Brain biopsy and pathological diagnosis for drug-associated progressive multifocal leukoencephalopathy (PML) with...

Area of Science:

• Neurology
• Virology
• Immunology

Background:

• Progressive multifocal leukoencephalopathy (PML) is a serious central nervous system demyelinating disease caused by JC virus (JCV).
• PML is an emerging complication of immunosuppressive therapies, including disease-modifying drugs (DMDs) for multiple sclerosis (MS), and can also occur in other immunosuppressed states.
• Early PML manifestations are often unrecognized, complicating diagnosis compared to later-stage or AIDS-related cases.

Purpose of the Study:

• To review the pathology of PML, particularly early cytopathological changes observed in brain biopsies.
• To highlight the diagnostic challenges associated with early PML, including subtle MR imaging findings and low viral loads.
• To discuss the role of host immune responses, PML-IRIS, and potential associations with immune checkpoint inhibitors (ICIs).

Main Methods:

• Review of PML pathology based on brain biopsy findings.
• Analysis of cytopathological characteristics of JCV-infected cells.
• Examination of immune responses and associated conditions like PML-IRIS.

Main Results:

• Early cytopathological changes in JCV-infected cells include characteristic dot-shaped inclusions associated with promyelocytic leukemia nuclear bodies (PML-NBs).
• Diagnostic difficulties arise from subtle MR imaging and low CSF viral loads in early PML.
• Variability in host immune responses and the potential impact of ICIs are noted.

Conclusions:

• Understanding the histopathology of early PML is essential for refining diagnostic approaches.
• Optimizing diagnostic strategies and therapeutic interventions based on pathological insights can improve patient prognosis.
• Further research into the role of ICIs in PML pathogenesis is warranted.