during a 6-min walking test is observed in persons with MS (pwMS). Measuring coordination during a 6-min seated coordination task with minimized balance and strength requirements, is assumed to examine a more fundamental interlimb antiphase coordination pattern in pwMS. This research aimed to answer the following research question: How does interlimb antiphase coordination pattern change during a seated coordination task in pwMS with walking fatigability (WF), non-walking fatigability (NWF) and Healthy Controls (HC)?Methods: Thirty-five pwMS and 13 HC participated. Interlimb coordination was assessed by a seated 6-min coordination task (6MCT) with the instruction to perform antiphase lower leg movements as fast as possible. Outcomes were Phase Coordination Index (PCI) and movement parameters (amplitude, frequency).Results: Mixed models revealed a significant effect of time for the the variability of generating interlimb movements, with a difference in mean values between WF and HC. A significant group∗time interaction effect was found for movement amplitude, represented by a significant decrease in movement amplitude in the WF group from minute 1 to the end of the task.Conclusion: The higher variability in interlimb coordination and decrease in movement amplitude over time during the 6MCT in the WF group could be an indicator of decreased control of fundamental antiphase coordination pattern in pwMS with walking fatigability.Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT04142853 (registration date: October 29, 2019) and NCT03938558 (registration date: May 6, 2019).

Pandemic restrictions have led to changes in therapy plans and disrupted rehabilitation services for people with multiple sclerosis. CogEx is an international, multicentre MS dual-intervention (cognitive rehabilitation, aerobic exercise) randomized, controlled rehabilitation trial confined to people with progressive disease. The primary outcome is cognition (processing speed).There are 11 treatment sites in six countries with participants required to make 27 site visits over 12 weeks. Collectively, the large, in-person demands of the trial, and the varying international policies for the containment of COVID-19, might disproportionately impact the administration of CogEx. During the first lockdown, all centres closed on average for 82.9 (SD = 24.3) days. One site was required to lockdown on two further occasions. One site remained closed for 16 months. Ten staff (19.2%) were required to quarantine and eight staff (15.4%) tested positive for COVID. 10 of 264 (3.8%) participants acquired COVID-19. All survived. The mean duration of enrollment delay has been [236.7 (SD = 214.5) days]. Restarting participants whose interventions were interrupted by the pandemic meant recalculating the intervention prescriptions for these individuals. While the impact of the pandemic on CogEx has been considerable, all study sites are again open. Participants and staff have shown considerable flexibility and resilience in keeping a complex, international endeavour running. The future in general remains uncertain in the midst of a pandemic, but there is cautious optimism the study will be completed with sufficient sample size to robustly evaluate our hypothesis and provide meaningful results to the MS community on the impact of these interventions on people with progressive MS. Trial registration: The trial was registered on September 20th 2018 at www.clinicaltrials.gov having identifier NCT03679468. Registration was performed before recruitment was initiated.

In Persons with Multiple Sclerosis (PwMS), coupling walking to beats/pulses in short bursts is reported to be beneficial for cadence and perceived fatigue. However it is yet to be investigated if coupling and its effects can be sustained for longer durations, required for task-oriented training strategy in PwMS.To investigate if PwMS compared to healthy controls (HC) sustain synchronization for 12 min when walking to music and metronome, and its effects on perceived physical and cognitive fatigue, motivation and gait compared to walking in silence.Participants walked for 12 min in three conditions (music, metronome and silence). The tempo of the auditory conditions was individualized. Auditory-motor coupling and spatio-temporal gait parameters were measured during walking. The visual analogue scale was used for perceived fatigue, and the Likert scale for motivation.27 PwMS and 28 HC participated. All participants synchronized to both stimuli, yet PwMS synchronized better to music. Overall, participants had lower cadence, speed and stride length when over time all conditions, with an exception of HC, with increasing cadence during the music condition. PwMS perceived less cognitive fatigue, no difference in perceived physical fatigue and a higher motivation walking to music compared to metronomes and silence.12 min of uninterrupted walking was possible in PwMS in all conditions, while better synchronization, low perception of cognitive fatigue and high motivation occurred with music compared to other conditions. Coupling walking to music could offer novel paradigms for motor task-oriented training in PwMS.

In the last decade, rehabilitation technology has been developed, investigated, and entered specialized clinical settings. In this chapter, we first discuss the potential of rehabilitation technology to support the achievement of key factors in motor recovery, such as delivering massed practice with good movement quality but also question task-specificity and cognitive motor control mechanisms. Second, we discuss available technology-supported rehabilitation methods for improving gait, balance and fitness, and upper limb function. Finally, we discuss considerations in relation to the professional workforce in order to deliver optimal rehabilitation.

Background As the prevalence of neurodegenerative diseases (such as dementia) continues to increase due to population aging, it is mandatory to understand the role of exercise for maintaining/improving brain health. Objectives To analyse the impact of aerobic, strength and combined aerobic/strength exercise training on peripheral brain-derived neurotrophic factor (BDNF) concentrations in older adults (minimum age 60 years). Methods This meta-analysis adhered to PRISMA guidelines. Inclusion criteria were: (i) studies with subjects aged ≥ 60 years, (ii) completing a single exercise bout or an exercise programme, with (iii) measurements of blood BDNF in the periphery; (iv) with comparison between (a) an intervention and control group or (b) two intervention groups, or (c) pre- and post-measurements of an exercise intervention without control group. Studies with specific interest in known chronic co-morbidities or brain diseases affecting the peripheral and/or central nervous system, except for dementia, were excluded. Results In general, peripheral blood BDNF concentrations increased significantly after a single aerobic/strength exercise bout (Z = 2.21, P = 0.03) as well as after an exercise programme (Z = 4.72, P

Background. Simultaneous execution of motor and cognitive tasks can result in worsened performance on one or both tasks, indicating cognitive-motor interference (CMI). A growing amount of research on CMI in persons with multiple sclerosis (pwMS) is observed. However, psychometric properties of dual-task outcomes have been scarcely reported. Objective. To investigate the between-day test-retest reliability of the motor and cognitive dual-task costs (DTCs) during multiple CMI test conditions with various task complexities in pwMS and matched healthy controls (HCs). Methods. A total of 34 pwMS (Expanded Disability Status Scale score 3.0 ± 0.8) and 31 HCs were tested and retested on 3 single cognitive, 4 single motor, and 12 cognitive-motor dual tasks. Cognitive tasks included serial subtraction by 7, titrated digit span backward, and auditory vigilance. Motor tasks were walking at self-selected speed, over obstacles, crisscross, and while carrying a water-filled cup. Outcome measures were cognitive and motor DTC, calculated as percentage change of dual-task performance compared with single-task performance. Intraclass correlations (ICCs) and Spearman correlation coefficients were calculated as appropriate. Results. For DTCmotor of gait speed, ICCs ranged from 0.45 to 0.81 and Spearman correlations from 0.74 to 0.82. For DTCcognitive, ICCs ranged from −0.18 to 0.49 and Spearman correlations from −0.28 to 0.26. Reliability depended on the type of motor and cognitive task. Conclusion. Reliability of the DTCmotor was, overall, good, whereas that of the DTCcognitive was poor. The “walking” and “cup” dual-task conditions were the most reliable regardless of the integrated cognitive task. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by RIMS by Novartis AG, MS Society Flanders, Swedish Promobilia Foundation, and SailingChallenge4MS.

Evidence for using auditory-motor coupling in neurological rehabilitation to facilitate walking is increasing. However, the distinction between spontaneous and intended coupling and its underlying mechanisms is yet to be investigated. In this study, we include 30 persons with multiple sclerosis and 30 healthy controls (HCs) in an experiment with two sessions in which participants were asked to walk to music with various tempi, matching their preferred walking cadence (PWC) up to 10% above in incremental steps of 2%. In the first session, no instructions were given to synchronize. In the second, participants were instructed to synchronize steps to the beats. Spontaneous synchronization was possible at 0% and +2% of the PWC, and fewer persons with multiple sclerosis were able to do so compared with HCs. Instruction was needed to synchronize at above +2% tempo in all participants. In the instructed session, the +6% condition marked a cutoff for cognitively impaired persons, as they were no longer able to synchronize. Based on our findings, we constructed a model illustrating that spontaneous entrainment is limited, operating during spontaneous coupling at only 0% and +2% of the PWC, and that at a higher tempo, entrainment requires intentional synchronization, with an active cognitive control mechanism.

OBJECTIVE: Force decline during strong contractions is dominated by changes in the periphery whereas during weaker contraction changes in voluntary activation become more important. We compared force decline and contributing factors in persons with multiple sclerosis (PwMS) during low and high intensity contractions.METHODS: Index finger abduction force, force evoked by electrical stimulation of the ulnar nerve at rest (RTw), and during MVCs were investigated in 19 PwMS and 19 controls. Participants performed contractions in sets of six contractions (7 s-on, 3 s-off) at 25% or 80% MVC. After each set, a 5 s-MVC was performed with superimposed nerve stimulation followed by RTw. Contractions were repeated until MVC dropped below 80% of initial MVC.RESULTS: Low compared to high intensity contractions caused a greater decline in voluntary activation and a smaller decline in RTw. Compared to controls, PwMS accomplished equal sets of contractions but showed a smaller decline in RTw. Female PwMS showed poorer voluntary activation. The number of low intensity contractions was associated with sense of fatigue in PwMS.CONCLUSION: Although, no difference in fatigability was observed, the mechanism contributing to force decline differed between PwMS and controls during submaximal contractions.SIGNIFICANCE: During weak contractions, fatigue and fatigability are associated in PwMS.

COVID-19 has abruptly disrupted healthcare services; however, the continuity of rehabilitation could be guaranteed using mobile technologies. This review aims to analyze the feasibility and effectiveness of telehealth solutions proposed to guarantee the continuity of rehabilitation during the COVID-19 pandemic. The PubMed, Cochrane Library, Web of Science and PEDro databases were searched; the search was limited to randomized controlled trials, observational and explorative studies published up to 31 May 2022, assessing the feasibility and effectiveness of telerehabilitation during the COVID-19 pandemic. Twenty studies were included, for a total of 224,806 subjects: 93.1% with orthopedic complaints and 6.9% with non-orthopedic ones. The main strategies used were video and audio calls via commonly available technologies and free videoconferencing tools. Based on the current evidence, it is suggested that telerehabilitation is a feasible and effective solution, allowing the continuity of rehabilitation while reducing the risk of infection and the burden of travel. However, it is not widely used in clinical settings, and definitive conclusions cannot be currently drawn. Telerehabilitation seems a feasible and safe option to remotely deliver rehabilitation using commonly available mobile technologies, guaranteeing the continuity of care while respecting social distancing. Further research is, however, needed to strengthen and confirm these findings.

Funding Acknowledgements Type of funding sources: None. Background Frailty is accompanied by, or can be caused by, a combination of several physical, psychosocial and cognitive problems, and is highly prevalent in older patients with cardiovascular disease (CVD). However, different frailty assessment batteries (e.g. Fried and Vigorito) remain to be compared in terms of prognosis, as well as the subcomponents within those batteries. Purpose To examine which frailty measurements contribute to the prediction of frailty in CVD patients, and prognosis, and thus should be executed in clinical settings. Methods In 133 CVD patients (mean age 78.1 ± 6.7 years) the presence of frailty was examined by the Fried criteria and compared with the outcome from the multi-component frailty assessment tool of Vigorito including the Mini Nutritional Assessment (MNA), Katz-scale, 4.6 m gait speed, Timed Up and Go Test (TUG), handgrip strength, Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15) and number of medications. Additional tests were executed to further enhance the prediction of frailty. Patients were followed to register hospitalisations (general and urgent) and mortality up to 6 months after the frailty assessment. First, it was then analysed whether the Fried or Vigorito test battery would equally predict complications during follow-up, and secondly a new frailty test battery was developed with evaluation towards complication risk predictions. Results According to the tool of Vigorito, significantly more CVD patients suffered from minor vs. moderate frailty (34% vs. 10%, p Significant associations were found between hospitalisations and frailty according to Fried while mortality was significantly associated with frailty according to Vigorito and the newly developed formula (p = 0.013). Finally, based on the multivariate regression model (R2 = 0.95), sex, MNA, Katz scale, TUG, handgrip strength (dominant hand), MMSE, GDS-15, total number of medications and the interaction effect between the Katz-scale and TUG should be assessed to detect frailty. Based on these parameters, a new formula to detect frailty was developed (r = 0.95 with Vigorito score, p Conclusions In comparison with the frailty assessment tool of Vigorito, the Fried criteria may overestimate frailty and its severity. Moreover, frailty seems to be significantly associated with 6-months hospitalisations as well as with mortality. The newly developed frailty assessment battery has the potential to detect frailty in a multidimensional way, and, moreover, to predict mortality.

Background Persons with multiple sclerosis (pwMS) experience walking impairments, characterized by decreased walking speeds. In healthy subjects, the self-selected walking speed is the energetically most optimal. In pwMS, the energetically most optimal walking speed remains underexposed. Therefore, this review aimed to determine the relationship between walking speed and energetic cost of walking (Cw) in pwMS, compared with healthy subjects, thereby assessing the walking speed with the lowest energetic cost. As it is unclear whether the Cw in pwMS differs between overground and treadmill walking, as reported in healthy subjects, a second review aim was to compare both conditions. Method PubMed and Web of Science were systematically searched. Studies assessing pwMS, reporting walking speed (converted to meters per second), and reporting oxygen consumption were included. Study quality was assessed with a modified National Heart, Lung and Blood Institute checklist. The relationship between Cw and walking speed was calculated with a second-order polynomial function and compared between groups and conditions. Results Twenty-nine studies were included (n = 1535 pwMS) of which 8 included healthy subjects (n = 179 healthy subjects). PwMS showed a similar energetically most optimal walking speed of 1.44 m/s with a Cw of 0.16, compared with 0.14 mL O2/kg/m in healthy subjects. The most optimal walking speed in treadmill was 1.48 m/s, compared with 1.28 m/s in overground walking with a similar Cw. Conclusion Overall, the Cw is elevated in pwMS but with a similar energetically most optimal walking speed, compared with healthy subjects. Treadmill walking showed a similar most optimal Cw but a higher speed, compared with overground walking.

Background: In persons with Multiple Sclerosis (pwMS) performing a simultaneous cognitive task while walking often results in slower gait. Clinical characteristics associated with reduced dual task (DT) performance are not yet entirely clear. This multi-centre study aimed to determine the relationship between clinical and demographical characteristics with dual task (DT) walking performance in pwMS during multiple DT conditions. Methods: Nine DT conditions were analysed, consisting of combinations of three types of cognitive (‘digit span’, ‘subtraction’, ‘vigilance’) and three types of walking (‘walk’, ‘walk with cup’, ‘walk over obstacles’) conditions. Primary outcomes were DT gait speed (m/s) and motor DT cost of gait speed (DTCmotor, %). Secondary outcomes were clinical tests of physical and cognitive functioning and patient-reported and demographical outcomes. Firstly, univariate analyses and, subsequently, multivariate analyses with backward modelling, were conducted for each type of walking DT condition separately. Cognitive DT conditions were included in the models as main and as interaction effect with the secondary outcomes. Results: Analysis were performed in 81 pwMS (EDSS 3.3 ± 1.0). In the final models of DTCmotor, the significant main effects were in ‘walk’ DT-conditions the Symbol Digit Modalities Test (SDMT), in ‘cup’ conditions the SDMT and Dynamic Gait Index and in ‘obstacles’ conditions age. For DT gait speed, main effects were found for the 2-Minute Walking Test (2MWT) and the Multiple Sclerosis Walking Scale for all walking conditions. Additionally, interactions between cognitive DT-conditions and SDMT, age and 2MWT were found. Conclusion: Clinical characteristics related to DT walking performance differed according to cognitive-motor DT-condition used. Still, in general, pwMS with a better mobility demonstrated higher DT gait speed, while a faster information processing speed was related to a lower DTCmotor.

Background Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system with heterogeneous symptoms. Persons with MS (PwMS) show reduced walking capacity with changes in their gait pattern. It is unknown to which extent coordination deficits are present in PwMS, which can be measured by seated lower leg interlimb coordination tasks, and to which extent they are related to motor and cognitive function. Research question How is the control of interlimb coordination of the lower limbs characterized in PwMS compared to healthy controls (HC) during a seated rhythmical coordination task and what is the relationship between interlimb coordination, motor or cognitive function? Methods Rhythmical interlimb coordination was assessed during a single session in 38 PwMS and 13 HC, using a seated rhythmical coordination task, comprising of antiphase flexion-extension of the lower limbs, to metronomes at 0.75 Hz, 1.00 Hz, 1.50 Hz. Outcomes were phase coordination index (PCI), movement amplitude and movement frequency. Correlations between interlimb coordination, motor, and cognitive function were examined. Results PwMS showed impaired walking capacity but preserved cognitive function. Mixed model analysis revealed a significant effect of group and metronome frequency for PCI, attenuated by the variability in generating knee (antiphase flexion-extension) movements. Movement amplitude was highest at metronome frequency 1.00 Hz. In PwMS significant correlations were found between PCI and cognitive function when performing the task at metronome frequencies 0.75 Hz and 1.50 Hz, as well as motor function at 1.50 Hz. Significance PwMS had a higher variability in interlimb coordination compared to HC. The most stable interlimb antiphase coordination mode was performed at 1.00 Hz. Significant correlations support the existence of a relationship between information processing speed, as well as walking impairment, with interlimb coordination. While cognitive and motor control are always needed for interlimb coordination movements, associations are strongest in the deviant higher and lower metronome rhythms.

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.

Background:Cognitive-motor interference (CMI) is measured by dual-tasking (DT), which involves motor and cognitive tasks. There is no consensus as to whether CMI is present in multiple sclerosis (MS). Objectives:We investigated the effects of 16 DT conditions by measuring motor complexity, cognitive domain, and task difficulty. Method:In total, 40 persons with MS (pwMSs) with Expanded Disease Status Scale (EDSS) 3.2 +/- 1.7 and 31 age- and sex-matched healthy controls (HCs) completed 2 single walking, 8 single cognitive, and 2 complex walking tasks and 16 cognitive-motor DT. The main outcomes were mean values of gait velocity and the percentage change from single to DT (motor DT costs, mDTCs) and mean values of cognitive task accuracy and the percentage changes (cognitive DTC, cDTC). Results:Two-way analyses of variance showed the main effect of cognitive task yielded anFratio ofF((4, 268))= 72.35,p< 0.01, for mean gait velocity, and anFratio ofF((4, 304))= 17.12,p< 0.001, for mDTC, indicating that the mean velocity was significantly lower and the mDTC significantly higher for DS_B (mean = 1.27, SD = 0.03, and mean = 13.52, SD = 1.28, respectively). The main effect of cognitive task yielded anFratio ofF((4, 116))= 84.32,p< 0.001, with the lowest average accuracy for DS_B (mean = 43.95, SD = 3.33); no effect was found for cDTC. In pwMSs, the EDSS accounted for 28% (F= 13.65,p= 0.001) of variance in a model predicting the highest mDTC. Conclusions:Overall, among different cognitive tasks added, the Digit Span backward was the most interfering cognitive task over gait velocity and accuracy. The effect was similar independently from the motor complexity and the group. PwMSs and HCs behaved in a similar manner at all motor complexity levels and during all cognitive task. Leone, C (corresponding author), Hasselt Univ, REVAL Rehabil Res Ctr, Fac Rehabil Sci, Hasselt, Belgium. carmela.leone@uhasselt.be

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.

Background The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is currently the most widely validated, patient-reported outcome measure assessing patients’ perception of the impact of multiple sclerosis (MS) on walking ability. To date, the majority of previous studies investigating the MSWS-12 have focused on the total score despite individual items being potentially informative. Therefore, our objective was to examine the associations between the individual items of the MSWS-12 and mobility and whether these associations depend on disability level. Methods Participants completed the MSWS-12, Two-Minute Walk Test (2MWT), Timed 25-Foot Walk (T25FW), Timed Up and Go Test (TUG) and the Four Square Step Test (FSST). Subsequently, they were divided into two groups according to their disability level, classified as either “mildly” or “moderately-severely” disabled. The correlation between individual items of the MSWS-12 and clinical measures of mobility were separately examined by Spearman's correlation coefficients; linear regression analyses were performed for each disability group, with/without adjusting for cognition, age and gender. Results 242 people with MS (PwMS), 108 mildly and 134 moderately-severely disabled, were included. Stronger correlations between the MSWS-12 items and mobility tests were found in the mildly disabled compared to the moderately-severely disabled group. The linear regression analysis showed that in the mildly disabled, item 9 (use of support outdoors) explained 35.4%, 30.8%, and 23.7% of the variance related to the 2MWT, T25FW and TUG, respectively. As for the moderately-severely disabled, the linear regression analysis presented a model which included item 8 (use of support indoors), explaining 31.6%, 18.0%, 20.2% and 9.5% of the variance related to the 2MWT, T25FWT, TUG and FSST, respectively. Conclusions Items 8 and 9 of the MSWS-12 focusing on the patient's use of walking support in and outdoors, provide a robust indicator of mobility capabilities for mildly and moderately-severely disabled PwMS.

Background : In people with multiple sclerosis (pwMS), no formula exists to predict long walking capacity. Objective : To examine the accuracy of the timed 25-foot walk (T25FW) to predict long walking in pwMS with various degrees of walking dysfunction. Methods : A linear regression was made between the T25FW and the 6-minute walk test (6MWT) using data from 498 pwMS. Results : Prediction showed an excellent agreement between actual and predicted 6MWT distances, with an acceptable error of 10%, which increased as walking dysfunction increased. Conclusions : The T25WT provided acceptable prediction of the 6MWT in pwMS, although less accurate at higher degrees of dysfunction.

Performing a cognitive task and a motor task simultaneously is an everyday act that can lead to decreased performance on both tasks.To provide insight into the neural correlates associated with cognitive-motor dual tasking in individuals with a neurologic disorder.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.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.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.

Background : Dance therapy is increasingly reported in neurological diseases for improving several motor and cognitive functions, but was mostly studied in partner dance. No individual choreo-based dance program has ever been reported in MS. Objectives : The aim of this pilot study is to investigate effects of a ten-week choreo-based dance intervention on different impairments in MS. Participants : Seventeen participants with MS were allocated to a dance group (DG) or an art group (AG) for a ten-week intervention program, with a public live performance at the end of the intervention. Methods : The DG received choreo-based dance courses twice a week for 90 min, while the active control AG weekly contributed to the production by painting, music, spoken word and photo- or videography. Measurements for fatigue and fatigability, physical capacity and coordination, sensory function, cognitive capacity, quality of life and dual task performance took place before and after the intervention. Differences were analysed with Wilcoxon Signed Rank test. Results : Both groups improved significantly on executive cognitive performance during dual task and fatigue. Only the DG improved significantly on functional lower limb strength, hand function, coordination, self-reported balance and walking, and showed a trend towards improving on cognition (PASAT). The AG showed significant improvements in on cognitive function (SDMT). Conclusion : A ten-week multimodal dance intervention has positive effects on impact of fatigue, physical capacity and coordination, and cognitive performance during a dual task. Larger samples, follow-up measurements and research in different disability groups is recommended.

Background Trunk control is essential for movement, balance and walking and is ignored in the regular medical follow-up. Objective First, to describe the distribution of trunk impairments in the full range of disability levels in individuals with MS. Second, to identify the relationship between trunk control, measured by the Trunk Impairment Scale (TIS 2.0.), and general disability measured by the Expanded Disability Status Scale (EDSS). Methods 154 individuals with MS were included (mean age 53.6; SD 11.06), EDSS ranging from 1.0- 8.5 (mean 4.47; SD 2.55). The relationship between EDSS and TIS 2.0. was calculated by Spearman correlation coefficient for the total sample and subgroups, EDSS ≤ 4 versus EDSS ≥ 4.5. Results Trunk impairments were detected throughout the full range of disability, including individuals with low disability. Pelvic elevation and lower trunk rotation appeared most difficult to perform. In the total sample, a moderate correlation was found (rho= -0.608**) between disability (EDSS) and trunk performance (TIS 2.0.). Sub-analyses revealed a poor correlation (rho= -0.193) for the EDSS ≤ 4 subgroup and a strong correlation for the EDSS ≥ 4.5 subgroup (rho= -0.712**). Conclusion The results advocate for including trunk assessment already at early disease stages of MS, particularly of pelvic elevation and trunk rotation, and dedicated rehabilitation strategies.

Background: MOBILE and ENHANCE were similarly designed randomized trials of walking-impaired adults with relapsing-remitting or progressive multiple sclerosis (MS) who received placebo or 10 mg prolonged-release (PR)-fampridine twice daily for 24 weeks. Both studies showed sustained and clinically meaningful improvement in broad measures of walking and balance over 24 weeks of PR-fampridine treatment. Objective: To evaluate the functional benefits and safety of PR-fampridine versus placebo using a post hoc integrated efficacy analysis of MOBILE and ENHANCE data. Methods: Data from the intention-to-treat (ITT) populations of MOBILE and ENHANCE studies were pooled in a post hoc analysis based on the following outcome measures: 12-item MS Walking Scale (MSWS-12), Timed Up and Go (TUG) speed, Berg Balance Scale (BBS), MS Impact Scale physical impact subscale (MSIS-29 PHYS), EQ-5D utility index score, visual analogue scale (VAS), and adverse events. The primary analysis was the proportion of people with MS (PwMS) with a mean improvement in MSWS-12 score (⩾8 points) from baseline over 24 weeks. A subgroup analysis based on baseline characteristics was performed. Findings: In the ITT population ( N = 765; PR-fampridine, n = 383; placebo, n = 382), a greater proportion of PR-fampridine–treated PwMS than placebo-treated PwMS achieved a clinically meaningful improvement in the MSWS-12 scale over 24 weeks (44.3% versus 33.0%; p Conclusion: The pooled analysis of MOBILE and ENHANCE confirms previous evidence that treatment with PR-fampridine results in clinically meaningful improvements in walking, mobility and balance, self-reported physical impact of MS, and quality of life and is effective across a broad range of PwMS.

Background: Cerebellar ataxia is a hindering impairment, affecting movement and quality of life. Rehabilitation remains an essential part of management of persons presenting with cerebellar ataxia. Coupling steps to auditory stimuli have been shown to improve gait in neurological disorders such as Parkinson's disease and multiple sclerosis (MS), yet it is unclear whether these techniques are applicable for persons with cerebellar damage. We investigate the impact of bilateral cerebellar lesions and marked ataxia on the ability to synchronize finger-taps and foot-steps to music and metronomes. Case description: 55 years old male with MS (Expended Disability Status Scale 6.5) with marked cerebellar ataxia (Scale for the Assessment and Rating of Ataxia 21) but overall preserved muscle strength. Methods: Synchronization of finger-taps and foot-steps to beats in music and metronomes were investigated at tempi ranging from -12% to +12% with respect to the spontaneous tapping tempo and natural walking cadence, in increments of 4% (randomized). Results: During the tapping task, the patient was able to synchronize his finger-taps to both auditory stimuli, with the highest synchronization consistency at the -12% tempo. At this tempo, we observed that his upper extremity movements became more coordinated. During the walking task, the patient was not able to synchronize his foot-steps to music and metronomes across the different tempi, with the exception of walking to metronomes at -12% tempo where he was able to synchronize, yet very poorly. At this tempo, the patient's cadence, stride length and speed also increased compared to his baseline. Conclusion: Sensorimotor synchronization of motor tasks with auditory stimuli was feasible in this case study of a patient diagnosed with MS with marked cerebellar ataxia. Rehabilitation of motor control should consider applying training at frequencies lower than usual movement frequencies of the patient.

People with multiple sclerosis (PwMS) are less physically active compared with the general population. This might also be because of the perception of temporary worsening of symptoms during physical activity. Forty-two PwMS with a mild level of disability underwent a maximal exercise test on a bicycle ergometer. Fifteen minutes before and 15 and 75min after the maximal exercise test, the 6-minute walking test was conducted and the rate of perceived exertion was recorded. Twice before and three times after the maximal exercise test, participants rated the symptom inventory, including symptom domains of general fatigue, muscle fatigue, balance, gait pattern, muscle weakness, spasticity, pain, sensory disturbance, dizziness, and visual impairment. The visual analogue scale was used to rate the perceived symptoms from 0 (no intensity) to 10 (maximal intensity). The 6-minute walking test distance increased significantly over time, whereas the rate of perceived exertion increased temporarily after the maximal exercise test. Immediately after the maximal exercise test, significant temporary increases were found in balance, gait pattern, muscle weakness, and visual impairment. General and muscle fatigue were elevated, compared with the baseline, till 15 and 75min after the maximal exercise test, respectively. A short-term impact of a single maximal exercise test was considered as the temporary worsening of perceived symptoms, especially (muscle) fatigue and the gait pattern, in PwMS with a mild level of disability. However, a recovery was observed after 75min. Walking endurance was not affected by the maximal exercise test.

Objectives: Activity-related travel behaviour is a prerequisite for participation. Knowledge about key factors influencing activity-related travel behaviour is necessary, in order to define guidelines for interventions to optimize this behaviour. The present study 1. investigated to which degree the activity-related travel behaviour in Multiple Sclerosis (MS) does decrease with increasing ambulatory dysfunction and 2. assessed the impact of health condition and contextual factors on activity-related travel behaviour in MS. Methods: A convenience sample of 108 persons with MS was studied, distinguished in three disability subgroups based on Disease Steps (DS). Health condition was assessed by standardized clinical tests about physical, cognitive and psychosocial functioning. Contextual factors (personal and environmental) were collected. Activity-related travel diaries and GPS tracking devices were used to investigate activity-related travel behaviour in terms of number of trips and transport modes used. The influence of health condition measures and contextual factors with activityrelated travel behaviour measures was analyzed using Spearman correlations and multiple linear regressions. Results: 1. Activity-related travel behaviour in MS decreased significantly with increasing ambulatory dysfunction. Significant changes were found regarding travel modes, number, type and planning of activities. 2. Activity-related travel behaviour in MS correlated with both health condition measures and contextual factors. A limited number of standardized tests of health condition and contextual factors (driving ability, household size) can predict activity-related travel behaviour in MS. Conclusions: Both health condition (mostly physical functioning) and contextual factors are predictive for activity-related travel behaviour in MS. Multi-disciplinary teams should include counselling on living situation and on advice regarding environmental factors. Policy makers should be recommended to integrate medical and other services in the community. The studywasfinanciallysupportedbyaPhDfellowshipfromtheResearchcouncilofHasseltUniversity(BOF-grant) The authors want to thank all PwMS for their voluntary participation. We also acknowledge Veronik Truyens and Greet Adriaenssens, heads of paramedical services of the Rehabilitation Center Overpelt and De Mick Rehabilitation Center Brasschaat, respectively, for facilitation of the study and patient recruitment; as well as vzw Lidwina for facilitation of patient recruitment.

Background: Physical rehabilitation can improve walking capacity in persons with multiple sclerosis (MS). However, changes in spatiotemporal gait parameters after rehabilitation are not frequently evaluated, and it is unknown to what extent potential effects depend on baseline disability level. The objective was to investigate the effectiveness of rehabilitation programs on gait parameters at usual and fastest speeds in persons with MS categorized according to walking speed. Methods: This nonrandomized multinational study in “real-world” settings evaluated participants before and after conventional rehabilitation. Outcome measurements included spatiotemporal gait parameters assessed by an electronic walkway (at usual and fastest speeds), walking capacity tests (Timed 25-Foot Walk test, 2-Minute Walk Test, 6-Minute Walk Test), and the patient-reported 12-item Multiple Sclerosis Walking Scale. Patients were allocated into three subgroups based on walking speed (1.14 m/s) and MS center. Results were calculated for the total group and subgroups. Results: Forty-two persons with MS (26 women; mean ± SD age, 44.6 ± 11.0 years; mean ± SD Expanded Disability Status Scale score, 3.5 ± 1.5) receiving rehabilitation treatment were enrolled. After rehabilitation treatment, the group demonstrated a significant decrease in double support time and an increase in stride length and step length (left leg) at usual and fastest speeds. Velocity and step length (right leg) increased only at usual speed. Subgroup analysis revealed greatest and clinically meaningful improvements in more disabled persons with MS. Conclusions: Physical rehabilitation induced changes in spatiotemporal gait parameters in persons with MS. The magnitude of improvement was greater in participants with more walking impairment.

BACKGROUND: The relationship between fatigue impact and walking capacity and perceived ability in patients with multiple sclerosis (MS) is inconclusive in the existing literature. A better understanding might guide new treatment avenues for fatigue and/or walking capacity in patients with MS.OBJECTIVE: To investigate the relationship between the subjective impact of fatigue and objective walking capacity as well as subjective walking ability in MS patients.METHODS: A cross-sectional multicenter study design was applied. Ambulatory MS patients (n = 189, age: 47.6 ± 10.5 years; gender: 115/74 women/men; Expanded Disability Status Scale (EDSS): 4.1 ± 1.8 [range: 0-6.5]) were tested at 11 sites. Objective tests of walking capacity included short walking tests (Timed 25-Foot Walk (T25FW), 10-Metre Walk Test (10mWT) at usual and fastest speed and the timed up and go (TUG)), and long walking tests (2- and 6-Minute Walk Tests (MWT). Subjective walking ability was tested applying the Multiple Sclerosis Walking Scale-12 (MSWS-12). Fatigue impact was measured by the self-reported modified fatigue impact scale (MFIS) consisting of a total score (MFIStotal) and three subscales (MFISphysical, MFIScognitiveand MFISpsychosocial). Uni- and multivariate regression analysis were performed to evaluate the relation between walking and fatigue impact.RESULTS: MFIStotalwas negatively related with long (6MWT, r = -0.14, p = 0.05) and short composite (TUG, r = -0.22, p = 0.003) walking measures. MFISphysicalshowed a significant albeit weak relationship to walking speed in all walking capacity tests (r = -0.22 to -0.33, p CONCLUSIONS: The physical impact of fatigue is weakly related to objective walking capacity, while general, physical, cognitive and psychosocial fatigue impact are weakly to moderately related to subjective walking ability, when analysed in a large heterogeneous sample of MS patients.

Background: Multiple sclerosis (MS) rehabilitation evidence is limited due to methodological factors, which may be addressed by a data repository. We describe the perceived challenges of, motivators for, interest in participating in, and key features of an international MS rehabilitation data repository. Methods: A multimethod sequential investigation was performed with the results of two focus groups, using nominal group technique, and study aims informing the development of an online questionnaire. Percentage agreement and key quotations illustrated questionnaire findings. Subgroup comparisons were made between clinicians and researchers and between participants in North America and Europe. Results: Rehabilitation professionals from 25 countries participated (focus groups: n = 21; questionnaire: n = 166). The top ten challenges (C) and motivators (M) identified by the focus groups were database control/management (C); ethical/legal concerns (C); data quality (C); time, effort, and cost (C); best practice (M); uniformity (C); sustainability (C); deeper analysis (M); collaboration (M); and identifying research needs (M). Percentage agreement with questionnaire statements regarding challenges to, motivators for, interest in, and key features of a successful repository was at least 80%, 85%, 72%, and 83%, respectively, across each group of statements. Questionnaire subgroup analysis revealed a few differences (P < .05), including that clinicians more strongly identified with improving best practice as a motivator. Conclusions: Findings support clinician and researcher interest in and potential for success of an international MS rehabilitation data repository if prioritized challenges and motivators are addressed and key features are included.

Background: Exercise therapy studies in persons with multiple sclerosis (pwMS) primarily focused on motor outcomes in mid disease stage, while cognitive function and neural correlates were only limitedly addressed. Objectives: This pragmatic randomized controlled study investigated the effects of a remotely supervised community-located “start-to-run” program on physical and cognitive function, fatigue, quality of life, brain volume, and connectivity. Method: In all, 42 pwMS were randomized to either experimental (EXP) or waiting list control (WLC) group. The EXP group received individualized training instructions during 12 weeks (3×/week), to be performed in their community aiming to participate in a running event. Measures were physical (VO2max, sit-to-stand test, Six-Minute Walk Test (6MWT), Multiple Sclerosis Walking Scale-12 (MSWS-12)) and cognitive function (Rao’s Brief Repeatable Battery (BRB), Paced Auditory Serial Attention Test (PASAT)), fatigue (Fatigue Scale for Motor and Cognitive Function (FSMC)), quality of life (Multiple Sclerosis Impact Scale-29 (MSIS-29)), and imaging. Brain volumes and diffusion tensor imaging (DTI) were quantified using FSL-SIENA/FIRST and FSL-TBSS. Results: In all, 35 pwMS completed the trial. Interaction effects in favor of the EXP group were found for VO2max, sit-to-stand test, MSWS-12, Spatial Recall Test, FSMC, MSIS-29, and pallidum volume. VO2max improved by 1.5 mL/kg/min, MSWS-12 by 4, FSMC by 11, and MSIS-29 by 14 points. The Spatial Recall Test improved by more than 10%. Conclusion: Community-located run training improved aerobic capacity, functional mobility, visuospatial memory, fatigue, and quality of life and pallidum volume in pwMS.