The Central Vein Sign in Radiologically Isolated Syndrome

Abstract

Background and purpose: Radiologically isolated syndrome describes asymptomatic individuals with incidental radiologic abnormalities suggestive of multiple sclerosis. Recent studies have demonstrated that >40% of white matter lesions in MS (and often substantially more) have visible central veins on MR imaging. This "central vein sign" reflects perivenous inflammatory demyelination and can assist in differentiating MS from other white matter disorders. We therefore hypothesized that >40% of white matter lesions in cases of radiologically isolated syndrome would show the central vein sign.

Materials and methods: We recruited 20 participants diagnosed with radiologically isolated syndrome after evaluation by a neurologist. We performed 3T MR imaging of the brain and cervical spinal cord. White matter lesions were analyzed for the central vein sign.

Results: Of 391 total white matter lesions, 292 (75%) demonstrated the central vein sign (central vein sign+). The median proportion of central vein sign+ lesions per case was 87% (range, 29%-100%). When the "40% rule" that has been proposed to distinguish MS from other disorders was applied, of 20 participants, 18 cases of radiologically isolated syndrome (90%) had ≥40% central vein sign+ lesions (range, 55%-100%). Two participants (10%) had <40% central vein sign+ lesions (29% and 31%). When the simpler "rule of 6" was applied, 19 participants (95%) met these criteria. In multivariable models, the number of spinal cord and infratentorial lesions was associated with a higher proportion of central vein sign+ lesions (P = .002; P = .06, respectively).

Conclusions: Most cases of radiologically isolated syndrome had a high proportion of central vein sign+ lesions, suggesting that lesions in these individuals reflect perivenous inflammatory demyelination. Moreover, we found correlations between the proportion of central vein sign+ lesions and spinal cord lesions, a known risk factor for radiologically isolated syndrome progressing to MS. These findings raise the possibility, testable prospectively, that the central vein sign may have prognostic value in distinguishing patients with radiologically isolated syndrome at risk of developing clinical MS from those with white matter lesions of other etiologies.

Fig 1.

Proportion of white matter lesions demonstrating the central vein sign per case and the 40% rule. Eighteen patients with RIS (90%) met the 40% rule, whereas 2 did not.

Fig 2.

White matter lesions with evident central vein signs in 2 different radiologically isolated syndrome cases, as seen on axial reconstructed 3D-T2*-weighted segmented echo-planar imaging sequences and 3D-T2-weighted FLAIR sequences of the brain, and sagittal T1-weighted phase-sensitive inversion recovery of the cervical spinal cord. A 50-year-old woman in whom most (90%) of the white matter lesions demonstrate the central vein sign (A, arrows). This individual also has evident infratentorial (B, arrows) and cervical spinal cord lesions (C, arrow). A 53-year-old woman with a small proportion (29%) of white matter lesions demonstrating the central vein sign (D, arrow). This individual did not have any infratentorial (E) or cervical spinal cord lesions (F).

Fig 3.

White matter lesions demonstrating the central vein sign in different brain regions, using 3D-T2*-weighted echo-planar imaging. A, Infratentorial. B, Deep white matter. C, Periventricular. D, juxtacortical.