New features of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy and natalizumab

Over the past three decades, progressive multifocal leukoencephalopathy (PML) evolved from being a clinical rarity to become an important cause of neurological complications in acquired immunodeficiency syndrome (AIDS) patients. Recently this disease unexpectedly occurred in patients receiving the novel immunomodulatory medication natalizumab. These changes in the epidemiology of PML also brought new questions with regard to the pathogenesis of this disease. The authors review the current challenges in the diagnosis and management of patients with PML, based on the recent advances in the understanding of the JC virus biology and discuss potential methods to monitor disease evolution and predict outcome.