Rethinking prognosis in multiple sclerosis: a multiaxial perspective

Thompson, A. J., Baranzini, S. E., Geurts, J., Hemmer, B. & Ciccarelli, O. Multiple sclerosis. Lancet 391, 1622–1636 (2018).

Article  PubMed  Google Scholar 

Rotstein, D. & Montalban, X. Reaching an evidence-based prognosis for personalized treatment of multiple sclerosis. Nat. Rev. Neurol. 15, 287–300 (2019).

Article  PubMed  Google Scholar 

Bjornevik, K. et al. Serum neurofilament light chain levels in patients with presymptomatic multiple sclerosis. JAMA Neurol. 77, 58–64 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Müller, J. et al. Harmonizing definitions for progression independent of relapse activity in multiple sclerosis: a systematic review. JAMA Neurol. 80, 1232–1245 (2023).

Article  PubMed  Google Scholar 

Kuhlmann, T. et al. Multiple sclerosis progression: time for a new mechanism-driven framework. Lancet Neurol. 22, 78–88 (2023).

Article  PubMed  Google Scholar 

Portaccio, E. et al. Multiple sclerosis: emerging epidemiological trends and redefining the clinical course. Lancet Reg. Health Eur. 44, 100977 (2024).

Article  PubMed  PubMed Central  Google Scholar 

Antel, J., Antel, S., Caramanos, Z., Arnold, D. L. & Kuhlmann, T. Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity? Acta Neuropathol. 123, 627–638 (2012).

Article  PubMed  Google Scholar 

Vollmer, T. L., Nair, K. V., Williams, I. M. & Alvarez, E. Multiple sclerosis phenotypes as a continuum: the role of neurologic reserve. Neurol. Clin. Pract. 11, 342–351 (2021).

Article  PubMed  PubMed Central  Google Scholar 

van der Walt, A. et al. Advancing multiple sclerosis management in older adults. Nat. Rev. Neurol. 21, 432–448 (2025).

Article  PubMed  Google Scholar 

Confavreux, C. & Vukusic, S. Age at disability milestones in multiple sclerosis. Brain 129, 595–605 (2006).

Article  PubMed  Google Scholar 

Cohen, M. et al. Should we still only rely on EDSS to evaluate disability in multiple sclerosis patients? A study of inter and intra rater reliability. Mult. Scler. Relat. Disord. 54, 103144 (2021).

Article  PubMed  Google Scholar 

Scalfari, A. et al. The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability. Brain 133, 1914–1929 (2010).

Article  PubMed  PubMed Central  Google Scholar 

He, A. et al. Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol. 19, 307–316 (2020).

Article  CAS  PubMed  Google Scholar 

Gasperini, C. et al. Unraveling treatment response in multiple sclerosis: a clinical and MRI challenge. Neurology 92, 180–192 (2019).

Article  PubMed  Google Scholar 

Weideman, A. M., Tapia-Maltos, M. A., Johnson, K., Greenwood, M. & Bielekova, B. Meta-analysis of the age-dependent efficacy of multiple sclerosis treatments. Front. Neurol. 8, 577 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Manouchehri, N. et al. Efficacy of disease modifying therapies in progressive MS and how immune senescence may explain their failure. Front. Neurol. 13, 854390 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Di Filippo, M., Portaccio, E., Mancini, A. & Calabresi, P. Multiple sclerosis and cognition: synaptic failure and network dysfunction. Nat. Rev. Neurosci. 19, 599–609 (2018).

Article  PubMed  Google Scholar 

Schoonheim, M. M., Broeders, T. A. A. & Geurts, J. J. G. The network collapse in multiple sclerosis: an overview of novel concepts to address disease dynamics. Neuroimage Clin. 35, 103108 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Lebrun-Frénay, C. et al. The radiologically isolated syndrome: revised diagnostic criteria. Brain 146, 3431–3443 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Yusuf, F. L. A. et al. A systematic review of morbidities suggestive of the multiple sclerosis prodrome. Expert Rev. Neurother. 20, 799–819 (2020).

Article  CAS  PubMed  Google Scholar 

Harding, K. E., Kreft, K. L., Ben-Shlomo, Y. & Robertson, N. P. Prodromal multiple sclerosis: considerations and future utility. J. Neurol. 271, 2129–2140 (2024).

Article  PubMed  PubMed Central  Google Scholar 

Marrie, R. A. et al. From the prodromal stage of multiple sclerosis to disease prevention. Nat. Rev. Neurol. 18, 559–572 (2022).

Article  PubMed  Google Scholar 

Okuda, D. T. et al. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology 72, 800–805 (2009).

Article  CAS  PubMed  Google Scholar 

De Stefano, N. & Rovira, À Do we need new MRI criteria for the diagnosis of radiologically isolated syndrome? Brain 146, e102–e103 (2023).

Article  PubMed  Google Scholar 

Lebrun-Frénay, C. et al. Risk factors and time to clinical symptoms of multiple sclerosis among patients with radiologically isolated syndrome. JAMA Netw. Open 4, e2128271 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Abou Mrad, T., Naja, K., Khoury, S. J. & Hannoun, S. Central vein sign and paramagnetic rim sign: from radiologically isolated syndrome to multiple sclerosis. Eur. J. Neurol. 30, 2912–2918 (2023).

Article  PubMed  Google Scholar 

Matute-Blanch, C. et al. Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome. Brain 141, 1085–1093 (2018).

Article  PubMed  Google Scholar 

Schneider, R. et al. Plasma glial fibrillary acidic protein levels correlate with paramagnetic rim lesions in people with radiologically isolated syndrome. Mult. Scler. 30, 156–165 (2024).

Article  CAS  PubMed  Google Scholar 

Muñoz-San Martín, M. et al. Radiologically isolated syndrome: targeting miRNAs as prognostic biomarkers. Epigenomics 12, 2065–2076 (2020).

Article  PubMed  Google Scholar 

Filippatou, A. et al. Spinal cord and infratentorial lesions in radiologically isolated syndrome are associated with decreased retinal ganglion cell/inner plexiform layer thickness. Mult. Scler. 25, 1878–1887 (2019).

Article  CAS  PubMed  Google Scholar 

Roldán, M. et al. Assessing the visual afferent pathway with the multifocal visual evoked potentials in the radiologically isolated syndrome. Sci. Rep. 14, 20169 (2024).

Article  PubMed  PubMed Central  Google Scholar 

Okuda, D. T. et al. Dimethyl fumarate delays multiple sclerosis in radiologically isolated syndrome. Ann. Neurol. 93, 604–614 (2023).

Article  CAS  PubMed  Google Scholar 

Lebrun-Frénay, C. et al. Teriflunomide and time to clinical multiple sclerosis in patients with radiologically isolated syndrome: the TERIS randomized clinical trial. JAMA Neurol. 80, 1080–1088 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Montalban, X. et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol. 24, 850–865 (2025).

Article  PubMed 

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