The Changing Landscape of Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a rare but devastating neurologic disease that affects the immunosuppressed population. The etiologic agent is a polyomavirus, JC virus—a double-stranded DNA virus with a high prevalence of infection globally. PML is believed to occur from reactivation of the latent virus infection caused by immunosuppression. After 1980, a dramatic increase in the incidence and prevalence of PML was attributed to the HIV/AIDS pandemic, with a decline noted after the introduction of highly active antiretroviral treatment (HAART). Newer populations are being added to the risk pool for the development of PML with the introduction of biologic agents that target specific arms of the immune system. Natalizumab and efalizumab seem to have the highest risk for the development of PML, although PML can develop with the other biologic agents. As more patients are treated with these agents, effective risk mitigation strategies are needed to prevent PML.