Progressive Multifocal Leukoencephalopathy in HIV-Uninfected Individuals

Abstract

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by the human neurotropic polyomavirus JC (JCV). The disease occurs virtually exclusively in immunocompromised individuals, and, prior to the introduction of antiretroviral therapy, was seen most commonly in the setting of HIV/AIDS. More recently, however, the incidence of PML in HIV-uninfected persons has increased with broader use of immunosuppressive and immunomodulatory medications utilized in a variety of systemic and neurologic autoimmune disorders. In this review, we discuss the epidemiology and clinical characteristics of PML in HIV-uninfected individuals, as well as diagnostic modalities and the limited treatment options. Moreover, we describe recent findings regarding the neuropathogenesis of PML, with specific focus on the unique association between PML and natalizumab, a monoclonal antibody that prevents trafficking of activated leukocytes into the CNS that is used for the treatment of multiple sclerosis.

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