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

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

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.status: publishe

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

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.status: publishe

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

Influence of increased weight on gait characteristics in children with cerebral palsy

SUMMARY Objective of the study was to explore changes in gait patterns caused by artificially enlarging the impact of weakness in children with cerebral palsy (CP). CONCLUSIONS Walking with 10% extra weight in children with CP resulted in reduced walking speed, increased crouch and decreased pelvic ROM. INTRODUCTION One of the primary neurological motor deficits in CP is weakness. Overall moderate correlations were found between lower limb strength and gait data1,2,3,4. Prediction on gait patterns based upon clinical measurements, such as strength evaluation, remains limited5. Manipulating primary neurological deficits, such as weakness, may enable a more precise evaluation and objective quantification of the impact of the deficit on the gait pattern. PATIENTS, MATERIALS AND METHODS Ten children with CP (6 hemi-, 4 diplegia, mean age 8.9 years) were included into this prospective pilot study (inclusion criteria: diagnosis of CP, 5-12 years of age, no history of surgery or recent BTX-A treatment). All children first received full barefoot gait analysis (lower limb kinematics and kinetics, 8 camera vicon system, 2 AMTI force plates, PlugInGait markerset). Subsequently, extra gait trials were collected after indirectly enlarging the impact of weakness on the gait pattern. Muscle strength was therefore relatively reduced by adding 10% weight to the body, by means of a diving belt (lead was fixed to the belt). To avoid asymmetry, the weight was evenly distributed around the waist, close to S-2, which is considered to be the approximate location of the centre of mass. For each patient the gait analysis data of two trials were used. 72 gait parameters per gait trial were compared between the baseline and extra weight condition by one-way ANOVA (with posthoc Tuckey). RESULTS Children with CP who walked with increased weight showed significantly reduced walking speed and a delayed timing of toeoff compared to the baseline condition. Extra weight also caused increased knee flexion at initial contact and an overall more flexed position in stance. Significant changes due to extra weight were also recognized at the hip and pelvis (Table 1). DISCUSSION This pilot study highlighted some changes in gait due to extra weight, which may be considered as parameters that measure the ‘provoked’ weakness. Our conclusions concerning gait parameters that are sensitive to weakness should be tentative as we have a limited number of analysed patients so far. Future analysis in a larger group, including a control group of typical children, and with increased intersubject variability for strength and functional level, can help to recognize patients who walk with a gait pattern that is mainly related to overall weakness. REFERENCES [1] Ross et al. (2007), Arch Phys Med Rehabil 8(8):1114-1120. [2] Damiano et al. (2001), Eur J Neurol 8(5):40-49. [3] Engsberg et al. (2006) Pediatr Phys Ther 18(4):266-275. [4] Morton et al. (2005) Clinic Rehab 19(3):283-289.status: publishe

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 re-lapsing 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 pro-gression 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

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

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.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.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.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