OBJECTIVES: Progressive Multifocal Leukoencephalopathy (PML) is a rare, often fatal demyelinating disease of the central nervous system triggered by the reactivation of the JC Polyomavirus (JCPyV). It predominantly affects individuals with compromised immune systems, making underlying diseases a significant risk factor. This study aims to identify and analyse the underlying diseases reported at the time of symptom onset in PML-diagnosed individuals, as documented in the literature.

METHODS: A systematic literature review was conducted in PubMed® in October 2023 and data was extracted and validated by two independent reviewers. The review included case reports and case series of individuals diagnosed with PML, provided that the age at the last visit or death was reported. We evaluated the underlying disease and outcomes for each group, with a focus on mortality rates.

RESULTS: From 323 individuals with PML, the most common underlying diseases were Human Immunodeficiency Virus (HIV) (20.4%), Multiple Sclerosis (MS) (16.7%), Haematological Malignancies (HM) (14.9%), Autoimmune and Inflammatory Diseases (AID) (11.4%) and Primary Immunodeficiencies (PID) (3.7%). Mortality rates were highest in untreated PML individuals: HIV (70.0 %), HM (83.3%), and AID (50.0%). Early PML diagnosis (≤3 months) varied by region, with the highest rates in South-East Asia for HIV (85.7%), Western Pacific for MS (80%) and HM (85.7%) and Europe for PID (80%). Mortality rates for PML diagnoses made >3 months were PID (100%), HIV (41.6%), HM (71.4%), and AID (12.5 %).

CONCLUSIONS: Highlighting the diverse range of underlying diseases associated with PML underscores the need for awareness and monitoring in various at-risk populations. Understanding this spectrum is crucial for improving diagnostic and therapeutic strategies.