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N Engl J Med. 2009 Sep 10;361(11):1081-7. doi: 10.1056/NEJMoa0810316.

Progressive multifocal leukoencephalopathy after natalizumab monotherapy.

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Neurology Unit, Division of Internal Medicine, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.


We describe progressive multifocal leukoencephalopathy (PML) caused by infection with human polyomavirus JC virus in a patient with multiple sclerosis who was treated with natalizumab. The first PML symptoms appeared after 14 monthly infusions of the drug. Magnetic resonance imaging (MRI) showed a presumed multiple sclerosis lesion, and JC virus DNA was not detected on polymerase-chain-reaction (PCR) assay of cerebrospinal fluid. The patient's symptoms worsened, and the diagnosis of PML was established with a more sensitive quantitative PCR assay after 16 infusions of natalizumab. Plasma exchange was used to accelerate clearance of natalizumab. Approximately 3 weeks after plasma exchange, an immune-reconstitution inflammatory syndrome appeared. JC virus DNA was no longer detectable on quantitative PCR assay, and the patient's symptoms improved.

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