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Images in Neurology
November 2008

Leflunomide-Associated Progressive Multifocal Leukoencephalopathy

Arch Neurol. 2008;65(11):1538-1539. doi:10.1001/archneur.65.11.1538

A 68-year-old man had a subacute progressive decline in speech and right-sided weakness after his rheumatoid arthritis regimen was changed from azathioprine to leflunomide. His primary care physician diagnosed a stroke. Three months later, in our neurology clinic, the patient sought treatment for transcortical motor aphasia and mild right hemiparesis, and magnetic resonance imaging (MRI) was performed (Figure 1). Results showed bilateral subcortical, asymmetrical hyperintensities, without notable mass effect, in the frontal lobes, greater on the left than the right, and in the left parietal lobe. Gadolinium images (not shown) revealed no abnormal enhancement. Cerebrospinal fluid analysis revealed 3 white blood cells, no red blood cells, a glucose level within the reference range, an elevated protein level (48 mg/dL), and no organisms. Results of a polymerase chain reaction analysis for John Cunningham (JC) virus were negative. Analysis of a brain biopsy specimen confirmed the presence of progressive multifocal leukoencephalopathy (PML)1,2 (Figure 2). The patient's condition improved with discontinuation of leflunomide and treatment with cytosine arabinoside (2 mg/kg intravenously each day for 5 days).

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