ABSTRACT
Progressive multifocal leukoencephalopathy (PML) with its characteristically unique histopathological triad of demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei has been increasingly recognized since its initial description in 1958. The etiology is a ubiquitous polyoma virus, the JC virus, that has been demonstrated by seroepidemiological studies to have infected the majority of the world’s adult population, yet PML remains vanishingly rare and other neurological disorders seen with JC virus including granular cell degeneration of the cerebellum, JCV encephalitis, and JCV meningitis, rare still. The infrequency of these JCV CNS disorders suggests that there are multiple high barriers to their development, chief among them, effective cell-mediated immunity. PML occurs with a wide variety of predisposing conditions, most commonly hematological malignancies, especially, B cell malignancies, and HIV infection. Following the introduction of natalizumab for multiple sclerosis and efalizumab for psoriasis, it was recognized the certain therapeutic agents can uniquely predispose to PML; although many immunosuppressive and immunomodulatory agents have been associated with the disease, with significantly lower frequencies. While a variety of drugs have been demonstrated to suppress JCV replication in vitro, they have been disappointing in the clinical setting and efforts to treat PML by boosting underlying immunity to the virus with cell-based therapies and PD-1 inhibitors are under investigation.
