Related Experiment Video
Updated: May 22, 2025
Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains
Published on: June 3, 2020
Histomorphological variations in progressive multifocal leukoencephalopathy correlated with JCV replication in brain
Kenta Takahashi1, Yuko Sato1, Hideki Hasegawa1,2
1Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security, Shinjuku, Tokyo, Japan.
Abstract:
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by JC polyomavirus (JCV). The histopathology of PML is morphologically diverse and characterized by the classical triad of demyelination, enlarged oligodendroglial nuclei, and bizarre astrocytes. Pathological diagnostic criteria for PML require both the classical triad and viral detection in brain tissue. However, the frequency of this triad in surgical pathology specimens and its correlation with disease progression and viral loads remain unclear. In this study, 117 brain tissues from 91 pathologically confirmed PML patients were investigated. PML histopathology was found to be spatially and temporally pleomorphic, and not all brain tissues exhibited the complete classical triad. The sensitivity of quantitative PCR for detecting JCV in brain tissues was 100%, whereas that of immunohistochemistry (IHC) was 83.5-87.8%. Viral loads in biopsy samples were significantly higher than those in autopsy samples and decreased over time after disease onset. To systematically characterize PML lesions from the outer border to the demyelinated center, we developed a histological classification based on the classical triad and macrophage infiltration. This classification correlated with viral loads, with subtypes characterized by abundant enlarged oligodendroglial nuclei at the demyelination border exhibiting the highest levels of JCV DNA. Pathological variability was influenced by spatial and temporal factors rather than by underlying diseases, although PML associated with acquired immunodeficiency syndrome exhibited more severe demyelination. In conclusion, histomorphological variability in PML reflects viral replication activity, emphasizing the importance of comprehensive pathological evaluation. Combining histomorphology, tissue-based PCR for viral DNA detection, and IHC for viral antigens is crucial for assessing disease progression. Early brain biopsy from the demyelination border offers the best opportunity for a definitive diagnosis of PML and may guide therapy targeting active lesions.
Insights
Histopathological variability in progressive multifocal leukoencephalopathy (PML) reflects viral activity. Comprehensive evaluation combining histomorphology, PCR, and IHC is crucial for diagnosis and assessing disease progression.
Area of Science:
- Neuropathology
- Virology
- Infectious Diseases
Background:
- Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by JC polyomavirus (JCV).
- PML histopathology is classically defined by demyelination, enlarged oligodendroglial nuclei, and bizarre astrocytes.
- The frequency of this triad and its correlation with disease progression and viral load are unclear.
Purpose of the Study:
- To investigate the histopathological diversity of PML.
- To correlate histopathological findings with JC polyomavirus (JCV) loads and disease progression.
- To develop a histological classification system for PML lesions.
Main Methods:
- Analysis of 117 brain tissues from 91 pathologically confirmed PML patients.
- Quantitative PCR and immunohistochemistry (IHC) for JCV detection.
- Development of a histological classification based on the classical triad and macrophage infiltration.
Main Results:
- PML histopathology is pleomorphic, with not all cases showing the complete classical triad.
- Quantitative PCR achieved 100% sensitivity for JCV detection; IHC sensitivity ranged from 83.5-87.8%.
- Viral loads were higher in biopsies than autopsies and decreased over time; classification correlated with viral loads.
Conclusions:
- Histomorphological variability in PML reflects viral replication activity.
- Comprehensive pathological evaluation, including histomorphology, PCR, and IHC, is crucial for assessing disease progression.
- Early brain biopsy from the demyelination border aids definitive diagnosis and guides therapy.
More Related Videos
05:51Intracerebroventricular and Intravascular Injection of Viral Particles and Fluorescent Microbeads into the Neonatal Brain
Published on: July 24, 2016
10:04Quantification of Cerebral Vascular Architecture using Two-photon Microscopy in a Mouse Model of HIV-induced Neuroinflammation
Published on: January 12, 2016
