Progressive Multifocal Leukoencephalopathy

Before embarking on experimental therapies for progressive multifocal leukoencephalopathy (PML), the diagnosis needs to be unequivocally established. Improving the underlying immunodeficiency state is the best initial approach to the management of PML. Immunosuppressive therapies should be discontinued when feasible. In the patient with AIDS, highly active antiretroviral therapy should be administered; this appears to prolong survival. At present, no therapy has been demonstrated to be effective in a well-designed prospective trial. Cytosine arabinoside, which has demonstrated efficacy in vitro against JC virus, has not been effective when administered intravenously or intrathecally to patients with AIDS and PML. The failure of regimens employing cytosine arabinoside in PML may have been the consequence of inadequate penetration of the drug to sites of infection in the brain. Other drugs with established in vitro activity against JC virus, such as topoisomerase and camptothecin, are poorly tolerated. The use of cidofovir in patients with AIDS and PML remains anecdotal, although it is currently under investigation. Interferon alfa may improve survival in patients with AIDS and PML and may have general applicability to PML regardless of the cause of the underlying immunodeficient state. Approximately 7% to 9% of patients with PML demonstrate prolonged survival (>12 months) and associated improvement in clinical and radiographic abnormalities in the absence of specific therapy. In patients with AIDS-related PML, prolonged survival correlates with PML as the presenting manifestation of AIDS, higher CD4 T-lymphocyte counts, and contrast enhancement of PML lesions on radiographic imaging. A brisk inflammatory response may also be associated with improved survival. The increased understanding of the pathophysiology of JC virus provides hope for the development of curative strategies. The growing number of persons affected with PML has allowed the organization of carefully designed therapeutic trials to address this issue.