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

Mult Scler. 2020 Apr;26(4):433-441. doi: 10.1177/1352458519882282. Epub 2019 Oct 31.


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.

Keywords: Demyelinating autoimmune diseases; central nervous system; diagnosis; diagnostic imaging; magnetic resonance imaging; misdiagnosis; multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Cerebral Veins / diagnostic imaging*
  • Diagnostic Errors
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Magnetic Resonance Imaging / standards*
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnostic imaging*
  • Pilot Projects
  • Prognosis
  • Prospective Studies
  • Uncertainty
  • White Matter / diagnostic imaging*


  • Biomarkers