{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T11:29:50Z","timestamp":1781177390952,"version":"3.54.1"},"reference-count":22,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero della Salute \u201cRicerca Corrente\u201d project"},{"name":"Sviluppo di agenti diagnostici multimodali per bioimaging avanzato"},{"DOI":"10.13039\/100031478","name":"#NEXTGENERATIONEU","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry of University and Research"},{"name":"National Recovery and Resilience Plan"},{"DOI":"10.13039\/501100003196","name":"project MNESYS","doi-asserted-by":"publisher","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation of the Romanian Society of Neurology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Disability accumulation in multiple sclerosis often occurs independent of relapses and inflammatory activity, yet reliable predictors for early progression remain limited. Our aim was to evaluate the utility of baseline fluid and optical coherence tomography (OCT) biomarkers for predicting early disability progression in newly diagnosed relapsing\u2013remitting MS (RRMS). We performed a monocentric observational cohort study on 72 RRMS patients that were enrolled within 6 months of diagnosis and followed for 2 years. Baseline serum and cerebrospinal fluid (CSF) samples were analyzed for neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (CHI3L1). Confirmed disability progression at 1 year (1yCDP) was defined by either an increase in Expanded Disability Status Scale or a \u226520% worsening on Nine-Hole Peg Test or Timed 25-Foot Walk. Seventeen patients (23.6%) developed 1yCDP. Elevated baseline CSF GFAP (OR = 5.79, 95% CI 1.72\u201319.45; p = 0.005) and CSF CHI3L1 thickness (OR = 4.14, 95% CI 1.49\u201311.49; p = 0.006) and reduced ganglion cell-inner plexiform layer (GCIPL) thickness (OR = 0.90, 95% CI 0.84\u20130.97; p = 0.006) independently predicted 1yCDP. A multivariate model including age, CSF GFAP and GCIPL achieved AUC = 0.831, with a sensitivity of 87.5% and specificity of 61.5%. This study provides evidence that baseline patient profiling using CSF GFAP, CSF CHI3L1 and GCIPL thickness may help predict early disability progression in RRMS.<\/jats:p>","DOI":"10.3390\/ijms262411774","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T10:50:38Z","timestamp":1764931838000},"page":"11774","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["GFAP, CHI3L1 and GCIPL Thickness as Baseline Predictors of Early Disability Progression in MS"],"prefix":"10.3390","volume":"26","author":[{"given":"Ion Iulian","family":"Enache","sequence":"first","affiliation":[{"name":"Neurology Department, Emergency University Hospital Bucharest, Splaiul Independen\u021bei 169, 050098 Bucharest, Romania"},{"name":"Department of Clinical Neurosciences-Neurology, Carol Davila University of Medicine and Pharmacy, Bulevardul Eroii Sanitari 8, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4315-9292","authenticated-orcid":false,"given":"Vlad Eugen","family":"Tiu","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences-Neurology, Carol Davila University of Medicine and Pharmacy, Bulevardul Eroii Sanitari 8, 050474 Bucharest, Romania"},{"name":"Neurology Department, Elias University Emergency Hospital, Bulevardul M\u0103r\u0103\u0219ti 17, 011461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u0103t\u0103lina Andreea","family":"Anghel","sequence":"additional","affiliation":[{"name":"Neurology Department, Elias University Emergency Hospital, Bulevardul M\u0103r\u0103\u0219ti 17, 011461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8532-6218","authenticated-orcid":false,"given":"Cristina","family":"Tiu","sequence":"additional","affiliation":[{"name":"Neurology Department, Emergency University Hospital Bucharest, Splaiul Independen\u021bei 169, 050098 Bucharest, Romania"},{"name":"Department of Clinical Neurosciences-Neurology, Carol Davila University of Medicine and Pharmacy, Bulevardul Eroii Sanitari 8, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4189-6571","authenticated-orcid":false,"given":"Alina","family":"Popa-Cherecheanu","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Carol Davila University of Medicine and Pharmacy, Bulevardul Eroii Sanitari 8, 050474 Bucharest, Romania"},{"name":"Ophthalmology Department, Emergency University Hospital Bucharest, Splaiul Independen\u021bei 169, 050098 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4996-2656","authenticated-orcid":false,"given":"Mihai","family":"Bostan","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Carol Davila University of Medicine and Pharmacy, Bulevardul Eroii Sanitari 8, 050474 Bucharest, Romania"},{"name":"Ophthalmology Department, Emergency University Hospital Bucharest, Splaiul Independen\u021bei 169, 050098 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Scippa","sequence":"additional","affiliation":[{"name":"IRCCS SYNLAB SDN, Via G. Ferraris 144, 80146 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Balestrieri","sequence":"additional","affiliation":[{"name":"IRCCS SYNLAB SDN, Via G. Ferraris 144, 80146 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1989-4740","authenticated-orcid":false,"given":"Giovanni","family":"Smaldone","sequence":"additional","affiliation":[{"name":"IRCCS SYNLAB SDN, Via G. Ferraris 144, 80146 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Soricelli","sequence":"additional","affiliation":[{"name":"IRCCS SYNLAB SDN, Via G. Ferraris 144, 80146 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1093\/brain\/awac016","article-title":"How patients with multiple sclerosis acquire disability","volume":"145","author":"Lublin","year":"2022","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Guerra, T., and Iaffaldano, P. (2025). A window into new insights on progression independent of relapse activity in multiple sclerosis: Role of therapies and current perspective. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26030884"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1001\/jamaneurol.2020.1568","article-title":"Contribution of relapse-independent progression vs. relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials","volume":"77","author":"Kappos","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/S0140-6736(16)31320-4","article-title":"Progressive multiple sclerosis: Prospects for disease therapy, repair, and restoration of function","volume":"389","author":"Ontaneda","year":"2017","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/S1474-4422(25)00249-2","article-title":"Blood and CSF biomarkers for multiple sclerosis: Emerging clinical applications","volume":"24","author":"Chitnis","year":"2025","journal-title":"Lancet Neurol."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"e200052","DOI":"10.1212\/NXI.0000000000200052","article-title":"Serum GFAP and NfL levels differentiate subsequent progression and disease activity in patients with progressive multiple sclerosis","volume":"10","author":"Barro","year":"2023","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1164","DOI":"10.1212\/NXI.0000000000001164","article-title":"Role of chitinase 3-like 1 as a biomarker in multiple sclerosis: A systematic review and meta-analysis","volume":"9","author":"Floro","year":"2022","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1002\/ana.27034","article-title":"Smouldering-associated worsening in multiple sclerosis: An international consensus statement on definition, biology, clinical implications, and future directions","volume":"96","author":"Scalfari","year":"2024","journal-title":"Ann. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1002\/acn3.52187","article-title":"Serum glial fibrillary acidic protein predicts disease progression in multiple sclerosis","volume":"11","author":"Madill","year":"2024","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/ana.27096","article-title":"Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression Under B\u2014Cell Depleting Treatment in Multiple Sclerosis","volume":"97","author":"Benkert","year":"2025","journal-title":"Ann. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1177\/13524585211010082","article-title":"CSF chitinase 3-like 1 is associated with iron rims in patients with a first demyelinating event","volume":"28","author":"Comabella","year":"2022","journal-title":"Mult. Scler. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1177\/1352458518767043","article-title":"Cerebrospinal fluid chitinase-3-like protein 1 level is not an independent predictive factor for the risk of clinical conversion in radiologically isolated syndrome","volume":"25","author":"Thouvenot","year":"2019","journal-title":"Mult. Scler. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1002\/acn3.51473","article-title":"Optical coherence tomography in multiple sclerosis: A 3-year prospective multicenter study","volume":"8","author":"Paul","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/S1474-4422(25)00275-3","article-title":"The use of optical coherence tomography and visual evoked potentials in the 2024 McDonald diagnostic criteria for multiple sclerosis","volume":"24","author":"Saidha","year":"2025","journal-title":"Lancet Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1001\/jamaneurol.2022.5250","article-title":"Serum glial fibrillary acidic protein compared with neurofilament light chain as a biomarker for disease progression in multiple sclerosis","volume":"80","author":"Meier","year":"2023","journal-title":"JAMA Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Jatczak-Pawlik, I., Jurewicz, A., Domowicz, M., Ewiak-Paszy\u0144ska, A., and Stasio\u0142ek, M. (2024). CHI3L1 in multiple sclerosis\u2014From bench to clinic. Cells, 13.","DOI":"10.3390\/cells13242086"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e906","DOI":"10.1212\/NXI.0000000000000906","article-title":"Chitinase 3-like 1 and neurofilament light chain in CSF and CNS atrophy in MS","volume":"8","author":"Schneider","year":"2021","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tiu, V.E., Popescu, B.O., Enache, I.I., Tiu, C., Cherecheanu, A.P., and Panea, C.A. (2023). Serum neurofilaments and OCT metrics predict EDSS-plus score progression in early relapse-remitting multiple sclerosis. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020606"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1002\/acn3.52165","article-title":"Retinal optical coherence tomography measures in multiple sclerosis: A systematic review and meta-analysis","volume":"11","author":"Ismail","year":"2024","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S1474-4422(22)00009-6","article-title":"Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: A retrospective modelling and validation study","volume":"21","author":"Benkert","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","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."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11774\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T05:22:15Z","timestamp":1765084935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11774"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":22,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262411774"],"URL":"https:\/\/doi.org\/10.3390\/ijms262411774","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,5]]}}}