The “central vein sign” to differentiate multiple sclerosis from migraine

Abstract Objective To investigate, in two cohorts including patients with multiple sclerosis (MS) and migraine, (i) the prevalence of the “central vein sign” (CVS), (ii) the spatial distribution of positive CVS (CVS+) lesions, (iii) the threshold of CVS+ lesions able to distinguish MS from migraine with high sensitivity and specificity. Methods A total of 70 patients with MS/clinically isolated syndrome and 50 age‐ and sex‐matched patients with migraine underwent a 3‐T magnetic resonance imaging scan. The CVS was evaluated according to current guidelines, excluding eight patients with migraine who did not show white matter (WM) lesions. A receiver operating characteristic curve analysis was performed to identify the best threshold in terms of proportion of CVS+ lesions and the absolute number of CVS+ lesions able to differentiate MS from migraine. Results Lesion volume was different between CVS+ and CVS negative lesions (median 1043 vs. 176.5 mm 3 for MS cohort; median 35.1 vs. 52.2 mm 3 for migraine cohort; p < 0.001 for all). A higher proportion of CVS+ lesions was associated with a higher probability of being diagnosed as MS (adjusted odds ratio 1.09, 95% confidence interval [CI] 1.04–1.14; p < 0.001). CVS+ lesion volume and number were higher in MS with respect to migraine, both considering the whole brain and its subregions ( p < 0.001). The proportion of CVS+ lesions in juxtacortical and infratentorial areas was higher in MS than in migraine ( p = 0.015 and p = 0.034, respectively). The best CVS proportion‐based threshold able to differentiate MS from migraine was 35.0% (sensitivity 97.1%, specificity 85.7%) with an area under the curve of 0.95 (95% CI 0.90–1.00). The “select 6” rule seemed to be preferable in terms of specificity with respect to the “select 3” rule. Conclusions A CVS proportion‐based threshold of 35.0% is capable of distinguishing MS from migraine with high sensitivity and specificity. The “select 6” algorithm may be useful in the clinical setting.