Complications neurologiques de l’infection par le virus JC : revue générale

Abstract

Although human polyomavirus JC (JCV) seroprevalence in the general population is high, its neurological complications are rare and progressive multifocal leukoencephalopathy (PML), a lethal central nervous system (CNS) demyelinating disease, is the most well-known. After an usually asymptomatic primary infection during late childhood, a latent JCV form persists in different sites, notably the kidneys and lymphocytes. Rearrangement of that archetype into the prototypical neurotropic strain can reactivate JCV, thereby enabling its CNS penetration and infection of glial cells. In a context of defective immune defenses (HIV infection, cancer or immunosuppressant therapies) this infection leads to oligodendrocyte death that contributes, via demyelinization, to PML but also, as more recently described, to other CNS complications, e.g., JCV granule cell neuronopathy, meningitis or encephalitis. Clinical manifestations depend on the localization of the lesions. The increasingly widespread use of new immunomodulatory monoclonal antibodies to treat multiple sclerosis and other inflammatory systemic diseases has increased PML frequency in those previously rarely affected entities. Diagnosis relies on magnetic resonance imaging, JCV detection in cerebrospinal fluid and, when necessary, brain histology. PML is often lethal. No specific, evidence-based treatment with clinically relevant efficacy is available. The therapeutic objective is to restore host immune responses to JCV, while avoiding immune-reconstitution inflammatory syndrome.