Abstract
This review aims to synthesize contemporary evidence on progressive multifocal leukoencephalopathy (PML), a rare, demyelinating disease of the central nervous system caused by reactivation of the John Cunningham virus (JCV) in immunocompromised individuals. Since its initial description in 1958, PML has evolved from being predominantly associated with hematological malignancies to a multifaceted opportunistic infection seen in HIV/AIDS, autoimmune disorders, transplantation medicine, and in patients receiving monoclonal antibody therapies such as natalizumab. The global epidemiology of PML reflects both improved survival in immunocompromised populations and expanded iatrogenic risk due to modern immunomodulatory agents. This review synthesizes contemporary evidence on the epidemiology, pathogenesis, diagnostic strategies, and therapeutic approaches to PML, with an emphasis on comparing international patterns to emerging data from Korea. Although Korean reports remain limited, recent case studies reveal unique patterns of presentation, delayed diagnosis, and frequent misattribution to alternative neurological disorders, underscoring the need for heightened clinical vigilance. The review critically examines diagnostic limitations, including the imperfect sensitivity of cerebrospinal fluid JCV PCR, and highlights emerging biomarkers and neuroimaging signatures that may improve early detection. Therapeutic options remain largely supportive, with immune reconstitution representing the most effective strategy; however, novel antiviral and immunomodulatory approaches are under investigation. The review concludes with an agenda for future research, calling for international registry development, standardized diagnostic protocols, and cross-disciplinary collaborations to address the persistently high morbidity and mortality associated with PML. By integrating global and Korean perspectives, this paper aims to advance a more nuanced, regionally informed understanding of PML’s evolving clinical landscape.
Keywords
Progressive multifocal leukoencephalopathy, John Cunningham virus, Immunosuppression, Korea, Asian populations, Global epidemiology, Neuroimaging