Last update:
07-Jul-2019

Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease of the central nervous system caused in immunocompromised hosts by the ubiquitous polyomavirus John Cunningham (JCV). Originally considered an extremely rare disease, occurring only in patients with lymphoproliferative diseases, when first described in 1958, it has emerged as a relatively common complication in HIV infected patients, especially before the introduction of combined antiretroviral therapy (cART). In recent years, PML has also been associated with the use of immunosuppressive and immunomodulatory therapy, most notably natalizumab in multiple sclerosis (MS). The clinical manifestations of PML vary widely, since virtually any area of the brain may be involved, but the most common findings include behavioral and cognitive abnormalities, motor weakness, visual field deficits, dysarthria, dysphasia, gait abnormalities and incoordination. The diagnosis is challenging and requires either a combination of typical clinical, radiographic and laboratory features or histopathological confirmation obtained by brain biopsy. Despite recent advances in understanding the pathophysiology of the disease, there is still no effective treatment, the mortality rate is high and those who survive can be left with severe neurological disability. This review covers the various aspects of the disease, ranging from pathophysiology to diagnosis and prevention and potential future therapy.

Key words: JC virus (JCV), Immune Reconstitution Inflammatory Syndrome (IRIS), Natalizumab, Progressive multifocal leukoencephalopathy (PML).