The Central Vein Sign identifies patients diagnosed with multiple sclerosis probably carrying different diseases and showing milder disease course

Frequency of Multiple sclerosis (MS) misdiagnosis seems around 10%.The central vein sign (CVS) is a brain MRI marker based on the analysis of perivenular lesions (PVL) frequency in T2* sequences. CVS can distinguish definite MS from MS mimics as migraine, small vessel disease, NMO spectrum disorder and other inflammatory or autoimmune disease of central nervous system. The threshold of CVS frequency typical of MS has been thus far established at ⩾50% (50% rule). Aims of this study are to evaluate: 1) if the 50% rule can identify MS diagnosed patients with red flags of better explanation (MS-Plus) that may actually carry a different underlying disease; 2) disease courses of MS-plus patients stratified according to CVS sign frequency. CVS frequency analysis shows that a subset of MS-plus patients (about 40%) does not meet the 50% rule and that the disease course of these patients seems milder than MS or MS-plus meeting the rule. These data suggest that the MS-plus patients with < 50%PVL probably carry MS-like syndromes sustained by different underlying disease(s) thus probably based on pathogenic mechanisms different from MS. Further studies are on course to better characterize this subpopulation of patients and to define markers capable to identify possible alternative diagnosis.