{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T06:11:26Z","timestamp":1759817486566,"version":"build-2065373602"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"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. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The measurement of brain atrophy in patients with relapsing\u2013remitting multiple sclerosis (RRMS) may be a marker of the disease activity. However, currently this method is not widely used in clinical practice. In the presented study, the relationship between lesions (T2) in magnetic resonance imaging (MRI), including contrast-enhancing (Gd+), clinical relapses and no evidence of disease activity (NEDA-3) with volumetric changes was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical and MRI data from RRMS patients treated with cladribine tablets (CLAD) and alemtuzumab (ALEM) were retrospectively analyzed at 4 time points (pretreatment and 3\u202fyears of follow-up). Volumetric data were obtained using the FreeSurfer. Annual volumetric changes and new T2\/Gd\u202f+\u202flesions were pooled together to assess short-term relationships, baseline T2\/Gd\u202f+\u202flesions were correlated with 3-year volume changes and years with NEDA-3 and without NEDA-3 were compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study included 33 patients treated with CLAD and 19 patients treated with ALEM. In the year-to-year analysis (n<jats:sub>CLAD<\/jats:sub> =\u202f59, n<jats:sub>ALEM<\/jats:sub> =\u202f36) within the CLAD group, new T2 lesions were significantly associated with a decrease in thalamic (<jats:italic>p<\/jats:italic> =\u202f0.02), cerebellum (<jats:italic>p<\/jats:italic> =\u202f0.05) and deep grey matter (<jats:italic>p<\/jats:italic> =\u202f0.05) volume. When analyzing the correlation between baseline T2 lesions and overall 3-year volume changes (N<jats:sub>CLAD<\/jats:sub> =\u202f9, N<jats:sub>ALEM<\/jats:sub> =\u202f7), in the CLAD group, strong associations were found with whole brain (<jats:italic>p<\/jats:italic>\u202f=\u202f0.001, <jats:italic>\ua7b5<\/jats:italic> =\u202f\u22120.89), cerebellum (<jats:italic>p<\/jats:italic>\u202f=\u202f0.002, <jats:italic>\ua7b5<\/jats:italic> =\u202f\u22120.20), cerebellar cortex (<jats:italic>p<\/jats:italic>\u202f=\u202f0.003, <jats:italic>\ua7b5<\/jats:italic> =\u202f\u22120.19) and DGM (<jats:italic>p<\/jats:italic> =\u202f0.015, <jats:italic>\ua7b5<\/jats:italic> =\u202f\u22120.04) atrophy, as well as with lateral ventricular volume increase (<jats:italic>p<\/jats:italic>\u202f=\u202f0.00001, <jats:italic>\ua7b5<\/jats:italic> =\u202f0.1). A similar situation occurred when only the first year of treatment was analyzed (N<jats:sub>CLAD<\/jats:sub> =\u202f29, N<jats:sub>ALEM<\/jats:sub> =\u202f13). It was not observed in the ALEM group. Interestingly, no correlation was noted between Gd\u202f+\u202flesions and volumetric changes. Remarkably, no statistically significant differences between years with and without relapses were observed. However, years without NEDA-3 (<jats:italic>n<\/jats:italic>\u202f=\u202f31) were characterized by greater atrophy in white matter (<jats:italic>p<\/jats:italic>\u202f=\u202f0.04), thalamus (<jats:italic>p<\/jats:italic>\u202f=\u202f0.02), and putamen (<jats:italic>p<\/jats:italic>\u202f=\u202f0.04).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results of the presented study suggested an association of increased brain atrophy with radiological activity rather than with relapsing disease activity. However, further studies with larger numbers of patients are needed to verify these associations more precisely.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2025.1661539","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T05:34:49Z","timestamp":1759815289000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of brain atrophy as a promising marker of radiological activity in patients with relapsing\u2013remitting multiple sclerosis"],"prefix":"10.3389","volume":"19","author":[{"given":"Aleksandra","family":"Pogoda-Weso\u0142owska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacy","family":"Stachura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Szuka\u0142o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Wieczorek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"St\u0119pie\u0144","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"108342","DOI":"10.1016\/j.clineuro.2024.108342","article-title":"Continuous diffuse brain atrophy independent of relapse as a hallmark of multiple sclerosis beginning from relapsing-remitting stage","volume":"242","author":"Akaishi","year":"2024","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1016\/j.athoracsur.2015.11.024","article-title":"Adjust for multiple comparisons? It's not that simple","volume":"101","author":"Althouse","year":"2016","journal-title":"Ann. Thorac. Surg."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13317-019-0117-5","article-title":"Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options","volume":"10","author":"Andravizou","year":"2019","journal-title":"Auto Immun. Highlights"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1756286418823462","DOI":"10.1177\/1756286418823462","article-title":"Comparing longitudinal brain atrophy measurement techniques in a real-world multiple sclerosis clinical practice cohort: towards clinical integration?","volume":"12","author":"Beadnall","year":"2019","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"102945","DOI":"10.1016\/j.msard.2021.102945","article-title":"A real-world single-Centre analysis of alemtuzumab and cladribine for multiple sclerosis","volume":"52","author":"Bose","year":"2021","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1001\/jamaneurol.2022.1025","article-title":"Association of Brain Atrophy with Disease Progression Independent of relapse activity in patients with relapsing multiple sclerosis","volume":"79","author":"Cagol","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1093\/brain\/awf025","article-title":"Brain atrophy in clinically early relapsing-remitting multiple sclerosis","volume":"125","author":"Chard","year":"2002","journal-title":"Brain"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"103555","DOI":"10.1016\/j.msard.2022.103555","article-title":"Contribution of relapse-associated worsening to overall disability accrual in patients with relapsing-onset multiple sclerosis: a mediation analysis","volume":"59","author":"Chen","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1212\/WNL.0000000000004354","article-title":"Alemtuzumab CARE-MS II 5-year follow-up: efficacy and safety findings","volume":"89","author":"Coles","year":"2017","journal-title":"Neurology"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1111\/ene.15579","article-title":"Reduction in grey matter atrophy in patients with relapsing multiple sclerosis following treatment with cladribine tablets","volume":"30","author":"Cortese","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s40263-024-01066-3","article-title":"Real-world retrospective analysis of Alemtuzumab outcomes in relapsing-remitting multiple sclerosis: the LEMCAM study","volume":"38","author":"Costa-Frossard Fran\u00e7a","year":"2024","journal-title":"CNS Drugs"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1177\/1352458517690269","article-title":"Reduced brain atrophy rates are associated with lower risk of disability progression in patients with relapsing multiple sclerosis treated with cladribine tablets","volume":"24","author":"De Stefano","year":"2018","journal-title":"Mult. Scler."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s40263-017-0415-2","article-title":"Effect of fingolimod on brain volume loss in patients with multiple sclerosis","volume":"31","author":"De Stefano","year":"2017","journal-title":"CNS Drugs"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/S1474-4422(18)30451-4","article-title":"Association between pathological and MRI findings in multiple sclerosis","volume":"18","author":"Filippi","year":"2019","journal-title":"Lancet Neurerrool."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1212\/wnl.55.11.1714","article-title":"Whole brain volume changes in patients with progressive MS treated with cladribine","volume":"55","author":"Filippi","year":"2000","journal-title":"Neurology"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/s0896-6273(02)00569-x","article-title":"Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain","volume":"33","author":"Fischl","year":"2002","journal-title":"Neuron"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1093\/cercor\/bhg087","article-title":"Automatically parcellating the human cerebral cortex","volume":"14","author":"Fischl","year":"2004","journal-title":"Cereb. Cortex"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1148\/radiol.2019190306","article-title":"Atrophied brain T2 lesion volume at MRI is associated with disability progression and conversion to secondary progressive multiple sclerosis","volume":"293","author":"Genovese","year":"2019","journal-title":"Radiology"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1056\/NEJMoa0902533","article-title":"A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis","volume":"362","author":"Giovannoni","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1093\/brain\/awab029","article-title":"Quantitative magnetic resonance imaging towards clinical application in multiple sclerosis","volume":"144","author":"Granziera","year":"2021","journal-title":"Brain"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"459","DOI":"10.3389\/fneur.2019.00459","article-title":"Thalamic atrophy without whole brain atrophy is associated with absence of 2-year NEDA in multiple sclerosis","volume":"10","author":"H\u00e4nninen","year":"2019","journal-title":"Front. Neurol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1212\/WNL.0000000000004313","article-title":"Alemtuzumab CARE-MS I 5-year follow-up: durable efficacy in the absence of continuous MS therapy","volume":"89","author":"Havrdova","year":"2017","journal-title":"Neurology"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e0300415","DOI":"10.1371\/journal.pone.0300415","article-title":"Predictors of multiple sclerosis progression: a systematic review of conventional magnetic resonance imaging studies","volume":"19","author":"Lomer","year":"2024","journal-title":"PLoS One"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"104714","DOI":"10.1016\/j.msard.2023.104714","article-title":"The association between brain volume loss and disability in multiple sclerosis: a systematic review","volume":"74","author":"Matthews","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1002\/acn3.534","article-title":"Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study","volume":"5","author":"Miller","year":"2018","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"104187","DOI":"10.1016\/j.msard.2022.104187","article-title":"Assessment of T2 lesion-based disease activity volume outcomes in predicting disease progression in multiple sclerosis over 10 years","volume":"67","author":"Oship","year":"2022","journal-title":"Mult. Scler. Relat. 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Neurol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1097\/WCO.0000000000000946","article-title":"Central vein sign and iron rim in multiple sclerosis: ready for clinical use?","volume":"34","author":"Preziosa","year":"2021","journal-title":"Curr. Opin. Neurol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e1059","DOI":"10.1212\/NXI.0000000000001059","article-title":"Prognostic accuracy of NEDA-3 in long-term outcomes of multiple sclerosis","volume":"8","author":"Prosperini","year":"2021","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1212\/WNL.0000000000001281","article-title":"Correlation between brain volume loss and clinical and MRI outcomes in multiple sclerosis","volume":"84","author":"Radue","year":"2015","journal-title":"Neurology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1146\/annurev-pathol-052920-040318","article-title":"The immune response in multiple sclerosis","volume":"17","author":"Rodr\u00edguez Mur\u00faa","year":"2022","journal-title":"Annu. Rev. Pathol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1177\/13524585241267211","article-title":"Effectiveness of cladribine compared to fingolimod, natalizumab, ocrelizumab and alemtuzumab in relapsing-remitting multiple sclerosis","volume":"30","author":"Roos","year":"2024","journal-title":"Mult. Scler."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1007\/s00062-022-01144-3","article-title":"Magnetic resonance imaging in primary progressive multiple sclerosis patients: review","volume":"32","author":"Siger","year":"2022","journal-title":"Clin. Neuroradiol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"3343","DOI":"10.1007\/s00415-020-09983-1","article-title":"CAMMS223, CAMMS03409, and TOPAZ investigators. Long-term efficacy and safety of alemtuzumab in patients with RRMS: 12-year follow-up of CAMMS223","volume":"267","author":"Steingo","year":"2020","journal-title":"J. Neurol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"371","DOI":"10.5603\/PJNNS.a2023.0050","article-title":"Cladribine tablets for highly active relapsing-remitting multiple sclerosis in Poland: a real-world, multi-Centre, retrospective, cohort study during the COVID-19 pandemic","volume":"57","author":"St\u0119pie\u0144","year":"2023","journal-title":"Neurol. Neurochir. Pol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1007\/s00415-019-09643-z","article-title":"A multimodal approach to assess the validity of atrophied T2-lesion volume as an MRI marker of disease progression in multiple sclerosis","volume":"267","author":"Tavazzi","year":"2020","journal-title":"J. Neurol."},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.92.15_supplement.P5.2-007","article-title":"The association between serum neurofilament light chain, atrophied lesion volume and brain atrophy with disability progression in multiple sclerosis","author":"Tavazzi","year":"2019","journal-title":"Neurology"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"523","DOI":"10.3390\/jcm11030523","article-title":"Brain volume loss can occur at the rate of normal aging in patients with multiple sclerosis who are free from disease activity","volume":"11","author":"Temmerman","year":"2022","journal-title":"J. Clin. Med."},{"key":"ref40","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":"ref41","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1212\/WNL.88.16_supplement.P2.104","article-title":"Alemtuzumab durably slows brain volume loss over 6 years in the absence of continuous treatment in patients with active RRMS who were treatment-naive (CARE-MS I) or had an inadequate response to prior therapy (CARE-MS II) [poster P1181]","volume":"88","author":"Traboulsee","year":"2016","journal-title":"ECTRIMS"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1007\/s10072-018-3487-y","article-title":"Brain volume loss is present in Japanese multiple sclerosis patients with no evidence of disease activity","volume":"39","author":"Yokote","year":"2018","journal-title":"Neurol. Sci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1007\/s40263-020-00749-x","article-title":"Efficacy and safety of Alemtuzumab through 9 years of follow-up in patients with highly active disease: post hoc analysis of CARE-MS I and II patients in the TOPAZ extension study","volume":"34","author":"Ziemssen","year":"2020","journal-title":"CNS Drugs"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"446","DOI":"10.3174\/ajnr.A5987","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","year":"2019","journal-title":"AJNR Am. J. 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