Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by reactivation of John Cunningham (JC) virus, which destroys oligodendrocytes. It is associated with human immunodeficiency virus (HIV) / AIDS, usually in patients with CD4 counts less than 200, and can also occur after initiation of highly active antiretroviral therapy. In addition, the disease is seen after treatment with immune-modulating therapies such as natalizumab.

Focal neurologic symptoms are typically subacute and evolve over weeks. Symptoms can include weakness, sensory loss, ataxia, vision changes, aphasia, cognitive decline, or behavioral changes. Seizures can also occur.

PML classically affects the subcortical white matter and U-fibers. Prognosis depends on severity of the underlying disease, although it is generally poor, and the disease is often fatal within months.