The detection of atypical and sometimes aggressive or tumefactive demyelinating lesions of the central nervous system often poses difficulties in the differential diagnosis. The clinical presentation is generally aspecific, related to the location and similar to a number of different lesions, including neoplasms and other intracranial lesions with mass effect. CSF analysis may also be inconclusive, especially for lesions presenting as a single mass at onset. As a consequence, a brain biopsy is frequently performed for characterization. Advanced MRI imaging plays an important role in directing the diagnosis, reducing the rate of unnecessary biopsies and allowing a prompt start of therapy that is often crucial, especially in the case of infratentorial lesions. In this review, the main pattern of presentation of atypical inflammatory demyelinating diseases is discussed, with particular attention on the differential diagnosis and how to adequately define the correct etiology.
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