Marburg type and Balò's concentric sclerosis are considered particular variants of multiple sclerosis, clinically characterized by a severe, rapidly evolving clinical course, and by unusual neuropathological changes, often large tumor-like demyelinating plaques in Marburg type and concentric layers of partial demyelination alternating with demyelinating bands in Balò's concentric sclerosis. These forms now can be diagnosed in vivo, with complete clinical and laboratory examination and MRI follow up. Although in some patients a favourable clinical course has been described, the poor prognosis of the majority of these cases justifies a treatment with intense immunosuppression.