Between-Day Reliability of the Gait Characteristics and Their Changes During the 6-Minute Walking Test in People With Multiple Sclerosis.

BACKGROUND: Gait characteristics and their changes during the 6-minute walking test (6MWT) in people with multiple sclerosis (pwMS) have been described in the literature, which one may refer to as walking fatigability in the body function level of the International Classification of Functioning, Disability, and Health. However, whether these metrics are reliable is unknown. OBJECTIVE: To investigate the between-day reliability of the gait characteristics and their changes in pwMS and healthy controls (HCs). METHODS: Forty-nine pwMS (EDSS 4.82 ± 1.22 and 54.7 ± 9.36 years) and 23 HCs (50.6 ± 6.1 years) performed the 6MWT, as fast as possible but safely while wearing Inertial Measurement Units. Gait characteristics were measured in the pace, rhythm, variability, asymmetry, kinematics, coordination, and postural control domains and were obtained in intervals of 1 minute during the 6MWT. In addition, gait characteristics change in the last minute compared with the first minute were calculated for all gait variables using a fatigability index (ie, distance walking index). The intraclass correlation coefficient (ICC), Bland-Altman Plots, and Standard error of measurement were applied to investigate reliability. RESULTS: Reliability of gait characteristics, minute-by-minute, and for their changes (ie, using the fatigability index) ranged from poor to excellent (pwMS: ICC 0.46-0.96; HC: ICC 0.09-0.97 and pwMS: ICC 0-0.72; HC: ICC 0-0.77, respectively). CONCLUSION: Besides coordination, at least 1 variable of each gait domain showed an ICC of moderate or good reliability for gait characteristics changes in both pwMS and HC. These metrics can be incorporated into future clinical trials and research on walking fatigability.Clinical Trial Registration: NCT05412043.

Safety and effectiveness of cladribine tablets for multiple sclerosis: Results from a single-center real-world cohort.

BACKGROUND: Cladribine tablets are a highly effective immune reconstitution therapy licensed for treating relapsing multiple sclerosis (RMS) in Europe since 2017. Currently, there is a high demand for real-world data from different clinical settings on the effectiveness and safety profile of cladribine in MS. METHODS: Within this report, we retrospectively evaluated the outcomes of RMS patients who received cladribine between August 2018 and November 2021 at our Belgian institute. Patients with data for three effectiveness endpoints, more specifically, relapses, MRI observations, and confirmed disability worsening were incorporated into the analysis of 'no evidence of disease activity' (NEDA-3) re-baselined at 3 months. Safety endpoints included lymphopenia, liver transaminases, and adverse events (AEs) during follow-up. Descriptive statistics and time-to-event analysis were performed, including subgroup analysis by pre-treatment. RESULTS: Of the 84 RMS patients included in this study (age 42 [33-50], 64.3% female, diagnosis duration 6 [2-11] years, baseline EDSS 2.5 [1.5-3.6]), 14 (16.7%) patients experienced relapses, while disability progression and brain MRI activity occurred in 8.5% (6/71) and 6.3% (5/79). This resulted in 72.6% (n = 69, standard error 6%) retaining NEDA-3 status at the mean follow-up time of 22.6 ± 11.5 months. During the first year after cladribine initiation, disease activity prevailed more in patients with ≥2 prior DMTs and those switching from fingolimod, although both trends were not statistically significant. In terms of safety, 67.9% reported at least one AE during follow-up, the most frequent being fatigue (64.9%) and skin-related problems (38.6%). CONCLUSION: Overall, our research results confirm cladribine's safety and effectiveness among RMS patients in real-world conditions. After the re-baseline, we observed high rates of NEDA-3-retention, and no new safety signals were noted.

Measuring Motor Fatigability in the Upper Limbs in Individuals With Neurologic Disorders: A Systematic Review.

OBJECTIVE: To summarize the literature on definitions, assessment protocols, and outcome measures for motor fatigability in patients with neurologic problems and investigates the known clinimetric properties according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. DATA SOURCES: Two databases were consulted for studies published between January 2003 and November 2018 using the terms "motor fatigability," "nervous system disease," and "upper limb." STUDY SELECTION: Studies were included if they were (1) not older than 15 years; (2) written in English, German, or Dutch; (3) involved upper limbs of patients with neurologic disease; and (4) adequately described protocols using maximum voluntary contractions. DATA EXTRACTION: Thirty-three studies were included, describing 14 definitions, 37 assessment protocols, and 9 outcome measures. The following data were obtained: (1) author and publication year; (2) aim; (3) fatigability definition; (4) sample characteristics; (5) fatigability protocol; (8) measurement system; and (9) outcome measure. DATA SYNTHESIS: Protocols relating to body function level of the International Classification of Functioning (ICF) were most often performed in patients with multiple sclerosis (MS) including maximal or submaximal, isometric or concentric, and eccentric contractions of variable duration. For ICF activities level, most protocols included wheelchair-related tasks. Clinimetric properties were known in 2 included protocols. Test-retest reliability in patients with MS were moderate to excellent for the static fatigue index and moderate for the dynamic fatigue index. CONCLUSIONS: Based on physiology, recommendations are made for protocols and outcome measures for motor fatigability at the ICF body function level. For the ICF activities level, too little is known to make sound statements on the use of protocols in populations with neurologic disease. Clinimetric properties should be further investigated for populations with neurologic problems.

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.

Force decline after low and high intensity contractions in persons with multiple sclerosis.

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.

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.

The Assessment of Motor Fatigability in Persons With Multiple Sclerosis: A Systematic Review.

BACKGROUND: Persons with multiple sclerosis (PwMS) are often characterized by increased motor fatigability, which is a performance change on an objectively measured criterion after any type of voluntary muscle contractions. This review summarizes the existing literature to determine which protocols and outcome measures are best to detect or study motor fatigability and the underlying mechanisms in MS. METHODS: Two electronic databases, PubMed and Web of Science, were searched for relevant articles published until August 2016 with a combination of multiple sclerosis, fatigability, muscle fatigue, and motor fatigue. RESULTS: A total of 48 articles were retained for data extraction. A variety of fatigability protocols were reported; protocols showed differences in type (isometric vs concentric), duration (15 to 180 s), and number of contractions (fixed or until exhaustion). Also, 12 articles reported motor fatigability during functional movements, predominantly assessed by changes in walking speed; 11 studies evaluated the mechanisms underlying motor fatigability, using additional electrical nerve or transcranial magnetic stimulation. Three articles reported psychometrics of the outcomes. CONCLUSIONS: The disparity of protocols and outcome measures to study different aspects of motor fatigability in PwMS impedes direct comparison between data. Most protocols use maximal single-joint isometric contractions, with the advantage of high standardization. Because there is no head-to-head comparison of the different protocols and only limited information on psychometric properties of outcomes, there is currently no gold standard to assess motor fatigability. The disability level, disease phenotype, and studied limb may influence the assessment of motor fatigability in PwMS.

Motor fatigability after low-intensity hand grip exercises in persons with multiple sclerosis.

INTRODUCTION: During maximal, sustained contractions, persons with multiple sclerosis (PwMS) show higher motor fatigability in comparison with healthy persons. It is not known if motor fatigability is also different between PwMS and healthy persons during low-intensity exercises. Thus, the aim of this study was to determine the difference in hand grip fatigability between healthy persons and PwMS for both hands during low-intensity hand grip exercises. METHODS: 19 PwMS and 19 healthy controls performed 18min of hand grip exercises at a maximum of 25% of the maximal voluntary strength, with an electronic hand dynamometer. Perceived fatigability, maximal hand grip strength and muscle activity (electromyography) of the wrist flexors and extensors were recorded in between these exercises for the dominant and non-dominant hand. RESULTS AND DISCUSSION: There was a significant decrease in maximal hand grip strength after exercising in both groups and for both hands, mainly situated in the first 6min. In contrast to what was hypothesized, PwMS did not show more decline in strength than healthy controls, neither in the dominant nor the non-dominant hand. There was no group difference in the increase of the perceived fatigability in the dominant hand. However, for the non-dominant hand, the perceived fatigability after exercising increased more in PwMS than in healthy controls. Additionally, there was no relation between fatigue indices, as assessed with short maximal contractions and the strength decline after low-intensity repetitive exercises.

Upper Limb Rehabilitation in People With Multiple Sclerosis: A Systematic Review.

Background There has been an increasing research interest in upper limb rehabilitation in multiple sclerosis (MS). The current changes in the research field inquire a new literature review. Objective This systematic review aimed to provide an overview of the upper limb rehabilitation strategies in people with MS (PwMS). Methods Articles published in PubMed and Web of Knowledge were selected when written in English, published in the past 25 years, peer reviewed, that included at least 5 PwMS, and described the effects of an intervention study including rehabilitation strategies targeting the upper limbs. Included articles were screened based on title/abstract and full text by 2 independent reviewers. Results Thirty articles met the criteria and were included for data extraction. Only half of the included studies investigated the effects of a training program specially targeted toward the upper limbs, while in the other studies, a general whole body therapy was used. The therapy content and dosage varied greatly between the different included studies. Multidisciplinary and robot-based rehabilitation were the most investigated rehabilitation strategies and showed to improve upper limb capacity. Strength and endurance training improved the upper limb body functions and structures but did not influence the upper limb capacity and performance. Conclusions The results of this systematic review indicated that different types of upper limb rehabilitation strategies can improve upper limb function in PwMS. Further research is necessary to compare directly the effects of different rehabilitation strategies and to investigate the optimal therapy dosage according to the upper limb disability level.

Prevalence of Walking-Related Motor Fatigue in Persons With Multiple Sclerosis: Decline in Walking Distance Induced by the 6-Minute Walk Test.

OBJECTIVE: To investigate the individual occurrence of walking-related motor fatigue in persons with multiple sclerosis (PwMS), according to disability level and disease phenotype.Study design This was a cross-sectional, multinational study.Participants They were 208 PwMS from 11 centers with Expanded Disability Status Scale (EDSS) scores up to 6.5. METHODS: The percentage change in distance walked (distance walked index, DWI) was calculated between minute 6 and 1 (DWI(6-1)) of the 6-Minute Walk Test (6MWT). Its magnitude was used to classify participants into 4 subgroups: (1) DWI(6-1)[≥5%], (2) DWI(6-1)[5%; -5%], (3) DWI(6-1)[-5%; > -15%], and (4) DWI(6-1)[≤-15%]. The latter group was labeled as having walking-related motor fatigue. PwMS were stratified into 5 subgroups based on the EDSS (0-2.5, 3-4, 4.5-5.5, 6, 6.5) and 3 subgroups based on MS phenotype (relapsing remitting [RR], primary progressive [PP], and secondary progressive [SP]). RESULTS: The DWI6-1was ≥5% in 16 PwMS (7.7%), between 5% and -5% in 70 PwMS (33.6%), between -5% and -15% in 58 PwMS (24%), and ≤-15% in 64 PwMS (30.8%). The prevalence of walking-related motor fatigue (DWI(6-1)[≤-15%]) was significantly higher among the progressive phenotype (PP = 50% and SP = 39%; RR = 15.6%) and PwMS with higher disability level (EDSS 4.5-5.5 = 48.3%, 6 = 46.3% and 6.5 = 51.5%, compared with EDSS 0-2.5 = 7.8% and 3-4 = 16.7%;P< .05). Stepwise multiple regression analysis indicated that EDSS, but not MS phenotype, explained a significant part of the variance in DWI(6-1)(R(2)= 0.086;P< .001). CONCLUSION: More than one-third of PwMS showed walking-related motor fatigue during the 6MWT, with its prevalence greatest in more disabled persons (up to 51%) and in those with progressive MS phenotype (up to 50%). Identification of walking-related motor fatigue may lead to better-tailored interventions.

Investigation of Fatigability during Repetitive Robot-Mediated Arm Training in People with Multiple Sclerosis.

BACKGROUND: People with multiple sclerosis (MS) are encouraged to engage in exercise programs but an increased experience of fatigue may impede sustained participation in training sessions. A high number of movements is, however, needed for obtaining optimal improvements after rehabilitation. METHODS: This cross-sectional study investigated whether people with MS show abnormal fatigability during a robot-mediated upper limb movement trial. Sixteen people with MS and sixteen healthy controls performed five times three minutes of repetitive shoulder anteflexion movements. Movement performance, maximal strength, subjective upper limb fatigue and surface electromyography (median frequency and root mean square of the amplitude of the electromyography (EMG) signal of the anterior deltoid) were recorded during or in-between these exercises. After fifteen minutes of rest, one extra movement bout was performed to investigate how rest influences performance. RESULTS: A fifteen minutes upper limb movement protocol increased the perceived upper limb fatigue and induced muscle fatigue, given a decline in maximal anteflexion strength and changes of both the amplitude and the median frequency of EMG the anterior deltoid. In contrast, performance during the 3 minutes of anteflexion movements did not decline. There was no relation between changes in subjective fatigue and the changes in the amplitude and the median frequency of the anterior deltoid muscle, however, there was a correlation between the changes in subjective fatigue and changes in strength in people with MS. People with MS with upper limb weakness report more fatigue due to the repetitive movements, than people with MS with normal upper limb strength, who are comparable to healthy controls. The weak group could, however, keep up performance during the 15 minutes of repetitive movements. DISCUSSION AND CONCLUSION: Albeit a protocol of repetitive shoulder anteflexion movements did not elicit a performance decline, fatigue feelings clearly increased in both healthy controls and people with MS, with the largest increase in people with MS with upper limb weakness. Objective fatigability was present in both groups with a decline in the muscle strength and increase of muscle fatigue, shown by changes in the EMG parameters. However, although weak people with multiple sclerosis experienced more fatigue, the objective signs of fatigability were less obvious in weak people with MS, perhaps because this subgroup has central limiting factors, which influence performance from the start of the movements.

Hand grip fatigability in persons with multiple sclerosis according to hand dominance and disease progression.

BACKGROUND: Hand grip strength in both the dominant and non-dominant hands is often used to assess upper limb impairment. Excessive hand grip fatigability is another important measure, as fatigability may also influence activities of daily living. OBJECTIVE: To investigate to what extent hand grip fatigability in multiple sclerosis is dependent on hand dominance, muscle strength and disease progression. METHODS: Thirty persons with multiple sclerosis and 16 healthy controls performed 15 repeated maximal hand grip contractions and a 30 s sustained contraction in order to determine dynamic and static fatigue indices. Fatigability was compared between the dominant and non-dominant hands and between the more and less affected hands in a subgroup of persons with multiple sclerosis with asymmetrical hand grip strength impairment. Furthermore, fatigability was compared between controls and subgroups of persons with multiple sclerosis with different disease progression. RESULTS: There was no difference in fatigability between dominant and non-dominant hands in healthy controls or in persons with multiple sclerosis. Similarly, there was no difference between the more and less affected hands in the subgroup of persons with multiple sclerosis with asymmetrical hand grip impairment. The dynamic fatigue index did not discriminate persons with multiple sclerosis from controls. While the static fatigue index was not different between healthy controls and persons with multiple sclerosis with low to moderate (< 6) Expanded Disability Status Scale (EDSS), it was significantly higher in persons with multiple sclerosis with high (≥ 6) EDSS scores. The static fatigue index was related to the EDSS score, but not to maximal grip strength. CONCLUSION: Fatigability of hand grip strength in persons with multiple sclerosis is not influenced by hand dominance or muscle strength, but there is a correlation with disease progression. Differences in fatigability between healthy controls and, in particular, persons with multiple sclerosis with high EDSS, were found during sustained, but not during dynamic, contractions.

Self-reported use of the upper limbs related to clinical tests in persons with multiple sclerosis.

PURPOSE: This study investigated the relationship between self-reported use of the upper limbs and clinical tests in persons with multiple sclerosis (pwMS). METHODS: This cross-sectional study involved 25 pwMS with upper limb dysfunction. The Motor Activity Log (MAL) was bilaterally applied to investigate the self-reported use of both upper limbs. Clinical tests on function level were the Motricity Index (MI) and the Brunnström-Fugl-Meyer (BFM). On activity level, the Action Research Arm test (ARAt) was conducted. To identify the relationship between the self-reported use and the clinical tests, Spearman correlation coefficients were calculated. Subgroups of dominant and non-dominant arms were differentiated, and compared with the Wilcoxon Signed rank test. RESULTS: The highest correlations were found between the MAL and function level tests: MI (r = 0.83, p < 0.01) and BFM (r = 0.75, p < 0.01). A lower correlation was found between the MAL and the ARAt (r = 0.49, p < 0.01). For all outcome measures, the absolute scores were higher for the dominant hand. Higher correlations were found for the non-dominant compared to the dominant hand. CONCLUSION: The self-reported use of the upper limbs was highly associated with measures on function level. The association with activity level was, however, less pronounced. Magnitudes of relationships were influenced by hand dominance. Implications for Rehabilitation Self-reported use of the upper limbs in persons with MS, measured by the MAL, is highly associated with muscle strength and movement control. The ARAt (activity level of the ICF) is less associated with self-reported use compared to outcome measures at function level. The ARAt seems to be less sensitive to mild arm dysfunction. This study indicates that it is feasible and clinically relevant to apply the MAL as a self-reported outcome measure of upper limb use in MS.

Time course of trunk, arm, leg, and functional recovery after ischemic stroke.

BACKGROUND: Patterns of recovery provide useful information concerning the potential of physical recovery over time and therefore the setting of realistic goals for rehabilitation programs. OBJECTIVE: To compare the time course of trunk recovery with the patterns of recovery of arm, leg, and functional ability. METHODS: Consecutive stroke patients were recruited in 2 acute neurology wards. Participants were evaluated at 1 week, 1 month, and 3 and 6 months after stroke. Patients were assessed with the Trunk Impairment Scale, Fugl-Meyer arm and leg test, and Barthel Index. RESULTS: Thirty-two patients were included in the study. There were no dropouts. Repeated measures analysis of the recovery patterns of motor and functional performance revealed the most striking improvement for all measures from 1 week to 1 month (P value between .0021 and <.0001) and a significant improvement from 1 month to 3 months after stroke (P value ranges from .0008 to <.0001). No significant improvement was found between 3 and 6 months after stroke for any of the measures. Statistical analysis revealed no significant difference between time course of trunk, arm, leg, and functional recovery (P = .2565). No significant differences in level of motor and functional recovery were found at the different time points. CONCLUSIONS: Separate analyses of motor and functional recovery patterns after stroke confirm the importance of the first month for recovery. Contrary to common belief, the time course of recovery of the trunk is similar to the recovery of arm, leg, and functional ability.