Progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a rare, severe demyelinating disease of the central nervous system caused by reactivation of the JC polyomavirus (John Cunningham virus, JCPyV). The virus is widespread in the general population, with seroprevalence estimates of 50–80%, but it typically remains latent and harmless. PML occurs almost exclusively in individuals with significant immunosuppression, including those with HIV/AIDS, hematologic malignancies, organ transplant recipients on immunosuppressive therapy, and patients receiving certain immunomodulatory medications such as natalizumab (used for multiple sclerosis) or rituximab. The virus preferentially infects and destroys oligodendrocytes, the cells responsible for producing myelin in the brain, leading to progressive, multifocal areas of white matter destruction. Clinical features of PML are highly variable depending on the location and extent of the white matter lesions. Common symptoms include progressive cognitive decline, visual disturbances (including hemianopia and cortical blindness), motor weakness (hemiparesis or quadriparesis), speech and language difficulties (aphasia, dysarthria), ataxia, and personality or behavioral changes. Seizures may also occur. The disease typically progresses over weeks to months and can be rapidly fatal. Diagnosis is supported by characteristic findings on brain MRI showing multifocal, asymmetric white matter lesions without mass effect, and confirmed by detection of JC virus DNA in cerebrospinal fluid via polymerase chain reaction (PCR) or by brain biopsy. There is currently no specific antiviral therapy proven effective against JC virus. The primary treatment strategy is restoration of immune function, which is the most important prognostic factor. In HIV-positive patients, initiation or optimization of antiretroviral therapy (ART) can improve survival, though immune reconstitution inflammatory syndrome (IRIS) is a recognized complication. In patients on immunosuppressive medications, withdrawal or reduction of the offending agent is essential. Despite these measures, PML carries a high mortality rate, and survivors frequently have significant residual neurological disability. Research into novel therapeutic approaches, including checkpoint inhibitors and adoptive T-cell therapy, is ongoing.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Progressive multifocal leukoencephalopathy