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Recently, a number of PML cases have been associated with administration of natalizumab for treatment of multiple sclerosis (MS) patients. Diagnosis and management of PML became a major concern after its occurrence in multiple sclerosis patients treated with natalizumab. Diagnosis of PML usually rests on neuroimaging in the appropriate clinical context and is further confirmed by cerebrospinal fluid polymerase chain reaction (PCR) for JCV DNA. Treatment with antiretroviral therapies in HIV\u2010seropositive patients or discontinuing natalizumab in MS patients with PML may lead to the development of immune reconstitution inflammatory syndrome (IRIS) which presents with deterioration of the previous symptoms and may lead to death. In patients under treatment with monoclonal antibodies in routine practice, or new ones in ongoing clinical trials, differentiating PML from new MS lesions on brain MRI is critical for both the neurologists and neuroradiologists. In this review, we discuss the clinical features, neuroimaging manifestations of PML, IRIS and neuroimaging clues to differentiate new MS lesions from PML. In addition, various neuroimaging features of PML on the non\u2010conventional MR techniques such as diffusion\u2010weighted imaging (DWI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS) are discussed.<\/jats:p>","DOI":"10.1111\/j.1468-1331.2011.03597.x","type":"journal-article","created":{"date-parts":[[2011,12,5]],"date-time":"2011-12-05T06:53:13Z","timestamp":1323067993000},"page":"1060-1069","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Progressive multifocal leukoencephalopathy: a review of the neuroimaging features and differential diagnosis"],"prefix":"10.1111","volume":"19","author":[{"given":"M. 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