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Systematic Review on Exercise Training as a Neuroplasticity-Inducing Behavior in Multiple Sclerosis.

ABSTRACT: Background. Exercise training is associated with functional improvements in persons with multiple sclerosis (MS), perhaps based on neuroplasticity. However, inferences regarding neuroplasticity require observations of exercise-related changes in the central nervous system that explain functional adaptations. This systematic review critically evaluated studies on exercise training, neuroimaging outcomes, and functional outcomes in MS based on consistency with a well-established conceptual model for characterizing exercise training as a possible neuroplasticity-inducing behavior in this population. Methods. We performed targeted and comprehensive searches of multiple databases for papers involving exercise training interventions on functional and neuroimaging outcomes in persons with MS. Acceptable study designs included randomized controlled trials, single-group pre/post designs, and quasi-experimental designs. Four independent reviewers extracted relevant data from each eligible paper on characteristics of participants, exercise interventions, neuroimaging outcomes, functional outcomes, pattern of study results, and potential risks of bias. Results. The literature search returned only 10 papers (involving 8 original interventions) that met eligibility criteria wherein inferences regarding neuroplasticity could be drawn, based on inclusion of neuroimaging and functional endpoints. Within those 10 papers, there is mixed evidence for exercise training as a neuroplasticity-inducing behavior in persons with MS. Conclusions. Such a paucity of evidence supporting exercise-induced neuroplasticity in MS is likely a product of a very small number of papers that do not sufficiently examine hypothesized mechanisms of action. Future research might consider examining specific neural changes that might result from exercise prescriptions that are specifically designed to induce certain functional changes among persons with MS.

SUBMITTER: Sandroff BM

PROVIDER: S-EPMC7885181 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Systematic Review on Exercise Training as a Neuroplasticity-Inducing Behavior in Multiple Sclerosis.

Sandroff Brian M BM Jones C Danielle CD Baird Jessica F JF Motl Robert W RW

Neurorehabilitation and neural repair 20200526 7

<i>Background</i>. Exercise training is associated with functional improvements in persons with multiple sclerosis (MS), perhaps based on neuroplasticity. However, inferences regarding neuroplasticity require observations of exercise-related changes in the central nervous system that explain functional adaptations. This systematic review critically evaluated studies on exercise training, neuroimaging outcomes, and functional outcomes in MS based on consistency with a well-established conceptual ...[more]

PMID: 32452269

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Project description:BackgroundThere has been an exponential growth in the number of clinical research studies regarding exercise training in multiple sclerosis, and literature reviews and meta-analyses have documented the many benefits of exercise training. This research further requires careful review for documenting the safety of exercise training in multiple sclerosis, as clarity on safety represents a major hurdle in the clinical prescription of exercise behaviour.ObjectivesTo enhance understanding of the feasibility of exercise in multiple sclerosis, we (1) provide a protocol of a systematic review and meta-analysis that summarises rates and risks of clinical relapse, adverse events (i.e., an unfavourable outcome that occurs during the intervention delivery time period), and serious adverse events (i.e., an untoward occurrence that results in death or is life threatening, requires hospitalisation, or results in disability during the intervention delivery time period), as well as retention, adherence, and compliance, from randomised controlled trials of exercise training in persons with multiple sclerosis; and (2) identify moderators of relapse, adverse events, and serious adverse event rates.MethodsEight field-relevant databases will be searched electronically. Studies that involve a randomised controlled trial of exercise training (with non-exercise, non-pharmacological, comparator), report on safety outcomes, and include adults with multiple sclerosis will be included. Rates and relative risks of the three primary outcomes (relapse, adverse event, and serious adverse event) will be calculated and reported each with standard error and 95% confidence interval. Random-effects meta-analysis will estimate mean population relative risk for outcomes. Potential sources of variability, including participant characteristics, features of the exercise stimulus, and comparison condition, will be examined with random-effects meta-regression with maximum likelihood estimation.DiscussionThe results from this systematic review and meta-analysis will inform and guide healthcare practitioners, researchers, and policymakers on the safety of exercise training in persons with multiple sclerosis. Where possible, we will identify the impact of exercise type, exercise delivery style, participant disability level, and the prescription of exercise guidelines, on the safety of exercise training. The result will identify critical information on the safety of exercise in persons with multiple sclerosis, while also identifying gaps in research and setting priorities for future enquiries.Systematic review registrationPROSPERO 2020 CRD42020190544.

Project description:Evidence indicates that exercise holds the potential to counteract neurodegeneration experienced by persons with multiple sclerosis (pwMS), which is in part believed to be mediated through increases in neurotrophic factors. There is a need to summarize the existing evidence on exercise-induced effects on neurotrophic factors alongside neuroprotection in pwMS. To (1) systematically review the evidence on acute (one session) and/or chronic (several sessions) exercise-induced changes in neurotrophic factors in pwMS and (2) investigate the potential translational link between exercise-induced changes in neurotrophic factors and neuroprotection. Five databases (Medline, Scopus, Web of Science, Embase, Sport Discus) were searched for randomized controlled trials (RCT) examining the effects of exercise (all modalities included) on neurotrophic factors as well as measures of neuroprotection if reported. The quality of the study designs and the exercise interventions were assessed by use of the validated tool TESTEX. From N = 337 identified studies, N = 14 RCTs were included. While only N = 2 of the identified studies reported on the acute changes in neurotrophic factors, all N = 14 RCTs reported on the chronic effects, with N = 9 studies revealing between-group differences in favor of exercise. This was most prominent for brain-derived neurotrophic factor (BDNF), with between-group differences in favor of exercise being observed in N = 6 out of N = 12 studies. Meta-analyses were applicable for three out of 10 different identified neurotrophic factors and revealed that exercise can improve the chronic levels of BDNF (delta changes; N = 9, ES = 0.78 (0.27; 1.28), p = 0.003, heterogeneity between studies) and potentially also ciliary neurotrophic factor (CNTF) (N = 3, ES = 0.24 (-0.07; 0.54), p = 0.13, no heterogeneity between studies) but not nerve growth factor (NGF) (N = 4, ES = 0.28 (-0.55; 1.11), p = 0.51, heterogeneity between studies). Indicators of neuroprotection (e.g., with direct measures of brain structure assessed by MRI) were assessed in N = 3 of the identified studies only, with N = 2 partly supporting and thus indicating a potential translational link between increases in neurotrophic factors and neuroprotection. The present study reveals that exercise can elicit improvements in chronic levels of BDNF in pwMS, whereas the effects of exercise on chronic levels of other neurotrophic factors and on acute levels of neurotrophic factors in general, along with a potential translational link (i.e., with exercise-induced improvements in neurotropic factors being associated with or even mediating neuroprotection), are sparse and inconclusive. There is a need for more high-quality studies that assess neurotrophic factors (applying comparable methods of blood handling and analysis) concomitantly with neuroprotective outcome measures. Review Registration: PROSPERO (ID: CRD42020177353).

Project description:Background: Over the past two decades, various novel disease-modifying drugs for multiple sclerosis (MS) have been approved. However, there is high variability in the patient response to the available medications, which is hypothesized to be partly attributed to genetics. Objectives: To conduct a systematic review of the current literature on the pharmacogenomics of MS therapy. Methods: A systematic literature search was conducted using PubMed/MEDLINE database searching for articles investigating a role of genetic variation in response to disease-modifying MS treatments, published in the English language up to October 9th, 2018. PRISMA guidelines for systematic reviews were applied. Studies were included if they investigated response or nonresponse to MS treatment defined as relapse rate, by expanded disability status scale score or based on magnetic resonance imaging. The following data were extracted: first author's last name, year of publication, PMID number, sample size, ethnicity of patients, method, genes, and polymorphisms tested, outcome, significant associations with corresponding P-values and confidence intervals, response criteria, and duration of the follow-up period. Results: Overall, 48 articles published up to October 2018, evaluating response to interferon-beta, glatiramer acetate, mitoxantrone, and natalizumab, met our inclusion criteria and were included in this review. Among those, we identified 42 (87.5%) candidate gene studies and 6 (12.5%) genome-wide association studies. Existing pharmacogenomic evidence is mainly based on the results of individual studies, or on results of multiple studies, which often lack consistency. In recent years, hypothesis-free approaches identified novel candidate genes that remain to be validated. Various study designs, including the definition of clinical response, duration of the follow-up period, and methodology as well as moderate sample sizes, likely contributed to discordances between studies. However, some of the significant associations were identified in the same genes, or in the genes involved in the same biological pathways. Conclusions: At the moment, there is no available clinically actionable pharmacogenomic biomarker that would enable more personalized treatment of MS. More large-scale studies with uniform design are needed to identify novel and validate existing pharmacogenomics findings. Furthermore, studies investigating associations between rare variants and treatment response in MS patients, using next-generation sequencing technologies are warranted.

Dataset Information

Systematic Review on Exercise Training as a Neuroplasticity-Inducing Behavior in Multiple Sclerosis.

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Systematic Review on Exercise Training as a Neuroplasticity-Inducing Behavior in Multiple Sclerosis.

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