Inez Wens

Responsiveness and Clinically Meaningful Improvement, According to Disability Level, of Five Walking Measures After Rehabilitation in Multiple Sclerosis A European Multicenter Study

Background. Evaluation of treatment effects on walking requires appropriate and responsive outcome measures. Objectives. To determine responsiveness of 5 walking measures and provide reference values for clinically meaningful improvements, according to disability level, in persons with multiple sclerosis (pwMS). Methods. Walking tests were measured pre- and postrehabilitation in 290 pwMS from 17 European centers. Combined anchor- and distribution-based methods determined responsiveness of objective short and long walking capacity tests (Timed 25-Foot Walk [T25FW] and 2- and 6-Minute Walk Tests [2MWT and 6MWT] and of the patient-reported Multiple Sclerosis Walking Scale–12 [MSWS-12]). A global rating of change scale, from patients’ and therapists’ perspective, was used as external criteria to determine the area under the receiver operating characteristic curve (AUC), minimally important change (MIC), and smallest real change (SRC). Patients were stratified into disability subgroups (Expanded Disability Status Scale score ≤4 [n = 98], >4 [n = 186]). Results. MSWS-12, 2MWT, and 6MWT were more responsive (AUC 0.64-0.73) than T25FW (0.50-0.63), especially in moderate to severely disabled pwMS. Clinically meaningful changes (MICs) from patient and therapist perspective were −10.4 and −11.4 for MSWS-12 (P < .01), 9.6 m and 6.8 m for 2MWT (P < .05), and 21.6 m (P < .05) and 9.1 m (P = .3) for 6MWT. In subgroups, MIC was significant from patient perspective for 2MWT (10.8 m) and from therapist perspective for MSWS-12 (−10.7) in mildly disabled pwMS. In moderate to severely disabled pwMS, MIC was significant for MSWS-12 (−14.1 and −11.9). Conclusions. Long walking tests and patient-reported MSWS-12 were more appropriate than short walking tests in detecting clinically meaningful improvement after physical rehabilitation, particularly the MSWS-12 for moderate to severely disabled pwMS.

Risk factors related to cardiovascular diseases and the metabolic syndrome in multiple sclerosis – a systematic review

Despite many epidemiological studies examining comorbidity in people with multiple sclerosis (pMS), there are conflicting opinions on whether pMS are at more or less risk of cardiovascular disease (CVD) and the metabolic syndrome compared with the general population. As pMS can now expect longer survival, this as an important question both at an individual and public health level. This study aimed to systematically review the literature linking MS to CVD risks and to the risk factors constituting the metabolic syndrome. This systematic review is based on a comprehensive literature search of six databases (Swemed+, Pubmed, Embase, Cochrane, PEDro and CINAHL). In total 34 studies were identified. Despite the high number of identified papers, only limited and inconsistent data exist on the risk factors of the metabolic syndrome and MS. Overall, the data suggest an increased CVD risk in pMS. From the existing studies it is not clear whether the increased risk of CVD is related to an increased risk of obesity or changes in body composition, hypertension, dyslipidemia or type II diabetes in pMS, indicating the need for future research in the field, if we are to advise pMS adequately in avoiding preventable comorbidity.

Multiple sclerosis affects skeletal muscle characteristics.

Background The impact of multiple sclerosis (MS) on skeletal muscle characteristics, such as muscle fiber cross sectional area (CSA), fiber type proportion, muscle strength and whole muscle mass, remains conflicting. Methods In this cross sectional study, body composition and muscle strength of the quadriceps were assessed in 34 MS (EDSS: 2.5±0.19) patients and 18 matched healthy controls (HC). Hereafter a muscle biopsy (m.vastus lateralis) was taken. Results Compared to HC, mean muscle fiber CSA of all fibers, as well as CSA of type I, II and IIa fibers were smaller and muscle strength of the quadriceps was lower in MS patients. Whole body composition was comparable between groups. However, compared to HC, the biopsied leg tended to have a higher fat percentage (p = 0.1) and a lower lean mass (p = 0.06) in MS patients. Conclusion MS seems to negatively influence skeletal muscle fiber CSA, muscle strength and muscle mass of the lower limbs of mildly affected MS patients. This emphasises the need for rehabilitation programs focusing on muscle preservation of the lower limb. Trial Registration ClinicalTrials.gov NCT01845896

High Intensity Exercise in Multiple Sclerosis: Effects on Muscle Contractile Characteristics and Exercise Capacity, a Randomised Controlled Trial.

Introduction Low-to-moderate intensity exercise improves muscle contractile properties and endurance capacity in multiple sclerosis (MS). The impact of high intensity exercise remains unknown. Methods Thirty-four MS patients were randomized into a sedentary control group (SED, n = 11) and 2 exercise groups that performed 12 weeks of a high intensity interval (HITR, n = 12) or high intensity continuous cardiovascular training (HCTR, n = 11), both in combination with resistance training. M.vastus lateralis fiber cross sectional area (CSA) and proportion, knee-flexor/extensor strength, body composition, maximal endurance capacity and self-reported physical activity levels were assessed before and after 12 weeks. Results Compared to SED, 12 weeks of high intensity exercise increased mean fiber CSA (HITR: +21±7%, HCTR: +23±5%). Furthermore, fiber type I CSA increased in HCTR (+29±6%), whereas type II (+23±7%) and IIa (+23±6%,) CSA increased in HITR. Muscle strength improved in HITR and HCTR (between +13±7% and +45±20%) and body fat percentage tended to decrease (HITR: -3.9±2.0% and HCTR: -2.5±1.2%). Furthermore, endurance capacity (Wmax +21±4%, time to exhaustion +24±5%, VO2max +17±5%) and lean tissue mass (+1.4±0.5%) only increased in HITR. Finally self-reported physical activity levels increased 73±19% and 86±27% in HCTR and HITR, respectively. Conclusion High intensity cardiovascular exercise combined with resistance training was safe, well tolerated and improved muscle contractile characteristics and endurance capacity in MS. Trial Registration ClinicalTrials.gov NCT01845896

Slowed Exercise-Onset Vo2 Kinetics During Submaximal Endurance Exercise in Subjects With Multiple Sclerosis:

Background. Low physical activity levels in persons with multiple sclerosis (MS) may reduce skeletal muscle oxidative capacity. Rehabilitation strategies might be altered by a measure of capacity that did not require invasive techniques or maximal exercise testing. For this purpose, we measured exercise onset and offset oxygen uptake (Vo2) kinetics during endurance exercise. Objective. This study compared exercise-onset and -offset Vo2 kinetics in mildly affected persons with MS with healthy matched participants. Methods. From 38 MS patients who had a mean Expanded Disability Status Scale of 3.1 and 16 healthy participants, exercise-onset and -offset Vo2 kinetics (mean response time [MRT]) were determined during two 6-minute submaximal bouts of exercise separated by a 6-minute recovery interval. Blood lactate, heart rate, expiratory volume, and Borg ratings of perceived exertion were assessed during exercise and compared between groups. Relationships between clinical characteristics and MRT were assessed. Results. During exercise, blood lactate, heart rate, and expiratory volume did not differ between groups (P > .05), but exercise-onset MRT was significantly slower in MS versus healthy participants (P = .007). Exercise-onset MRT was independently related to having MS (P = .02). Exercise-offset MRT was not different between groups or was independently related to having MS (P > .05). No independent relationships between clinical characteristics of MS and exercise-onset or -offset MRT were found. Conclusions. Exercise-onset Vo2 kinetics during submaximal endurance exercise are significantly slowed in mildly disabled persons with MS, suggesting low skeletal muscle oxidative capacity. Using mean response time testing, rehabilitation interventions for this reduction in exercise capacity can be assessed and targeted.

Impact of 24 Weeks of Resistance and Endurance Exercise on Glucose Tolerance in Persons with Multiple Sclerosis.

BackgroundRecently, the authors reported an elevated prevalence of impaired glucose tolerance in individuals with multiple sclerosis (MS), compared with matched healthy controls, indicating metabolic defects that may increase comorbidity. MS also leads to a more inactive lifestyle, increasing the likelihood to develop fat accumulation, muscle wasting/weakness, and exercise intolerance. In other populations, these health complications can partly be reversed by physical exercise. ObjectiveThe aim of this study was to determine the impact of a mild-to-moderate–intensity exercise program on glucose tolerance, ranging between normal and impaired, in persons with MS. DesignPersons with MS (mean expanded disability status scale, 3.3 ± 0.2; mean age, 48 ± 15 yrs) were randomized to an exercise group (n = 29) or a nonexercise control group (n = 15). Glucose tolerance, as well as muscle strength, exercise tolerance, and body composition to validate the applied exercise program, was determined in both groups at baseline and after 6, 12, and 24 wks of mild-to-moderate–intensity combined endurance and resistance training. ResultsNo effects on blood glucose and serum insulin were detected. However, 6 mos of exercise improved muscle strength, exercise tolerance, and lean tissue mass within the intervention group as compared with baseline. In the control group, no changes were detected. ConclusionTwenty-four weeks of mild-to-moderate–intensity combined endurance and resistance training was not able to improve glycemic control in this cohort of persons with MS. Future research is warranted to investigate the influence of higher exercise intensities on glucose tolerance, in an attempt to remediate metabolic deficits and to decrease the prevalence of comorbidities in MS.

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.

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

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.

Exercise-onset heart rate increase is slowed in multiple sclerosis patients: Does a disturbed cardiac autonomic control affect exercise tolerance?

OBJECTIVE To explore the etiology of exercise intolerance in patients with MS, it is analyzed whether a disturbed cardiac autonomic control could be observed during exercise testing in patients with MS, and is related to exercise tolerance. PATIENTS AND METHOD From 26 MS patients and 15 healthy subjects, exercise-onset (first 20 and 60 seconds) and -offset (1-minute recovery) HR change was determined during a 6-minute constant-load exercise bout on bike. Blood lactate, HR, oxygen uptake, expiratory volume and perceived exertion were assessed during exercise, and compared between groups. In 15 MS patients, a 6-min walking test was executed. RESULT Twenty-second exercise-onset HR increase was significantly smaller in MS patients (14 ± 7 bts/min) vs. healthy subjects (20 ± 8 bts/min, p < 0.05), and independently related to MS and age in total group (p < 0.05). Sixty-second exercise-onset and -offset HR changes were not different between groups, nor independently related to MS presence (p > 0.05). A significant correlation was found between 20-second exercise-onset HR increase and walking capacity in MS patients (r = 0.64, p < 0.01). CONCLUSION In MS patients, the early increase in heart rate during endurance exercise is significantly slowed, indicating a disturbed cardiac autonomic control, and is related to exercise tolerance.

Is Walking Capacity in Subjects with Multiple Sclerosis Primarily Related to Muscle Oxidative Capacity or Maximal Muscle Strength? A Pilot Study

Background and Purpose. Walking capacity is reduced in subjects with multiple sclerosis (MS). To develop effective exercise interventions to enhance walking capacity, it is important to determine the impact of factors, modifiable by exercise intervention (maximal muscle strength versus muscle oxidative capacity), on walking capacity. The purpose of this pilot study is to discriminate between the impact of maximal muscle strength versus muscle oxidative capacity on walking capacity in subjects with MS. Methods. From 24 patients with MS, muscle oxidative capacity was determined by calculation of exercise-onset oxygen uptake kinetics (mean response time) during submaximal exercise bouts. Maximal muscle strength (isometric knee extension and flexion peak torque) was assessed on dynamometer. All subjects completed a 6-minute walking test. Relationships between walking capacity (as a percentage of normal value) and muscle strength (of knee flexors and extensors) versus muscle oxidative capacity were assessed in multivariate regression analyses. Results. The expanded disability status score (EDSS) showed a significant univariate correlation (r = −0.70, P < 0.004) with walking capacity. In multivariate regression analyses, EDSS and mean response time, but not muscle strength, were independently related to walking capacity (P < 0.05). Conclusions. Walking distance is, next to disability level and not taking neurologic symptoms/deficits into account, primarily related to muscle oxidative capacity in subjects with MS. Additional study is needed to further examine/verify these findings.