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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.

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

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. 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.

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: 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.

Impaired manual dexterity is a frequently reported disability in people with multiple sclerosis (MS) and is increasingly prevalent with worsening disease. While various tests and patient-reported outcome measures are available, the Nine-Hole Peg Test (NHPT) is considered as a gold standard measure of manual dexterity and most frequently used in MS research and clinical practice. The MS Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. Among the MSOAC goals are acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step for these neuroperformance metrics is elucidation of clinically relevant benchmarks, well-defined degrees of disability, and gradients of change that are deemed clinically meaningful. This article addresses the NHPT, the proposed MSOAC measure for upper extremity function. We find that the NHPT is reliable within and between test sessions, discriminates between healthy subjects and MS patients with different levels of upper limb impairment, and shows high convergent validity with other manual dexterity as well as more comprehensive upper limb measures. Ecological validity is established by its relation to perceived upper limb use in daily life and perceived difficulty in performing activities of daily living. The NHPT is responsive to deterioration in longitudinal studies, and research suggests that a 20% change in test score is commonly used to define clinically meaningful worsening, a definition that needs further validation in all stages of the disease.

Background: Multiple sclerosis (MS) is a progressive disease associated with a large variety of symptoms and changing patients’ needs during the disease course. In order to provide appropriate care in every disease stage and let patients live their lives to the full, a multi-disciplinary approach and patient activation is needed. Objective: To summarise the multi-disciplinary perspective of MS, with focus on the organisation of a multi-disciplinary care team and possibilities to support patient activation. Methods: This review reflects the content of the presentations, audience polling results and discussions on the multi-disciplinary perspective of MS during the second Pan-European MS Multi-stakeholder Colloquium. Results: In many countries, the neurologist with or without the support of an MS nurse is responsible for the long-term care of MS patients. When needed, they should refer to other (non-)medical specialists. However, the patient should be empowered as well to manage his/her disease and to implement a physically active lifestyle in order to improve treatment outcomes and quality of life. Conclusion: To create equal access to care for MS patients across Europe, evidence-based standards of care, symptom self-monitoring tools and educational programmes for patients and healthcare professionals including non-medical treatment strategies should be developed at the European level.

Background: Adherence to medical interventions is a global problem. With an increasing amount of partially effective but expensive drug treatments adherence is increasingly relevant in multiple sclerosis (MS). Perceived lack of efficacy and side effects as well as neuropsychiatric factors such as forgetfulness, fatigue and depression are major determinants. However, research on adherence to behavioural interventions as part of rehabilitative interventions has only rarely been studied. Methods: In a one-day meeting health researchers as well as patient representatives and other stakeholders discussed adherence issues in MS and developed a general draft research agenda within a focus group session. Results: The focus group addressed four major areas: (1) focussing patients and their informal team; (2) studying health care professionals; (3) comparing practice across cultures; and (4) studying new adherence interventions. Conclusions: A focus on patient preferences as well as a non-judgemental discussion on adherence issues with patients should be at the core of adherence work.

The need to fully assess upper limb function in multiple sclerosis (MS) has become increasingly clear with recent studies revealing a high prevalence of upper limb dysfunction in persons with MS leading to increased dependency and reduced quality of life. It is important that clinicians and researchers use tailored outcome measures to systematically describe upper limb (dys)function and evaluate potential deterioration or improvement on treatment. This topical review provides a comprehensive summary of currently used upper limb outcome measures in MS, classified according to the levels of the International Classification of Functioning (ICF). The clinical utility, strengths, weaknesses and psychometric properties of common upper limb outcome measures are discussed. Based on this information, recommendations for selecting appropriate upper limb outcome measures are given. The current shortcomings in assessment which need to be addressed are identified.

The 6-minute walk test (6MWT) is often used to assess walking distance in multiple sclerosis (MS), but can be both time consuming for the investigator and exhausting for people with MS (pwMS). The present report compared the 6MWT scores of 40 ambulatory pwMS with their scores on the shorter 2-minute walk test (2MWT). The 2MWT estimated the 6MWT results with a mean relative error of 5% ( R2 = 0.96; p

Background. Patients with Parkinson disease (PD) are often profoundly slow in their performance of physical tasks, as well as in motor imagery (MI). This may limit the implementation and potential benefits of MI practice during rehabilitation. Objective. The authors investigated whether the quality of MI could be improved by external cueing. Methods. Fourteen patients with PD and 14 healthy controls physically executed and visually imagined a goal-directed aiming task and a box-and-block task, both in the presence and absence of visual and auditory cues. Mental chronometry and eye movement recording allowed objective evaluation of the temporal and spatial characteristics of MI when compared with physical execution. Visual analogue scales were used to assess imagery vividness. Results. The presence of visual cues significantly reduced the patients’ bradykinesia during MI and increased their imagery vividness. Conclusions. Visual cueing optimizes MI quality for PD patients and is a potential tool to increase the efficacy of MI practice in PD rehabilitation.