Comparison of the Diagnostic Performance of the Central Vein Sign and CSF Oligoclonal Bands Supporting the Diagnosis of Multiple Sclerosis

Allen, Christopher Martin; Clarke, Margareta A.; Pai, Hari V.; Cauchi, Marija; Hawken, Jonathan; Htet, Zin M.; Allen-Philbey, Kimberley; Mohamed, Bader; Fitzsimmons, Deborah; Das Nair, Roshan; Morgan, Paul; Partlett, Christopher; Dineen, Rob A.; Schmierer, Klaus; Tallantyre, Emma Clare; Evangelou, Nikos

Abstract

Background and Objectives
The central vein sign (CVS) describes the presence of venules within multiple sclerosis (MS) brain lesions, visible on T2*-weighted MRI. In the upcoming revision of the MS diagnostic criteria, the simplified “rule of 6” (i.e., finding 6 lesions with a central venule) can support the diagnosis of MS as an alternative to lumbar puncture (LP). We evaluated whether a T2*-weighted MRI scan is more sensitive than oligoclonal bands (OCBs) for diagnosing MS at presentation with a typical clinically isolated syndrome (CIS). We also compared the tolerability of LP and the additional MRI.

Methods
Participants requiring an LP to meet the 2017 McDonald diagnostic criteria for MS were enrolled in this multicenter, prospective, diagnostic superiority study from 3 UK neuroscience centers. A six-minute T2*-weighted sequence was used to assess the CVS using 2 definitions: a 40% threshold of all eligible lesions and the rule of 6. These were compared with OCBs, using the clinical diagnosis at 18 months as the reference standard.

Results
Of 113 participants, 99 (mean age: 38, female: 73%) have completed all study activities: 80 were diagnosed with MS, 10 remained CIS, 8 had alternative diagnoses, and 1 remained without a diagnosis. No significant difference in diagnostic sensitivity was detected between 40% CVS threshold (90% [CI 81%–96%]) and OCB testing (84% [CI 74%–91%]) (p = 0.332). The rule of 6 had a sensitivity of 91% (CI 83%–96%). Side effects were reported by 75% following LP compared with 9% following MRI. All participants preferred their MRI scan over their LP.

Discussion
CVS and OCB testing is equally sensitive in supporting the diagnosis of MS in cases of typical CIS. CVS assessed using the 40% threshold, and the simpler rule of 6 produces equivalent diagnostic performance. Compared with OCB testing, CVS testing seems safer and better tolerated by patients. Further studies are needed to evaluate CVS specificity, particularly outside of typical CIS cases, as studied here.

Classification of Evidence
This study provides Class IV evidence that CSF OCBs and the CVS are equally sensitive in supporting a diagnosis of MS in patients presenting with CIS.

Citation

Allen, C. M., Clarke, M. A., Pai, H. V., Cauchi, M., Hawken, J., Htet, Z. M., Allen-Philbey, K., Mohamed, B., Fitzsimmons, D., Das Nair, R., Morgan, P., Partlett, C., Dineen, R. A., Schmierer, K., Tallantyre, E. C., & Evangelou, N. (2025). Comparison of the Diagnostic Performance of the Central Vein Sign and CSF Oligoclonal Bands Supporting the Diagnosis of Multiple Sclerosis. Neurology Open Access, 1(2), Article e000017. https://doi.org/10.1212/WN9.0000000000000017

• Journal Article Type: Article
• Acceptance Date: Mar 27, 2025
• Online Publication Date: May 16, 2025
• Publication Date: 2025-06
• Deposit Date: May 16, 2025
• Publicly Available Date: May 19, 2025
• Journal: Neurology Open Access
• Electronic ISSN: 2998-7601
• Publisher: American Academy of Neurology
• Peer Reviewed: Peer Reviewed
• Volume: 1
• Issue: 2
• Article Number: e000017
• DOI: https://doi.org/10.1212/WN9.0000000000000017
• Public URL: https://nottingham-repository.worktribe.com/output/49008696
• Publisher URL: https://www.neurology.org/doi/10.1212/WN9.0000000000000017
• Additional Information: Received: 2025-01-07; Accepted: 2025-03-27; Published: 2025-05-16