To present a case of progressive multifocal leukoencephalopathy (PML) diagnosed with brain biopsy in a patient with atypical, occult immunosuppression and negative JC virus PCR in cerebral spinal fluid.

PML is a demyelinating, lytic infection of oligodendrocytes caused by reactivation of the John Cunningham virus (JCV) in the setting of profound immunosuppression, most often attributable to malignancy and HIV. Here, we add to an emerging body of evidence demonstrating PML pathogenesis in patients with minimal or occult immunosuppression.

A 70-year-old woman with a history of cirrhosis secondary to chronic hepatitis C and thrombotic thrombocytopenic purpura treated with a single-dose of rituximab a year prior presented with a three-week history of right-sided weakness and coordination difficulties. Neurological exam exhibited right upper extremity weakness and apraxia. MRI showed a large left parietal white matter hyperintensity with focal enhancement and nearby punctate enhancement, radiographically consistent with PML. A lumbar puncture was performed which was nonspecific but without clear pleocytosis. CSF studies returned negative for a broad infectious workup, notably with negative JCV PCR and ultrasensitive quantitative JCV PCR tests. Her condition continued to deteriorate, and the decision was made to pursue brain biopsy, ultimately confirming the diagnosis of PML.