New insights into progressive multifocal leukoencephalopathy

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Abstract
Progressive multifocal leukoencephalopathy is a deadly demyelinating disease of the central nervous system, which occurs in immunosuppressed individuals. It is caused by a reactivation of the polyomavirus JC, which induces a lytic infection of oligodendrocytes. This review covers recent developments in the clinical and pathological presentations of progressive multifocal leukoencephalopathy, and advances in the understanding of JC virus biology. The availability of highly active antiretroviral therapy has changed the clinical spectrum of progressive multifocal leukoencephalopathy in HIV-infected individuals; although the incidence has not diminished, mortality has decreased from 90% to approximately 50% during the first 3 months as a result of recovery of the immune system. More progressive multifocal leukoencephalopathy patients are now negative for JC virus in the cerebrospinal fluid by polymerase chain reaction, which calls for a new consensus terminology. Inflammatory forms of the disease are also becoming more frequent, and are associated with a strong cellular immune response mediated by JC virus-specific CD8 cytotoxic T lymphocytes, which are instrumental in preventing disease progression. Advances in the understanding of JC virus biology have shed new light on the pathogenesis of progressive multifocal leukoencephalopathy, and on its possible role in cerebellar atrophy in HIV-infected individuals. Findings on the cellular immune response against the virus have direct implications for patient management, and may lead to new forms of immunotherapies for progressive multifocal leukoencephalopathy. An animal model of progressive multifocal leukoencephalopathy in non-human primates will facilitate the development of novel therapeutic strategies.