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.

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.

Rhythmic interlimb coordination of the lower limbs in multiple sclerosis during auditory pacing to three different frequencies.

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.

Interlimb Coordination Performance in Seated Position in Persons With Multiple Sclerosis: Reduced Amplitude Over 6 min and Higher Coordination Variability in Persons With Walking Fatigability.

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).

Is maximal muscle strength and fatigability of three lower limb muscle groups associated with walking capacity and fatigability in multiple sclerosis? An exploratory study.

BACKGROUND: Both muscle fatigability and walking fatigability are prevalent in persons with MS (pwMS), but their associations remains unclear. The aim of this study was to examine the association of muscle strength and fatigability from both isometric and concentric protocols of three different muscle groups, and their association to walking capacity and walking fatigability. METHODS: Twenty-seven pwMS and 13 Healthy Controls (HC) were included in this exploratory study. All participants performed a six-minute walking test (6MWT), where the distance walked index (DWI) was calculated to measure walking fatigability with a cut-off score of -10%. In three different muscle groups (knee extensors (KE), knee flexors (KF), ankle dorsiflexors (DF)), isometric and concentric muscle fatigability protocols (FIisometric or FIconcentric) were used to quantify maximal voluntary contraction (MVC) and muscle fatigability. Pearson or Spearman correlation coefficients and linear regression models were calculated to establish the association between muscle strength/fatigability and walking capacity/fatigability. RESULTS: Higher MVCs values for all muscle groups were found in HC compared to pwMS (mainly those having walking fatigability) (p < 0.05). FIisometric of DF was lower in pwMS having walking fatigability compared to no walking fatigability. MVC of KE, KF and DF had a low to moderate association with walking capacity (range r = 0.52-0.56; p < 0.05) and walking fatigability in pwMS (range r-rs: 0.39-0.50; p<0.05). FIconcentric of KF and DF, but not of KE, were associated with walking fatigability (r = 0.39 and rs = 0.47, respectively; p < 0.05). In contrast, FIisometric for all muscle groups were not related to walking capacity or walking fatigability. CONCLUSION: MVC of KE, KF and DF are associated with walking capacity and walking fatigability, while concentric (but not isometric) muscle fatigability of KF and DF are associated with walking fatigability.

Clinical manifestation and perceived symptoms of walking-related performance fatigability in persons with multiple sclerosis.

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) ≤6] and 28 healthy controls (HC) performed a 6MWT. The perceived severity of 11 common symptoms was rated on a visual analogue scale of 0-10 before, immediately after, and 10, 20 and 30 minutes after the 6MWT by means of the symptom inventory. Short motor impairment screening tests at baseline together with other descriptive measures were performed. Twenty pwMS were categorized in the WF group and were more disabled (EDSS: 4.16 ± 1.41) than the non-walking fatigability group (n = 29, EDSS: 2.62 ± 1.94). PwMS showed exacerbations of several perceived symptoms in MS, where most symptoms returned to baseline within 10 minutes after the walking test. The WF group showed significantly more muscle weakness and gait impairment, together with balance problems, and experienced an increase in spasticity, pain and dizziness after 6MWT. Our findings showed that perceived severity of symptoms are higher in pwMS presenting WF, and increase temporally after the 6MWT. Future research with quantitative measurement during and after walking is recommended.

Effects of a 10-week multimodal dance and art intervention program leading to a public performance in persons with multiple sclerosis - A controlled pilot-trial.

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.

Measuring walking-related performance fatigability in clinical practice: a systematic review.

INTRODUCTION: Fatigability, a change in performance according to tasks and circumstances, can contribute to walking limitations in daily life. Walking-related fatigability (WF) has been assessed subjectively, but current knowledge on best objective measurement methods is limited. The aim of this study was to provide an overview of objective clinical measurement methods assessing WF in different populations. EVIDENCE ACQUISITION: Articles were searched in Pubmed and Web Of Science by two independent raters. Studies were included when meeting inclusion criteria of measuring WF objectively in a clinical setting, with no exclusion towards any population. Case studies and reviews were not included in the review (systematic review registration number: PROSPERO - CRD42017074121). In total, 28 articles were included. The study populations were older adults (N.=7), multiple sclerosis (N.=14), spinal muscle atrophy (N.=3), osteoarthritis (N.=3), interstitial lung diseases (N.=1), and myasthenia gravis (N.=1). Data about patient characteristics, walking task, WF formula and interpretation (cut-off values and/or psychometric properties) got extracted from included literature. Every included article got checked for quality and risk of bias. EVIDENCE SYNTHESIS: WF was mostly measured during longer walking test such as six-minute walking test (6MWT) and 500 or 400-m walking test, by comparing the first and last minute or lap for spatiotemporal or kinematic changes in well-defined formulas. No gold standard is however available yet given different tasks or outcome measures across study populations. CONCLUSIONS: Longer walking test were most often used, with a preference towards the 6MWT, thereby comparing the changes over the last and first part of the test. Psychometric properties need more documentation before inclusion as experimental outcome.

Feasibility study of a 10-week community-based program using the WalkWithMe application on physical activity, walking, fatigue and cognition in persons with Multiple Sclerosis.

BACKGROUND: People with Multiple Sclerosis (pwMS) show diverse symptoms, such as fatigue and decline in motor and cognitive function. Physical activity shows to have a positive impact on many of these symptoms. However, many pwMS lead sedentary lives. Objectives of this study were to evaluate the feasibility of prolonged use of the WalkWithMe, a personalized mobile application that supports pwMS in walking at home, and its effect on physical activity, walking, fatigue and cognition in persons with MS. METHODS: Nineteen pwMS were enrolled in a 10-week home-based intervention with the WalkWithMe application after setting personal goals based on baseline testing values, where twelve patients completed the program. Before and after the intervention, motor (6MWT, T25FW, 5-STS, NHPT) and cognitive function (PASAT and SDMT) were evaluated, together with the patient reported impact on walking, physical activity, quality of life and fatigue by MSWS-12, IPAQ, SF-36, MSIS-29, MFIS and FSS, respectively. RESULTS: Significant improvement was seen for some parts of self-reported physical activity and quality of life (IPAQ: walking, p = 0.04, leisure, p = 0.02; SF-36: physical functioning, p = 0.02), cognition (SDMT, p = 0.01), cognitive fatigability (PASAT, p = 0.05), lower limb strength (5-STS, p = 0.05) and dominant hand function (NHPT, p = 0.002). CONCLUSION: This feasibility study was successful at improving categories of self-reported physical activity, lower limb functional strength, hand function and cognition, but results need to be interpreted with caution, given the small and not always clinically relevant changes. Larger sample sizes in a controlled experimental design are needed to confirm these results.

Continuous 12 min walking to music, metronomes and in silence: Auditory-motor coupling and its effects on perceived fatigue, motivation and gait in persons with multiple sclerosis.

BACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Structured Cognitive-Motor Dual Task Training Compared to Single Mobility Training in Persons with Multiple Sclerosis, a Multicenter RCT.

The aim was to compare the effectiveness of dual-task training (DTT) compared to single mobility training (SMT) on dual-task walking, mobility and cognition, in persons with Multiple Sclerosis (pwMS). Forty pwMS were randomly assigned to the DTT or SMT groups. The DTT-group performed dual-task exercises using an interactive tablet-based application, while the SMT-group received conventional walking and balance exercises. Both interventions were supervised and identical in weeks (8) and sessions (20). Nine cognitive-motor dual-task conditions were assessed at baseline, after intervention and at 4-weeks follow-up (FU). The dual-task cost (DTC), percentage change of dual-task performance compared to single-task performance, was the primary outcome. Mobility and cognition were secondarily assessed. Mixed model analyses were done with group, time and the interaction between group and time as fixed factors and participants as random factors. Significant time by group interactions were found for the digit-span walk and subtraction walk dual-task conditions, with a reduction in DTC (gait speed) for the DTT maintained at FU. Further, absolute dual-task gait speed during walking over obstacles only improved after the DTT. Significant improvements were found for both groups in various motor and cognitive measures. However, the DTT led to better dual-task walking compared to the SMT.

Motor fatigability in persons with multiple sclerosis: Relation between different upper limb muscles, and with fatigue and the perceived use of the arm in daily life.

BACKGROUND: Motor fatigability is increasingly acknowledged in persons with MS (pwMS). It is unknown whether fatigability is generalized across upper limb muscles and relates to fatigue and perceived difficulties in upper limb use. METHODS: This observational case-controlled study included twenty PwMS (median EDSS = 3, range 1.5-6.5) and twenty healthy controls who performed 30″ sustained maximal muscle contractions for index finger abduction, hand grip, elbow flexion and shoulder abduction. A static fatigue index (SFI) was calculated to assess motor fatigability for each muscle group. PwMS completed the Fatigue Severity Scale (FSS) and Modified Fatigue Index Scale (MFIS), to quantify severity and perceived impact of fatigue and the Manual Ability Measure (MAM-36) reflecting perceived difficulty in using the upper limbs. Comparisons between groups and muscles was made by t-tests. Associations between outcomes were calculated with correlation coefficients. RESULTS: Fatigue was highest in pwMS. PwMS showed preserved muscle strength and a greater motor fatigability in elbow flexors compared to healthy controls. SFI of elbow flexors and shoulder abductors were associated, and contributed to FSS and MFIS. SFI of elbow flexors and finger abductors predicted half of the variation in MAM-36. CONCLUSION: Increased motor fatigability was only present in elbow flexors of PwMS, indicating that expression of motor fatigability is not generalized. Fatigability was associated with perceived fatigue (impact) and daily life upper limb use. Results are preliminary given the small sample size with predominantly persons with mild MS.

Walking endurance and perceived symptom severity after a single maximal exercise test in persons with mild disability because of multiple sclerosis.

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 75 min 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 75 min 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 75 min. Walking endurance was not affected by the maximal exercise test.