The Changing Landscape of Progressive Multifocal Leukoencephalopathy

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare but devastating neurologic disease that affects the immunosuppressed population. The etiologic agent is a polyomavirus, JC virus-a double-stranded DNA virus with a high prevalence of infection globally. PML is believed to occur from reactivation of the latent virus infection caused by immunosuppression. After 1980, a dramatic increase in the incidence and prevalence of PML was attributed to the HIV/AIDS pandemic, with a decline noted after the introduction of highly active antiretroviral treatment (HAART). Newer populations are being added to the risk pool for the development of PML with the introduction of biologic agents that target specific arms of the immune system. Natalizumab and efalizumab seem to have the highest risk for the development of PML, although PML can develop with the other biologic agents. As more patients are treated with these agents, effective risk mitigation strategies are needed to prevent PML.

Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

“…However, cases of PML have recently been reported after immunotherapy with monoclonal antibodies, including approximately 260 cases in MS patients treated with natalizumab (Tysabri) as of July 30, 2012. The risk of PML increases with the number of natalizumab doses administered with highest incidence after 24 [2]–[4]. The 2.1/1000 overall risk of PML [2] is a major consideration in the decision to treat with natalizumab.…”

Progressive Multifocal Leukoencephalopathy in a Heart Transplant Recipient Following Rituximab Therapy for Antibody-Mediated Rejection

“…Infection proliferates in the setting of immunodeficiency, particularly T cell impairments, leading to the typical white matter degeneration of PML. Thus, the development of PML is a multistep process requiring infection, reactivation, neural invasion and viral proliferation in the setting of immunodeficiency .…”

“…The seroprevalence of JCV ranges from 10% in children to 60% in adults . Prior to the human immunodeficiency virus (HIV) epidemic PML was considered a rare disease seen in patients with hematological malignancies and associated with autoimmune disorders (Table ).…”

Progressive Multifocal Leukoencephalopathy with Immune Reconstitution Inflammatory Syndrome (PML-IRIS): Two Case Reports of Successful Treatment with Mefloquine and a Review of the Literature

“…This is most commonly associated with advanced human immunodefi ciency virus (HIV) infection, but is also described after biological therapies such as natalizumab, and rarely other conditions. 1 In the early years of HIV treatment, PML frequently resulted in death irrespective of medical interventions. The development of antiretroviral therapy (ART) has greatly improved this prognosis.…”