A 46-year-old woman with relapsing–remitting multiplesclerosis died from progressive multifocal leukoencephalopathy(PML) after having received 37 doses of natalizumab (300 mgevery four weeks) as part of a clinical trial of natalizumaband interferon beta-1a. PML was diagnosed on the basis of thefinding of JC viral DNA in cerebrospinal fluid on polymerase-chain-reactionassay and was confirmed at autopsy. Nearly every tissue sectionfrom bilateral cerebral hemispheres contained either macroscopicor microscopic PML lesions. There was extensive tissue destructionand cavitation in the left frontoparietal area, large numbersof bizarre astrocytes, and inclusion-bearing oligodendrocytes,which were positive for JC virus DNA on in situ hybridization.
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From the Departments of Pathology (B.K.K.-D.), Neurology (B.K.K.-D., K.L.T.), Neurosurgery (B.K.K.-D.), Medicine (K.L.T.), Microbiology (K.L.T.), and Immunology (K.L.T.), University of Colorado Health Sciences Center; and the Denver Veterans Affairs Medical Center (K.L.T.) — both in Denver. This article was published at www.nejm.org on June 9, 2005.
Address reprint requests to Dr. Kleinschmidt-DeMasters at the Department of Pathology, B-216, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, CO 80262.
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