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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Fluid-attenuated inversion recovery (A) and T2-weighted (B) images show bilateral, asymmetrical subcortical white matter hyperintensities in the frontal and left parietal lobes, without mass effect. The gadolinium-enhanced sequence (not shown) demonstrated no abnormal enhancement.
Analysis of a left frontal brain biopsy specimen revealed multiple areas of demyelination on the Luxol fast blue stain (A) with many lipid-laden macrophages that were immunoreactive for major histocompatibility antigen (HLA-DR) (B). There was relative preservation of axons in these foci with the Bielschowsky silver stain (C). Viral inclusions within oligodendrocyte nuclei were detected with immunohistochemical analysis for papovavirus using an antibody to SV40 (D; inset shows high magnification of an infected oligodendrocyte), which confirmed the diagnosis of progressive multifocal leukoencephalopathy (all images ×200, except inset to D, ×1000).
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