This review provides the reader with the up-to-date evidence-based basis for prescribing exercise as medicine in the treatment of 26 different diseases: psychiatric diseases (depression, anxiety, stress, schizophrenia); neurological diseases (dementia, Parkinson's disease, multiple sclerosis); metabolic diseases (obesity, hyperlipidemia, metabolic syndrome, polycystic ovarian syndrome, type 2 diabetes, type 1 diabetes); cardiovascular diseases (hypertension, coronary heart disease, heart failure, cerebral apoplexy, and claudication intermittent); pulmonary diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis); musculo-skeletal disorders (osteoarthritis, osteoporosis, back pain, rheumatoid arthritis); and cancer. The effect of exercise therapy on disease pathogenesis and symptoms are given and the possible mechanisms of action are discussed. We have interpreted the scientific literature and for each disease, we provide the reader with our best advice regarding the optimal type and dose for prescription of exercise.

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Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases

Exercise Physiology: Energy, Nutrition and Human Performance

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammatory demyelination and neurodegeneration within the CNS. This damage of CNS structures leads to deficits of body functions, which, in turn, affect patient activities, such as walking, and participation. The pathogenesis and resulting consequences of MS have been described as concepts within the International Classification of Functioning, Disability and Health (ICF) model--an international standard to describe and measure health and disability. Evidence suggests that exercise training in people with MS has the potential to target and improve many of the components outlined in the ICF model. Although the body of research examining the effects of exercise training on depression, cognition and participatory outcomes is not sufficiently developed, some preliminary evidence is promising. Exercise training is proposed to affect inflammation, neurodegeneration, and CNS structures, but current evidence is limited. In this Review, we discuss evidence from clinical trials that suggests beneficial effects of exercise training on muscle strength, aerobic capacity and walking performance, and on fatigue, gait, balance and quality of life. Issues with current studies and areas of future research are highlighted.

The benefits of exercise training in multiple sclerosis

Summary Exercise can be a beneficial rehabilitation strategy for people with multiple sclerosis to manage symptoms, restore function, optimise quality of life, promote wellness, and boost participation in activities of daily living. However, this population typically engages in low levels of health-promoting physical activity compared with adults from the general population, a fact which has not changed in the past 25 years despite growing evidence of the benefits of exercise. To overcome this challenge, the main limitations to promoting exercise through the patient–clinician interaction must be addressed. These limitations are the inadequate quality and scope of existing evidence, incomplete understanding of the mechanisms underlying the beneficial effects of exercise in people with multiple sclerosis, and the absence of a conceptual framework and toolkit for translating the evidence into practice. Future research to address those limitations will be essential to inform decisions about the inclusion of exercise in the clinical care of people with multiple sclerosis.

Exercise in patients with multiple sclerosis

Background
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system affecting an estimated 1.3 million people worldwide. It is characterised by a variety of disabling symptoms of which excessive fatigue is the most frequent. Fatigue is often reported as the most invalidating symptom in people with MS. Various mechanisms directly and indirectly related to the disease and physical inactivity have been proposed to contribute to the degree of fatigue. Exercise therapy can induce physiological and psychological changes that may counter these mechanisms and reduce fatigue in MS.

Objectives
To determine the effectiveness and safety of exercise therapy compared to a no-exercise control condition or another intervention on fatigue, measured with self-reported questionnaires, of people with MS.

Search methods
We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Trials Specialised Register, which, among other sources, contains trials from: the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 10), MEDLINE (from 1966 to October 2014), EMBASE (from 1974 to October 2014), CINAHL (from 1981 to October 2014), LILACS (from 1982 to October 2014), PEDro (from 1999 to October 2014), and Clinical trials registries (October 2014). Two review authors independently screened the reference lists of identified trials and related reviews.

Selection criteria
We included randomized controlled trials (RCTs) evaluating the efficacy of exercise therapy compared to no exercise therapy or other interventions for adults with MS that included subjective fatigue as an outcome. In these trials, fatigue should have been measured using questionnaires that primarily assessed fatigue or sub-scales of questionnaires that measured fatigue or sub-scales of questionnaires not primarily designed for the assessment of fatigue but explicitly used as such.

Data collection and analysis
Two review authors independently selected the articles, extracted data, and determined methodological quality of the included trials. Methodological quality was determined by means of the Cochrane 'risk of bias' tool and the PEDro scale. The combined body of evidence was summarised using the GRADE approach. The results were aggregated using meta-analysis for those trials that provided sufficient data to do so.

Main results
Forty-five trials, studying 69 exercise interventions, were eligible for this review, including 2250 people with MS. The prescribed exercise interventions were categorised as endurance training (23 interventions), muscle power training (nine interventions), task-oriented training (five interventions), mixed training (15 interventions), or 'other' (e.g. yoga; 17 interventions). Thirty-six included trials (1603 participants) provided sufficient data on the outcome of fatigue for meta-analysis. In general, exercise interventions were studied in mostly participants with the relapsing-remitting MS phenotype, and with an Expanded Disability Status Scale less than 6.0. Based on 26 trials that used a non-exercise control, we found a significant effect on fatigue in favour of exercise therapy (standardized mean difference (SMD) -0.53, 95% confidence interval (CI) -0.73 to -0.33; P value 58%). The mean methodological quality, as well as the combined body of evidence, was moderate. When considering the different types of exercise therapy, we found a significant effect on fatigue in favour of exercise therapy compared to no exercise for endurance training (SMDfixed effect -0.43, 95% CI -0.69 to -0.17; P value < 0.01), mixed training (SMDrandom effect -0.73, 95% CI -1.23 to -0.23; P value < 0.01), and 'other' training (SMDfixed effect -0.54, 95% CI -0.79 to -0.29; P value < 0.01). Across all studies, one fall was reported. Given the number of MS relapses reported for the exercise condition (N = 25) and non-exercise control condition (N = 26), exercise does not seem to be associated with a significant risk of a MS relapse. However, in general, MS relapses were defined and reported poorly.

Authors' conclusions
Exercise therapy can be prescribed in people with MS without harm. Exercise therapy, and particularly endurance, mixed, or 'other' training, may reduce self reported fatigue. However, there are still some important methodological issues to overcome. Unfortunately, most trials did not explicitly include people who experienced fatigue, did not target the therapy on fatigue specifically, and did not use a validated measure of fatigue as the primary measurement of outcome.

Exercise therapy for fatigue in multiple sclerosis

https://www.archives-pmr.org/article/S0003-9993(13)00361-4/pdf

Effects of Exercise Training on Fitness, Mobility, Fatigue, and Health-Related Quality of Life Among Adults With Multiple Sclerosis: A Systematic Review to Inform Guideline Development

Body weight supported locomotor training uses neuroplasticity principles to improve recovery following a spinal cord injury (SCI). Steady state locomotion using the same body weight support (BWS) percent was compared in 7 males (42.6 ± 4.29 years) with incomplete SCI and matched (gender, age) noninjured controls (42.7 ± 5.4 years) using the Lokomat, Manual Treadmill, and ZeroG. The VO2000, Polar Heart Rate (HR) Monitor, and lower limb electromyography (EMG) electrodes were worn during the 2-minute sessions. Oxygen uptake (VO2) and HR were expressed as percentage of peak values obtained using progressive arm ergometry; VO2 was also expressed relative to resting metabolic equivalents (METS). Filtered EMG signals from tibialis anterior (TA), rectus femoris (RF), biceps femoris (BF), and medial gastrocnemius (MG) were normalized to ZeroG stepping. The Lokomat required 30% of VO2 peak (2METS) compared to ~54% (3METS) for Manual Treadmill and ZeroG sessions. HR was 67% of peak during Lokomat sessions compared to ~83% for Manual Treadmill and ZeroG. Muscle activation was higher in treadmill conditions compared to the ZeroG primarily due to increased BF activity. At the same level of BWS, locomotion using the Manual Treadmill or the ZeroG is more aerobically demanding than the Lokomat. Treadmill modalities encourage greater hip extensor activation compared to overground locomotion.

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Metabolic Demand and Muscle Activation during Different Forms of Bodyweight Supported Locomotion in Men with Incomplete SCI

INTRODUCTION Body weight-supported locomotor training has created enthusiasm in clinical populations and service providers as a rehabilitation tool to improve overground walking ability and other health outcomes [1]. Varying the amount of body weight supported by such devices alters the intensity of training sessions; unloading the individual decreases the muscular demands of the lower limbs [2]. For individuals with neurological impairments (e.g., spinal cord injury) evidence suggests that by offsetting body weight, appropriate gait pattern expression may be facilitated and even normalized. Adult spinal cat models provided initial indications of the possibility of locomotor recovery following interactive treadmill gait training programs, which provided graded body weight support (BWS) [3]. Persons with spinal cord injury (complete and incomplete) have demonstrated the ability to increase weight-bearing capacity of lower-limb extensors through body weight-supported treadmill training, in addition to increasing appropriate gastrocnemius and decreasing inappropriate tibialis anterior (TA) activation [4]. An overground body weight-supported walking study (0/30/100% BWS at natural cadence) in individuals with chronic stroke found offloading resulted in reduced hip range of motion, with individuals responding to the support by decreasing their walking speed and taking shorter strides [5]. As this information suggests, there are a variety of therapeutic training approaches that offset body weight as a patient progresses through his or her rehabilitation program. These options include manual or robotic-assisted treadmill training, as well as treadmill or overground training with or without electrical stimulation of the peroneal nerve [6]. Each training approach has its respective advantages and disadvantages; for example, robotic-assisted training provides stepping consistency but does not allow the movement variability associated with overground walking [7]. In addition, this therapeutic option is treadmill-based and, as a result, is not as task-specific or transferable to daily living as overground training programs [5]. Currently, there is a need for a body weight-supported overground walking device equipped with a motor that moves along an overhead track independent of the user in order to eliminate the possibility that a drag force created by the system itself affects gait performance [5]. The newly developed ZeroG system (Aretech LLC; Ashburn, Virginia), created by Hidler et al., attempts to provide this dynamic BWS through the use of a custom-series elastic actuator during overground walking and balance training (Figure 1) [8]. It has been suggested that more natural ground reaction forces and gait characteristics can be achieved through the use of dynamic BWS [8]. To date, no study has investigated the effects of BWS on muscle activation patterns during walking using the ZeroG. It would be beneficial to know "normal" responses to partial weight bearing using this device before using it in a rehabilitation setting. Therefore, the purpose of this study was to collect normative data from walking trials in nondisabled participants using the ZeroG at varying degrees of BWS (0/20/40/60/80% BWS). We hypothesized that decreased levels of activation primarily in the ankle plantar flexors (e.g., calves) would be experienced with increased BWS. The results from this study will eventually be used as a model for comparison with individuals that have mobility impairments who use this rehabilitation tool for gait therapy. METHODS Subjects Thirteen nondisabled individuals (6 males, 7 females) with an average age of 23.8 [+ or -] 2.7 yr and weight of 68.3 [+ or -] 8.0 kg participated in the study. "Nondisabled" was defined as an individual without musculoskeletal disease (e.g., multiple sclerosis, cerebral palsy) or injury within the past year (e.g., sprain, strain) of the lower leg and who was able to comfortably walk 30 m unassisted. …

https://www.rehab.research.va.gov/jour/2014/511/pdf/JRRD-2013-01-0005.pdf

Muscle activation during body weight-supported locomotion while using the ZeroG.

Sleep hygiene practices may hinder university athletes from obtaining quality sleep to support health and performance. We sought to provide a comprehensive evaluation of sleep quality and behaviors in varsity athletes using validated sleep questionnaires: the Athlete Sleep Screening Questionnaire (ASSQ) and the Athlete Sleep Behavior Questionnaire (ASBQ). Sixty-four (n = 64) athletes participated (54% female; 71% Caucasian). The mean age was 20.3 ± 1.7 years and the mean BMI was 23.3 ± 3.3. Fifty-one percent met the threshold for adequate sleep (7+ h) and 54% reported being somewhat/very satisfied with sleep quality. Global scores for ASSQ Sleep Difficulty and ASBQ sleep behaviors were significantly correlated (r = 0.31; p = 0.014) and not significantly different across age, academic year, or residence. According to the ASSQ, 11% and 24% were classified as having severe or moderate sleep problems, respectively. The ASBQ categorized 62% as having “poor” sleep behaviors. Notable sleep-influencing factors included a high frequency of emotional/cognitive processing of sport-performance issues (46.9%), frequent use of light-emitting devices before bed (90%), training after 7 pm (65%), and the use of sleep medication (19%). Half of the university athletes did not meet the thresholds for adequate sleep, and some may require a referral for clinical sleep issues. The majority of these athletes' sleep behaviors do not promote adequate sleep. The ASSQ shows utility to assess gradations in clinical sleep difficulty; the ASBQ could be used in concert with the ASSQ to discern “cognitive and physiological arousal” targets for use in educational workshops designed to promote optimal sleep hygiene in university athletes.

https://www.frontiersin.org/articles/10.3389/fspor.2022.906663/pdf

Alyssa Fenuta

Papers

Effects of Exercise Training on Fitness, Mobility, Fatigue, and Health-Related Quality of Life Among Adults With Multiple Sclerosis: A Systematic Review to Inform Guideline Development

Metabolic Demand and Muscle Activation during Different Forms of Bodyweight Supported Locomotion in Men with Incomplete SCI

Muscle activation during body weight-supported locomotion while using the ZeroG.

Sleep Quality and Sleep Behaviors in Varsity Athletes: A Pilot Study

Body Weight−Supported Treadmill Training After Spinal Cord Injury: Is There An Ideal Prescription For Intervention?