Is the impact of fatigue related to walking capacity and perceived ability in persons with multiple sclerosis? A multicenter study.

BACKGROUND: The relationship between fatigue impact and walking capacity and perceived ability in patients with multiple sclerosis (MS) is inconclusive in the existing literature. A better understanding might guide new treatment avenues for fatigue and/or walking capacity in patients with MS. OBJECTIVE: To investigate the relationship between the subjective impact of fatigue and objective walking capacity as well as subjective walking ability in MS patients. METHODS: A cross-sectional multicenter study design was applied. Ambulatory MS patients (n = 189, age: 47.6 ±â€¯10.5 years; gender: 115/74 women/men; Expanded Disability Status Scale (EDSS): 4.1 ±â€¯1.8 [range: 0-6.5]) were tested at 11 sites. Objective tests of walking capacity included short walking tests (Timed 25-Foot Walk (T25FW), 10-Metre Walk Test (10mWT) at usual and fastest speed and the timed up and go (TUG)), and long walking tests (2- and 6-Minute Walk Tests (MWT). Subjective walking ability was tested applying the Multiple Sclerosis Walking Scale-12 (MSWS-12). Fatigue impact was measured by the self-reported modified fatigue impact scale (MFIS) consisting of a total score (MFIStotal) and three subscales (MFISphysical, MFIScognitive and MFISpsychosocial). Uni- and multivariate regression analysis were performed to evaluate the relation between walking and fatigue impact. RESULTS: MFIStotal was negatively related with long (6MWT, r = -0.14, p = 0.05) and short composite (TUG, r = -0.22, p = 0.003) walking measures. MFISphysical showed a significant albeit weak relationship to walking speed in all walking capacity tests (r = -0.22 to -0.33, p < .0001), which persisted in the multivariate linear regression analysis. Subjective walking ability (MSWS-12) was related to MFIStotal (r = 0.49, p < 0.0001), as well as to all other subscales of MFIS (r = 0.24-0.63, p < 0.001), showing stronger relationships than objective measures of walking. CONCLUSIONS: The physical impact of fatigue is weakly related to objective walking capacity, while general, physical, cognitive and psychosocial fatigue impact are weakly to moderately related to subjective walking ability, when analysed in a large heterogeneous sample of MS patients.

Muscle strength and power in persons with multiple sclerosis - A systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease in the central nervous system which causes a number of physical symptoms including impairments of muscle mechanical function (muscle strength, muscle power and explosive muscle strength (~rate of force development, RFD)). However, a full overview of the existing knowledge regarding muscle mechanical function in persons with MS (PwMS) is still pending. OBJECTIVES: To systematically review 1) the psychometric properties of isokinetic dynamometry testing in PwMS, and 2) studies comparing muscle mechanical function in PwMS to matched healthy controls (HC). In addition, a meta-analysis will evaluate 3) the effects of progressive resistance training on muscle mechanical function in PwMS. METHODS: A systematic literature search was performed in eight databases. To be included in the review, the study had to 1) enroll participants with a confirmed diagnosis of MS; 2) assess muscle mechanical function 3) had undergone peer-review. The psychometric properties of isokinetic dynamometry were reviewed with respect to validity, reliability, and responsiveness. Comparison of muscle strength between PwMS and HC was performed across contraction velocities, contraction modes and muscle groups, as were the rate of force development. The effects of progressive resistance training on muscle mechanical function were evaluated in a meta-analysis using a random effects model and standardized mean difference (SMD). RESULTS: A total of four, twenty-four, and ten studies were identified for aim 1, 2, and 3, respectively. High Intraclass correlations coefficients (range: 0.87-0.99) for isokinetic dynamometry was reported when assessing knee extensor and knee flexor muscle strength independent of contraction velocity. Compared to match HC, PwMS display impaired muscle strength, power and explosive muscle strength. Muscle strength impairments were most pronounced during maximal moderate to fast dynamic muscle contractions of the lower extremities. Progressive resistance training has a small but significant effect on muscle mechanical function in PwMS (SMD=0.45, 95% CI: 0.18-0.72, p=0.001). CONCLUSIONS: The present review showed that 1) isokinetic dynamometry has a high reliability in PwMS; 2) muscle strength, power and rate of force development is impaired in PwMS compared to HC, and muscle strength impairments are most pronounced during maximal moderate to fast dynamic muscle contractions of the lower extremities; and 3) progressive resistance training can improve muscle mechanical function in PwMS. Future studies should evaluate progressive resistance training designed to optimize maximal moderate to fast dynamic muscle contractions of the lower extremities.

Brain derived neurotrophic factor in multiple sclerosis: effect of 24 weeks endurance and resistance training.

BACKGROUND AND PURPOSE: Brain derived neurotrophic factor (BDNF) is suggested to play a neuroprotective role in multiple sclerosis (MS). However, the BDNF response to long-term exercise in MS remains unknown. Our objective was to compare resting BDNF profiles of healthy controls (HCs) and persons with relapsing-remitting MS (RRMS) and to investigate the impact of a 24-week exercise intervention on serum BDNF release in MS. METHODS: At baseline, blood BDNF levels were assessed in MS (n = 22, mean Expanded Disability Status Scale 2.6 ± 0.2, mean age 43 ± 2 years) and HCs (n = 19, mean age 47 ± 1 year). Next, persons with MS were randomized to an exercise intervention group (EX, n = 15) or a sedentary control group (SED, n = 7) completing a 24-week randomized controlled trial. In persons with MS, muscle strength, exercise tolerance and body composition were assessed, as compliance measures, at baseline and after 24 weeks. RESULTS: At baseline, the BDNF concentration of persons with RRMS was 21% lower than HCs. Following 24 weeks of intervention, changes in BDNF concentrations differed significantly between EX and SED. In particular, within EX BDNF concentrations increased 13.9% ± 8.8%, whereas it decreased 10.5% ± 4.1% within SED. Furthermore, 24 weeks of exercise induced changes in the compliance measures between EX and SED. In addition, within EX muscle strength, exercise tolerance and lean tissue mass improved, whereas these remained stable within SED. CONCLUSION: In conclusion, BDNF concentration of persons with RRMS was lower compared to HCs and increased after 24 weeks of exercise in persons with MS, compared to the non-exercise MS control group.

Impact of high intensity exercise on muscle morphology in EAE rats.

The impact of high-intensity exercise on disease progression and muscle contractile properties in experimental autoimmune encephalomyelitis (EAE) remains unclear. Control (CON) and EAE rats were divided into sedentary and exercise groups. Before onset (experiment 1, n=40) and after hindquarter paralysis (experiment 2, n=40), isokinetic foot extensor strength, cross sectional area (CSA) of tibialis anterior (TA), extensor digitorum longus (EDL) and soleus (SOL) and brain-derived neurotrophic factor (BDNF) levels were assessed. EAE reduced muscle fiber CSA of TA, EDL and SOL. In general, exercise was not able to affect CSA, whereas it delayed hindquarter paralysis peak. CON muscle work peaked and declined, while it remained stable in EAE. BDNF-responses were not affected by EAE or exercise. In conclusion, EAE affected CSA-properties of TA, EDL and SOL, which could, partly, explain the absence of peak work during isokinetic muscle performance in EAE-animals. However, exercise was not able to prevent muscle fiber atrophy.

Ventilatory function during exercise in multiple sclerosis and impact of training intervention: cross-sectional and randomized controlled trial.

BACKGROUND: Patients with MS (pwMS) often experience resting ventilatory anomalies. Ventilatory function during exercise and impact of long-term training intervention remains however uncertain. AIM: The aim of this study was to examine the ventilatory function during exercise and impact of a 6-month training intervention in pwMS. DESIGN: Combination of a cross-sectional (part 1) and randomized controlled trial (part 2). SETTING: University rehabilitation facility. POPULATION: Caucasian patients with MS and healthy controls. METHODS: In part 1, the ventilatory function during submaximal endurance exercise was compared between pwMS (N.=37) and healthy participants (N.=15). In part 2, pwMS were then randomly assigned to a 6-month training intervention (N.=16) or usual care (N.=11). Following training intervention, ventilatory function during exercise was re-evaluated. RESULTS: Despite comparable relative exercise testing intensities between groups in part 1, significantly elevated steady-state exercise dead space/tidal volume ratio, O2 uptake and CO2 output equivalent, end-tidal O2 pressure, ratings of perceived exertion and lowered end-tidal CO2 pressure and O2 pulse was observed in pwMS (P<0.05). The degree of ventilatory dysfunction during exercise correlated significantly with ratings of perceived exertion and blood lactate content (P<0.05). In part 2, despite an improved exercise tolerance (based on reductions in heart rate, blood lactate content and ratings of perceived exertion during exercise at similar workload) after a 6-month training intervention, ventilatory dysfunction remained present during endurance exercise (P>0.05). CONCLUSION: Patients with MS experience a ventilatory dysfunction during endurance exercise, which is related to worse exercise tolerance. This ventilatory anomaly remains present after long-term training intervention. CLINICAL REHABILITATION IMPACT: Patients with MS experience ventilatory dysfunction during exercise. This dysfunction is related to exercise tolerance and ratings of perceived exertion. Long-term exercise training did not remediate this ventilatory dysfunction. The systematic examination of the pulmonary/cardiovascular system at rest and during exercise is recommended in MS.

Is long-term exercise intervention effective to improve cardiac autonomic control during exercise in subjects with multiple sclerosis? A randomized controlled trial.

BACKGROUND: Patients with multiple sclerosis (MS) suffer from a disturbed cardiac autonomic control during exercise (based on heart rate (HR) changes during exercise), which affects exercise tolerance. Whether long-term exercise intervention improves HR changes during exercise in patients with MS remains unknown. AIM: To examine whether long-term exercise intervention improves HR changes during exercise, and correlates with improvements in exercise tolerance, in patients with MS. DESIGN: Randomized controlled trial. SETTING: University rehabilitation facility. POPULATION: Twenty-three patients with MS were randomly assigned to six months of follow-up (n=9) or six months of exercise training (n=14, 54-60 training sessions). METHODS: At baseline and after three and six months of follow-up, exercise-onset (first 20 and 60 seconds) and -offset (1-minute recovery) heart rate (HR) change was determined during a constant-load exercise test: these data reflect the (re)activation of the (para)sympathetic nervous system at initiation and/or cessation of exercise. Blood lactate, HR, oxygen uptake, expiratory volume and ratings of perceived exertion (RPE) were assessed during exercise as indicators for exercise tolerance. RESULTS: Exercise-onset and -offset HR and exercise tolerance did not change during follow-up in the control group (P>0.05). In the exercise intervention group, blood lactate content and RPE during exercise decreased significantly (group/time interaction effect P<0.05), but exercise-onset and -offset HR did not change (P>0.05). No correlations were found between changes in exercise tolerance and changes in exercise-onset and -offset HR (P>0.05). CONCLUSION: In patients with MS, long-term exercise intervention does not improve HR changes during exercise, despite improvements in exercise tolerance, indicating that cardiac autonomic control during exercise is not easily improved by exercise intervention in patients with MS. CLINICAL REHABILITATION IMPACT: This study indicates that patients with MS suffer from a disturbed cardiac autonomic control during exercise, based on heart rate changes, which is not easily remediated by exercise intervention. Because a disturbed cardiac autonomic control is related to exercise intolerance in MS, it should further be explored how to remediate this anomaly through exercise intervention or other approaches.

Does multiple sclerosis affect glucose tolerance?

Based on current literature, it is not clear if multiple sclerosis (MS) patients are at increased risk to develop impaired glucose tolerance (IGT). Eighty-one MS patients and 45 healthy controls (HC) performed an oral glucose tolerance test. IGT was defined as a fasting glucose concentration of 6.1-6.9 mmol/l and two-hour post-load glucose of 7.8-11.1 mmol/l. The prevalence of impaired fasting glucose concentrations (17% vs 2%) and IGT (11% vs 0%) was higher in MS patients than HC. Accordingly, the areas under the glucose and insulin curves were higher in MS patients. The current study demonstrates an elevated IGT-prevalence in MS.

Spatio-temporal gait parameters change differently according to speed instructions and walking history in MS patients with different ambulatory dysfunction.

BACKGROUND: Different walking capacity test formats are applied, but their impact on the gait pattern in persons with MS (pwMS) has not yet been investigated according to baseline velocity performance. OBJECTIVE: To assess, in pwMS with different ambulation dysfunction, the impact of speed instructions and previous walking tests (2 and 6min walking test; 2MWT and 6MWT) on spatiotemporal gait parameters. METHODS: 27 participants, divided in three groups based on usual gait speed (Most Limited Community Walkers; MLCW<0.82m/s, CW>1.14m/s, LCW show intermediate values), completed the 2MWT and 6MWT. Before and after each test, they walked on the GAITRite walkway system at both usual and fastest speed. Spatio-temporal gait parameters were measured and analyzed with ANOVA. RESULTS: All gait parameters in the MLCW were significantly different from other groups. In contrast to the MLCW, the LCW and CW subgroups showed greater velocity in the fastest compared to usual speed condition, associated with a significant increase in cadence and step length. After the 6MWT, small changes in cadence at usual speed and step time at fastest speed were observed in the MLCW subgroup only. No impact of the 2MWT on gait parameters was found in any group. CONCLUSIONS: The ability to accelerate was dependent on the severity of ambulatory dysfunction. Prolonged walking during the 6MWT has, in contrast to the 2MWT, some impact on gait parameters in the most disabled group only.