Primary P rogressive M ultiple S clerosis E volving F rom R adiologically I solated S yndrome
Open accessAbstract
Objective: The aim of this work was to evaluate the preprogressive phase in subjects with radiologically isolated syndrome (RIS) who evolve to primary progressive multiple sclerosis (PPMS). Methods: A multicenter RIS cohort was previously established. Demographic, clinical, and radiological characteristics of subjects with RIS that evolved directly to PPMS were compared to those that developed a relapsing disease course from onset (clinically isolated syndrome [CIS] or relapsing‐remitting MS) and were also compared to two other population‐ and clinic‐based PPMS cohorts. Results: Of the 453 subjects with RIS, 128 evolved to symptomatic MS during the follow‐up (113 developed a first acute clinical event consistent with CIS/MS, 15 evolved to PPMS). PPMS prevalence (11.7%) and onset age (mean ± standard deviation; 49.1 ± 12.1) in the RIS group were comparable to other PPMS populations (p > 0.05). Median time to PPMS was 3.5 years (range, 1.6–5.4). RIS evolved to PPMS more commonly in men (p = 0.005) and at an older age (p < 0.001) when compared to CIS/MS, independent of follow‐up duration. Subjects who evolved to PPMS had more spinal cord lesions (100%) before symptomatic evolution than those that developed CIS/MS (64%) and those that remained asymptomatic (23%) within the follow‐up period (P = 0.005). Other MRI characteristics in the preprogressive phase of PPMS were indistinguishable from CIS/MS. Interpretation: Subjects with RIS evolve to PPMS at the same frequency as expected from general MS populations in an age‐dependent manner. Besides age, unequivocal presence of spinal cord lesions and being male predicted evolution to PPMS. Our findings further suggest that RIS is biologically part of the MS spectrum. Ann Neurol 2016;79:288–294
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Factors predicting increased risk of subsequent MS diagnosis in RIS are similar to those predicting MS diagnosis after a CIS: younger age, higher cerebral lesion load, asymptomatic infratentorial or spinal cord lesions, gadolinium-enhancing lesions, presence of CSF OCBs, and abnormal VEP.
“The factors predicting increased risk of subsequent MS diagnosis are similar to those predicting MS diagnosis after a CIS: younger age, higher cerebral lesion load, asymptomatic infratentorial or spinal cord lesions, gadolinium-enhancing lesions, presence of CSF OCBs, and abnormal VEP. 87,89”
From Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria (2018) · cites this paper as [89]
The supplied passages are a repository listing for the paper, not its study text; the file listing labels the manuscript as a post-print but gives no findings. Searches for RIS conversion risk factors, lesion load, oligoclonal bands, and abnormal visual evoked potentials returned only title and author information. Our available copy therefore does not establish whether the paper supports the claimed predictors or their similarity to predictors after CIS. (LLM, conf=0.74)
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Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria
Polman, C. H., Reingold, S. C., Banwell, B., Clanet, M., Cohen, J. A., Filippi, M., Fujihara, K., Havrdova, E., Hutchinson, M., Kappos, L., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22366 · Cited by 9,802 · see citing works
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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-citationHow neuroinflammation contributes to neurodegeneration
Ransohoff, R. M. (2016) · Science · doi:10.1126/science.aag2590 · Cited by 1,967 · see citing works
Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function
Ontaneda, D., Thompson, A. J., Fox, R. J., & Cohen, J. A. (2017) · The Lancet · doi:10.1016/s0140-6736(16)31320-4 · Cited by 298 · see citing works
Prognostic factors for multiple sclerosis symptoms in radiologically isolated syndrome
Fissolo, N., Schaedelin, S., Villar, L. M., Lünemann, J. D., Correale, J., Rejdak, K., Schwab, N., Vilaseca, A., Held, F., García-Merino, A., et al. (2025) · JAMA Neurology · doi:10.1001/jamaneurol.2025.1481 · Cited by 27 · see citing works
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- Authors
- Kantarci, O. H., Lebrun, C., Siva, A., Keegan, M. B., Azevedo, C. J., Inglese, M., Tintoré, M., Newton, B. D., Durand‐Dubief, F., Amato, M. P., De Stefano, N., Sormani, M. P., Pelletier, D., & Okuda, D. T.
- Affiliations
- Mayo Clinic (US)
- Hôpital Pasteur, Service de Neurologie Nice France
- Department of Neurology Cerrahpasa School of Medicine, University of Istanbul Istanbul Turkey
- University of Southern California (US)
- Icahn School of Medicine at Mount Sinai (US)
- Vall d'Hebron Hospital Universitari (ES)
- The University of Texas Southwestern Medical Center (US)
- Service de Neurologie, Hôpital Neurologique Bron France
- University of Florence (IT)
- Department of Neurology Neurosurgery and Behavioral Sciences, University of Siena Siena Italy
- University of Genoa (IT)
- Corresponding author
- Kantarci, Orhun H.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2015-12-29
- Volume
- 79
- Issue
- 2
- Pages
- 288-294
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2173194334
- Cited by
- 167
- References
- 1
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 15 · 2023: 16 · 2022: 11 · 2021: 18 · 2020: 16 · 2019: 14 · 2018: 29 · 2017: 16 · 2016: 11
- FWCI
- 14.83
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- primary progressive multiple sclerosis, radiologically isolated syndrome, disease progression, spinal cord lesions, clinically isolated syndrome, relapsing-remitting multiple sclerosis, MRI lesions, age of onset, sex differences
- MeSH terms
- Adolescent, Adult, Age Factors, Child, Demyelinating Diseases, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Sex Factors, Disease Progression, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Relapsing-Remitting, Young Adult
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