{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T20:32:06Z","timestamp":1775766726446,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Multiple sclerosis (MS) is a chronic demyelinating disease with a heterogeneous clinical course, making long-term disability prediction challenging. Visual evoked potentials (VEPs), particularly amplitude-based parameters, may serve as sensitive biomarkers of neurodegeneration and functional decline undetected by conventional clinical measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the relationship between longitudinal changes in P100\u2013N145 amplitude and concurrent Expanded Disability Status Scale (EDSS) changes in relapsing\u2013remitting MS (RRMS) and the relative utility of baseline and longitudinal VEP parameters in representing disability status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this retrospective cohort study, 45 MS patients (90 eyes) with available VEP and EDSS data were followed for a median period of 48\u202fmonths. The primary endpoints were (1) change in EDSS score over time and (2) EDSS progression, defined as any increase in EDSS score from baseline to follow-up. Generalized estimating equations (GEE) and logistic regression were used to investigate the relationships between the VEP parameters at baseline and follow-up and EDSS progression, accounting for inter-eye correlation; partial correlation analysis assessed amplitude\u2013EDSS change associations, controlling for age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EDSS progression was observed in 17.8% of patients. A longitudinal decrease in P100\u2013N145 amplitude from baseline to follow-up was significantly associated with EDSS progression (OR: 1.511, 95% CI, <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001). In addition, partial correlation analysis adjusting for age revealed a significant negative association between the difference in P100\u2013N145 amplitude and EDSS difference (defined as baseline minus follow-up) in both eyes (right eye: <jats:italic>r<\/jats:italic>\u202f=\u202f\u22120.339, <jats:italic>p<\/jats:italic>\u202f=\u202f0.024; left eye: <jats:italic>r<\/jats:italic>\u202f=\u202f\u22120.406, <jats:italic>p<\/jats:italic>\u202f=\u202f0.006). In contrast, the changes in P100 latency and N75\u2013P100 amplitude did not correlate significantly with EDSS worsening. Baseline VEP parameters, including P100 latency, N75\u2013P100, and P100\u2013N145 amplitudes, did not predict EDSS progression or change over time (all <jats:italic>p<\/jats:italic>\u202f&amp;gt;\u202f0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate that a reduction in P100\u2013N145 amplitude over time is associated with worsening disability in RRMS. This suggests that the P100\u2013N145 may be an underestimated marker of progressive functional deterioration in RRMS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1649998","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T04:12:15Z","timestamp":1759119135000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["From demyelination to neurodegeneration in multiple sclerosis: reassessing the role of visual evoked potential P100-N145 amplitudes: a missing piece of the puzzle?"],"prefix":"10.3389","volume":"16","author":[{"given":"Nurhan","family":"Kaya Tutar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nilufer","family":"Kale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s00415-025-12917-4","article-title":"Towards a biological view of multiple sclerosis from early subtle to clinical progression: an expert opinion","volume":"272","author":"Filippi","year":"2025","journal-title":"J Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1212\/CON.0000000000000737","article-title":"Phases and phenotypes of multiple sclerosis","volume":"25","author":"Kantarci","year":"2019","journal-title":"Continuum"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1055\/s-0036-1579692","article-title":"Vision disturbances in multiple sclerosis","volume":"36","author":"Costello","year":"2016","journal-title":"Semin Neurol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2572","DOI":"10.1002\/acn3.52170","article-title":"Improving criteria for dissemination in space in multiple sclerosis by including additional regions","volume":"11","author":"Foster","year":"2024","journal-title":"Ann Clin Transl Neurol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e665","DOI":"10.1212\/NXI.0000000000000665","article-title":"Ms optic neuritis-induced long-term structural changes within the visual pathway","volume":"7","author":"Pawlitzki","year":"2020","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"ref6","article-title":"Visual evoked potential","volume-title":"StatPearls","author":"Baiano","year":"2025"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.cnp.2019.03.002","article-title":"The electrophysiological assessment of visual function in multiple sclerosis","volume":"4","author":"Barton","year":"2019","journal-title":"Clin Neurophysiol Pract"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/hbm.10010","article-title":"Cortical sources of the early components of the visual evoked potential","volume":"15","author":"Di Russo","year":"2002","journal-title":"Hum Brain Mapp"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol"},{"key":"ref10","doi-asserted-by":"publisher","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":"ref11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1023\/a:1001724411607","article-title":"Guidelines for calibration of stimulus and recording parameters used in clinical electrophysiology of vision. 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