Randomized control trial of effects of a 10-week inspiratory muscle training program on measures of pulmonary function in persons with multiple sclerosis

Pulmonary impairments have long been recognized as major causes of morbidity and mortality in individuals with advanced multiple sclerosis (MS). This study was designed to determine if a 10-week home exercise inspiratory training program in community-dwelling persons with MS improves pulmonary muscle strength and endurance. Forty-six ambulatory individuals with clinically diagnosed MS [Expanded Disability Status Scale (EDSS) 2.0-6.5, intervention group mean = 3.96 and control group mean = 3.36] were randomly assigned to an intervention group that received 10 weeks of inspiratory muscle strength training (IMT) or a nontreatment control group. Twenty-one subjects in the control group and 20 subjects in the intervention group completed the study. The intervention group demonstrated significantly greater improvement than the control group in maximal inspiratory pressure (P < 0.001). When compared to the control group, no significant differences were noted for maximal expiratory pressure or maximal ventilation volume after training in the intervention group. Baseline and postexercise training comparison of secondary pulmonary expiratory outcomes were significant in the intervention group for forced expiratory volume at one second (FEV1) (P = 0.014), forced vital capacity (FVC) (P = 0.041), and midexpiratory flow rate(FEF(25-75%)) (P = 0.011). No significant changes were noted for the control group. Thus, IMT significantly increased inspiratory muscle strength and resulted in generalized improvements in expiratory pulmonary function in persons with MS who have minimal to moderate disability. Future studies are needed that focus on the long-term effects of IMT with increased resistance and the impact it has on increasing pulmonary function and functional performance.     

Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in relapsing and primary progressive multiple sclerosis

Using radioimmunoassay we measured serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in patients with relapsing multiple sclerosis (MS) and a benign course (Expanded Disability Status Scale (EDSS) < or =3 despite > 10 years disease duration), relapsing MS with cumulative disability leading to an EDSS score >4 within 10 years of disease duration, primary progressive MS and healthy controls. We found no differences in IGF-1 and IGFBP-3 serum levels, and the IGF-1/IGFBP-3 ratio between the four groups. However, there was a significant correlation (P =0.005) between IGFBP-3 serum levels and both the progression index of disability and the Multiple Sclerosis Severity Score in patients with primary progressive MS.     

The benefits of an exercise program for people with schizophrenia: a pilot study

While the benefits of physical fitness have been extensively documented, there is a paucity of literature examining the impact of an exercise program on people experiencing a mental illness. An exploratory study was conducted with six patients diagnosed with schizophrenia who participated in a 3-month physical conditioning program. The findings suggest that most participants increased their physical strength and endurance and exhibited improvements in weight control and flexibility. The majority of patients reported increased fitness levels, exercise tolerance, reduced blood pressure levels, perceived energy levels and upper body and hand grip strength levels.     

Effects of a short outpatient rehabilitation treatment on disability of multiple sclerosis patients

It is well known that neurorehabilitation can reduce disability or improve handicap of people with multiple sclerosis (MS). The aim of this study was to evaluate the effectiveness of a short period (6 weeks) of a tailored, individualised outpatient rehabilitation program in people with progressive MS. A randomised-controlled trial was undertaken in patients with primary and secondary progressive MS referred to the Centro Sclerosi Multipla of Catania. One hundred and eleven patients were assessed at baseline and at 12 weeks with validated measures of disability (Functional Independence Measure (FIM)) and impairment (Expanded Disability Status Scale (EDSS) and Functional Systems Scale). Of the 111, 58 were randomly assigned to the treatment group and 53 to the control group. All patients had been previously trained in a home exercise program. Both groups were well matched for age, sex, disease duration and severity, disability and quality of life (Short Form-36). At the end of 6 weeks patients allocated to the rehabilitation treatment group showed significant improvement in their level of disability compared with the control group,while the level of impairment did not change. Thirty-two patients of the treatment group and four of the control group improved on the FIM by two or more steps at 12 weeks (p<0.0001). An improvement by 1 EDSS step occurred in only two patients of the treatment group and in one patient of the control group. Benefits were maintained for a further six weeks. This study demonstrates that a short outpatient rehabilitation treatment improves disability of MS patients, without changing their impairment and confirms the effectiveness of rehabilitation in people with MS.     

Long–term exercise improves functional impairment but not quality of life in multiple sclerosis

Regular exercise is important for patients with multiple sclerosis (MS) to maintain their functional ability and general health. The aim of this study was to determine whether a long–term exercise program has any effect on functional impairment or healthrelated quality of life (HRQOL) in subjects with mild to moderate MS. In a randomised controlled trial, subjects in the intervention group (n = 47) exercised according to a progressive exercise program, mainly consisting of resistance training, for six months. Subjects in the control group (n = 48) received no intervention. The subjects were assessed at baseline and at six months using the Multiple Sclerosis Functional Composite (MSFC), the Expanded Disability Status Scale (EDSS), the Functional Independence Measure (FIM), the MS Quality of Life–54 (MSQOL–54) questionnaire and the Centre for Epidemiologic Studies Depression Scale (CES–D). The drop–out rate was low (4%) with 91 subjects completing the study. At six months, the exercising subjects showed improvement on the MSFC (mean score change 0.114, 95% confidence interval [CI] 0.010 to 0.218), whereas the control subjects showed deterioration (mean score change –0.128, 95 % CI –0.232 to –0.025). The change between groups was statistically significant (interaction, p = 0.001). Consistent with the physical nature of the intervention, the change predominantly occurred in leg function/ambulation. The effect seen in the EDSS, FIM, MSQOL–54 or CES–D was nil. These findings indicate that MSFC is more sensitive than EDSS in the detection of improvement in functional impairment as a result of regular exercise. The unfavourable results from HRQOL do not rule out the possibility that other types of exercise programs may improve it in MS.     

A pilot study of proximal strength training in Charcot‐Marie‐Tooth disease

Gait analysis of people with Charcot‐Marie‐Tooth (CMT) disease revealed proximal adaptive gait strategies to compensate for foot drop. We previously demonstrated that hip flexor muscle fatigue can limit walking endurance. This pilot study used a single‐blinded cross over design to investigate the effect of a 16‐week home‐based programme of resistance training on hip flexor muscle strength. Measures of walking endurance, gait speed, exertion, fatigue, and general activity were also recorded. The exercise protocol was based on American College of Sports Medicine recommendations. A mixed effects model was used for analysis. Twenty‐six people finished the study, with average reported exercise participation of 93%. No negative effects of exercise were observed. Significant increase in hip flexor muscle strength was observed on the left, but not the right. No changes were observed in walking speed and endurance measures. This pilot study of home‐based resistance training showed a modest improvement in hip strength but only on one side. The lack of a more significant improvement and no improvement in walking measures suggests that this training protocol may not be optimal for people with CMT and that patients may need to stratified differently for training studies in CMT.     

Resistance training improves strength and functional capacity in persons with multiple sclerosis

The purpose of this study was to evaluate the effect of an eight-week progressive resistance training programme on lower extremity strength, ambulatory function, fatigue and self-reported disability in multiple sclerosis (MS) patients (mean disability score 3.7 +/- 0.8). Eight MS subjects volunteered for twice weekly training sessions. During the first two weeks, subjects completed one set of 8-10 reps at 50% of maximal voluntary contraction (MVC) of knee flexion, knee extension and plantarflexion exercises. In subsequent sessions, the subjects completed one set of 10-15 repetitions at 70% of MVC. The resistance was increased by 2-5% when subjects completed 15 repetitions in consecutive sessions. Isometric strength of the quadriceps, hamstring, plantarflexor and dorsiflexor muscle groups was assessed before and after the training programme using an isokinetic dynamometer. Magnetic resonance images of the thigh were acquired before and after the exercise programme as were walking speed (25-ft), number of steps in 3 min, and self-reported fatigue and disability. Knee extension (7.4%), plantarflexion (52%) and stepping performance (8.7%) increased significantly (P < 0.05). Self-reported fatigue decreased (P < 0.05) and disability tended to decrease (P = 0.07) following the training programme. MS patients are capable of making positive adaptations to resistance training that are associated with improved ambulation and decreased fatigue.     

High-intensity resistance training amplifies muscle hypertrophy and functional gains in persons with Parkinson's disease.

Strength deficits in persons with Parkinson's disease (PD) have been identified as a contributor to bradykinesia. However, there is little research that examines the effect of resistance training on muscle size, muscle force production, and mobility in persons with PD. The purpose of this exploratory study was to examine, in persons with PD, the changes in quadriceps muscle volume, muscle force production, and mobility as a result of a 12-week high-force eccentric resistance training program and to compare the effects to a standard-care control. Nineteen individuals with idiopathic PD were recruited and consented to participate. Matched assignment for age and disease severity resulted in 10 participants in the eccentric group and 9 participants in the control group. All participants were tested prior to and following a 12-week intervention period with testing and training conducted at standardized times in their medication cycle. The eccentric group performed high-force quadriceps contractions on an eccentric ergometer 3 days a week for 12 weeks. The standard-care group exercise program encompassed standard exercise management of PD. The outcome variables were quadriceps muscle volume, muscle force, and mobility measures (6-minute walk, stair ascent/descent time). Each outcome variable was tested using separate one-way analyses of covariance on the difference scores. Muscle volume, muscle force, and functional status improvements occurred in persons with PD as a result of high-force eccentric resistance training. The eccentric group demonstrated significantly greater difference scores for muscle structure, stair descent, and 6-minute walk (P < 0.05). Magnitude of effect size estimators for the eccentric group consistently exceeded those in the standard-care group for all variables. To our knowledge, this is the first clinical trial to investigate and demonstrate the effects of eccentric resistance training on muscle hypertrophy, strength, and mobility in persons with PD. Additional research is needed to determine the anatomical and neurological mechanisms of the observed strength gains and mobility improvements.     

Self-rated physical health predicts change in disability in multiple sclerosis

OBJECTIVE: To examine whether self-rated physical health, as measured by the Physical Functioning Scale (PF) and the Role-physical Scale (RF) of the SF-36 Health Survey, could predict change in disability measured by the Expanded Disability Status Scale (EDSS) in patients with multiple sclerosis (MS) over a follow-up period of 3 years. METHODS: A group of 156 clinically definite MS patients (Poser criteria), who had never been treated with disease-modifying therapies, were recruited consecutively from an outpatient clinic setting at the Institute of Neurology, Belgrade. The self-rated physical health was measured by using PF and RF of the SF-36. RESULTS: At follow-up, 33 out of 156 patients (21%) had dropped out. The mean EDSS score had increased from 3.7 to 4.5. Multiple regression analyses using change in EDSS as the dependent variable and baseline scores of EDSS and RF as independent variables showed a significant effect for RF (standardized beta= -0.21). A similar but non-significant effect was found for PF. Dichotomizing change in disability according to clinically meaningful deterioration and using logistic regression, an odds ratio of 1.27 (95% confidence interval 1.01-1.62) was found for the smallest unit of change in the self-rated scale. This means that patients who rated their own physical health as poor had a higher increase in disability compared with patients with the same level of disability at baseline who rated their physical health better. CONCLUSIONS: MS patients' perception of their health comprises information predictive for disease development not included in the more objective measure of disability status.     

Exercise capacity, disability and leisure physical activity of subjects with multiple sclerosis

The purpose of the present study was to examine exercise capacity and its relationship to neurological disability as measured using the Expanded Disability Status Scale (EDSS) and to leisure physical activity in subjects with multiple sclerosis (MS). Thirty-four men and 61 women (mean age 44 +/- 6.7 years, mean disease duration 5.7 +/- 6.4 years) with mild to moderate disability (EDSS range 1.0-5.5) participated. They underwent an incremental exercise test on a leg cycling ergometer. Leisure physical activity was measured using a questionnaire. Peak oxygen uptake (VO2peak) in men was 27.0 +/- 5.2 mL/kg/min, and in women 21.7 +/- 5.5 mL/kg/min. The disability correlated inversely with the VO2peak both in men (r = - 0.50, P = 0.004) and in women (r = - 0.25, P = 0.05). No correlation between disease duration and VO2peak was found. In a multivariate regression analysis, neurological disability was confirmed as a predictor of VO2peak. No evidence of a relationship between leisure physical activity and VO2peak was found. A main finding was that disability and exercise capacity are inter-related, even in subjects who are not severely handicapped (84% had an EDSS of < 4.0). The level of disability should be taken into account in the planning of aerobic exercise programs for fully ambulatory MS subjects.     

Multiple sclerosis and brief moderate exercise. A randomised study

This is a randomised control study, to determine the effect of aerobic and strength exercise on physical fitness and quality of life in patients with mild multiple sclerosis (MS). Sixteen outpatients with definitive MS, aged 18-50, with an Expanded Disability Status Scale (EDSS) <4, completed the study. Every patient was evaluated according to physical fitness with peak oxygen consumption (V'O2peak), workload and anaerobic threshold; quality of life (SF-36); and degree of disability (EDSS). The patients were then randomised to an exercise group (EG) (n =6) or a control group (CG) (n = 10). The EG exercised three times a week for five weeks, and the CG did not change their habits regarding exercise. In the EG, the mean change in workload was 0.34 W/kg (95% confidence interval (CI): 0.09-0.58), the mean change in V'O2peak was 4.54 mL/kg per minute (95% CI: 1.65-7.44), and the mean change in anaerobic threshold was 0.32 L/min (95% CI: 0.08-0.57). There was a tendency towards improved quality of life, and no change was detected in the degree of disability. This study confirms that brief, moderate, aerobic exercise improves physical fitness in individuals with mild MS. No evidence was found for worsening of MS symptoms in association with exercises.     

Effects of psychological group therapy in patients with multiple sclerosis

OBJECTIVES: The aim of this pilot study was to evaluate a psychological therapy program used in the treatment of multiple sclerosis (MS) and including cognitive/behavioral strategies, relaxation training and physical exercise. MATERIAL AND METHODS: The participants were 29 patients with MS recruited from an outpatient unit; 14 patients were assigned to the 7-week psychological therapy group (one session per week), the remainder formed a control group. Before and immediately after the course of therapy and after a 2-month follow-up, the participants completed a series of questionnaires measuring factors such as depression, anxiety, coping and body image. RESULTS: Compared with the control group the therapy group showed long-term improvements in depressive stress coping style and a short-term improvement in "vitality and body dynamics". CONCLUSION: Further studies should investigate the differential effects of specific units of the therapy program and how the short-term improvements in "vitality and body dynamics" could be maintained for longer periods.     

Survey of multiple sclerosis in northern California. Northern California MS Study Group.

A random sample of 493 multiple sclerosis (MS) patients registered with the Northern California Chapter of the National MS Society was surveyed by mail and subsequently interviewed with regard to their MS, life style, diet, medical treatment, family history, and insurance coverage. Of this sample, 168 patients (34%) returned completed questionnaires. The answers on the questionnaire were entered into a database and scores on the extended disability status scale (EDSS), the neurologic rating scale (NRS), the ambulation index (AI), and the mean disability scale (MDS) were determined from the patient's answers to a portion of the questionnaire using a previously validated conversion program. This survey population of 168 patients seemed to represent well both the random sample and the frame population from which it was drawn. Patients commonly experienced symptoms for which there are medical treatments currently available such as bladder symptoms, fatigue, spasticity, pain, and depression. Surprisingly, however, with the exception of spasticity, patients were only infrequently treated for these complaints. In addition, despite the recent approval of the beta-interferons and copolymer I in the treatment of MS, only 74% of the appropriate candidates for such treatment had these options discussed with them and only 45% ever actually received such treatment. Certain clinical features and dietary habits were strongly associated with both EDSS scores and total disability. Not unexpectedly, either a progressive disease course or the presence of neurological dysfunction in any one of a number of functional areas (e.g. bladder, vision, cognitive change, etc.) correlated with higher EDSS scores and greater total disability. Fatigue was also strongly correlated with disability. Indeed, fatigue accounted (in whole or in part) for 65% of the disability experienced by patients; an observation which only underscores the fact that fewer than one third of the patients who experience fatigue have ever been tried on medications. Interestingly, the only factors associated with lower EDSS scores and less total disability were exercise and alcohol consumption. Such associations from a single survey, however, do not establish causation. It is the purpose of this study to establish a baseline level of function within this survey population so that future surveys in the same set of individuals can allow a prospective assessment of how health outcome has influenced different aspects of the patient's medical care, lifestyle, and insurance coverage.     

One year changes in disability in multiple sclerosis: neurological examination compared with patient self report

OBJECTIVE: To characterise prospectively the relation between one year changes in neurologist rating of neurological exam abnormalities as measured by the Expanded Disability Status Scale (EDSS) and changes in patient perceived disability as measured by the Guy's Neurological Disability Scale (GNDS) in patients with multiple sclerosis. METHODS: Two hundred and fifty patients with MS were recruited at an outpatient clinic. Disability at baseline and one year follow-up was assessed using the EDSS and GNDS. Correlations between change in EDSS, GNDS-sum score, Functional Systems and GNDS subcategories were studied as well as the significance of changes in EDSS associated with changes in perceived disability. RESULTS: The correlation between one year changes in EDSS versus GNDS was substantially lower (0.19) than cross-sectional correlations between EDSS and GNDS either at baseline (0.62) or at follow-up (0.77). Notably, changes in functional system scores that are based on neurological examination are poorly or not at all correlated with changes in disability as perceived by the patient. Analysing the impact of a significant worsening in EDSS-score, a commonly applied outcome criterion in clinical trials, we found that this was associated with significant worsening, insignificant change, and significant improvement in the patients' perceived disability in 45%, 39% and 15% of patients, respectively. CONCLUSION: Patients' perception of change in disability differs not only quantitatively but also qualitatively from that of an examining physician. This seems to be due both to the fact that there are true differences in change as perceived by the patient and that measured by the physician and to the fact that changes in many dimensions of disability that are relevant to the patient have no measurable impact on the EDSS.     

Improvements in physical fitness in adults with Down syndrome

The effectiveness of an exercise training program for 52 adults with Down syndrome (M age = 39.4 years) was evaluated. The training program consisted of cardiovascular (30 minutes) and strength exercise (15 minutes) for 12 weeks, 3 days a week for 45-minutes per session. Compared to control subjects, the training group improved significantly in cardiovascular fitness and muscular strength and endurance and had a slight but significant reduction in body weight. Greater effort must be made to promote increases in physical activity participation among persons with Down syndrome and developmental disabilities in order to reduce the potential health risks associated with low fitness and sedentary behavior.     

Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability

OBJECTIVE: To assess axonal damage and its contribution to disability at different stages of multiple sclerosis (MS). BACKGROUND: Recent in vivo imaging and in situ pathologic studies have demonstrated that substantial axonal damage accompanies the inflammatory lesions of MS. However, the relation of axonal damage to the duration of MS and its contribution to disability at different stages of the disease remain poorly defined. DESIGN: We performed proton magnetic resonance spectroscopic imaging in 88 patients with a wide range of clinical disability and disease duration to measure N-acetylaspartate (NAA, an index of axonal integrity) relative to creatine (Cr) in a large central brain volume that included mostly normal-appearing white matter on magnetic resonance imaging. RESULTS: We observed that the NAA/Cr values were abnormally low in the early stages of MS, even before significant disability (measured using the Expanded Disability Status Scale [EDSS]) was evident clinically, and declined more rapidly with respect to EDSS at lower than at higher EDSS scores (P<.001). The correlation of NAA/Cr values with EDSS score was significantly (P<.03) stronger in patients with mild disability (EDSS score <5, Spearman rank order correlation = -0.54, P<.001) than in patients with more severe disability (EDSS score >/=5, Spearman rank order correlation = -0.1, P<.9). When similar analyses were performed in patients with MS grouped for duration of disease, the subgroup with early disease duration (<5 years) also showed central brain NAA/Cr resonance intensity ratios significantly lower than healthy controls (P<.001). CONCLUSION: Cerebral axonal damage begins and contributes to disability from the earliest stages of the disease.     

Cladribine and progressive MS: clinical and MRI outcomes of a multicenter controlled trial. Cladribine MRI Study Group

OBJECTIVE: To evaluate the safety and efficacy of two doses of cladribine in patients with progressive MS. BACKGROUND: Treatment of progressive MS patients with cladribine in a previous single-center, placebo-controlled clinical trial was associated with disease stabilization. METHODS: In the current study, 159 patients with a median baseline Kurtzke's Expanded Disability Status Scale (EDSS) score of 6.0 were randomly assigned to receive placebo or cladribine 0.07 mg/kg/day for 5 consecutive days every 4 weeks for either two or six cycles (total dose, 0.7 mg/kg or 2.1 mg/kg, respectively), followed by placebo, for a total of eight cycles. Thirty percent had primary progressive MS (PPMS) and 70% had secondary progressive MS (SPMS). EDSS and Scripps Neurologic Rating Scale (SNRS) scores were assessed bi-monthly and MRI was performed every 6 months. The primary outcome measure was disability (mean change in EDSS). RESULTS: Mean changes in disability did not differ among the groups at the end of the 12-month double-blind phase. Both cladribine treatments were superior to placebo for the proportion of patients having gadolinium-enhanced T1 lesions and for the mean volume and number of such lesions (p < or = 0.003). Differences were statistically significant at the 6-month evaluation time, with < or =90% reduction in volume and number of enhanced T1 lesions, which was maintained through final evaluation. This effect segregated largely with the SPMS group. The T2 burden of disease showed a modest improvement in cladribine-treated patients and worsened in placebo-treated patients. Most adverse events were mild or moderate in severity and not treatment limiting. CONCLUSION: No significant treatment effects were found for cladribine in terms of changes in EDSS or SNRS scores. Both doses of cladribine produced and sustained significant reductions in the presence, number, and volume of gadolinium-enhanced T1 brain lesions on MRI, and cladribine 2.1 mg/kg reduced the accumulation of T2 lesion load. Cladribine at doses up to 2.1 mg/kg was generally safe and well tolerated.     

Plasma S100beta and NSE levels and progression in multiple sclerosis

Plasma levels of the glial cell marker S100beta and the neuronal marker neuron-specific enolase (NSE) are elevated in various conditions of central nervous system damage. In this study we investigated whether plasma levels of S100beta and NSE are related to disease progression in multiple sclerosis (MS). Plasma levels of S100beta and NSE were measured in 25 patients with relapsing remitting MS (RRMS), 23 with secondary progressive MS (SPMS) and 16 with primary progressive MS (PPMS). All MS patients were in a clinically stable phase. Progression and disability were evaluated during a follow-up period of five years. We found that plasma NSE levels were lower in patients with clinically relevant worsening on the Expanded Disability Status Scale (EDSS), defined as 1 point increase from EDSS <6.0 or 0.5 point increase from EDSS> or =6 after five years (p=0.042), and in patients with a progressive disease course (p=0.01). There was a significant negative correlation between plasma NSE levels and both EDSS and Multiple Sclerosis Severity Status (MSSS) scores at baseline and after five years of follow-up (r=-0.33 and -0.38, p=0.027 and 0.003). There were no significant differences between patient groups in plasma S100beta levels. Plasma NSE levels appear inversely related to disease progression in MS.