JC Virus

Epidemiology and Risk Factors. The JC virus is ubiquitous; antibodies to the virus are present in up to 85 percent of individuals by the age of 9 years. 'ikJ The JC virus is the etiological agent of progressive multifocal leukoencephalopathy (PML).

Pathogenesis and Pathophysiology. The kidneys are thought to be the site of latent JC viral persistence. Reactivation of the virus associated with immunosuppression results in hematogenous dissemination of the virus to the brain. Foci of PML are frequently located in proximity to blood vessels. '154' Progressive multifocal leukoencephalopathy occurs in patients with impaired cell-mediated immunity such as those with AIDS, chronic lymphocytic leukemia, Hodgkin's disease, other lymphomas, systemic lupus erythematosus, organ transplantation, and sarcoidosis. '153J , '154' The virus preferentially infects the myelin-producing oligodendrocytes, resulting in cell lysis and demyelination. 'ia^J

Clinical Features and Associated Findings. Focal neurological deficits (hemiparesis, dysarthria, and cerebellar limb and gait ataxia), seizure activity, and cognitive impairment characterized by memory impairment, psychomotor retardation, and inattentiveness characterize the clinical presentation of PML. '154'

Differential Diagnosis. On CT scan, PML appears as single or multiple nonenhancing, hypodense lesions in the white matter, most commonly in the parietal-occipital regions. On T2-weighted MRI scans, the lesions have increased signal intensity and do not enhance after contrast administration. Examination of the cerebrospinal fluid is usually normal.'™! The polymerase chain reaction technique can detect JC virus DNA in CSF with a reported sensitivity of 75 percent and a specificity of 96 percent.'™! Serum and CSF antibody titers for JC virus are not useful in establishing the diagnosis of PML because 80 percent of the population show antibodies to JC virus by adulthood.'™! Brain biopsy should be used for diagnosis in patients who have suspicious white matter lesions on MRI and in whom JC virus is not detected by PCR on CSF.W

Management. There is no proven therapy for PML, but clinical trials are ongoing. There is a correlation between the CD4 T-cell count and survival, in that patients with higher CD4 T-cell counts survive longer. Notable improvement in PML has been observed in AIDS patients treated with high-dose 3-azido-3-deoxythymidine (AZT), and it is hypothesized that the AZT-induced elevation of CD4 T-cell counts improves cell-mediated immunity sufficiently

to resist the JC virus infection. '154' The average length of survival from the onset of symptoms to death is 1 to 4 months, but a small percentage of patients reportedly have improved spontaneously and survived for several years. '154'

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