Background: The prognosis of people with multiple sclerosis (MS) has improved substantially in recent decades due to advances in diagnosis and treatment. Due to the unpredictable course and heterogenous treatment response in MS, there is a clear need for biomarkers that reflect disease activity in the clinical follow-up of these patients. We conducted a systematic review with Bayesian network meta-analysis with the aim of analyzing the effects of physical exercise on neurofilaments (NfL) and glial fibrillary acidic protein (GFAP) levels in patients with MS. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, starting with a PICO (patient/population, intervention, comparison, and outcome) question: what are the clinical effects of physical exercise (with independence of the type) on NfL and/or GFAP levels in patients with MS compared with other interventions or no intervention whatsoever? A systematically comprehensive literature search was conducted from January to March 2024 to identify original studies that answered the PICO question, using the main data sources. The quality of the studies included was assessed using the Quality Index of Downs & Black. For studies included in the systematic review that followed a randomized controlled trial (RCT) design, the methodological quality of each paper was assessed using the Physiotherapy Evidence Database (PEDro) Scale. Risk of bias was also explored by two independent reviewers. Finally, all articles were classified according to the levels of evidence and grades of recommendation for diagnosis studies established by the Oxford Center for Evidence-Based Medicine. For continuous outcome measures with enough comparisons and a methodological quality greater than or equal to good according to the PEDro scale, a Bayesian network meta-analysis (NMA) was applied. The statistical analyses were performed in R (version 4.1.3, R Core Team 2023) using the “BUGSnet” and “gemtc” packages. Bayesian NMA can be used to obtain a posterior probability distribution of all the relative treatment effects, which allows us to quantify the uncertainty of parameter estimates and to rank all the treatments in the network. Results: Eight studies were included in this systematic review and six articles in the NMA, and they were appraised for quality. The characteristics of the included studies, types of training and described protocols, methodological quality, risk of bias, and clinical effects on the studied biomarkers were outlined. Qualitative synthesis, effects of different exercise modalities in NfL with the Bayesian NMA, selection of the final model and model assessment, and ranking of interventions are also shown. Conclusions: Our findings indicated that moderate-intensity exercise is more likely to reduce NfL concentration compared to high-intensity exercise, and, in turn, high-intensity exercise is more likely to reduce NfL concentration than low-intensity exercise. However, the effects of high-intensity exercise on GFAP levels were inconclusive.

Introduction. The proliferation of immersive virtual reality (VR) technologies has transformed the way individuals interact with digital environments, offering unprecedented opportunities in fields ranging from entertainment and education to healthcare and mental health interventions. Immersive VR is increasingly being implemented in motor and cognitive programs in neurorehabilitation, where patient safety and treatment adherence are critical. Despite its relevance, the conceptualization and measurement of cybersickness (CS) remain fragmented across disciplines, with various assessment tools developed in isolation, targeting different symptom domains, populations, and use contexts. Aim. The aim of this systematic review is to identify, categorize, and critically appraise all existing instruments and scales developed to measure CS associated with immersive VR use. The secondary objectives involve examining the psychometric properties of the identified instruments to provide robust evidence for clinicians in assessing CS associated with VR, thereby supporting future scale development and standardization. Additionally, a further objective is to evaluate the specific applicability of these instruments and scales for measuring CS within neurorehabilitation settings, given the growing use of immersive VR in clinical practice with neurological populations. Methods. This systematic review was conducted in accordance with the Guideline for reporting systematic reviews of outcome measurement instruments (PRISMACOSMIN). The review protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO). Data extraction was performed independently by the two reviewers, and discrepancies were resolved by consensus or consultation with a third reviewer. To assess the psychometric robustness of existing CS assessment instruments used in virtual reality settings, we applied the methodology proposed by the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) initiative for systematic reviews of patient-reported outcome measures (PROMs). The evaluation was structured across three steps: Assessment of risk of bias; Quality of measurement properties and Summary of evidence; and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Results. Nine assessment instruments were included in this review. Following our analysis, the CSQ-VR and VRNQ received a Grade A recommendation, as they met sufficient criteria for both internal consistency and structural validity with high methodological quality. Few instruments have reported validations in specific clinical populations related to neurorehabilitation, including individuals with neurological conditions such as brain injury, multiple sclerosis (MS), migraine-associated vestibulopathy, vestibular disorders or cognitive impairment, indicating a critical gap in scale generalizability across clinical contexts. Conclusions. Despite the increasing use of immersive VR, few CS assessment tools have been designed and validated, reaching the CSQ-VR and VRNQ a Grade A recommendation. Among the nine identified assessment instruments, only the SSQ, MSAQ, CSQ-VR, VRNQ MSSQ and SEQ have been employed in samples with neurological disorders. There is a critical need for standardized CS VR-specific tools with robust psychometric properties to ensure safe and effective implementation in neurorehabilitation settings.

Background: Multiple sclerosis (MS) is an immune-mediated inflammatory disease that primarily targets the myelin of axons. Extremities are frequently affected, resulting in a negative impact on both activities of daily living (ADL) and quality of life. In recent years, there has been increasing interest in the potential benefits of exercise and blood flow restriction training (BFRT) programs as a therapeutic tool in people with neurological disorders. The aim of the present systematic review was to know the clinical effects of BFRT programs in people with MS. Methods: A systematically comprehensive literature search was conducted and registered in PROSPERO prior to its execution under the reference number CRD42024588963. The following data sources were used: Pubmed, Scopus, Web of Science (WOS) and the Cochrane Library. The following data were extracted from the papers: study design, sample, interventions, dosage, outcome measures and results. To assess the methodological quality of the papers included, the Quality Index of Downs and Black was used. Additionally, the articles were classified according to the levels of evidence and grades of recommendation for diagnosis studies established by the Oxford Center for Evidence-Based Medicine. Also, the Cochrane Handbook for Systematic Reviews of Interventions was used by two independent reviewers to assess risk of bias, assessing the six different domains. Results: Seven articles with a total of 71 participants were included in the review. Of the seven articles, five papers studied the effectiveness of BFRT combined with strengthening exercises and two papers studied the effect of BFRT combined with aerobic exercise. Of the five articles that analyzed BFRT combined with strengthening exercises, only two presented a control group. Both performed a low-load resistance training in combination with BFRT with four series, 30/15/15/15 repetitions and a rest of 1 min between the series and 3 min between the exercises. The control groups to which they were compared performed a high intensity strengthening exercise protocol which had the same exercises, sets, rests and duration of the protocol as the experimental groups. For those two papers which investigated the effects of BFRT combined with aerobic training, exercise was performed in two sessions per week for a period of 8 and 6 weeks, respectively. In both studies, the experimental protocol began with a warm-up phase and ended with a cool-down phase, and there were differences in cuff management. All these investigations found positive effects in the interventions that combined exercise with BFRT. The characteristics, outcome measures, effects of the interventions and the assessment of the methodological quality of the included studies and risk of bias are shown in the tables. Conclusions: BFRT in people with MS appears to be effective and safe for people with MS. BFRT might show positive clinical effects on strength, hypertrophy and balance outcomes. Nevertheless, future research should be conducted with better methodological quality to ensure the potential benefits of BFRT in people with MS since the studies analyzed present a high risk of bias and methodological limitations.

Background: In recent years, extended reality has gained traction in people with multiple sclerosis (MS) for their ability to deliver engaging, task-specific, and multisensory therapeutic experiences. Aim: This systematic review investigates the application of Mixed Reality (MR) and Augmented Reality (AR) technologies in neurorehabilitation for individuals with MS. Method: A comprehensive systematic review was conducted across seven databases and seven eligible studies were identified involving MR/AR interventions targeting motor and cognitive functions, in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The review protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO). Data extraction was performed independently by the two reviewers and discrepancies were resolved by consensus or consultation with a third reviewer. Participants were predominantly diagnosed with relapsing-remitting MS and presented mild to moderate disability. Technologies ranged from head-mounted displays to home-based AR platforms, with interventions addressing gait, upper-limb coordination, and dual-task performance. Outcome measures were mapped to the ICF framework, encompassing body function, activity, participation, and contextual factors. Results: Findings suggest short-term improvements in gait parameters, grip strength, and motor coordination, with enhanced engagement and usability reported. Methodological quality was moderate, with small sample sizes and heterogeneous protocols limiting generalizability. Risk of bias varied across study designs. Despite promising results, further research is needed to validate long-term efficacy, optimize cognitive load, and standardize intervention protocols. Conclusions: MR and AR may serve as effective complements to conventional and VR-based rehabilitation, particularly in personalized, task-oriented training for MS populations.

Objectives: The application of well-controlled, quantitative measurement systems has challenged the traditional notion that rigidity in Parkinson’s disease (PD) is a velocity-independent phenomenon. This review aimed to evaluate whether rigidity in PD is velocity-dependent or velocity-independent across different joints, body regions, testing speeds, and methodologies. Methods: This systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality of cross-sectional studies was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS), and reporting completeness was evaluated with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Results: Seventeen studies were included and analyzed by the body part assessed (wrist, elbow, hand, knee, trunk). Rigidity quantification in PD used various biomechanical technologies, sometimes combined with neurophysiological methods. Although rigidity is classically considered velocity-independent, experimental evidence suggests a more complex behavior, partially velocity-dependent, especially at moderate to high angular velocities. Methodological quality was variable but generally acceptable, with more recent studies showing stronger adherence to AXIS. However, compliance with STROBE reporting standards remained inconsistent. Conclusions: While rigidity in PD has not been classically defined as velocity-dependent, current evidence indicates that, under specific testing conditions, rigidity increases with passive movement velocity. These findings challenge traditional clinical assumptions and emphasize the need for standardized measurement protocols.

Posturography could serve as an early predictor of recovery of postural control and balance, especially if structural parameters are identified. This study aimed to explore the predictive value of posturographic measures for motor recovery after stroke using post-hoc analysis of a clinical trial cohort, to generate hypotheses for future confirmatory studies. A post hoc analysis was conducted in a cohort of thirty-eight individuals with subacute post-stroke hemiparesis presenting with balance and gait impairments. All participants were recruited from the Rehabilitation Department of the Rey Juan Carlos Hospital (Spain). Participants included in the study were individuals who had experienced a stroke. Posturographic variables were collected at baseline and after 4 weeks, and their changes were correlated with functional outcomes at follow-up. Univariate and multivariate binary logistic regression models were used to examine whether improvements exceeding the minimum detectable change in mediolateral structural parameters were associated with better functional outcomes based on Berg Balance Scale (BBS) scores ("High response)". Internal validation of the model was performed using bias-corrected and accelerated (BCa) bootstrap resampling." Participants who showed significant improvements in all three structural parameters of the X-axis demonstrated a strong association with High response in the univariate model (OR=6.8; 95% CI: 1.20-35.56; P=0.03). This association remained independently significant in the multivariable analysis (adjusted OR 6.9; 95% CI: 1.13-42.09; P=0.04). In contrast, no significant associations were observed for anteroposterior parameters. X-axis-related posturographic variables may have potential as predictors of rehabilitation response after stroke; however, given the post hoc nature of this analysis, these findings should be considered exploratory and require confirmation in prospective studies. Early improvements in mediolateral posturographic parameters may help identify individuals with stroke who are more likely to achieve meaningful balance recovery. However, given the exploratory, proof-of-concept nature of this study, these findings should be interpreted with caution and require confirmation in prospective studies, while potentially providing a starting point for future research in this area.