In multiple sclerosis (MS), MRI is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as CNS inflammatory vasculopathies, is missing. In a multicenter study, we assessed the frequency of perivenular lesions in MS vs. systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS (PACNS).