Effects of power training in older patients with multiple sclerosis on neurodegeneration, neuromuscular function, and physical function. A study protocol for the "power training in older multiple sclerosis patients (PoTOMS) randomized control trial.

Introduction: Approximately one-third of all persons with multiple sclerosis (pwMS) are older, i.e., having an age ≥60 years. Whilst ageing and MS separately elicit deteriorating effects on brain morphology, neuromuscular function, and physical function, the combination of ageing and MS may pose a particular challenge. To counteract such detrimental changes, power training (i.e., a type of resistance exercise focusing on moderate-to-high loading at maximal intended movement velocity) presents itself as a viable and highly effective solution. Power training is known to positively impact physical function, neuromuscular function, as well as brain morphology. Existing evidence is promising but limited to young and middle-aged pwMS, with the effects of power training remaining to be elucidated in older pwMS. Methods: The presented 'Power Training in Older MS patients (PoTOMS)' trial is a national, multi-center, parallel-group, randomized controlled trial. The trial compares 24 weeks of usual care(n = 30) to 24 weeks of usual care and power training (n = 30). The primary outcome is whole brain atrophy rate. The secondary outcomes include changes in brain micro and macro structures, neuromuscular function, physical function, cognitive function, bone health, and patient-reported outcomes. Ethics and dissemination: The presented study is approved by The Regional Ethics Committee (reference number 1-10-72-222-20) and registered at the Danish Data Protection Agency (reference number 2016-051-000001). All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences independent of the results. The www.clinicaltrials.gov identifier is NCT04762342.

The combined deleterious effects of multiple sclerosis and ageing on neuromuscular function.

BACKGROUND: The prevalence of older (>60 years) people with multiple sclerosis (pwMS) is increasing. This introduces numerous challenges, as both MS and ageing independently contribute to the deterioration of neuromuscular function. AIM: The aim was to compare the neuromuscular function in pwMS and healthy controls (HC) across three age groups: young, middle-aged, and old. METHODS: Using a cross-sectional study design, the maximal muscle strength (Fmax) and rate of force development (RFD) of the knee extensors (KE) and plantar flexors (PF) were assessed using an isokinetic dynamometer. In addition, voluntary activation (VA) and resting twitch (RT) were measured using the interpolated twitch technique. RESULTS: The Fmax, RFD, and VA of the KE were reduced in pwMS compared to HC across age groups. In pwMS, reductions were observed in PF Fmax, RFD, and RT, predominantly in the middle-aged and old age groups. Reductions increased with age in KE for both groups (except for VA) but in PF only for pwMS. The "trajectory" differed between pwMS and HC, as pwMS showed reductions from young to middle age, while HC showed reductions from middle to old age in KE. CONCLUSION: The combined negative effects of MS and ageing on neuromuscular function were especially present in the PF but also substantial in the KE. RFD showed large deficits for pwMS compared to HC across age groups. The findings can partly be explained by a reduction in VA and RT, but further investigations of neural regulation are needed to explain large RFD deficits.

Tuberculosis screening among newly arrived asylum seekers in Denmark.

BACKGROUND: Tuberculosis (TB) screening programmes among asylum seekers tend to focus on chest radiography (CXR) for early diagnosis, whereas knowledge on sputum examination is limited. We evaluated active TB screening using CXR and sputum culture among asylum seekers arriving in Denmark. In addition, we assessed the coverage of a voluntary health assessment. METHODS: Between 1 February 2017 and 31 March 2019, all newly arrived asylum seekers in Denmark ≥ 18 years from TB high-incidence countries or risk groups, who attended a voluntary general health assessment, were offered active TB screening with CXR and spot sputum examination. Sputum samples were examined by culture and smear microscopy. RESULTS: Coverage of the general health assessment was 65.1%. Among 1,154 referred for active TB screening, 923 (80.0%) attended. Of these, 854 were screened by CXR and one case of active TB was identified equivalent to a yield of 0.12%. Sputum samples were collected from 758 and one M. tuberculosis culture-positive TB case (also identified by CXR) was identified, equivalent to a yield of 0.13%. No cases were found by sputum culture screening only. In addition, screening found three cases of malignant disease. CONCLUSION: We suggest that TB screening should focus on asylum seekers from TB high-incidence countries. Furthermore, early health assessments should be of high priority to ensure migrant health.

Identification of disability status in persons with multiple sclerosis by lower limb neuromuscular function - Emphasis on rate of force development.

BACKGROUND: Neurodegeneration is an inevitable consequence of multiple sclerosis (MS) leading to impaired neuromuscular function, especially of the lower extremities. Whilst maximal muscle strength (or force; Fmax) is the most examined feature of neuromuscular function, the ability to rapidly increase muscle force (= rate of force development; RFD) appear to be preferentially sensitive towards neurodegeneration and potentially also of great importance for physical function. The purpose of the present study was to comprehensively examine and compare different outcome measures of neuromuscular function (with specific emphasis given to RFD) across disability status in persons with MS (pwMS), and in comparison, to age- and sex-matched healthy controls (HC). METHODS: A total of n=34 HC and n=99 pwMS were enrolled in the study, with the latter being divided into Expanded Disability Status Scale (EDSS) subgroups: MSmild (EDSS 0-2.5, n=51), MSmoderate (EDSS 3.0-4.5, n=33), and MSsevere (EDSS 5-6.5, n=15). Knee extensor neuromuscular function was assessed by Fmax and RFD (RFD50ms and RFD200ms, respectively; calculated in the interval 0-50 ms and 0-200 ms relative to the onset of contraction) with simultaneous electromyography (maximal EMG (EMGFmax) and rate of EMG rise (rEMG50ms and rEMG200ms, respectively)). Voluntary muscle activation derived from the interpolated twitch technique was also determined during additional Fmax trials. Lastly, physical function was assessed by the 5 x sit-to-stand test (5STS), the timed 25-foot walk test (T25FWT), and the 2-min walking test (2MWT). RESULTS: Substantial differences (∼deficits) (p<0.05) were observed for all pwMS subgroups compared to HC across all neuromuscular function outcome measures; RFD50ms (MSmild -22%, MSmoderate -36%, MSsevere -66%), RFD200ms (-12%, -21%, -51%), and Fmax (-11%, -14%, -33%). Somewhat comparable differences (∼deficits) (p<0.05) were observed for voluntary muscle activation (rEMG50ms, rEMG200ms, EMGFmax, and activation) and for physical function (5STS, T25FWT, and 2MT). Deficits in neuromuscular function were strongly associated with EDSS (p<0.05) (RFD50ms: slope steepness -13% per 1 point increase in EDSS, r2=0.79; RFD200ms: slope steepness -10%, r2=0.84; Fmax: slope steepness -6%, r2=0.82). Fmax and RFD were associated with physical function outcome measures (p<0.05) to a comparable extent (r2-values ranging from 0.21 to 0.35). CONCLUSION: Lower extremity neuromuscular function is impaired in pwMS compared to HC with differences (∼deficits) becoming greater with increasing disability status. RFD was preferentially sensitive in capturing differences (∼deficits) across disability status and by showing strong associations with EDSS. Altogether, knee extensor RFD could serve as a simple objective marker of disability status or even progression in pwMS, that may be helpful to both researchers and clinicians.

Physical activity is associated with neuromuscular and physical function in patients with multiple sclerosis independent of disease severity.

PURPOSE: Examine the association between physical activity and neuromuscular and physical function in patients with multiple sclerosis when also considering disease severity. METHODS: 91 patients with multiple sclerosis were enrolled. Assessments included physical activity by 7-day thigh-worn accelerometry, knee extensor neuromuscular function by dynamometry (maximal isometric muscle strength, rate of force development (0-50 ms)), and physical function by 5× sit-to-stand, 2-min walk test, and timed 25 ft walk test. Physical activity tertile comparisons along with simple and multiple regressions (adjusting for age, gender, EDSS, time since diagnosis) were performed. RESULTS: Physical activity tertiles revealed differences (p < 0.05) in maximal muscle strength (1.77 ≈ 1.97 < 2.28 Nm/kg), rate of force development (4.66 < 8.03 ≈ 10.55 Nm/kg/s), 5× sit-to-stand (11.4 ≈ 9.7 > 8.5 s), 2-min walk test (153 < 183 < 207 m), and timed 25 ft walk test (6.3 > 4.4 > 4.3 s). Moreover, physical activity was associated (p < 0.05) with maximal muscle strength and rate of force development (r2 = 0.13-0.15) along with 5× sit-to-stand, 2-min walk test, and timed 25 ft walk test (r2 = 0.18-0.24), also after adjusting for age + gender + EDSS + time since diagnosis (r2 = 0.25-0.37 and 0.24-0.52), with physical activity consistently being a strong predictor. CONCLUSIONS: Higher levels of physical activity are associated with greater neuromuscular and physical function in ambulatory patients with multiple sclerosis independent of disease severity. These findings emphasize the importance of performing regular physical activity at all stages of multiple sclerosis.IMPLICATIONS FOR REHABILITATIONPhysical activity is associated with neuromuscular and physical function, independent of disease severity.Physical activity may be important in improving or preserving neuromuscular and physical function at all stages of ambulatory multiple sclerosis patients, yet longitudinal studies are warranted.Clinicians and rehabilitation professionals should encourage ambulatory patients at all stages of their disease to be as physically active as possible.

How do resistance training and balance and motor control training affect gait performance and fatigue impact in people with multiple sclerosis? A randomized controlled multi-center study.

BACKGROUND: Despite a shared purpose of improving functional capacity, the principles of progressive resistance training (PRT) and balance and motor control training (BMCT) are fundamentally different. OBJECTIVES: To investigate the effects of PRT and BMCT on gait performance and fatigue impact in people with multiple sclerosis (PwMS). METHODS: A multi-center, single-blinded, cluster-randomized controlled trial with two intervention groups (PRT and BMCT) and a control group (CON). The interventions lasted 10 weeks. A total of 71 participants with impaired mobility (Timed 25-Foot Walk (T25FW) > 5 seconds or Six Spot Step Test (SSST) > 8 seconds) were enrolled. Primary outcomes were the T25FW and the SSST. Fatigue impact, self-perceived gait function, 6-minute walk, balance, and muscle strength were secondary outcomes. RESULTS: In total, 83% completed the study. The primary comparisons showed that BMCT, but not PRT, improved T25FW, SSST, and self-perceived gait function when compared to CON. Secondary comparisons showed that BMCT improved SSST more than PRT, while T25FW did not differ. Both BMCT and PRT reduced the fatigue impact. Finally, the effect of BMCT was superior to PRT on dynamic balance, while PRT was superior to BMCT on knee extensor muscle strength. CONCLUSION: BMCT, but not PRT, was superior to CON in improving gait performance, while both BMCT and PRT reduced fatigue.

Can we trust self-reported walking distance when determining EDSS scores in patients with multiple sclerosis? The Danish MS hospitals rehabilitation study.

BACKGROUND: In multiple sclerosis (MS), the Expanded Disability Status Scale (EDSS) reflects disease severity. Although parts of the EDSS are dependent on actual walking distance, self-reported statements are often applied. OBJECTIVES: The purpose of the present study was, therefore, to compare self-reported walking distance to actual walking distance to outline how this influences EDSS scoring. METHODS: MS patients with EDSS 4.0-7.5 (n = 273) were included from the Danish MS hospitals rehabilitation study (n = 427). All patients subjectively classified their maximal walking distance according to one of seven categories (>500; 300-499; 200-299; 100-199; 20-99; 5-19; 0-4 m). Subsequently, actual maximal walking distance was assessed and EDSS was determined from both self-reported walking distance (EDSSself-report) and actual walking distance (EDSSactual). RESULTS: In 145 patients (53%), self-reported walking distance was misclassified when compared to the actual walking distance. Misclassification was more frequent in patients using walking aids (64% vs. 44%, p < 0.05) and in patients with primary progressive MS (69%, p < 0.05). Misclassification of walking distance corresponded to incorrect EDSS scores (EDSSself-report vs EDSSactual) of ⩾0.5 point in 24%. CONCLUSION: In MS patients with EDSS 4.0-7.5, 53% misclassified their walking distance yielding incorrect EDSS scores in 24%. Therefore, correct EDSS determination must be based on measurement of actual walking distance.