{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:20:30Z","timestamp":1791350430870,"version":"4.3.1"},"reference-count":43,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100017694","name":"Hermann und Lilly Schilling-Stiftung f\u00fcr Medizinische Forschung","doi-asserted-by":"publisher","award":["to S.B."],"award-info":[{"award-number":["to S.B."]}],"id":[{"id":"10.13039\/100017694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG; SFB CRC-TR-128 project number 213904703 to F."],"award-info":[{"award-number":["DFG; SFB CRC-TR-128 project number 213904703 to F."]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Neurol Disord"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>In multiple sclerosis (MS), an increase in whole-brain lesion volume (LV) on MRI can be observed even in the absence of newly demarcated focal lesions or clinical relapses. However, it is unknown whether the presence of increasing LV alone is enough to justify changes in the therapeutic regimen. At this point, blood-based biomarkers may aid to identify patients at risk for progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To determine the prognostic value of blood-based biomarkers (serum neurofilament (sNfL) and serum glial fibrillary acidic protein (sGFAP)) on disability progression in MS patients without newly demarcated lesions or clinical relapses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Longitudinal cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In total, out of 291 MS patients who were retrospectively screened for this study, 171 patients underwent a detailed clinical and MRI assessment and were finally included in the analysis: 100 patients with increasing LV (mean baseline Expanded Disability Status Scale (EDSS)\u2009=\u20091.5) and 71 with stable LV over 2\u2009years (mean baseline EDSS\u2009=\u20091.0). Baseline blood-based measures (sNfL and sGFAP) and MRI metrics (total T2-weighted LV, gray matter (GM) volume) were acquired. EDSS worsening served as a clinical outcome measure and was determined through a 2-year follow-up. Receiver operator characteristic analyses were conducted to determine the predictive discriminative power of both blood-based biomarkers. Multivariate logistic regressions were performed to identify independent risk factors for EDSS progression in both cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      MS patients with increasing LV had lower GM volume (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0109,\n                      <jats:italic toggle=\"yes\">q<\/jats:italic>\n                      \u2009=\u20090.0490) and worse EDSS scores (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0065,\n                      <jats:italic toggle=\"yes\">q<\/jats:italic>\n                      \u2009=\u20090.0650) at clinical follow-up compared to patients with stable LV. Patients with increasing LV and EDSS progression had significantly higher sNfL (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0049,\n                      <jats:italic toggle=\"yes\">q<\/jats:italic>\n                      \u2009=\u20090.0196), but not sGFAP (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.7425,\n                      <jats:italic toggle=\"yes\">q<\/jats:italic>\n                      \u2009=\u20090.9900) levels. In the logistic regression model, sNfL levels remained an independent risk factor for EDSS progression in patients with increasing LV (odds ratio\u2009=\u20091.344, 95% confidence interval: 1.038\u20131.739,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.025), but not in patients with stable LV. Finally, in patients with increasing LV, sNfL levels, but not sGFAP levels, discriminated progressive from non-progressive MS patients upon clinical follow-up (area under the curve\u2009=\u20090.67,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.004;\n                      <jats:italic toggle=\"yes\">q<\/jats:italic>\n                      \u2009=\u20090.016).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>sNfL enhances the prediction of disease progression in MS patients with merely increasing LV on MRI but no new T2 lesions or other signs of inflammatory activity. These findings may support treatment decisions in seemingly stable patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17562864251374903","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T08:43:02Z","timestamp":1763714582000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Prognostic value of blood-based biomarkers in multiple sclerosis patients in the absence of clinical relapses or new MRI lesions"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7887-7211","authenticated-orcid":false,"given":"Tobias","family":"Brummer","sequence":"first","affiliation":[{"name":"Department of Neurology, Research Center for Immunotherapy and Focus Program Translational Neuroscience, Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Gonzalez-Escamilla","sequence":"additional","affiliation":[{"name":"Department of Neurology, Research Center for Immunotherapy and Focus Program Translational Neuroscience, Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falk","family":"Steffen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Research Center for Immunotherapy and Focus Program Translational Neuroscience, Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Jakob","sequence":"additional","affiliation":[{"name":"Department of Neurology, Research Center for Immunotherapy and Focus Program Translational Neuroscience, Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Beyreuther","sequence":"additional","affiliation":[{"name":"Department of Neurology, Research Center for Immunotherapy and Focus Program Translational Neuroscience, Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiu","family":"Groppa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Research Center for Immunotherapy and Focus Program Translational Neuroscience, Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Bittner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Research Center for Immunotherapy and Focus Program Translational Neuroscience, Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1231-1928","authenticated-orcid":false,"given":"Frauke","family":"Zipp","sequence":"additional","affiliation":[{"name":"Department of Neurology, Research Center for Immunotherapy and Focus Program Translational Neuroscience, Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3293-5121","authenticated-orcid":false,"given":"Vinzenz","family":"Fleischer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Focus Program Translational Neuroscience, Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55131, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2022.102588"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01473-3"},{"key":"e_1_3_4_4_2","first-page":"446","article-title":"A serial 10-year follow-up study of atrophied brain lesion volume and disability progression in patients with relapsing-remitting MS","volume":"40","author":"Zivadinov R","year":"2019","unstructured":"Zivadinov R, Horakova D, Bergsland N, et al. 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