Thesis title: Methods Used to Study the Efficacy of Whole-Body Vibration Training as a Symptom Management Strategy for People with Multiple Sclerosis
Background:
Multiple sclerosis (MS) is a chronic, immune-mediated disease in which the central nervous system (CNS) is damaged by inflammatory and neurodegenerative processes. Initially, most people with MS (PwMS) experience a relapsing–remitting course (RRMS), which is typically followed by a progressive phase (PMS) requiring a personalized, multimodal approach to rehabilitation and symptomatic therapy. Whole-body vibration (WBV) is a neuromuscular training modality used not only for the enhancement of physical performance, but also as a method for treatment or prophylaxis. Evidence from both animal models and human studies involving healthy individuals (such as athletes and older adults) as well as various clinical populations, including people with CNS diseases suggests that WBV may induce neurophysiological adaptations. Such evidence has increased interest in research aimed at identifying the optimal exposure parameters and dosage (e.g., number of training sessions, type of vibrating platform, vibration frequency and amplitude, body posture to be assumed during the treatment, duration of the stimulation, number of sets and recovery intervals) for its application both in the domain of sports performance and in neurorehabilitation. However, at present the evidence supporting these strategies is not particularly robust for PwMS. This may be due not only to the possible ineffectiveness of the method itself, but also to the methodological limitations of the studies conducted to date. In particular, the clinical and biological heterogeneity of the individuals undergoing treatment may represent a conditioning factor that leads to false negative results. Another issue could be the lack of adequate adaptation strategies during the delivery of WBV. Despite these limitations, WBV, when applied in a controlled manner, could be considered safe, physically undemanding, and easy to implement, particularly when PwMS encounter barriers to participating in standard conventional treatment program or when further clinical deterioration, together with fatigue, reduces tolerance to other interventions aimed at motor recovery. In such circumstances, it may serve as a supportive or compensatory intervention, helping at least to prevent secondary deconditioning. Clinical problem: Despite more than a decade of research, the existing evidence remains conceptually and methodologically fragmented. Most systematic reviews and meta-analyses have focused almost exclusively on motor outcomes, often without rigorous control conditions or a structured assessment of methodological quality. In addition, the marked heterogeneity among RCTs further increased by the limited consideration of different disease phenotypes and by the absence of clear and consistent parameters for vibration delivery has reduced both the interpretability of the results and their clinical applicability. This situation highlights not only a technical limitation but also a true conceptual gap: in many studies it is not clearly explained why or through which mechanisms WBV could provide a therapeutic benefit, resulting in a weak theoretical rationale and study designs that are not methodologically complete. For these reasons, moving from meta-analyses toward more rigorous qualitative and clinically oriented syntheses appears necessary to clarify efficacy, safety, and future methodological priorities. Objectives: This thesis pursues three primary objectives, three secondary objectives, and three tertiary objectives: 1) to evaluate the efficacy, safety, and tolerability of WBV treatment; 2) to analyse adherence in terms of the number of WBV sessions completed, the attrition rate, and the reasons for discontinuation of the treatment; 3) to examine the level of transparency in reporting, the clinical and methodological heterogeneity, and the patterns of delivery of the vibratory load (in terms of configuration, structure, and dosing logic) in RCTs investigating functional outcomes in PwMS.
Methods:
A systematic review was conducted. Five electronic databases (PubMed/MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and the Physiotherapy Evidence Database (PEDro)) were systematically searched to identify studies published from January 1, 2004, to December 31, 2024. As a supplementary strategy, hand-searches were also performed in six key journals in the field (Multiple Sclerosis Journal, Neurology, Archives of Physical Medicine and Rehabilitation, Clinical Rehabilitation, Neurorehabilitation and Neural Repair, and the Journal of Rehabilitation Medicine), scientific experts were consulted, and the reference lists of both included and excluded studies were screened, as well as those of previous secondary research (systematic reviews, meta-analyses, overviews, and umbrella reviews). The research question and eligibility criteria were defined prior to the start of the review. The search syntax was developed using MeSH terms, free-text methods, and expert consultation, and was structured according to the PICO model, from which the components related to the intervention, population, control condition, and primary outcomes were predefined. Eligible studies included WBV platform and compared with at least one control condition analogous to the WBV protocol but without active vibration, allowing the isolation of the specific effect of the vibratory stimulus. Studies employing different WBV protocols without a non-active control condition, studies with active sham or placebo comparators, inappropriate or poorly reported controls, unbalanced co-interventions, or focal (local) vibration were excluded. No restrictions were applied regarding the type of vibration platform, setting, language, measurement methods (including timepoints, tests, and tools), or study duration. Two reviewers independently selected the studies, assessed the risk of bias using the Verhagen nine-domain tool, and independently extracted the published data. Potential disagreements were resolved after consultation with a third investigator. Primary outcomes included motor performance (balance, functional mobility, gait speed, gait endurance, and knee flexor/extensor strength) and the reporting of safety and tolerability data. Secondary outcomes concerned adherence to the protocol and dropout/attrition rates with their related reasons. Tertiary outcomes included transparency of reporting, clinical and methodological heterogeneity, and the pattern of vibratory load delivery, described in terms of intensity, volume, and density, and classified as constant, modified/modulated, or not clearly reported. All tertiary outcomes were analysed using a 47-item checklist derived from two reporting guidelines for exercise-based interventions and WBV interventions in humans. A qualitative narrative synthesis was conducted and reported according to the PRISMA guidelines.
Results:
The search yielded 508 records. After screening, 17 studies were excluded and only six RCTs (183 participants) were deemed eligible. One study included exclusively women with RRMS, while the others recruited mixed samples (including PPMS, SPMS, and RRMS) with mild-to-moderate disability, mostly treated in outpatient settings; in one case, the intervention was partly self-managed in a gym environment. Methodological quality ranged from moderate to high, although reporting quality was generally poor. One study reported an improvement in the Berg Balance Scale and another in the 6-Minute Walk Test, whereas no between-group differences were observed for the remaining functional outcomes. Although a full comparison across studies was not fully feasible due to poor reporting and missing information, a marked variability emerged in the key delivery characteristics of the intervention. WBV was found to be safe, with only one reported adverse event in a crossover study, where a participant experienced a worsening of a pre-existing knee condition. Adherence was high, and delivery models of the vibratory load were heterogeneous.
Interpretation:
In PwMS, WBV appears feasible, however, its efficacy remains uncertain across most examined outcomes, with only preliminary indications of potential benefits for balance and aerobic endurance (6MWT). The lack of reproducible and dose-verified protocols limits interpretability. Future clinical trials should implement clearly defined dosing strategies tailored to MS phenotype, incorporate systematic verification procedures to ensure concordance between the planned protocol and the intervention actually delivered, and be accompanied by rigorously structured control conditions, objective and standardised safety assessments, and longitudinal follow-up capable of detecting delayed or late-onset effects. Furthermore, the use of highly sensitive outcome measures, collected through standardised and transparent procedures and able to detect small yet clinically meaningful changes, is essential to enable an accurate evaluation of intervention efficacy and to determine whether WBV may be truly effective for specific outcomes both in the short and long term.
Funding: No.