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Progressive multifocal leukoencephalopathy: Epidemiology, clinical manifestations, and diagnosis

Igor J Koralnik, MD
Section Editor
Francisco González-Scarano, MD
Deputy Editor
John F Dashe, MD, PhD


Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system that is caused by reactivation of the polyomavirus JC (JC virus) [1-3]. Asymptomatic primary infection with JC virus occurs in childhood and antibodies can be found in 86 percent of adults [4]. In most individuals, JC virus remains latent in kidneys and lymphoid organs, but, in the context of profound cellular immunosuppression, JC virus can reactivate, spread to the brain, and induce a lytic infection of oligodendrocytes, which are the CNS myelin-producing cells. (See "Virology, epidemiology, and pathogenesis of JC polyomavirus, BK polyomavirus, and other human polyomaviruses".)

The epidemiology, clinical features, and diagnosis of PML will be reviewed here. The treatment of PML is discussed separately. (See "Progressive multifocal leukoencephalopathy: Treatment and prognosis".)


Progressive multifocal leukoencephalopathy (PML) occurs almost exclusively in immunosuppressed individuals. There are only isolated case reports of PML in patients without apparent immunosuppression [5-9]. There are, however, reports of PML affecting patients who have conditions associated with minimal or occult immunosuppression, such as hepatic cirrhosis and renal failure [10].

PML was initially described in patients with lymphoproliferative and myeloproliferative diseases such as chronic lymphocytic leukemia, chronic myeloid leukemia, and Hodgkin lymphoma [11-16]. It was subsequently reported in rare patients with solid organ malignancies, granulomatous and inflammatory diseases, solid organ transplant recipients, and with the use of certain drugs. Rare cases of PML have been observed in CD8-positive T-cell leukopenic patients [17].

The prevalence of PML was estimated to be 0.07 percent among patients with hematologic malignancies [18] and 0.8 percent in a retrospective autopsy study of liver transplant recipients [19].

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Literature review current through: Nov 2017. | This topic last updated: Apr 28, 2017.
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