{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T02:34:26Z","timestamp":1769481266931,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006109","name":"VEGA","doi-asserted-by":"publisher","award":["01\/0092\/22"],"award-info":[{"award-number":["01\/0092\/22"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Introduction: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system, frequently associated with visual and oculomotor disturbances. Quantitative analysis of eye movements represents a non-invasive method for assessing central nervous system dysfunction beyond conventional imaging; however, the diagnostic and predictive value of oculomotor metrics remains insufficiently defined. Objectives: The aims of this study were to compare smooth pursuit gain and reflexive saccade parameters (latency, velocity, and precision) between individuals with MS and healthy controls, and to evaluate their ability to discriminate disease status. Methods: This cross-sectional study included 46 clinically stable patients with MS (EDSS \u2264 6.5) and 46 age- and sex-matched healthy controls. Oculomotor function was assessed using videonystagmography under standardized conditions. Group differences across horizontal and vertical gaze directions were analyzed using linear mixed-effects models. Random forest models were applied to assess the discriminative performance of oculomotor parameters, with permutation-based feature importance and receiver operating characteristic (ROC) curve analysis. Results: Patients with MS showed significantly reduced smooth pursuit gain across most horizontal and vertical directions compared with controls. Saccadic latency was significantly prolonged in all tested movement directions. Saccadic velocity exhibited selective directional impairment consistent with subtle medial longitudinal fasciculus involvement, whereas saccadic precision did not differ significantly between groups. A random forest model combining pursuit and saccadic parameters demonstrated only moderate discriminative performance between MS patients and controls (AUC = 0.694), with saccadic latency contributing most strongly to classification. Conclusions: Quantitative eye-movement assessment revealed widespread oculomotor abnormalities in MS, particularly reduced smooth pursuit gain and prolonged saccadic latency. Although the overall discriminative accuracy of oculomotor parameters was limited, these findings support their potential role as complementary markers of central nervous system dysfunction. Further longitudinal and multimodal studies are required to clarify their clinical relevance and prognostic value.<\/jats:p>","DOI":"10.3390\/neurolint18020022","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T15:48:30Z","timestamp":1769442510000},"page":"22","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative Analysis of Smooth Pursuit and Saccadic Eye Movements in Multiple Sclerosis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5630-9822","authenticated-orcid":false,"given":"Pavol","family":"Skacik","sequence":"first","affiliation":[{"name":"Neurology Department, University Hospital Martin, Kollarova 2, 036 01 Martin, Slovakia"},{"name":"Jessenius Faculty of Medicine Martin, Comenius University Bratislava, Mala Hora 4, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5677-4010","authenticated-orcid":false,"given":"Lucia","family":"Kotulova","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine Martin, Comenius University Bratislava, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4305-3607","authenticated-orcid":false,"given":"Ema","family":"Kantorova","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital Martin, Kollarova 2, 036 01 Martin, Slovakia"},{"name":"Jessenius Faculty of Medicine Martin, Comenius University Bratislava, Mala Hora 4, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1025-6830","authenticated-orcid":false,"given":"Egon","family":"Kurca","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital Martin, Kollarova 2, 036 01 Martin, Slovakia"},{"name":"Jessenius Faculty of Medicine Martin, Comenius University Bratislava, Mala Hora 4, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0348-3082","authenticated-orcid":false,"given":"Stefan","family":"Sivak","sequence":"additional","affiliation":[{"name":"Neurology Department, University Hospital Martin, Kollarova 2, 036 01 Martin, Slovakia"},{"name":"Jessenius Faculty of Medicine Martin, Comenius University Bratislava, Mala Hora 4, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e37297","DOI":"10.1097\/MD.0000000000037297","article-title":"Review of multiple sclerosis: Epidemiology, aetiology, pathophysiology, and treatment","volume":"103","author":"Haki","year":"2024","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5382","DOI":"10.1007\/s00415-022-11193-w","article-title":"Early use of high-efficacy disease-modifying therapies makes the difference in people with multiple sclerosis: An expert opinion","volume":"269","author":"Filippi","year":"2022","journal-title":"J. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/WCO.0000000000000772","article-title":"Eye movements in demyelinating, autoimmune, and metabolic disorders","volume":"33","author":"Kattah","year":"2020","journal-title":"Curr. Opin. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Serra, A., Chisari, C.G., and Matta, M. (2018). Eye movement abnormalities in multiple sclerosis: Pathogenesis, modelling, and treatment. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00031"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s43163-022-00373-0","article-title":"Ocular motor impairment in early-stage multiple sclerosis: A video-oculography assessment","volume":"39","author":"Ouattassi","year":"2023","journal-title":"Egypt. J. Otolaryngol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1017\/S0317167100017285","article-title":"Evaluation of brainstem involvement in multiple sclerosis","volume":"41","author":"Adamec","year":"2014","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ijpsycho.2020.05.010","article-title":"Best practices in eye-tracking research","volume":"155","author":"Carter","year":"2020","journal-title":"Int. J. Psychophysiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/7854_2022_409","article-title":"Eye tracking in virtual reality","volume":"Volume 65","author":"Anderson","year":"2023","journal-title":"Virtual Reality in Behavioral Neuroscience: New Insights and Methods"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.msard.2017.01.014","article-title":"Using endogenous saccades to characterise fatigue in multiple sclerosis","volume":"14","author":"Ferreira","year":"2017","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cecchetti, S., Duchowski, A.T., and Cavallo, M. (2025). Eye-tracking metrics as a digital biomarker for neurocognitive disorders in multiple sclerosis: A scoping review. Brain Sci., 15.","DOI":"10.3390\/brainsci15020149"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1007\/s00415-023-12173-4","article-title":"Prodromal multiple sclerosis: Considerations and future utility","volume":"271","author":"Harding","year":"2024","journal-title":"J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.21790\/rvs.2024.022","article-title":"Oculomotor manifestations in inflammatory central nervous system demyelinating diseases: A narrative review","volume":"24","author":"Lee","year":"2025","journal-title":"Res. Vestib. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1097\/WNO.0000000000000507","article-title":"Ocular motor manifestations of multiple sclerosis","volume":"37","author":"Nerrant","year":"2017","journal-title":"J. Neuroophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103073","DOI":"10.1016\/j.msard.2021.103073","article-title":"Quantification of smooth pursuit dysfunction in multiple sclerosis","volume":"54","author":"Rempe","year":"2021","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Grillini, A., Renken, R.J., Vrijling, A.C.L., Heutink, J., and Cornelissen, F.W. (2020). Eye movement evaluation in multiple sclerosis and Parkinson\u2019s disease using a standardised oculomotor and neuro-ophthalmic disorder assessment (SONDA). Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00971"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102848","DOI":"10.1016\/j.nicl.2021.102848","article-title":"Impaired saccadic eye movements in multiple sclerosis are related to altered functional connectivity of the oculomotor brain network","volume":"32","author":"Strijbis","year":"2021","journal-title":"NeuroImage Clin."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lizak, N., Clough, M., Millist, L., Kalincik, T., White, O.B., and Fielding, J. (2016). Impairment of smooth pursuit as a marker of early multiple sclerosis. Front. Neurol., 7.","DOI":"10.3389\/fneur.2016.00206"},{"key":"ref_18","first-page":"20552173241255008","article-title":"Abnormal eye movements increase as motor disabilities and cognitive impairments become more evident in multiple sclerosis","volume":"10","author":"Gerardo","year":"2024","journal-title":"Mult. Scler. J. Exp. Transl. Clin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1016\/0042-6989(95)00302-9","article-title":"Comparison of horizontal, vertical, and diagonal smooth pursuit eye movements in normal human subjects","volume":"36","author":"Rottach","year":"1996","journal-title":"Vis. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1097\/WNP.0000000000000579","article-title":"Eye movement disorders and the cerebellum","volume":"36","author":"Shemesh","year":"2019","journal-title":"J. Clin. Neurophysiol."},{"key":"ref_21","first-page":"55","article-title":"Where have eye movements been and where are they going?","volume":"76","author":"Foulsham","year":"2013","journal-title":"Vis. Res."},{"key":"ref_22","first-page":"121","article-title":"A comparison of the dynamics of horizontal and vertical smooth pursuit in normal human subjects","volume":"59","author":"Honrubia","year":"1988","journal-title":"Aviat. Space Environ. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/dmcn.12384","article-title":"Vertical and horizontal smooth pursuit eye movements in children with developmental coordination disorder","volume":"56","author":"Robert","year":"2014","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4409","DOI":"10.1167\/iovs.12-11369","article-title":"Directional asymmetries in human smooth pursuit eye movements","volume":"54","author":"Ke","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.visres.2020.01.003","article-title":"Saccadic delay in multiple sclerosis: A quantitative description","volume":"168","author":"Petzold","year":"2020","journal-title":"Vis. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1097\/00019052-200402000-00005","article-title":"Eye movement control by the cerebral cortex","volume":"17","author":"Milea","year":"2004","journal-title":"Curr. Opin. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1007\/s00415-012-6565-8","article-title":"Dynamics of saccade parameters in multiple sclerosis patients with fatigue","volume":"259","author":"Finke","year":"2012","journal-title":"J. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jns.2008.10.001","article-title":"Multiple sclerosis: Cognition and saccadic eye movements","volume":"277","author":"Fielding","year":"2009","journal-title":"J. Neurol. Sci."},{"key":"ref_29","first-page":"480","article-title":"Evaluation of saccadic abnormalities in multiple sclerosis using a novel clinical saccadometry test","volume":"30","author":"Polat","year":"2025","journal-title":"Audiol. Neurootol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kincses, B., H\u00e9r\u00e1k, B.J., Szab\u00f3, N., Bozsik, B., Farag\u00f3, P., Kir\u00e1ly, A., Ver\u00e9b, D., T\u00f3th, E., Kocsis, K., and Bencsik, K. (2019). Grey matter atrophy explaining subclinical oculomotor deficit in multiple sclerosis. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00589"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1136\/practneurol-2016-001428","article-title":"Internuclear ophthalmoplegia","volume":"17","author":"Virgo","year":"2017","journal-title":"Pract. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"103824","DOI":"10.1016\/j.msard.2022.103824","article-title":"Prevalence of internuclear ophthalmoparesis in a population-based multiple sclerosis cohort","volume":"63","author":"Hof","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1212\/WNL.27.7.614","article-title":"Subclinical eye movement disorders in patients with multiple sclerosis","volume":"27","author":"Solingen","year":"1977","journal-title":"Neurology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s00415-025-13275-x","article-title":"Saccadic eye movements in neurological disease: Cognitive mechanisms and clinical applications","volume":"272","author":"Wang","year":"2025","journal-title":"J. Neurol."}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/18\/2\/22\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T16:11:45Z","timestamp":1769443905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/18\/2\/22"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["neurolint18020022"],"URL":"https:\/\/doi.org\/10.3390\/neurolint18020022","relation":{},"ISSN":["2035-8377"],"issn-type":[{"value":"2035-8377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,26]]}}}