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. 2025 Jun;31(7):771-781.
doi: 10.1177/13524585251332115. Epub 2025 May 30.

Radiologically isolated syndrome: How could we accurately diagnose a subclinical period of multiple sclerosis?

Andreu Vilaseca  1   2 , Angela Vidal-Jordana  1   2 , Sofia Sceppacuercia  3 , Willem Calderon  3 , Georgina Arrambide  1   2 , Jordi Rio  1   2 , Carmen Tur  1   2 , Breogan Rodriguez-Acevedo  1   2 , Helena Ariño  1   2 , Ana Zabalza  1   2 , Alvaro Cobo-Calvo  1   2 , Neus Mongay-Ochoa  1   2 , Pere Carbonell-Mirabent  1   2 , Agustín Pappolla  1   2 , René Carvajal  1   2 , Joaquín Castilló  1   2 , Ingrid Galan  1   2 , Luciana Midaglia  1   2 , Luca Bollo  1   2 , Javier Villacieros-Álvarez  1   2 , Cristina Auger  3 , Jaume Sastre-Garriga  1   2 , Mar Tintoré  1   2   4 , Manuel Comabella  1   2 , Àlex Rovira  3 , Xavier Montalban  1   2   4
Affiliations

Radiologically isolated syndrome: How could we accurately diagnose a subclinical period of multiple sclerosis?

Andreu Vilaseca et al. Mult Scler. 2025 Jun.

Abstract

Background: Radiologically isolated syndrome (RIS) represents a subclinical period of multiple sclerosis (MS).

Objectives: We aimed to characterize and identify risk factors for developing MS in an RIS cohort and to assess various proposed RIS definitions for their predictive value in MS development.

Methods: This cohort study included all patients with at least one typical inflammatory-demyelinating lesion suggestive of MS on brain and/or spinal cord magnetic resonance imaging (MRI). The development of MS symptoms and new T2 lesions were the primary and secondary outcomes, respectively. Cox regression was used to identify risk factors, and diagnostic performance was assessed.

Results: Eighty-eight patients were included, with 25.0% developing MS symptoms over a mean 55.1-month follow-up. Younger age and spinal cord and cortico-/juxtacortical lesions were associated with worse outcomes. The 2017 McDonald dissemination in space (DIS) criteria and 2023 Lebrun RIS definition, which correspond to either the 2005 McDonald DIS criteria or one brain inflammatory-demyelinating lesion associated with two among oligoclonal bands, a spinal cord lesion and dissemination in time during radiological follow-up, showed high sensitivity (0.82 and 0.94, respectively). However, the sensitivity decreased (0.79) when only the baseline characteristics of the 2023 Lebrun RIS definition were considered. Combining the 2017 McDonald DIS criteria with positivity for oligoclonal bands or contrast-enhancing lesions on baseline MRI, which are the current McDonald MS criteria, improved the specificity (to 0.64 and 0.90, respectively).

Conclusions: Our findings support the utility of the current DIS component of the 2017 McDonald MS criteria for RIS patients.

Keywords: Radiologically isolated syndrome; demyelinating lesions; multiple sclerosis; neuroimmunology.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: A.V. has received a Rio Hortega grant (CM22/00247) from the Institute of Health Carlos III (ISCIII). A.V.-J. has received support for contracts from Juan Rodes (JR16/00024) and Fondo de Investigación en Salud (PI17/02162 and PI22/01589) from the Instituto de Salud Carlos III, Spain, and has engaged in consulting and/or participating as speaker in events organized by Roche, Novartis and Merck. A.P. has received funding travel from Roche and speaking honoraria from Novartis. He performed an ECTRIMS Clinical Training Fellowship programme in 2021 and is currently performing an MSIF-ARSEP Fellowship programme. N.M.-O. has a predoctoral grant, Rio Hortega, from the Instituto de Salud Carlos III (CM21/00018). She has also received speaking honoraria and travel expenses from Merck and Roche. L.B. is supported by a 1-year stipend endowed by the NMSS/AAN John Dystel Prize for Multiple Sclerosis Research awarded to Prof. Xavier Montalban in 2022. B.R.-A. has received speaking honoraria from Merck and honoraria for consulting services from Novartis. A.Z. has a predoctoral grant, Rio Hortega, from the Instituto de Salud CarlosIII, Spain (CM22/00237), and has received travel expenses for scientific meetings from Biogen-Idec, Merck-Serono and Novartis, speaking honoraria from Eisai, and a study grant from Novartis. J.R. has received speaking honoraria and personal compensation for participating in advisory boards for Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Teva, Roche and Sanofi-Aventis. R.C. is currently being funded by the Vall d’Hebron Institut de Recerca. In 2023, he was awarded a Research Training Programme from the European Charcot Foundation. Between 2021 and 2022, he received ECTRIMS Clinical and Research Fellowship training. He has also engaged in consulting and/or participated as speaker in events organized by Roche, Novartis, BIIB-Colombia, Merck and Sanofi. H.A. has received a grant from the Instituto de Salud Carlos III, Spain (JR22/00072). A.C.-C. has received a grant from the Instituto de Salud Carlos III, Spain (JR19/00007). G.A. has received speaking honoraria and provided consulting services or participated on advisory boards from Sanofi, Roche and Horizon Therapeutics/Amgen and travel expenses for scientific meetings from Novartis, Roche, ECTRIMS and EAN. M.C. has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merck-Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme and Novartis. J.V.-Á. has received a grant from the Instituto de Salud Carlos III, Spain (FI21/00282). C.T. is currently being funded by a Junior Leader La Caixa Fellowship (fellowship code: LCF/BQ/PI20/11760008) awarded by the ‘la Caixa’ Foundation (ID 100010434). She also received the 2021 Merck’s Award for Investigation of MS, awarded by Fundación Merck Salud (Spain), and a grant awarded by the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación de España (PI21/01860). In 2015, she received an ECTRIMS Postdoctoral Research Fellowship and has received funding from the UK MS Society. She is a member of the Editorial Board of Neurology and Multiple Sclerosis Journal. She has also received honoraria from Roche and Novartis and is a steering committee member of the O’HAND trial and of the Consensus Group on Follow-on DMTs. J.S.-G. serves as Editor-in-Chief of the Multiple Sclerosis Journal and as Editor-in-Chief for Revista de Neurología; receives research support from Fondo de Investigaciones Sanitarias (19/950); and has served as a consultant/speaker for Biogen, Celgene/Bristol Meyers Squibb, Sanofi, Novartis and Merck. M.T. has received compensation for consulting services, speaking honoraria and research support from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Janssen, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio and Teva Pharmaceuticals, as well as serves on the Data Safety Monitoring Board for Parexel and UCB Biopharma. A.R. serves/has served on scientific advisory boards for Novartis, Sanofi-Genzyme, Synthetic MR, TensorMedical, Roche and Biogen; has received speaker honoraria from Bayer, Sanofi-Genzyme, Merck-Serono, Teva Pharmaceutical Industries Ltd., Novartis, Roche, Bristol-Myers and Biogen; is CMO and cofounder of TensorMedical; and receives research support from Fondo de Investigación en Salud (PI19/00950) from the Instituto de Salud Carlos III, Spain. X.M. has received speaking honoraria and travel expenses for participation in scientific meetings; has been a steering committee member of clinical trials; and has participated on advisory boards of clinical trials in recent years with AbbVie, Actelion, Alexion, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF and NMSS. The other authors report no disclosures.

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