Single Test to ARrive at Multiple Sclerosis (STAR-MS) diagnosis: A prospective pilot study assessing the accuracy of the central vein sign in predicting multiple sclerosis in cases of diagnostic uncertainty
Open accessAbstract
Background: Misdiagnosis is common in multiple sclerosis (MS) as a proportion of patients present with atypical clinical/magnetic resonance imaging (MRI) findings. The central vein sign has the potential to be a non-invasive, MS-specific biomarker. Objective: To test the accuracy of the central vein sign in predicting a diagnosis of MS in patients with diagnostic uncertainty at disease presentation using T2*-weighted, 3 T MRI. Methods: In this prospective pilot study, we recruited individuals with symptoms unusual for MS but with brain MRI consistent with the disease, and those with a typical clinical presentation of MS whose MRI did not suggest MS. We calculated the proportion of lesions with central veins for each patient and compared the results to the eventual clinical diagnoses. The optimal central vein threshold for diagnosis was established. Results: Thirty-eight patients were scanned, 35 of whom have received a clinical diagnosis. Median percentage of lesions with central veins was 51% in MS and 28% in non-MS. A threshold of 40.7% lesions with central veins resulted in 100% sensitivity and 73.9% specificity. Conclusion: The central vein sign assessed with a clinically available T2* scan can successfully diagnose MS in cases of diagnostic uncertainty. The central vein sign should be considered as a diagnostic biomarker in MS.
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In a recent prospective pilot study evaluating an emerging MRI diagnostic biomarker for MS ('central vein sign') in patients with diagnostic uncertainty, three out of 23 (13%) patients who did not have MS had FND or functional sensory symptoms.
“Lastly, in a recent prospective pilot study evaluating an emerging MRI diagnostic biomarker for MS (“central vein sign”) in patients with diagnostic uncertainty, three out of 23 (13%) patients who did not have MS had FND or functional sensory symptoms [28].”
From Functional neurological disorder and multiple sclerosis: a systematic review of misdiagnosis and clinical overlap (2022) · cites this paper as [28]
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Walzl, D., Solomon, A. J., & Stone, J. (2022) · Journal of Neurology · doi:10.1007/s00415-021-10436-6 · Cited by 62 · see citing works
Toljan, K., Amin, M., & Ontaneda, D. (2025) · Clinical Radiology · doi:10.1016/j.crad.2025.106984 · Cited by 9 · see citing works
- Authors
- Clarke, M. A., Samaraweera, A. P., Falah, Y., Pitiot, A., Allen, C. M., Dineen, R. A., Tench, C. R., Morgan, P. S., & Evangelou, N.
- Affiliations
- Nottingham University Hospitals NHS Trust (GB)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Laboratory of Image & Data Analysis, Ilixa Ltd., Nottingham, UK
- University of Nottingham (GB)
- ORCID
- Venue
- Multiple Sclerosis Journal
- Publisher
- SAGE Publications
- Published
- 2019-10-31
- Volume
- 26
- Issue
- 4
- Pages
- 433-441
- ISSN
- 1352-4585 (ISSN-L)
- 1477-0970
- OpenAlex
- W2984030614
- Cited by
- 43
- References
- 0
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 6 · 2023: 1 · 2022: 6 · 2021: 8 · 2020: 9
- FWCI
- 4.23
- Type
- journal article
- Language
- en
- Open access
- Locations
- Multiple Sclerosis Journal (publishedVersion)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Funders
- Nottingham Hospitals Charity (PP-N EVANGELOU-NOV 2014)
- 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 › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- multiple sclerosis, central vein sign, diagnostic uncertainty, T2-weighted MRI, diagnostic biomarkers, misdiagnosis, brain lesions, diagnostic accuracy
- MeSH terms
- Adult, Aged, Cerebral Veins, Diagnostic Errors, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Pilot Projects, Prognosis, Prospective Studies, Biomarkers, Uncertainty, White Matter
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