Progressive Multifocal Leukoencephalopathy Diagnosed by Brain Biopsy, not by the DNA Test for JC Virus

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a lytic infection of oligodendrocytes due to the presence of JC polyomavirus (JCV). The disease occurs mostly in immunocompromised patients and is associated with a high mortality rate. The diagnosis of PML is based on a polymerase chain reaction (PCR) assay for JC viral DNA in cerebrospinal fluid (CSF). However, case reports of the diagnosis of PML established with brain biopsy despite negative JCV CSF PCR analysis when clinical and neuroimaging features are suggestive of PML have been published. A 44-year-old male with a 6-year history of acquired immunodeficiency syndrome developed mental confusion and memory impairment despite 3 months of highly active antiretroviral therapy. Magnetic resonance imaging revealed multiple subcortical white matter lesions in bilateral hemispheres and subcortical nuclei including the thalamus and basal ganglia. JCV DNA was not detected in CSF study, but a brain biopsy showed a high JCV DNA titer. The diagnosis of PML was established with brain biopsy. An early brain biopsy may be important in the diagnosis of PML in patients with clinical manifestations and neuroimaging findings if JCV DNA is undetectable in the CSF PCR.