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The neuroradiology of progressive multifocal leukoencephalopathy: a clinical trial perspective
Laura E Baldassari1, Mike P Wattjes2, Irene C M Cortese3
1Division of Neurology 2, Office of Neuroscience, Office of New Drugs, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993, USA.
Abstract:
Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the CNS caused by the JC virus, which infects white and grey matter cells and leads to irreversible demyelination and neuroaxonal damage. Brain MRI, in addition to the clinical presentation and demonstration of JC virus DNA either in the CSF or by histopathology, is an important tool in the detection of PML. In clinical practice, standard MRI pulse sequences are utilized for screening, diagnosis and monitoring of PML, but validated imaging-based outcome measures for use in prospective, interventional clinical trials for PML have yet to be established. We review the existing literature regarding the use of MRI and PET in PML and discuss the implications of PML histopathology for neuroradiology. MRI not only demonstrates the localization and extent of PML lesions, but also mirrors the tissue destruction, ongoing viral spread, and resulting inflammation. Finally, we explore the potential for imaging measures to serve as an outcome in PML clinical trials and provide recommendations for current and future imaging outcome measure development in this area.
Insights
Progressive multifocal leukoencephalopathy (PML) is a JC virus infection causing brain damage. Current MRI and PET imaging show promise for monitoring PML in clinical trials, but validated outcome measures are needed.
Area of Science:
- Neuroscience
- Infectious Diseases
- Radiology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a severe opportunistic CNS infection caused by the JC virus.
- PML leads to irreversible demyelination and neuroaxonal damage, impacting white and grey matter.
- Current diagnostic tools include clinical presentation, CSF analysis, histopathology, and brain MRI.
Purpose of the Study:
- To review the current literature on MRI and PET imaging in PML.
- To discuss the implications of PML histopathology for neuroradiology.
- To explore the potential of imaging measures as outcomes in PML clinical trials.
Main Methods:
- Literature review of existing studies on MRI and PET in PML.
- Analysis of PML histopathology and its relevance to neuroradiology.
- Exploration of imaging-based outcome measures for PML clinical trials.
Main Results:
- MRI effectively demonstrates PML lesion localization, extent, and pathological processes like tissue destruction and inflammation.
- PET imaging also shows potential in assessing PML activity and response to treatment.
- Validated imaging-based outcome measures for PML clinical trials are currently lacking.
Conclusions:
- MRI and PET are crucial for PML detection, diagnosis, and monitoring.
- Further development and validation of imaging outcome measures are essential for advancing PML clinical trials.
- Integrating histopathology insights can refine neuroradiological assessments of PML.
