Progressive multifocal leukoencephalopathy (PML) is a rare, usually fatal demyelinating disease of the brain caused by the JC virus (JCV). Although infection with JCV occurs in about 70%-90% of adults, symptomatic disease is uncommon and usually limited to severely immunosuppressed patients. Prior to the AIDS pandemic, PML was most often seen in older patients with hematological malignancies, patients receiving immunosuppressive agents for non-malignant diseases, and very rarely in patients with no identifiable immunodeficiency.
JCV, like the related BK virus (BKV), is a Polyomavirus of the Papovavirus family. Both JCV and BKV are small ( 45 nm), nonenveloped viruses with closed, circular, double-stranded DNA. Infection with both viruses is common, and occurs early in life. BKV infection usually occurs between the ages of 3-4 years, and JCV infection usually occurs between ages 10-14 years. During the viremia which follows infection with either JCV or BKV virus, renal seeding may occur and result in a chronic, asymptomatic renal infection. Most patients who reactivate JCV or BKV infections during pregnancy or even long periods of immunosuppression remain asymptomatic. Although the pathogenesis of PML is unclear, the three major hypotheses are: (1) a latent infection in the kidneys causes a viremia resulting in infection of the central nervous system (CNS); (2) a latent infection of the CNS occurs at the time of primary infection, but viral replication leading to PML occurs only after some immuno-suppressive event; or (3) a primary, progressive JCV infection in an immunosuppressed patient. In each case, infection of oligodendrocytes by JCV precedes demyelination. Presently, PML occurs in 4% of AIDS patients, and fuels the recent four-fold increase in PML cases.
Patients with PML often present with rapidly progressive focal findings of cognitive impairment, hemiparesis, and visual field defects. Symptoms may progress to include aphasia, ataxia, cranial nerve deficits, cortical blindness, quadriparesis, profound dementia, and coma. Findings are usually localized to the white matter, and death frequently occurs within 6 months of presentation. In patients with AIDS, longer survival may correlate with CD4+ cell counts > 90/mm3. PML may be suspected when computed tomography or magnetic resonance imaging demonstrates multiple areas of cerebral white matter demyelination. However, a specific diagnosis of PML requires demonstration of characteristic histopathology in biopsied brain tissue. Since anti-JCV antibodies are common in the general population, and JCV-DNA sequences can be detected by the polymerase chain reaction (PCR) in brain tissue of patients with and without PML, neither serologic methods nor PCR can establish a definitive diagnosis of PML.
Prophylaxis: None. The majority of patients with JCV infection, including immunosuppressed patients with renal or bone marrow transplants or pregnant patients, are asymptomatic. Therapy: No specific therapy is of proven efficacy; intravenous and intrathecal cytosine arabinoside have produced equivocal therapeutic results in PML. Interferon-, with or without concomitant cytosine arabinoside, has also not proven effective.