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N Engl J Med. 2005 Jul 28;353(4):369-74. Epub 2005 Jun 9.

Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis.

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  • 1Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA.


A 46-year-old woman with relapsing-remitting multiple sclerosis died from progressive multifocal leukoencephalopathy (PML) after having received 37 doses of natalizumab (300 mg every four weeks) as part of a clinical trial of natalizumab and interferon beta-1a. PML was diagnosed on the basis of the finding of JC viral DNA in cerebrospinal fluid on polymerase-chain-reaction assay and was confirmed at autopsy. Nearly every tissue section from bilateral cerebral hemispheres contained either macroscopic or microscopic PML lesions. There was extensive tissue destruction and cavitation in the left frontoparietal area, large numbers of bizarre astrocytes, and inclusion-bearing oligodendrocytes, which were positive for JC virus DNA on in situ hybridization.

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