{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:31:21Z","timestamp":1760059881906,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background and Objectives: Recent technological advances have introduced new interventions in the field of stroke rehabilitation. Among them, visual feedback (VF) and non-invasive brain stimulation (NIBS) have gained considerable attention, with growing evidence supporting their efficacy. However, their combined application in lower limb recovery remains to be established. This systematic review aims to evaluate the current evidence on the therapeutic effect of combining VF and NIBS for lower limb motor rehabilitation in stroke patients. Methods: Following PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane databases were searched for randomized controlled trials and observational studies comparing VF and NIBS interventions with either their monotherapy, placebo, or standard treatment. The outcomes evaluated for lower limb function included balance, gait, and motor performance. Results: From 997 studies screened, 5 studies (3 RCTs and 2 cohort studies) were included. Despite heterogeneity in the immersion level, NIBS protocols, and outcome measures, evidence emerged supporting the efficacy of combined VF and NIBS across multiple outcomes. However, the degree to which these interventions outperform standard therapies remains uncertain, primarily due to a limited number of comparator studies and the quality of the existing data. Conclusions: This review provides preliminary insights into the potential of combining VF and NIBS in stroke patients affected by lower limb motor impairments. Future research should focus on standardizing protocols and addressing demographic variability to enhance the reliability and comparability of findings.<\/jats:p>","DOI":"10.3390\/jcm14145027","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T10:46:05Z","timestamp":1752662765000},"page":"5027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combining Visual Feedback and Noninvasive Brain Stimulation for Lower Limb Motor Rehabilitation in Stroke: A Systematic Review of the Current Evidence"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7237-633X","authenticated-orcid":false,"given":"Leonardo","family":"Di Cosmo","sequence":"first","affiliation":[{"name":"School of Medicine, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4877-527X","authenticated-orcid":false,"given":"Santiago Nieto","family":"Cuervo","sequence":"additional","affiliation":[{"name":"School of Medicine, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7484-668X","authenticated-orcid":false,"given":"Francesca","family":"Pellican\u00f2","sequence":"additional","affiliation":[{"name":"School of Medicine, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5064-7746","authenticated-orcid":false,"given":"Francesca Romana","family":"Centini","sequence":"additional","affiliation":[{"name":"School of Medicine, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6048-891X","authenticated-orcid":false,"given":"Jad","family":"El Choueiri","sequence":"additional","affiliation":[{"name":"School of Medicine, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Learmonth","sequence":"additional","affiliation":[{"name":"School of Medicine, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo Emanuele","family":"Colella","sequence":"additional","affiliation":[{"name":"School of Medicine, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6950-0414","authenticated-orcid":false,"given":"Lorenzo","family":"De Rossi","sequence":"additional","affiliation":[{"name":"School of Medicine, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1611-0840","authenticated-orcid":false,"given":"Delia","family":"Cannizzaro","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, ASST Ovest Milano Legnano Hospital, Legnano, 20025 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Baricich","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy"},{"name":"Rehabilitation Unit, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E153","DOI":"10.1161\/CIR.0000000000001052","article-title":"Heart Disease and Stroke Statistics\u20142022 Update: A Report from the American Heart Association","volume":"145","author":"Tsao","year":"2022","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S1474-4422(16)30073-4","article-title":"Global burden of stroke and risk factors in 188 countries, during 1990\u20132013: A systematic analysis for the Global Burden of Disease Study 2013","volume":"15","author":"Feigin","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e259","DOI":"10.1016\/S2214-109X(13)70089-5","article-title":"Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990\u20132010: Findings from the Global Burden of Disease Study 2010","volume":"1","author":"Krishnamurthi","year":"2013","journal-title":"Lancet Glob. Health"},{"key":"ref_4","first-page":"e18","article-title":"Heart Disease and Stroke Statistics\u20142011 Update: A Report from the American Heart Association","volume":"123","author":"Roger","year":"2011","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0022-510X(03)00169-2","article-title":"Chronic stroke motor recovery: Duration of active neuromuscular stimulation","volume":"215","author":"Cauraugh","year":"2003","journal-title":"J. Neurol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"21S","DOI":"10.1177\/1545968311410941","article-title":"Neurological Principles and Rehabilitation of Action Disorders: Common Clinical Deficits","volume":"25","author":"Sathian","year":"2011","journal-title":"Neurorehabilit. Neural Repair"},{"key":"ref_7","first-page":"S225","article-title":"Principles of experience-dependent neural plasticity: Implications for rehabilitation after brain damage","volume":"51","author":"Kleim","year":"2008","journal-title":"J. Speech Lang. Hear. Res. JSLHR"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1080\/02699052.2020.1725126","article-title":"Virtual reality therapy for upper limb rehabilitation in patients with stroke: A meta-analysis of randomized clinical trials","volume":"34","author":"Mekbib","year":"2020","journal-title":"Brain Inj."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Soleimani, M., Ghazisaeedi, M., and Heydari, S. (2024). The efficacy of virtual reality for upper limb rehabilitation in stroke patients: A systematic review and meta-analysis. BMC Med. Inform. Decis. Mak., 24.","DOI":"10.1186\/s12911-024-02534-y"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Potcovaru, C.-G., Cintez\u0103, D., S\u0103ndulescu, M.I., Poenaru, D., Chiriac, O., Lambru, C., Moldoveanu, A., Anghel, A.M., and Berteanu, M. (2024). The Impact of Virtual Reality as a Rehabilitation Method Using TRAVEE System on Functional Outcomes and Disability in Stroke Patients: A Pilot Study. Biomedicines, 12.","DOI":"10.3390\/biomedicines12112450"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/s12984-024-01474-y","article-title":"Impact of the combination of virtual reality and noninvasive brain stimulation on the upper limb motor function of stroke patients: A systematic review and meta-analysis","volume":"21","author":"Zhang","year":"2024","journal-title":"J. NeuroEng. Rehabil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1515\/revneuro-2019-0047","article-title":"Motor stroke recovery after tDCS: A systematic review","volume":"31","author":"Conversano","year":"2020","journal-title":"Rev. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6310","DOI":"10.1007\/s00415-022-11338-x","article-title":"Transcranial direct current stimulation in neglect rehabilitation after stroke: A systematic review","volume":"269","author":"Marron","year":"2022","journal-title":"J. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hara, T., Shanmugalingam, A., McIntyre, A., and Burhan, A.M. (2021). The Effect of Non-Invasive Brain Stimulation (NIBS) on Attention and Memory Function in Stroke Rehabilitation Patients: A Systematic Review and Meta-Analysis. Diagnostics, 11.","DOI":"10.3390\/diagnostics11020227"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1177\/02692155241235336","article-title":"Transcranial direct current stimulation for upper extremity motor dysfunction in poststroke patients: A systematic review and meta-analysis","volume":"38","author":"Tang","year":"2024","journal-title":"Clin. Rehabil."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Carlos, B.M., Menezes, L.T., Rosa, B., Furumoto, B.F., Feitosa, S.S., Fernandes, C.A., Ferreira-Melo, S.E., Pereira, J.D., Almeida, S., and Brand\u00e3o, A.F. (2024). Graph network and symmetry analysis after combined XR and tDCS in stroke rehabilitation. Biomed. Signal Process. Control, 96.","DOI":"10.1016\/j.bspc.2024.106499"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"625","DOI":"10.4283\/JMAG.2017.22.4.625","article-title":"The Effect of Low-Frequency (1 Hz) rTMS on the Cerebellar Cortex in Patients with Ataxia After a Posterior Circulation Stroke: Randomized Control Trial","volume":"22","author":"Cha","year":"2017","journal-title":"J. Magn."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cheng, H.L., Lin, C.H., Tseng, S.H., Peng, C.W., and Lai, C.H. (2023). Effectiveness of Repetitive Transcranial Magnetic Stimulation Combined with Visual Feedback Training in Improving Neuroplasticity and Lower Limb Function after Chronic Stroke: A Pilot Study. Biology, 12.","DOI":"10.3390\/biology12040515"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ahmad, Z., Ishtiaq, S., Ilyas, S., Shahid, I., Tariq, I., Malik, A.N., Liu, T., and Wang, J. (2022). Short term effects of anodal cerebellar vs. anodal cerebral transcranial direct current stimulation in stroke patients, a randomized control trial. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.1035558"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Salameh, A., McCabe, J., Skelly, M., Duncan, K.R., Chen, Z., Tatsuoka, C., Bikson, M., Hardin, E.C., Daly, J.J., and Pundik, S. (2022). Stance Phase Gait Training Post Stroke Using Simultaneous Transcranial Direct Current Stimulation and Motor Learning-Based Virtual Reality-Assisted Therapy: Protocol Development and Initial Testing. Brain Sci., 12.","DOI":"10.3390\/brainsci12060701"},{"key":"ref_21","unstructured":"Invernizzi, M., Negrini, S., Carda, S., Lanzotti, L., Cisari, C., and Baricich, A. (2025, June 06). The Value of Adding Mirror Therapy for Upper Limb Motor Recovery of Subacute Stroke Patients: A Randomized Controlled Trial. Published Online 2013. Available online: https:\/\/air.unimi.it\/handle\/2434\/721399."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12984-023-01129-4","article-title":"Effects of non-invasive brain stimulation on motor function after spinal cord injury: A systematic review and meta-analysis","volume":"20","author":"Chen","year":"2023","journal-title":"J. NeuroEng. Rehabil."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Donati, D., Pinotti, E., Mantovani, M., Casarotti, S., Fini, A., Tedeschi, R., and Caselli, S. (2025). The Role of Immersive Virtual Reality in Upper Limb Rehabilitation for Subacute Stroke: A Review. J. Clin. Med., 14.","DOI":"10.3390\/jcm14061903"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.apmr.2021.06.024","article-title":"Effects of Virtual Reality Intervention on Neural Plasticity in Stroke Rehabilitation: A Systematic Review","volume":"103","author":"Hao","year":"2022","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Thieme, H., Morkisch, N., Mehrholz, J., Pohl, M., Behrens, J., Borgetto, B., and Dohle, C. (2025, June 08). Mirror Therapy for Improving Motor Function After Stroke\u2014Thieme, H\u20142018|Cochrane Library. Available online: https:\/\/www.cochranelibrary.com\/cdsr\/doi\/10.1002\/14651858.CD008449.pub3\/full.","DOI":"10.1002\/14651858.CD008449.pub3"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1093\/brain\/awp135","article-title":"The use of visual feedback, in particular mirror visual feedback, in restoring brain function","volume":"132","author":"Ramachandran","year":"2009","journal-title":"Brain J. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S103","DOI":"10.1006\/nimg.2001.0832","article-title":"Neural Simulation of Action: A Unifying Mechanism for Motor Cognition","volume":"14","author":"Jeannerod","year":"2001","journal-title":"NeuroImage"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1007\/s10072-023-06742-8","article-title":"Comparison of immersive and non-immersive virtual reality for upper extremity functional recovery in patients with stroke: A systematic review and network meta-analysis","volume":"44","author":"Hao","year":"2023","journal-title":"Neurol. Sci."},{"key":"ref_29","first-page":"6187328","article-title":"Best Practices for The Interdisciplinary Rehabilitation Team: A Review of Mental Health Issues in Mild Stroke Survivors","volume":"2018","author":"Terrill","year":"2018","journal-title":"Stroke Res. Treat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"pzab051","DOI":"10.1093\/ptj\/pzab051","article-title":"Effect of Virtual Reality Gait Training on Participation in Survivors of Subacute Stroke: A Randomized Controlled Trial","volume":"101","author":"Punt","year":"2021","journal-title":"Phys. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.cnp.2022.05.002","article-title":"Non-invasive brain stimulation and neuroenhancement","volume":"7","author":"Antal","year":"2022","journal-title":"Clin. Neurophysiol. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.brs.2020.03.020","article-title":"Effects of high-frequency repetitive transcranial magnetic stimulation over the contralesional motor cortex on motor recovery in severe hemiplegic stroke: A randomized clinical trial","volume":"13","author":"Wang","year":"2020","journal-title":"Brain Stimul."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9394156","DOI":"10.1155\/2018\/9394156","article-title":"Dynamic Network Analysis Reveals Altered Temporal Variability in Brain Regions after Stroke: A Longitudinal Resting-State fMRI Study","volume":"2018","author":"Hu","year":"2018","journal-title":"Neural Plast."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"106294","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.106294","article-title":"Are There Differences in Long-Term Functioning and Recovery Between Hemorrhagic and Ischemic Stroke Patients Receiving Rehabilitation?","volume":"31","author":"Oosterveer","year":"2022","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"891651","DOI":"10.1155\/2015\/891651","article-title":"Rehabilitation Outcomes: Ischemic versus Hemorrhagic Strokes","volume":"2015","author":"Perna","year":"2015","journal-title":"Behav. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e30606","DOI":"10.1097\/MD.0000000000030606","article-title":"The prevention of stroke by statins: A meta-analysis","volume":"101","author":"San","year":"2022","journal-title":"Medicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"117339","DOI":"10.1016\/j.jns.2021.117339","article-title":"Trends in ischemic stroke outcomes in a rural population in the United States","volume":"422","author":"Chaudhary","year":"2021","journal-title":"J. Neurol. Sci."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/14\/5027\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:10:33Z","timestamp":1760033433000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/14\/5027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,16]]},"references-count":37,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14145027"],"URL":"https:\/\/doi.org\/10.3390\/jcm14145027","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,7,16]]}}}