{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T23:41:09Z","timestamp":1776469269362,"version":"3.51.2"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002957","name":"Technische Universit\u00e4t Dresden","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002957","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Reliable biomarkers for disability progression independent of relapse activity (PIRA) in multiple sclerosis (MS) applicable in routine patient care are urgently needed. This study reports results from an ongoing multicenter, prospective, observational study with the primary objective of investigating the association of change in brain MRI biomarkers and PIRA.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In total 453 active relapsing remitting patients from 19 sites with baseline (BL) and one-year follow-up (FU) visits were included. At each visit, medication, relapse activity, and EDSS were recorded. MRI included 3D-T1 and 2D\/3D-FLAIR. BL and FU scans enabled extraction of new\/enlarged T2-lesions and brain volume loss (BVL) (annualized). Correlations and logistic regression assessed associations between EDSS progression and BVL\/year.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n At BL an EDSS (25%\/50%\/75%) of 1.5\/2.0\/2.5 and a time since first MS diagnosis of 2.1\/5.7\/11.4\u00a0years were observed. Change (FU-BL): \u0394EDSS was 0.0\/0.0\/0.0, BVL\/year was\n \n \n $$-$$<\/jats:tex-math>\n \n -<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n 0.5\/\n \n \n $$-$$<\/jats:tex-math>\n \n -<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n 0.3\/\n \n \n $$-$$<\/jats:tex-math>\n \n -<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n 0.0%, age-adjusted BVL\/year was\n \n \n $$-$$<\/jats:tex-math>\n \n -<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n 0.4\/\n \n \n $$-$$<\/jats:tex-math>\n \n -<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n 0.1\/0.2%, and number of new\/enlarged T2-lesions per year was 0.0\/0.0\/0.6. 75% of patients were relapse activity-free during the observation period, 72% had no new\/enlarged T2-lesions, and 56% were free of both. BVL\/year (adjusted for age) correlated with \u0394EDSS (\n r<\/jats:italic>\n =\n \n \n $$-$$<\/jats:tex-math>\n \n -<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n 0.14,\n p<\/jats:italic>\n \u2009=\u20090.002) for all patients, but also for sub-cohorts of patients without new\/enlarged T2-lesions and without relapses (\n r<\/jats:italic>\n =\n \n \n $$-$$<\/jats:tex-math>\n \n -<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n 0.17,\n p\u2009<\/jats:italic>\n =\u20090.008). BVL\/year was significantly associated with EDSS progression in the logistic regression model (\n p<\/jats:italic>\n \u2009<\u20090.001). The risk of EDSS progression increases from 15% to 19% (relative risk increase of 26%), when BVL\/year declines from\n \n \n $$-$$<\/jats:tex-math>\n \n -<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n 0.5% to\n \n \n $$-$$<\/jats:tex-math>\n \n -<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n 1.0%.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n BVL over one year was significantly associated with EDSS progression in the absence of relapses or new lesions, confirming its value as a short-term risk marker for disability progression in MS.<\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s00415-025-13343-2","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T06:42:10Z","timestamp":1761028930000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Whole brain volume loss is associated with a short-term disability progression in relapse-activity free multiple sclerosis"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9911-5478","authenticated-orcid":false,"given":"Roland","family":"Opfer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lothar","family":"Spies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Kr\u00fcger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Buddenkotte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Roick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manda","family":"Jankovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolaj","family":"Witt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylke","family":"Domke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Kubalek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Reifschneider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Kunz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilias","family":"Nastos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felicita","family":"Heidler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Trendelenburg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Stockert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah K.","family":"Erhart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayrettin","family":"Tumani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hagen H.","family":"Kitzler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tjalf","family":"Ziemssen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"13343_CR1","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1177\/1352458516649452","volume":"22","author":"F Barkhof","year":"2016","unstructured":"Barkhof F (2016) Brain atrophy measurements should be used to guide therapy monitoring in MS - NO. 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GR: nothing to disclose, JKu: Research grants, travel grants and honoraria for serving as a speaker at clinical and scientific meetings and for participating at adboards were granted from Bayer Healthcare, Biogen, Daiichi-Sankyo, Genzyme, Merck, Novartis, Pfizer, Roche, Teva and UCB. IN: nothing to disclose, FH: nothing to disclose, GT: nothing to disclose, AS: nothing to disclose, DE: Nothing to disclose. HT: Has participated in meetings sponsored by or received honoraria for acting as an advisor\/speaker for Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, Diamed, Fresenius, Fujirebio, GlaxoSmithKline, Hexal, Horizon, Janssen-Cilag, Merck, Novartis, Roche, Sanofi-Genzyme, Siemens, Teva, and Viatris. He also acknowledges research support by DMSG (German Multiple Sclerosis Society), MWK-BW (Ministry of Science, Research and Arts of the State Baden-W\u00fcrttemberg), BMG (Federal Ministry of Health), University of Ulm, and Chemische Fabrik Karl Bucher. HK: Has received travel grants, speaker honoraria, financial research support, and consultancy fees from Bayer, Biogen Idec, Novartis, Siemens, and Teva; served on advisory boards for Biogen, Ixico, and Novartis; received research grants from Novartis. TZ: Has received advisory board fees from Viatris, Biogen, Bristol Myers Squibb, Merck, Novartis, Neuraxpharm, Roche, Sanofi and Teva; speaker fees from Almirall, Alexion, Biogen, Bristol Myers Squibb, Sanoz, Novartis, Roche, Sanofi, Neuraxpharm, Teva, and Viatris and research support from Neuraxpharm, Novartis, Roche, Sanofi.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest"}}],"article-number":"715"}}