{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:53:12Z","timestamp":1783947192582,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Professional Association of Physiotherapists of Castilla y Le\u00f3n (CPFCYL)","award":["INV2020-15"],"award-info":[{"award-number":["INV2020-15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Background: The relationship between fragility and neurological diseases is extensive and affects many patients with multiple sclerosis (MS), whose risk factors are related to fragility. Objective: To study the effects of exercise and transcranial direct current stimulation (tDCS) in MS patients with fatigue from four dimensions: functional mobility, balance, fatigue, and depression. Methods: A total of 12 patients who belonged to two associations of people with physical disabilities participated. Functional mobility, depression, balance, and fatigue were assessed before and after the intervention. Transcranial direct current stimulation and the exercise program were carried out over a 4-week period with a wash-out period of 5 months. Results: After the application of tDCS, we found significant improvements in balance (p &lt; 0.05, g = 0.632), depression (p &lt; 0.05, g = 0.402), functional mobility (p &lt; 0.05, g = 0.297), and fatigue (p &lt; 0.05, g = 0.526). After the exercise program, significant improvements were shown in balance (p &lt; 0.01, g = 0.418), depression (p &lt; 0.001, g = 0.540), functional mobility (p &lt; 0.01, g = 0.262), and fatigue (p &lt; 0.01, g = 0.742). Two-way mixed-measures ANOVA showed that all variables improved in both groups, with significant differences over time but not between groups. Secondary analysis showed significant correlations between balance and functional mobility (r = 0.671, p = 0.017), depression and fatigue (r = 0.586, p = 0.044) and between intensity of rehabilitation and balance (r = 0.622, p = 0.031). CONCLUSION: Participating in an exercise program and receiving tDCS separately improved the variables of depression, balance, mobility, and fatigue.<\/jats:p>","DOI":"10.3390\/ijerph191912747","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T22:19:27Z","timestamp":1665267567000},"page":"12747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Effect of Combining Transcranial Direct Current Stimulation Treatment and an Exercise Program on Fragility in a Population with Multiple Sclerosis: Cross-Over Design Trial"],"prefix":"10.3390","volume":"19","author":[{"given":"In\u00e9s","family":"Mu\u00f1oz-Paredes","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, University of Leon, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azael J.","family":"Herrero","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, European University Miguel de Cervantes, 47012 Valladolid, Spain"},{"name":"Research Center on Physical Disability, ASPAYM Castilla y Le\u00f3n, 47008 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5606-261X","authenticated-orcid":false,"given":"Roc\u00edo","family":"Llamas-Ramos","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8887-6669","authenticated-orcid":false,"given":"Vicente","family":"Rodr\u00edguez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, University of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7818-9777","authenticated-orcid":false,"given":"Jes\u00fas","family":"Seco-Calvo","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (BIOMED), University of Leon, 24071 Le\u00f3n, Spain"},{"name":"Physiology Department, University of the Basque Country, 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neuron.2011.06.031","article-title":"Selective Neuronal Vulnerability in Neurodegenerative Diseases: From Stressor Thresholds to Degeneration","volume":"71","author":"Saxena","year":"2011","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/S1474-4422(12)70191-6","article-title":"Cognitive Reserve in Ageing and Alzheimer\u2019s Disease","volume":"11","author":"Stern","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"M146","DOI":"10.1093\/gerona\/56.3.M146","article-title":"Frailty in Older Adults: Evidence for a Phenotype","volume":"56","author":"Fried","year":"2001","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_4","first-page":"27","article-title":"Body Size and Physical Exercise, and the Risk of Multiple Sclerosis","volume":"101","author":"Cortese","year":"2017","journal-title":"Mult. Scler. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1177\/1352458511415143","article-title":"Multiple Sclerosis Relapses Are Not Associated with Exercise","volume":"18","author":"Tallner","year":"2012","journal-title":"Mult. Scler. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1532-5415.2008.02136.x","article-title":"Cognitive Impairment Improves the Predictive Validity of the Phenotype of Frailty for Adverse Health Outcomes: The Three-City Study","volume":"57","author":"Amieva","year":"2009","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1177\/1756285611430719","article-title":"Exercise and Disease Progression in Multiple Sclerosis: Can Exercise Slow down the Progression of Multiple Sclerosis?","volume":"5","author":"Dalgas","year":"2012","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1007\/s00415-019-09493-9","article-title":"Physical Exercise Improves Quality of Life, Depressive Symptoms, and Cognition across Chronic Brain Disorders: A Transdiagnostic Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"268","author":"Meenakshi","year":"2021","journal-title":"J. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jns.2016.11.015","article-title":"Effects of Left DLPFC versus Right PPC TDCS on Multiple Sclerosis Fatigue","volume":"372","author":"Chalah","year":"2017","journal-title":"J. Neurol. Sci."},{"key":"ref_11","first-page":"293","article-title":"A Single Session of 1 MA Anodal TDCS-Supported Motor Training Does Not Improve Motor Performance in Patients with Multiple Sclerosis","volume":"32","author":"Meesen","year":"2014","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_12","first-page":"57","article-title":"The Use of Brain Stimulation in the Rehabilitation of Walking Disability in Patients with Multiple Sclerosis: A Randomized Double-Blind Clinical Trial Study","volume":"18","author":"Oveisgharan","year":"2019","journal-title":"Curr. J. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3389\/fneur.2020.00310","article-title":"Gait and Functional Mobility in Multiple Sclerosis: Immediate Effects of Transcranial Direct Current Stimulation (TDCS) Paired With Aerobic Exercise","volume":"11","author":"Pilloni","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"420","DOI":"10.3389\/fnhum.2019.00420","article-title":"Transcranial Direct Current Stimulation (TDCS) to Improve Gait in Multiple Sclerosis: A Timing Window Comparison","volume":"13","author":"Workman","year":"2019","journal-title":"Front. Hum. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1191\/1352458505ms1117oa","article-title":"Evaluation of the Modified Fatigue Impact Scale in Four Different European Countries","volume":"11","author":"Kos","year":"2005","journal-title":"Mult. Scler."},{"key":"ref_16","first-page":"338","article-title":"Beck Depression Inventory-II","volume":"2","author":"Beck","year":"1996","journal-title":"Psychol. Corp."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/ene.12932","article-title":"Psychometric Properties and Validity of Beck Depression Inventory II in Multiple Sclerosis","volume":"23","author":"Sacco","year":"2016","journal-title":"Eur. J. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/j.1532-5415.1991.tb01616.x","article-title":"The Timed \u201cUp & Go\u201d: A Test of Basic Functional Mobility for Frail Elderly Persons","volume":"39","author":"Podsiadlo","year":"1991","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.apmr.2015.12.031","article-title":"Validity of the Timed Up and Go Test as a Measure of Functional Mobility in Persons With Multiple Sclerosis","volume":"97","author":"Sebastiao","year":"2016","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.2522\/ptj.20070007","article-title":"Reliability and Validity of the Tinetti Mobility Test for Individuals with Parkinson Disease","volume":"87","author":"Kegelmeyer","year":"2007","journal-title":"Phys. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0211-139X(07)73570-9","article-title":"Experiencia En La Evaluaci\u00f3n Del Riesgo de Ca\u00eddas. Comparaci\u00f3n Entre El Test de Tinetti y El Timed Up & Go","volume":"42","author":"Roqueta","year":"2007","journal-title":"Rev. Esp. Geriatr. Gerontol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/01.FCH.0000264411.20766.0c","article-title":"Physical Activity and Multiple Sclerosis: Validity of Self-Report and Objective Measures","volume":"30","author":"Gosney","year":"2007","journal-title":"Fam. Community Heal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1249\/01.MSS.0000078924.61453.FB","article-title":"International Physical Activity Questionnaire: 12-Country Reliability and Validity","volume":"35","author":"Craig","year":"2003","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","unstructured":"Meyer-Moock, S., Feng, Y.S., Maeurer, M., Dippel, F.W., and Kohlmann, T. (2014). Systematic Literature Review and Validity Evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in Patients with Multiple Sclerosis. BMC Neurol., 14.","DOI":"10.1186\/1471-2377-14-58"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jns.2013.05.023","article-title":"Psychometric Properties of the Fatigue Severity Scale and the Modified Fatigue Impact Scale","volume":"331","author":"Learmonth","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"ref_27","first-page":"354","article-title":"Correlation: Not All Correlation Entails Causality","volume":"66","year":"2019","journal-title":"Rev. Alerg. Mex."},{"key":"ref_28","unstructured":"Associated, L.E. (1988). Statistical Power Analysis for the Behavioral Sciences, Elsevier Science. [2nd ed.]."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1002\/acn3.51224","article-title":"Walking in Multiple Sclerosis Improves with TDCS: A Randomized, Double-Blind, Sham-Controlled Study","volume":"7","author":"Pilloni","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.neulet.2014.07.052","article-title":"Time up and Go Task Performance Improves after Transcranial Direct Current Stimulation in Patient Affected by Parkinson\u2019s Disease","volume":"580","author":"Manenti","year":"2014","journal-title":"Neurosci. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109143","DOI":"10.1016\/j.jneumeth.2021.109143","article-title":"Non-Invasive Brain Stimulation to Assess Neurophysiologic Underpinnings of Lower Limb Motor Impairment in Multiple Sclerosis","volume":"356","author":"Swanson","year":"2021","journal-title":"J. Neurosci. Methods"},{"key":"ref_32","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_33","first-page":"CD009956","article-title":"Exercise Therapy for Fatigue in Multiple Sclerosis","volume":"9","author":"Heine","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/mds.26561","article-title":"Mild Cognitive Impairment in Parkinson\u2019s Disease Is Improved by Transcranial Direct Current Stimulation Combined with Physical Therapy","volume":"31","author":"Manenti","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.apmr.2021.06.029","article-title":"Transcranial Direct Current Stimulation Associated With Functional Exercise Program for Treating Fibromyalgia: A Randomized Controlled Trial","volume":"103","author":"Matias","year":"2021","journal-title":"Arch. Phys. Med. Rehabil."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/19\/12747\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:46:53Z","timestamp":1760143613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/19\/12747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,5]]},"references-count":35,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijerph191912747"],"URL":"https:\/\/doi.org\/10.3390\/ijerph191912747","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,5]]}}}