The spectrum of progressive multifocal leukoencephalopathy: a practical approach

Area of Science:

• Neurovirology
• Immunology
• Neurology

Background:

• John Cunningham virus (JCV) infection of the central nervous system causes progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals.
• The landscape of PML risk is evolving due to increased use of modern immunotherapies and biologics for immune-mediated disorders.
• Atypical presentations of cerebral JCV disease, such as granule cell neuronopathy, are increasingly recognized.

Purpose of the Study:

• To review the changing spectrum of PML risk associated with modern immunotherapies.
• To highlight advancements in diagnostic tools, including JCV antibody indices and imaging markers.
• To discuss emerging treatment strategies and the importance of considering PML in at-risk patients.

Main Methods:

• Review of current literature on JCV, PML, and associated diagnostic and therapeutic advancements.
• Analysis of imaging findings in atypical PML presentations.
• Evaluation of novel risk stratification tools like JCV antibody indices.

Main Results:

• New tools like JCV antibody indices are introduced for risk assessment in drug-associated PML.
• Imaging markers assist in differentiating PML from multiple sclerosis lesions and identifying pre-clinical PML.
• Experimental treatments, including immunotherapy and IL-modulation, are under development.

Conclusions:

• PML diagnosis relies on brain biopsy or clinical, radiographic, and virological criteria.
• Early identification and risk stratification are crucial, especially with evolving therapeutic landscapes.
• PML must be considered in immunocompromised patients with progressive neurological symptoms.