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The observation that both inflammation and neurodegeneration are present from the onset of MS has resulted in a paradigm shift towards MS as a disease continuum driven by pathological mechanisms underlying clinical progression. Here we report the results from a meeting of Italian MS specialists, exploring the evolving perception of MS pathobiology and its implications for diagnosis and treatment. Insights garnered from the expert panel advocate for a redefined understanding of MS. This expert opinion paper reviews the disease continuum and the intertwined nature of inflammatory and neurodegenerative processes. Also, the need for changes in diagnostic criteria and treatment strategies, including the development of novel biomarkers and new therapies targeting smouldering disease, is discussed.<\/jats:p>","DOI":"10.1007\/s00415-025-12917-4","type":"journal-article","created":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T15:01:36Z","timestamp":1738422096000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Towards a biological view of multiple sclerosis from early subtle to clinical progression: an expert opinion"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-0479","authenticated-orcid":false,"given":"Massimo","family":"Filippi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Amato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Avolio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Gasperini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Inglese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girolama Alessandra","family":"Marfia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Patti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,1]]},"reference":[{"key":"12917_CR1","unstructured":"Murray TJ. 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PG has received grants and personal fees from Biogen Idec, Sanofi-Genzyme, and Merck Serono; grants and personal fees from Novartis; grants from the Department of Neuroscience, University of Padua; grants from the Veneto Region of Italy; grants from the Italian Association for Multiple Sclerosis (AISM); and grants from the Italian Ministry of Public Health. CG has received fees as an invited speaker or travel expenses for attending meetings from Biogen, Genzyme, Merck Serono, Mylan, Novartis, Sanofi, Almirall, Astra Zeneca, Sandoz; MI has received grants from the Italian Multiple Sclerosis Society Foundation (FISM), the Italian National Institute of Health, and the National MS Society (NMSS); has received fees for consultation from Biogen, Bristol Myers Squibb, Genzyme, Janssen, Merck, Novartis, Roche, and Sanofi. GAM is an Advisory Board member of Biogen Idec, Sanofi-Genzyme, Merck-Serono, Novartis, F. 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