Multiple biomarkers improve the prediction of multiple sclerosis in clinically isolated syndromes
Abstract
Objectives Since its introduction, MRI had a major impact on the early and more precise diagnosis of multiple sclerosis (MS), and the 2010 diagnostic criteria even allow a diagnosis to be made just after a single attack if stringent MRI criteria are met. Several other clinical and paraclinical markers have been reported to be associated with an increased risk of MS independently of MRI in patients with clinically isolated syndromes (CIS), but the incremental usefulness of adding them to the current criteria has not been evaluated. In this study, we determined whether multiple biomarkers improved the prediction of MS in patients with CIS in a real-world clinical practice. Materials and methods This was a retrospective study involving patients with CIS admitted to our department between 2000 and 2013. We evaluated baseline clinical, MRI, neurophysiological, and cerebrospinal fluid (CSF) data. Results During follow-up (median, 7.2 years), 127 of 243 participants (mean age, 31.6 years) developed MS. Cox proportional-hazards models adjusted for established MRI criteria, age at onset, number of T1 lesions, and presence of CSF oligoclonal bands significantly predicted the risk of developing MS at 2 and 5 years. The use of multiple biomarkers led to 29% net reclassification improvement at 2 years (P Conclusions The simultaneous addition of several biomarkers significantly improved the risk stratification for MS in patients with CIS beyond that of a model based only on established MRI…
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In a recent analysis, changing the requirement from one periventricular lesion to three improved specificity of DIS from 0.37 to 0.46 but decreased sensitivity from 0.88 to 0.83.
“In a recent analysis, changing the requirement from one periventricular lesion to three improved specificity of DIS from 0.37 to 0.46 but decreased sensitivity from 0.88 to 0.83. 72”
From Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria (2018) · cites this paper as [72]
The recent MAGNIMS analysis showed that adding optic nerve involvement detected by MRI or VEP as a fifth anatomic site led to a minor improvement in sensitivity from 0.88 to 0.91 but substantially reduced specificity from 0.52 from 0.41.
“The recent MAGNIMS analysis showed that adding optic nerve involvement detected by MRI or VEP as a fifth anatomic site led to a minor improvement in sensitivity from 0.88 to 0.91 but substantially reduced specificity from 0.52 from 0.41. 72”
From Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria (2018) · cites this paper as [72]
The analysis did not include OCT.
“The analysis did not include OCT.”
From Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria (2018) · cites this paper as [72]
The lesions detected by special MRI techniques for cortical lesions are primarily of the leukocortical type; subpial lesions are rarely detected.
“The lesions detected by these techniques are primarily of the leukocortical type; subpial lesions are rarely detected.”
From Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria (2018) · cites this paper as [72]
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Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria
Thompson, A. J., Banwell, B. L., Barkhof, F., Carroll, W. M., Coetzee, T., Comi, G., Correale, J., Fazekas, F., Filippi, M., Freedman, M. S., et al. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30470-2 · Cited by 8,167 · see citing works
Self-citationSaidha, S., Green, A. J., Leocani, L., Vidal-Jordana, A., Kenney, R. C., Bsteh, G., Outteryck, O., Thompson, A., Montalban, X., Coetzee, T., et al. (2025) · The Lancet Neurology · doi:10.1016/s1474-4422(25)00275-3 · Cited by 66 · see citing works
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- Authors
- Martinelli, V., Dalla Costa, G., Messina, M. J., Di Maggio, G., Sangalli, F., Moiola, L., Rodegher, M., Colombo, B., Furlan, R., Leocani, L., Falini, A., & Comi, G.
- Affiliations
- IRCCS Ospedale San Raffaele (IT)
- Department of Neurology; San Raffaele Hospital; Milan Italy
- IRCCS Policlinico San Donato (IT)
- Corresponding author
- Martinelli, V.
- Venue
- Acta Neurologica Scandinavica
- Publisher
- Wiley
- Published
- 2017-04-09
- Volume
- 136
- Issue
- 5
- Pages
- 454-461
- ISSN
- 0001-6314 (ISSN-L)
- OpenAlex
- W2605244028
- Cited by
- 27
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 2
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Acta Neurologica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- Ministero della Salute (RF 2011-02349698)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Family Practice › Clinical Reasoning and Diagnostic Skills
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Keywords
- multiple sclerosis, clinically isolated syndrome, biomarkers, risk prediction, MRI criteria, neurophysiological markers, net reclassification improvement, risk stratification, early diagnosis
- MeSH terms
- Adult, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Biomarkers, Proportional Hazards Models, Age of Onset
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