Synaptic Immunopathology Lab, Department of Systems Medicine, Tor Vergata University, Rome, Italy
Immunomodulatory Effects of Exercise in Experimental Multiple Sclerosis.
Multiple Sclerosis (MS) is a demyelinating and neurodegenerative disease. Though a specific antigen has not been identified, it is widely accepted that MS is an autoimmune disorder characterized by myelin-directed immune attack. Pharmacological treatments for MS are based on immunomodulatory or immunosuppressant drugs, designed to attenuate or dampen the immune reaction, to improve neurological functions. Recently, rehabilitation has gained increasing attention in the scientific community dealing with MS. Engagement of people with MS in exercise programs has been associated with a number of functional improvements in mobility, balance, and motor coordination. Moreover, several studies indicate the effectiveness of exercise against fatigue and mood disorders that are frequently associated with the disease. However, whether exercise acts like an immunomodulatory therapy is still an unresolved question. A good tool to address this issue is provided by the study of the immunomodulatory effects of exercise in an animal model of MS, including the experimental autoimmune encephalomyelitis (EAE), the Theiler's virus induced-demyelinating disease (TMEV-IDD) and toxic-demyelinating models, cuprizone (CPZ), and lysolecithin (LPC). So far, despite the availability of different animal models, most of the pre-clinical data have been gained in EAE and to a lesser extent in CPZ and LPC. These studies have highlighted beneficial effects of exercise, suggesting the modulation of both the innate and the adaptive immune response in the peripheral blood as well as in the brain. In the present paper, starting from the biological differences among MS animal models in terms of immune system involvement, we revise the literature regarding the effects of exercise in EAE, CPZ, and LPC, and critically highlight the advantages of either model, including the so-far unexplored TMEV-IDD, to address the immune effects of exercise in MS.
Department of Neuroscience, Carleton University, Ottawa, Canada
A systematic review of aerobic and resistance exercise and inflammatory markers in people with multiple sclerosis.
Inflammation is a driver in the demyelination process in patients with multiple sclerosis (MS) and can influence disability levels. Both single and repeated bouts of exercise can decrease inflammatory markers in people with MS (PwMS). This systematic review evaluates whether exercise can influence inflammation and disability in individuals with MS. Experimental studies were reviewed that had to meet the following eligibility requirements: a sample of PwMS, an intervention of exercise (either aerobic, resistance, or a combination of each), and an outcome that included at least one inflammatory (cytokine) reaction. The main outcome measure was an evaluation of inflammation, as indicated by a change in any cytokine level. Other measures included muscle strength, balance, flexibility, walking ability, disability statues, and quality of life (QOL). A total of nine studies were included in the final review. Exercise interventions included predominantly cycling, although a few resistance training trials were mentioned. Small decreases were found in IL-17 and IFN-γ after exercise. Functional outcome measures and perceived disability status were improved posttraining. We conclude that while interventions such as exercise may impact QOL, they do not have a significant influence on inflammation associated with MS. Exercise is an accessible alternative that not only helps to decrease impairments but also limit the restrictions associated with participation in society. While functional outcomes after exercise improved, these improvements may not be attributable to changes in levels of cytokines or inflammatory markers.
Physical Therapy Department, College of Health Sciences, University of Michigan-Flint
Effects of inspiratory muscle training in advanced multiple sclerosis
Respiratory training using Threshold Inspiratory Muscle Trainer (IMT) has not been examined adequately in multiple sclerosis (MS). The primary objective in this study of persons with advanced MS was to investigate the training effect of IMT. The secondary objective was to evaluate the retention of IMT benefits.
This study was a repeated measures within-subject design (before-after trial).. Participants were recruited from a long-term care facility specialized in progressive neurologic conditions. Thirty-six non-ambulatory persons with advanced MS volunteered. Inspiratory muscle exercise using the threshold IMT were performed daily for 10 weeks at 3 sets of 15 repetitions per day. Resistance was progressed weekly based on perceived rate of exertion and symptoms. Primary outcome measures were maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) that were measured at baseline, after 5 and 10 weeks of IMT exercises (training period), and at 4 and 8 weeks after the IMT training ended (retention). Linear mixed-effect regression models with time (i.e. weeks from baseline) as the fixed factor and participants as the random effect factor were applied separately to test each hypothesis. Effect size was calculated using partial eta square (η2p). Two-tailed significance level was p < 0.05.
Participants were 60.5 ± 8.6 years old. Expanded Disability Status Scale was 8.5 ± 0.4. Baseline MIP were 25.9 ± 16.4 cmH2O (33.2% %± 19.8% of predicted values) and MEP were 23.5 ± 15.7 cmH2O (25.8% %± 14.4% of predicted values). Compared to the baseline, MIP increased significantly to 30.1 ± 17.9 cmH2O (38.9% %± 22.4% of predicted values) and 30.6 ± 17.6 cmH2O (39.6% %± 22.3% of predicted values) after 5 (p < 0.05) and 10 weeks (p < 0.05) of IMT exercises. MIP improvements were retained in an 8-week washout period. MEP did not differ significantly by time.
In persons with advanced MS, 10-week IMT training increased inspiratory muscle strength. This study is the first to demonstrate the retention of benefits following daily IMT exercises at 8 weeks after training ended.
Department of Education, Psychology, Philosophy, University of Cagliari, Italy
The Relationships between Physical Activity, Self-Efficacy, and Quality of Life in People with Multiple Sclerosis.
Regular physical activity (PA) can enhance the physical and mental health of people with Multiple Sclerosis (MS) because of its impact on muscular strength, mobility, balance, walking, fatigue, pain and health-related quality of life (HRQoL). Previous studies have hypothesized that the relationship between PA and HRQoL is mediated by self-efficacy. The aim of this research is to evaluate whether self-efficacy in goal setting and self-efficacy in the management of symptoms, mediate the relationship between PA and HRQoL, in a similar way to exercise self-efficacy. A sample of 28 participants with MS (18 females) and different levels of physical activity have been recruited and completed the following measures: a) physical activity (GLTEQ); b) health-related quality of life (SF-12); c) self-efficacy in the management of Multiple Sclerosis (SEMS) and, d) exercise self-efficacy (EXSE). The statistical analysis highlighted that self-efficacy in goal setting mediated the relationship between PA and mental health better than exercise self-efficacy. Our findings suggest that self-efficacy in goal setting can contribute to the adoption and maintenance of regular physical activity for long-lasting times, supporting and increasing the mental quality of life of people suffering from MS.
University of Pécs, Faculty of Health Sciences, Department of Diagnostic Imaging, Pécs, Hungary
Exercise Effects on Multiple Sclerosis Quality of Life and Clinical-Motor Symptoms
Different therapies can improve clinical and motor symptoms of multiple sclerosis (MS) similarly but studies comparing the effects of different exercise therapies on clinical and motor outcomes are scant. We compared the effects of exergaming (EXE), balance (BAL), cycling (CYC), proprioceptive neuromuscular facilitation (PNF), and a standard care wait-listed control group (CON) on clinical and motor symptoms and quality of life (QoL) in people with MS (PwMS).
PwMS (n=68, 90% females; age: 47.0y, Expanded Disability Status Scale: 5 to 6) were randomized to 5 groups. Before and after the interventions (5x/week for 5 weeks) PwMS were tested for: MS-related clinical and motor symptoms (Multiple Sclerosis Impact Scale-29; MSIS-29, primary outcome), QoL (EQ-5D), symptoms of depression, gait and balance ability (Tinetti Assessment Tool, TAT), static and dynamic balance and fall risk (Berg Balance Scale (BBS), walking capacity (six-minute walk test, 6MWT), and standing posturography on a force platform.
EXE, BAL, and CYC improved MSIS-29 scores similarly. EXE and CYC improved QoL and walking capacity similarly but more than BAL. Only EXE improved gait and balance scores (TAT). EXE and BAL improved fall risk and standing balance similarly but more than CYC. PNF and CON revealed no changes. EQ-5D moderated the exercise effects on MSIS-29 scores only in EXE. Changes in QoL and changes in MSIS-29 scores correlated R=0.73 only in EXE.
In conclusion, BAL and CYC but EXE in particular, but not PNF, can improve clinical and motor symptoms and QoL in PwMS (EDSS: 5 to 6), expanding the evidence-based exercise options to reduce mobility limitations in PwMS.
Faculty of Health Sciences, Division of Physiotherapy and Rehabilitation, Istanbul University-Cerrahpasa, Istanbul, Turkey
Comparison of the effects of two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis: A randomized controlled trial.
Balance disorders, fatigue, and walking impairments are the most common symptoms of multiple sclerosis (MS), which lead to a decrease in quality of life. To cope with these disability-increasing symptoms, it is important to select and regularly apply appropriate rehabilitation approaches. In recent years, virtual reality approaches have been suggested as a potentially useful tool in rehabilitation. Exergaming systems are used in the treatment of symptoms associated with MS, but there are few randomized controlled studies investigating the efficacy of these systems.
To investigate and compare the effects of exercise training with two different exergaming systems on balance, functionality, fatigue, and quality of life in people with multiple sclerosis (PwMS).
Forty-seven volunteer PwMS were included in the study and randomized to the group I (Nintendo Wii Fit), group II (Balance Trainer), and group III (control group). The participants in the study groups underwent an exercise program under the supervision of a physiotherapist on 2 days a week for 8 weeks. Outcome measures were the Berg Balance Scale (BBS), Timed Up and Go test (TUG), Six-Minute Walk Test (6MWT), Fatigue Severity Scale (FSS), and Multiple Sclerosis International Quality of Life Questionnaire (MusiQol), which were performed before and after the treatment.
Forty-two participants completed the study protocol. All parameters evaluated in group I and II showed statistically significant improvement after treatment. Changes in all outcome measures were found to be superior in group I compared with group III. Similarly, all measures except the 6MWT were found to be superior in group II compared with group III. Changes in BBS and MusiQol were found to be superior in group I compared with group II.
In comparison with no intervention, exergaming with Nintendo Wii Fit and Balance Trainer improves balance, increases functionality, reduces fatigue severity, and increases quality of life in PwMS.
Recovery & Performance Laboratory, Faculty of Medicine, Memorial University of Newfoundland, Canada
Vigorous Cool Room Treadmill Training to Improve Walking Ability in People With Multiple Sclerosis Who Use Ambulatory Assistive Devices: A Feasibility Study
https://pubmed.ncbi.nlm.nih.gov/3196913 ... ity-study/
Background: Aerobic training has the potential to restore function, stimulate brain repair, and reduce inflammation in people with Multiple Sclerosis (MS). However, disability, fatigue, and heat sensitivity are major barriers to exercise for people with MS. We aimed to determine the feasibility of conducting vigorous harness-supported treadmill training in a room cooled to 16 °C (10 weeks; 3times/week) and examine the longer-term effects on markers of function, brain repair, and inflammation among those using ambulatory aids.
Methods: Ten participants (9 females) aged 29 to 74 years with an Expanded Disability Status Scale ranging from 6 to 7 underwent training (40 to 65% heart rate reserve) starting at 80% self-selected walking speed. Feasibility of conducting vigorous training was assessed using a checklist, which included attendance rates, number of missed appointments, reasons for not attending, adverse events, safety hazards during training, reasons for dropout, tolerance to training load, subjective reporting of symptom worsening during and after exercise, and physiological responses to exercise. Functional outcomes were assessed before, after, and 3 months after training. Walking ability was measured using Timed 25 Foot Walk test and on an instrumented walkway at both fast and self-selected speeds. Fatigue was measured using fatigue/energy/vitality sub-scale of 36-Item Short-Form (SF-36) Health Survey, Fatigue Severity Scale, modified Fatigue Impact Scale. Aerobic fitness (maximal oxygen consumption) was measured using maximal graded exercise test (GXT). Quality-of-life was measured using SF-36 Health Survey. Serum levels of neurotrophin (brain-derived neurotrophic factor) and cytokine (interleukin-6) were assessed before and after GXT.
Results: Eight of the ten participants completed training (attendance rates ≥ 80%). No adverse events were observed. Fast walking speed (cm/s), gait quality (double-support (%)) while walking at self-selected speed, fatigue (modified Fatigue Impact Scale), fitness (maximal workload achieved during GXT), and quality-of-life (physical functioning sub-scale of SF-36) improved significantly after training, and improvements were sustained after 3-months. Improvements in fitness (maximal respiratory exchange ratio and maximal oxygen consumption during GXT) were associated with increased brain-derived neurotrophic factor and decreased interleukin-6.
Conclusion: Vigorous cool room training is feasible and can potentially improve walking, fatigue, fitness, and quality-of-life among people with moderate to severe MS-related disability.
Trial registration: The study was approved by the Newfoundland and Labrador Health Research Ethics Board (reference number: 2018.088) on 11/07/2018 prior to the enrollment of first participant (retrospectively registered at ClinicalTrials.gov: NCT04066972. Registered on 26 August 2019.
Department of Exercise Physiology, Kish International Campus (International Branch of University of Tehran), University of Tehran, Kish Island, Iran; Department of Education, Faculty of Social Science, Umeå University, Sweden; Department of Community Medicine and Rehabilitation, Section of Sports Medicine, Umeå University, Sweden
Exercise Modulates the Levels of Growth Inhibitor Genes Before and After Multiple Sclerosis
https://pubmed.ncbi.nlm.nih.gov/3202812 ... sclerosis/
Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system. The animal model of MS, experimental autoimmune encephalomyelitis (EAE), is commonly used for studies of human inflammatory demyelinating diseases and has been shown to be suitable for studying the effects of exercise on MS pathophysiology. The present study was conducted to determine the impact of forced swimming and voluntary running wheel exercises before and after the induction of EAE on expression of Nogo-A, NgR, and ROCK genes in the brain tissue. A total of 96 C57BL/6 mice were randomly divided into two groups, namely exercises before (EXb, n = 48) and after (EXa, n = 48) induction of EAE. Each group was divided into four subgroups: Forced Swimming + EAE (n = 12), Voluntary Running Wheel + EAE (n = 12), NoEX-EAE (n = 12), and Control group (n = 12). Animals performed either swimming exercise for 30 min per day or running wheel for one hour per day, five days per week for four weeks. Results of Luxal Fast Blue (LFB) staining demonstrated that the degree of demyelination was significantly less in the experimental exercised compared to NoEX-EAE groups (P < .05). Amazingly, both modes of exercise reduced the severity of MS symptoms in mice exposed to swimming and wheel running, evaluated as body weight, clinical scores, degree of demyelination, and gene expressions, regardless of whether the exercise was performed before or after EAE induction.
Graduate School of Health Sciences, Dokuz Eylül University, Izmir, TurkeyEffect of Video-Based Exergaming on Arm and Cognitive Function in Persons With Multiple Sclerosis: A Randomized Controlled Trial
https://pubmed.ncbi.nlm.nih.gov/3204586 ... led-trial/
Background: Developments in rehabilitation technology such as video-based exergaming contributes to the treatment process as well as to increase the active participation of persons with multiple sclerosis (pwMS). The aim was to investigate the effect of video-based exergaming training on upper extremity and cognitive function as well as core stability, walking, depression, fatigue, and quality of life in pwMS.
Methods: This randomized controlled trial included 60 pwMS who were randomly divided into three groups; video-based exergaming (n = 21), conventional rehabilitation (n = 19), and control groups (n = 20). The experimental groups received therapy sessions once a week for 8 weeks. All the participants were assessed at baseline and after 8 weeks. The outcome measures included upper extremity and cognitive functions as well as core stability, walking, depression, fatigue, and quality of life measures.
Results: Significant improvements were observed in the primary outcome, measured by Nine-Hole Peg Test in the video-based exergaming [before= 25.8 (11.1) s; after= 22.3 (11.0) s] and conventional rehabilitation [before= 23.3 (8.1) s; after= 19.9 (3,8) s] groups (p < 0.05). Cognitive functions (with the exception of processing speed in the conventional rehabilitation group), most of the lower extremity functions, balance-related measures, fatigue and quality of life levels were significantly improved in the video-based exergaming and conventional rehabilitation groups, however, only the depression level was significantly decreased in the video-based exergaming (p < 0.05). Several significant differences were observed in the changes of the control group compared to the video-based exergaming and conventional rehabilitation groups (p < 0.05).
Conclusion: This study suggests that video-based exergaming is almost as effective as conventional rehabilitation regarding improving walking, upper and lower extremity functions, cognitive functions, fatigue, depression, and health-related quality of life in pwMS.
a Swedish Neuroscience Institute, Swedish Medical Center , Seattle
Does Treadmill Training With Hybrid Assistive Limb (HAL) Impact the Quality of Life? A First Case Series in the United States
https://pubmed.ncbi.nlm.nih.gov/3004468 ... ed-states/
Introduction: Recently published studies show remarkable improvements in functional mobility after treadmill training with HAL® in patients with spinal cord injuries. The aim of this study was to evaluate the impact of HAL®-assisted treadmill training on quality of life. Patient/Method: A case series of six patients participating in a single-centre prospective, interventional pilot study, who were suffering neurologic motor deficits. The quality of life was assessed using the EQ-5D questionnaire and mobility was assessed using the PROMIS v1.2 Physical Function - Mobility Score before treadmill training, at 12-weeks, and at 6-months. Results: Five out of six patients showed improvement in the PROMIS v1.2 Physical Function - Mobility score. Four patients did not show changes in the EQ-5D at 6 months follow-up, relative to baseline. The EQ-5D score of one patient worsened while improved in another patient at 6 months follow-up compared to the baseline. Conclusion: Our study details the first experience in a larger series regarding the effects of HAL®-assisted treadmill training on quality of life. Whereas five out of six patients showed improvements in mobility scores, only one patient showed improvement of life quality at 6 months follow-up. Life quality is influenced by a multitude of factors and lager randomized trials are needed to assess the effect of HAL®-assisted training on quality of life. Implications for Rehabilitation Treadmill training with HAL is safe and feasible for patients with neurologic disorders Treadmill training with HAL improved the functional mobility Improvements in the quality of life were unverifiable.
Department of Sport Physiology and Corrective Exercise, Sport Sciences Faculty, Urmia University, Urmia, Iran
The effect of combined functional training on BDNF, IGF-1, and their association with health-related fitness in the multiple sclerosis women.
OBJECTIVE: Exercise-induced changes in the neurotrophic factors and the physical function are essential for the rehabilitation of the multiple sclerosis (MS) persons. The aim of this study was investigating of effectiveness of the combined functional training (CFT) on brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and their association with health-related fitness in the MS women.
DESIGN: Twenty women with relapsing-remitting MS randomly assigned to CFT and control (CON) groups. The CFT consisted of 8 weeks (3 days per week) rhythmic aerobic exercise, TRX suspension training, elastic band training, and bodyweight training. BDNF, IGF-1, and health-related fitness components were assessed before and after the intervention.
RESULTS: There was no significant difference in BDNF level between the CFT and the CON group. In contrast, IGF-1, walking speed, and strength of the right- and left-hand was significantly increased in the CFT compared with the CON group. Furthermore, there was a significant and positive correlation between IGF-1 and some fitness components.
CONCLUSIONS: The findings indicated that CFT might a useful training mode in the rehabilitation of the MS women. CFT improved IGF-1 level that is a neuroprotective agent in MS. Positive and significant association between IGF-1 and some health-related fitness components indicates of the importance of IGF-1 in the rehabilitation of the MS persons than BDNF.
Department of Neuromuscular Exercise Physiology, Kish International Campus, Tehran University, Kish Island, Iran
The Role of Forced and Voluntary Training on Accumulation of Neural Cell Adhesion Molecule and Polysialic Acid in Muscle of Mice with Experimental Autoimmune Encephalomyelitis.
It has been suggested that depletion of adhesion molecules is one of the factors associated with or possibly responsible for multiple sclerosis (MS) progression. The aim of this study was to investigate the effect of forced and voluntary training before and after induction of experimental autoimmune encephalomyelitis (EAE) on accumulation of neural cell adhesion molecule (NCAM) and polysialic acid (PSA) in neuromuscular junction denervation in plantaris and soleus muscles in C57BL/6 female mice. A total of 40 female C57BL/6 mice, 10-week-old, were randomly divided into four groups, including induced control groups without EAE induction, induced EAE without training, and forced and voluntary training groups. Myelin oligodendrocyte glycoprotein peptide 35-55 (300 μg in saline; MOG 35-55; KJ Ross-Petersen ApS, Denmark) was injected subcutaneously at the base of the tail of each mouse. Clinical assessment of EAE was performed daily using a 15-point scoring system following immunization. Training groups performed the swimming program for 30 min/day, 5 times/week, for 4 weeks. Mice had access to a treadmill for one hour per day, 5times/week, for 4 weeks in individual cage. The mice were scarified, and the plantaris and soleus muscles were then isolated for investigation of proteins expression using IHC. An analysis of the preventive exercise (before) and recovery exercise (after) of the EAE was performed. Images of the stained sections were taken using a fluorescent microscope. Quantitative image analysis was performed using ImageJ software package. The obtained data from the mean percentage expression of PSA and NCAM in pre- and post-soleus and plantaris muscles showed that the highest and lowest expression levels of PSA and NCAM belonged to control and swim EAE (SE) groups, respectively. The low expression levels of PSA and NCAM were detected in rat with MS without intervention. In conclusion, the relationship between increasing levels of NCAM and PSA protein expression and voluntary and compulsory activity were detectable both in pre and post-soleus and plantaris. However, voluntary activity resulted in more expression levels of NCAM and PSA than that of compulsory. In conclusion, since it has been suggested that depletion of NCAM is one of the factors associated with or possibly responsible for MS progression, these findings show exercise MS progression may be reduced by increasing expression of exercise-related adhesion molecule such as NCAM and PSA (a glycan modification of the NCAM).
Rehabilitation Science, School of Health Professions, University of Alabama at Birmingham
Immediate and Sustained Effects of Interventions for Changing Physical Activity in People with Multiple Sclerosis: Meta-Analysis of Randomized Controlled Trials
To examine the immediate and sustained effects of interventions for changing physical activity behavior in people with multiple sclerosis (MS), and explore factors that might moderate intervention effects on physical activity behavior (e.g., intervention type and duration, type of physical activity measurement, intensity of theory integration [degree of theory used in study design], and study quality).
Systematic searches were conducted in four databases, including MEDLINE, CINAHL, PsychINFO, Google Scholar, in October 2017 and October 2018. Updated searches were conducted in September 2019 with two additional databases (Embase and Scopus) and enhanced search terms.
Studies were included that (1) incorporated a randomized controlled trial design of interventions that targeted change in physical activity behavior in adults with MS, namely, exercise training and behavioral intervention (alone and combined); (2) included self-reported and/or device-measured physical activity as an outcome; and (3) contained pre-post assessments.
Data were extracted for immediate (pre- to post-intervention) and sustained (pre-intervention to follow-up) physical activity outcomes and study characteristics. Weighted mean effect sizes were expressed as standardized mean differences (SMD). Heterogeneity between each categorical moderator was compared using Q between statistics.
The mean SMD was 0.56 for immediate changes (n=24) and 0.53 for sustained changes (n=7) of physical activity outcomes. Self-reported physical activity measures yielded larger effects (SMD = 0.64; n=22) than those of device-measured physical activity (0.26; n=7). There appeared to be larger immediate effects of behavioral interventions (SMD = 0.71; n=9) than exercise training (0.53; n=7) and combined interventions (0.37; n=8).
Current evidence demonstrates that interventions are efficacious for increasing and potentially sustaining physical activity behavior in adults with MS. The effects appear optimized based on the delivery of behavioral interventions alone, and these interventions may be capable of supporting long-term behavior change.
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