17 - Progressive multifocal leukoencephalopathy

Abstract

Progressive multifocal leukoencephalopathy (PML) is a human, virus-induced, subacute, fatal, demyelinating, neurodegenerative disease. PML reached epidemic proportions when an increasing proportion of the population was becoming immunosuppressed with the onset of the acquired immune deficiency syndrome (AIDS), which is caused by human immunodeficiency virus type 1 (HIV-1). PML is a unique demyelinating disease with distinctive pathology consisting of multiple foci of demyelination of varying size, from pinpoint lesions to areas of several centimeters. The lesions may occur anywhere but are usually in the cerebral hemispheres, less often in the cerebellum and brainstem, and rarely in the spinal cord. The significantly higher incidence of PML in AIDS is due to molecular interactions between HIV-1 and the JC virus (JCV), via the HIV-1–encoded trans-regulatory Tat protein, which are responsible for the activation of the JCV enhancer-promoter in the non-coding control region (NCCR) part of the JCV genome. PML was initially described in the context of immunosuppression caused by chemotherapy. With the development of HIV-1–induced immunosuppression, the prevalence of PML increased and further insights into the interaction between cellular transcription factors and the replication of JCV within central nervous system (CNS) and non-CNS cells were identified. PML occurring before the onset of AIDS and PML occurring in AIDS patients is similar in the lack of optic nerve involvement, together with the presence of visual field defects at presentation. Weakness and speech disturbances, especially dysarthria, were common presentations of PML in both groups of patients.