{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:40:22Z","timestamp":1787319622731,"version":"build-2736575974"},"reference-count":36,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Multiple Sclerosis Journal \u2013 Experimental, Translational and Clinical"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Progression independent of relapse activity (PIRA) may occur in patients with relapsing multiple sclerosis (MS) and is a major contributor to disability accumulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We evaluated whether a panel of cerebrospinal fluid (CSF) biomarkers (neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), total-Tau (T-Tau), ubiquitin C-terminal hydrolase 1 (UCHL-1), and the phospho-Tau (P-Tau)181\/T-Tau ratio) at diagnosis could discriminate patients who will develop PIRA in early disease phases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CSF levels of NfL, GFAP, T-Tau, and UCHL-1 were measured with SIMOA, of P-Tau181, and the ratio P-Tau181\/T-Tau with chemiluminescent immunoassay in 80 newly diagnosed MS patients who were followed up for three years with six-month Expanded Disability Status Scale (EDSS) assessments and yearly MRI scans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nineteen participants developing PIRA exhibited elevated GFAP and UCHL-1 levels, and reduced P-Tau181\/T-Tau ratio. These biomarkers remained significant predictors of the outcome after adjusting for confounders, particularly older age at onset and higher baseline EDSS. Additionally, we identified moderate positive correlations between NfL-GFAP, NfL-UCHL-1, and GFAP-UCHL-1 levels, and moderate negative correlations between P-Tau181\/T-Tau ratio and NfL, GFAP, and UCHL-1 levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The elevation of GFAP and UCHL-1 likely reflects the role of astrocytic activation, while the reduction of the P-Tau181\/T-Tau ratio may indicate disrupted Tau metabolism in individuals at risk of PIRA. Our findings suggest that combining these innovative biomarkers with clinical risk factors could improve early prognostic accuracy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20552173251372751","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T05:20:15Z","timestamp":1757740815000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Analysis of an innovative fluid biomarker panel for early prediction of progression independent of relapse activity in multiple sclerosis"],"prefix":"10.1177","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6546-5745","authenticated-orcid":false,"given":"Edoardo Dalmato","family":"Schilke","sequence":"first","affiliation":[{"name":"PhD program in Neuroscience, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy"},{"name":"Neurology, IRCCS San Gerardo dei Tintori Foundation Hospital, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Frigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Letizia","family":"Fusco","sequence":"additional","affiliation":[{"name":"Neurology, IRCCS San Gerardo dei Tintori Foundation Hospital, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Cappellani","sequence":"additional","affiliation":[{"name":"Clinical Chemistry Laboratory, IRCCS San Gerardo dei Tintori Foundation Hospital, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diletta","family":"Cereda","sequence":"additional","affiliation":[{"name":"Neurology, IRCCS San Gerardo dei Tintori Foundation Hospital, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1654-4996","authenticated-orcid":false,"given":"Chiara Paola","family":"Zoia","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology, Department of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy"},{"name":"Milan Centre for Neuroscience, University of Milan-Bicocca, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4128-2406","authenticated-orcid":false,"given":"Guido","family":"Cavaletti","sequence":"additional","affiliation":[{"name":"Neurology, IRCCS San Gerardo dei Tintori Foundation Hospital, Monza, Italy"},{"name":"Experimental Neurology Unit, Department of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1568"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac016"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.11.1444"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.4655"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac111"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-023-07228-3"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.105131"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2021-328568"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3997"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2004.03.039"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1191\/135248506ms1263oa"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1191\/1352458506ms1288sr"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51969"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33158-8"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2021.102810"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67934-2"},{"key":"e_1_3_3_18_2","article-title":"Serum GFAP and NfL levels differentiate subsequent progression and disease activity in patients with progressive multiple sclerosis","volume":"10","author":"Barro C","year":"2022","unstructured":"Barro C, Healy BC, Liu Y, et al. Serum GFAP and NfL levels differentiate subsequent progression and disease activity in patients with progressive multiple sclerosis. Neurology(R) Neuroimmunology & Neuroinflammation 2022; 10. https:\/\/pubmed.ncbi.nlm.nih.gov\/36376097\/.","journal-title":"Neurology(R) Neuroimmunology & Neuroinflammation"},{"key":"e_1_3_3_19_2","article-title":"Serum glial fibrillary acidic protein and neurofilament light chain levels reflect different mechanisms of disease progression under B-cell depleting treatment in multiple sclerosis","volume":"97","author":"Benkert P","year":"2024","unstructured":"Benkert P, Maleska Maceski A, Schaedelin S, et al. Serum glial fibrillary acidic protein and neurofilament light chain levels reflect different mechanisms of disease progression under B-cell depleting treatment in multiple sclerosis. Ann Neurol 2024; 97. https:\/\/pubmed.ncbi.nlm.nih.gov\/39411917\/.","journal-title":"Ann Neurol"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.5250"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101856"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3527"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03243-z"},{"key":"e_1_3_3_24_2","article-title":"The relevance of combined testing of cerebrospinal fluid glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 in multiple sclerosis and peripheral neuropathy","author":"Csecsei P","year":"2024","unstructured":"Csecsei P, Acs P, Gottschal M, et al. The relevance of combined testing of cerebrospinal fluid glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 in multiple sclerosis and peripheral neuropathy. Neurol Sci 2024. https:\/\/pubmed.ncbi.nlm.nih.gov\/39565457\/.","journal-title":"Neurol Sci"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-30237-3"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2001.tb00387.x"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-181297"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040296"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30470-2"},{"key":"e_1_3_3_30_2","article-title":"Prognostic accuracy of NEDA-3 in long-term outcomes of multiple sclerosis","volume":"8","author":"Prosperini L","year":"2021","unstructured":"Prosperini L, Ruggieri S, Haggiag S, et al. Prognostic accuracy of NEDA-3 in long-term outcomes of multiple sclerosis. Neurology(R) Neuroimmunol Neuroinflam 2021; 8. https:\/\/pubmed.ncbi.nlm.nih.gov\/34373345\/.","journal-title":"Neurology(R) Neuroimmunol Neuroinflam"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26913"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI86198"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.1"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11662"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2014.08.002"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51676"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.067313"}],"container-title":["Multiple Sclerosis Journal \u2013 Experimental, Translational and Clinical"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20552173251372751","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/20552173251372751","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20552173251372751","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T13:19:27Z","timestamp":1758115167000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/20552173251372751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1177\/20552173251372751"],"URL":"https:\/\/doi.org\/10.1177\/20552173251372751","relation":{},"ISSN":["2055-2173","2055-2173"],"issn-type":[{"value":"2055-2173","type":"print"},{"value":"2055-2173","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"article-number":"20552173251372751"}}