{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:05:10Z","timestamp":1779879910390,"version":"3.53.1"},"reference-count":71,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Multiple sclerosis (MS) is characterized by progressive disability and a spectrum of motor and cognitive impairments. Exergames and virtual reality (VR) are proposed as motivating exercise tools, potentially useful for improving adherence and expanding access to rehabilitation. The objectives are to explore the feasibility and safety of a supervised rehabilitation program based on a high-intensity exercise program with immersive virtual reality (IVR) in people with MS and to describe its effects on physical, cognitive, and functional domains, as well as on the serum biomarker neurofilament light chain (sNfL). Materials and Methods: Pre\u2013post exploratory study in five volunteers from a local MS Association [Vigo, Spain]. Intervention: 8 weeks, two sessions\/week, 10 min\/session of an IVR boxing-based exergame combined with usual rehabilitation, supervised by a physiotherapist. The variables studied were safety (Simulator Sickness Questionnaire [SSQ]), usability (System Usability Scale [SUS]), disability (Expanded Disability Status Scale [EDSS]), gait (25-Foot Walk Test [25FWT]), manual dexterity (9 Hole Peg Test [9HPT]), cognition (Symbol Digit Modalities Test [SDMT]), and axonal damage biomarker (sNfL). Results: The intervention could be feasible and safe (100% adherence, no adverse events (without SSQ symptoms), 95% usability [SUS]). There were positive changes in all variables studied (mean \u00b1 SD): EDSS \u22120.5 \u00b1 0.9; 25FWT \u22124.9 \u00b1 9.8 s; right 9HPT \u22123.3 \u00b1 0.9 s; sNfL \u22124.4 \u00b1 4.5 pg\/mL, except for left 9HPT +0.5 \u00b1 5.0 s and cognition (SDMT \u22122.4 \u00b1 1.3 points). Conclusions: A brief, supervised exercise program combing an IVR exergame with standard rehabilitation was feasible and safe in people with MS. Although the results seem promising with the proposed design, the clinical and biological changes are merely exploratory, and it is not possible to infer their efficacy. Our findings open the door to future controlled studies including perceived high-intensity exercise programs and larger sample sizes to explore efficacy and estimate clinically relevant effect sizes.<\/jats:p>","DOI":"10.3390\/medicina62050968","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T10:19:52Z","timestamp":1779877192000},"page":"968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Benefits of a Perceived High-Intensity Exercise Program with Immersive Virtual Reality Combined with Usual Rehabilitation in Multiple Sclerosis: Exploratory Study"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1706-5639","authenticated-orcid":false,"given":"Pablo","family":"Campo-Prieto","sequence":"first","affiliation":[{"name":"Departamento de Biolox\u00eda Funcional e Ciencias da Sa\u00fade, Facultade de Fisioterapia, Universidade de Vigo, 36005 Pontevedra, Spain"},{"name":"HealthyFit Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Pontevedra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"Gonz\u00e1lez-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Hospital \u00c1lvaro Cunqueiro, 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2903-3829","authenticated-orcid":false,"given":"Jos\u00e9 M\u00aa","family":"Cancela-Carral","sequence":"additional","affiliation":[{"name":"HealthyFit Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Pontevedra, Spain"},{"name":"Departamento de Did\u00e1cticas Especiais, Facultade de Ciencias da Educaci\u00f3n e do Deporte, Universidade de Vigo, 36005 Pontevedra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2720-1497","authenticated-orcid":false,"given":"Gustavo","family":"Rodr\u00edguez-Fuentes","sequence":"additional","affiliation":[{"name":"Departamento de Biolox\u00eda Funcional e Ciencias da Sa\u00fade, Facultade de Fisioterapia, Universidade de Vigo, 36005 Pontevedra, Spain"},{"name":"HealthyFit Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Pontevedra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy","volume":"19","author":"Ghasemi","year":"2017","journal-title":"Cell J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple Sclerosis","volume":"378","author":"Reich","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S1474-4422(18)30443-5","article-title":"Global, Regional, and National Burden of Multiple Sclerosis 1990\u20132016: A Systematic Analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Wallin","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1177\/1352458520970841","article-title":"Rising Prevalence of Multiple Sclerosis Worldwide: Insights from the Atlas of MS, Third Edition","volume":"26","author":"Walton","year":"2020","journal-title":"Mult. Scler. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/ene.13819","article-title":"Multiple Sclerosis\u2014A Review","volume":"26","author":"Dobson","year":"2019","journal-title":"Eur. J. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hao, Z., Zhang, X., and Chen, P. (2022). Effects of Different Exercise Therapies on Balance Function and Functional Walking Ability in Multiple Sclerosis Disease Patients\u2014A Network Meta-Analysis of Randomized Controlled Trials. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19127175"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"104424","DOI":"10.1016\/j.msard.2022.104424","article-title":"Mobility and Balance Rehabilitation in Multiple Sclerosis: A Systematic Review and Dose-Response Meta-Analysis","volume":"69","author":"Corrini","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1089\/g4h.2021.0096","article-title":"Active Videogaming Interventions in Adults with Neuromuscular Conditions: A Scoping Review","volume":"11","author":"Malone","year":"2022","journal-title":"Games Health J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.apmr.2021.08.008","article-title":"Effect of Exercise on Fatigue in Multiple Sclerosis: A Network Meta-Analysis Comparing Different Types of Exercise","volume":"103","year":"2022","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1016\/j.apmr.2013.04.020","article-title":"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","volume":"94","author":"Pilutti","year":"2013","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.pmr.2005.01.005","article-title":"Exercise and Rehabilitation for Individuals with Multiple Sclerosis","volume":"16","author":"Brown","year":"2005","journal-title":"Phys. Med. Rehabil. Clin. N. Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/978-981-15-1792-1_22","article-title":"Exercise and Multiple Sclerosis","volume":"Volume 1228","author":"Xiao","year":"2020","journal-title":"Physical Exercise for Human Health"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1097\/PHM.0000000000001174","article-title":"Exercise Training Guidelines for Multiple Sclerosis, Stroke, and Parkinson Disease: Rapid Review and Synthesis","volume":"98","author":"Kim","year":"2019","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_14","first-page":"CD012732","article-title":"Rehabilitation for People with Multiple Sclerosis: An Overview of Cochrane Reviews","volume":"1","author":"Amatya","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.msard.2017.01.016","article-title":"People with MS Are Less Physically Active than Healthy Controls but as Active as Those with Other Chronic Diseases: An Updated Meta-Analysis","volume":"13","author":"Adamson","year":"2017","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s10055-020-00495-x","article-title":"Immersive Virtual Reality as Physical Therapy in Older Adults: Present or Future (Systematic Review)","volume":"25","author":"Cancela","year":"2021","journal-title":"Virtual Real."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1177\/1539449218817291","article-title":"Immersive Virtual Reality for the Management of Pain in Community-Dwelling Older Adults","volume":"39","author":"Benham","year":"2019","journal-title":"OTJR Occup. Particip. Health"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Basalic, E.B., Roman, N., Tuchel, V.I., and Micl\u0103u\u0219, R.S. (2024). Virtual Reality Applications for Balance Rehabilitation and Efficacy in Addressing Other Symptoms in Multiple Sclerosis\u2014A Review. Appl. Sci., 14.","DOI":"10.3390\/app14104244"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105470","DOI":"10.1016\/j.msard.2024.105470","article-title":"Virtual Reality Rehabilitation in Patients Affected by Multiple Sclerosis: Impact on Quality of Life and Sexual Functions","volume":"84","author":"Maggio","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_20","first-page":"CD013834","article-title":"Virtual Reality for Multiple Sclerosis Rehabilitation","volume":"1","author":"Guida","year":"2025","journal-title":"Cocharne Database Syst. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e31020","DOI":"10.2196\/31020","article-title":"Immersive Virtual Reality and Vestibular Rehabilitation in Multiple Sclerosis: Case Report","volume":"10","year":"2022","journal-title":"JMIR Serious Games"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Fuentes, G., Ferreiro-G\u00f3mez, E., Campo-Prieto, P., and Cancela-Carral, J.M. (2024). Exergames and Immersive Virtual Reality as a Novel Therapy Approach in Multiple Sclerosis: Randomised Feasibility Study. J. Clin. Med., 13.","DOI":"10.3390\/jcm13195845"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Hern\u00e1ndez, M., Polonio-L\u00f3pez, B., Corregidor-S\u00e1nchez, A.-I., Mart\u00edn-Conty, J.L., Mohedano-Moriano, A., and Criado-\u00c1lvarez, J.-J. (2021). Effects of Specific Virtual Reality-Based Therapy for the Rehabilitation of the Upper Limb Motor Function Post-Ictus: Randomized Controlled Trial. Brain Sci., 11.","DOI":"10.3390\/brainsci11050555"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Castellano-Aguilera, A., Bivi\u00e1-Roig, G., Cuenca-Mart\u00ednez, F., Suso-Mart\u00ed, L., Calatayud, J., Blanco-D\u00edaz, M., and Casa\u00f1a, J. (2022). Effectiveness of Virtual Reality on Balance and Risk of Falls in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph192114192"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101092","DOI":"10.1016\/j.eujim.2020.101092","article-title":"Effect of Immersive Virtual Reality on Balance, Mobility, and Fatigue in Patients with Multiple Sclerosis: A Single-Blinded Randomized Controlled Trial","volume":"35","author":"Ozkul","year":"2020","journal-title":"Eur. J. Integr. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41531-024-00641-1","article-title":"Intense Exercise Increases Dopamine Transporter and Neuromelanin Concentrations in the Substantia Nigra in Parkinson\u2019s Disease","volume":"10","author":"Hoye","year":"2024","journal-title":"NPJ Park. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Fuentes, G., Campo-Prieto, P., and Cancela-Carral, J.M. (2024). Immersive Virtual Reality High-Intensity Aerobic Training to Slow Parkinson\u2019s Disease: The ReViPark Program. Appl. Sci., 14.","DOI":"10.3390\/app14114708"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106235","DOI":"10.1016\/j.msard.2024.106235","article-title":"Exploring the Potential of Immersive Virtual Reality (VR) as a Tool to Enhance Cognitive Functions and Alleviate Clinical Symptoms in Multiple Sclerosis (MS)","volume":"93","author":"Guinot","year":"2025","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_29","first-page":"e67633","article-title":"Extended Reality in Revolutionizing Neurological Disease: A New Era for Chronic Condition Treatment","volume":"16","author":"Hariharan","year":"2024","journal-title":"Cureus"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"World Medical Association (2013). World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA, 310, 2191.","DOI":"10.1001\/jama.2013.281053"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e56790","DOI":"10.2196\/56790","article-title":"Reporting Guidelines for the Early-Phase Clinical Evaluation of Applications Using Extended Reality: RATE-XR Qualitative Study Guideline","volume":"26","author":"Vlake","year":"2024","journal-title":"J. Med. Internet. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1249\/00005768-198205000-00012","article-title":"Psychophysical Bases of Perceived Exertion","volume":"14","author":"Borg","year":"1982","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Campo-Prieto, P., Cancela-Carral, J.M., and Rodr\u00edguez-Fuentes, G. (2022). Wearable Immersive Virtual Reality Device for Promoting Physical Activity in Parkinson\u2019s Disease Patients. Sensors, 22.","DOI":"10.3390\/s22093302"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10538135261418720","DOI":"10.1177\/10538135261418720","article-title":"Effectiveness of Virtual Reality on Hand Function for Patients with Hemiplegia After Stroke: A Meta-Analysis of Randomized Controlled Trials","volume":"58","author":"Rehman","year":"2026","journal-title":"NeuroRehabilitation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41746-025-02171-3","article-title":"Benefits of Virtual Reality Rehabilitation on Neurodegenerative Diseases: A Systematic Review","volume":"9","author":"Tu","year":"2025","journal-title":"NPJ Digit. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Halabchi, F., Alizadeh, Z., Sahraian, M.A., and Abolhasani, M. (2017). Exercise Prescription for Patients with Multiple Sclerosis; Potential Benefits and Practical Recommendations. BMC Neurol., 17.","DOI":"10.1186\/s12883-017-0960-9"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1207\/s15327108ijap0303_3","article-title":"Simulator Sickness Questionnaire: An Enhanced Method for Quantifying Simulator Sickness","volume":"3","author":"Kennedy","year":"1993","journal-title":"Int. J. Aviat. Psychol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"503","DOI":"10.47197\/retos.v43i0.87605","article-title":"Traducci\u00f3n y Adaptaci\u00f3n Transcultural al Espa\u00f1ol Del Simulator Sickness Questionnaire (Translation and Cross-Cultural Adaptation to Spanish of the Simulator Sickness Questionnaire)","volume":"43","year":"2021","journal-title":"Retos"},{"key":"ref_39","first-page":"4","article-title":"SUS-A Quick and Dirty Usability Scale","volume":"189","author":"Brooke","year":"1996","journal-title":"Usability Eval. Ind."},{"key":"ref_40","first-page":"44","article-title":"An\u00e1lisis Comparativo de La Escala de Usabilidad Del Sistema (EUS) En Dos Versiones\/Comparative Analysis of the System Usability Scale (SUS) in Two Versions","volume":"5","year":"2016","journal-title":"Rev. Iberoam. Cienc. Comput. Inf."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1212\/WNL.33.11.1444","article-title":"Rating Neurologic Impairment in Multiple Sclerosis: An Expanded Disability Status Scale (EDSS)","volume":"33","author":"Kurtzke","year":"1983","journal-title":"Neurology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1177\/1352458517690823","article-title":"Multiple Sclerosis Outcome Assessments Consortium. Validity of the Timed 25-Foot Walk as an Ambulatory Performance Outcome Measure for Multiple Sclerosis","volume":"23","author":"Motl","year":"2017","journal-title":"Mult. Scler. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1177\/1352458517690824","article-title":"Multiple Sclerosis Outcome Assessments Consortium. The Nine-Hole Peg Test as a Manual Dexterity Performance Measure for Multiple Sclerosis","volume":"23","author":"Feys","year":"2017","journal-title":"Mult. Scler. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1177\/1352458517690821","article-title":"Multiple Sclerosis Outcome Assessments Consortium. Validity of the Symbol Digit Modalities Test as a Cognition Performance Outcome Measure for Multiple Sclerosis","volume":"23","author":"Benedict","year":"2017","journal-title":"Mult. Scler. J."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"eBioMedicine (2024). Blood Biomarkers for Multiple Sclerosis: Neurofilament Light Chain and Beyond. eBioMedicine, 104, 105214.","DOI":"10.1016\/j.ebiom.2024.105214"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1007\/s00415-025-13093-1","article-title":"The Role of Serum Neurofilament Light (sNfL) as a Biomarker in Multiple Sclerosis: Insights from a Systematic Review","volume":"272","author":"Freedman","year":"2025","journal-title":"J. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s00421-012-2421-x","article-title":"Associations between Borg\u2019s Rating of Perceived Exertion and Physiological Measures of Exercise Intensity","volume":"113","author":"Scherr","year":"2013","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00415-024-12788-1","article-title":"Disability Worsening Outcome in Multiple Sclerosis Based on EDSS: Does Half a Point Matter?","volume":"272","author":"Filippi","year":"2025","journal-title":"J. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1111\/ene.15920","article-title":"Threshold Definitions for Significant Change on the Timed 25-foot Walk and Nine-hole Peg Test in Primary Progressive Multiple Sclerosis","volume":"30","author":"Koch","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/MRR.0000000000000209","article-title":"Reliability, Precision, and Clinically Important Change of the Nine-Hole Peg Test in Individuals with Multiple Sclerosis","volume":"40","author":"Hervault","year":"2017","journal-title":"Int. J. Rehabil. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1177\/1352458518808204","article-title":"Multiple Sclerosis Outcome Assessments Consortium (MSOAC). Symbol Digit Modalities Test: A Valid Clinical Trial Endpoint for Measuring Cognition in Multiple Sclerosis","volume":"25","author":"Strober","year":"2019","journal-title":"Mult. Scler. J."},{"key":"ref_52","first-page":"20552173211006139","article-title":"Virtual Reality Is a Feasible Intervention Platform in Multiple Sclerosis: A Pilot Protocol and Acute Improvements in Affect","volume":"7","author":"Shaw","year":"2021","journal-title":"Mult. Scler. J. Exp. Transl. Clin."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Campo-Prieto, P., Cancela-Carral, J.M., and Rodr\u00edguez-Fuentes, G. (2023). Immersive Virtual Reality Reaction Time Test and Relationship with the Risk of Falling in Parkinson\u2019s Disease. Sensors, 23.","DOI":"10.3390\/s23094529"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7864","DOI":"10.1080\/10447318.2023.2276524","article-title":"The Effects of Congruent and Incongruent Immersive Virtual Reality Modulated Exercise Environments in Healthy Individuals: A Pilot Study","volume":"40","author":"Runswick","year":"2023","journal-title":"Int. J. Hum. Comput. Interact."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5149","DOI":"10.1113\/JP287421","article-title":"Incongruent Virtual Reality Cycling Exercise Demonstrates a Role of Perceived Effort in Cardiovascular Control","volume":"603","author":"Bruce","year":"2025","journal-title":"J. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s13760-025-02829-5","article-title":"Heart Rate Variability in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis","volume":"126","author":"Mirmosayyeb","year":"2026","journal-title":"Acta Neurol. Belg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s12984-021-00848-w","article-title":"Immersive Virtual Reality during Gait Rehabilitation Increases Walking Speed and Motivation: A Usability Evaluation with Healthy Participants and Patients with Multiple Sclerosis and Stroke","volume":"18","author":"Winter","year":"2021","journal-title":"J. Neuroeng. Rehabil."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Pau, M., Arippa, F., Leban, B., Porta, M., Casu, G., Frau, J., Lorefice, L., Coghe, G., and Cocco, E. (2024). Cybersickness in People with Multiple Sclerosis Exposed to Immersive Virtual Reality. Bioengineering, 11.","DOI":"10.3390\/bioengineering11020115"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.33546\/bnj.3006","article-title":"Exercise-Based Gaming in Patients with Multiple Sclerosis: A Systematic Review and Meta-Analysis","volume":"10","author":"Elhusein","year":"2024","journal-title":"Belitung Nurs. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s12984-025-01788-5","article-title":"Fatigue influences embodiment perception and motor performance in multiple sclerosis subjects: A cross-sectional immersive virtual reality study","volume":"22","author":"Fregna","year":"2025","journal-title":"J. Neuroeng. Rehabil."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Calafiore, D., Invernizzi, M., Ammendolia, A., Marotta, N., Fortunato, F., Paolucci, T., Ferraro, F., Curci, C., Cwirlej-Sozanska, A., and De Sire, A. (2021). Efficacy of Virtual Reality and Exergaming in Improving Balance in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.773459"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12984-020-00718-x","article-title":"Effects of Virtual Reality Associated with Serious Games for Upper Limb Rehabilitation in Patients with Multiple Sclerosis: Randomized Controlled Trial","volume":"17","year":"2020","journal-title":"J. Neuroeng. Rehabil."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"jrm40641","DOI":"10.2340\/jrm.v56.40641","article-title":"Exercise-Based Telerehabilitation for Patients with Multiple Sclerosis Using Physical Activity: A Systematic Review","volume":"56","author":"Sladeckova","year":"2024","journal-title":"J. Rehabil. Med."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Ning, L., and Wang, B. (2022). Neurofilament Light Chain in Blood as a Diagnostic and Predictive Biomarker for Multiple Sclerosis: A Systematic Review and Meta-Analysis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0274565"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bl\u00e1zquez-Fern\u00e1ndez, A., Navarro-L\u00f3pez, V., Marcos-Ant\u00f3n, S., and Cano-de-la-Cuerda, R. (2025). Effects of Physical Exercise on Neurofilament Light Chain and Glial Fibrillary Acidic Protein Level in Patients with Multiple Sclerosis: A Systematic Review and Bayesian Network Meta-Analysis. J. Clin. Med., 14.","DOI":"10.3390\/jcm14030839"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.gaitpost.2010.06.002","article-title":"Walking While Talking\u2014Difficulties Incurred during the Initial Stages of Multiple Sclerosis Disease Process","volume":"32","author":"Kalron","year":"2010","journal-title":"Gait Posture"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"358","DOI":"10.33588\/rn.7310.2021330","article-title":"Estado actual de la realidad virtual inmersiva como herramienta de rehabilitaci\u00f3n f\u00edsica y funcional en pacientes con enfermedad de Parkinson: Revisi\u00f3n sistem\u00e1tica","volume":"73","year":"2021","journal-title":"Rev. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1177\/1352458515579442","article-title":"Effects of a Home-Based Step Training Programme on Balance, Stepping, Cognition and Functional Performance in People with Multiple Sclerosis\u2014A Randomized Controlled Trial","volume":"22","author":"Hoang","year":"2016","journal-title":"Mult. Scler. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"106256","DOI":"10.1016\/j.msard.2024.106256","article-title":"Enhancing the Effect of Rehabilitation on Multiple Sclerosis: A Randomized Clinical Trial Investigating the Impact of Remotely-Supervised Transcranial Direct Current Stimulation and Virtual Reality Telerehabilitation Training","volume":"94","author":"Pagliari","year":"2025","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Du, L., Xi, H., Zhang, S., Zhou, Y., Tao, X., Lv, Y., Hou, X., and Yu, L. (2024). Effects of Exercise in People with Multiple Sclerosis: A Systematic Review and Meta-Analysis. Front. Public Health, 12.","DOI":"10.3389\/fpubh.2024.1387658"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/S1474-4422(23)00280-6","article-title":"Cognitive Rehabilitation and Aerobic Exercise for Cognitive Impairment in People with Progressive Multiple Sclerosis (CogEx): A Randomised, Blinded, Sham-Controlled Trial","volume":"22","author":"Feinstein","year":"2023","journal-title":"Lancet Neurol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/968\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T10:29:07Z","timestamp":1779877747000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/5\/968"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":71,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["medicina62050968"],"URL":"https:\/\/doi.org\/10.3390\/medicina62050968","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}