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Cellular changes in the cerebellar granular layer in AIDS-associated PML
K Kuchelmeister1, M Bergmann, F Gullotta
1Institut für Neuropathologie, Universität Münster, Germany.
Neuropathology and Applied Neurobiology
|October 1, 1993
Summary
Researchers observed unusual cells in the cerebellum of six patients with progressive multifocal leukoencephalopathy (PML) and AIDS. These cells, possibly altered granule cells infected with JC virus (JCV), surrounded PML lesions.
Area of Science:
- Neuropathology
- Neurovirology
- Immunodeficiency
Background:
- Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system.
- PML is caused by the JC virus (JCV) and primarily affects individuals with compromised immune systems, such as those with acquired immunodeficiency syndrome (AIDS).
- Cerebellar involvement in PML is less common, and the cellular pathology within the cerebellum can be complex.
Purpose of the Study:
- To investigate peculiar cellular changes observed in the cerebellar granular layer of patients with AIDS-associated PML.
- To characterize the nature of these unique cells and their relationship to PML lesions.
- To determine the potential role of JC virus (JCV) and human immunodeficiency virus (HIV) in the observed cellular alterations.
Main Methods:
- Histopathological examination of cerebellar tissue from six cases of AIDS-associated PML.
- Immunocytochemistry to assess the cellular lineage (astrocytic, leukocytic, macrophage/microglial) of the observed cells.
- Detection of HIV antigen p 24 within the cells.
- Polymerase chain reaction (PCR) for JC virus (JCV) DNA detection.
- Ultrastructural analysis for papovavirus particles.
Main Results:
- Six cases of AIDS-PML showed distinct cellular changes exclusively in the cerebellar granular layer.
- These cells had hypochromatic nuclei, approximately twice the size of normal granule cells, and lacked discernible cytoplasm.
- The abnormal cells were consistently found surrounding PML foci.
- Immunocytochemistry largely excluded astrocytic, leukocytic, or macrophage/microglial origins.
- HIV p 24 antigen was not detected in these cells.
- JC virus (JCV) DNA detection was equivocal, and no viral particles were observed ultrastructurally.
Conclusions:
- The peculiar cells in the cerebellar granular layer of AIDS-PML cases are likely altered cerebellar granule cells.
- These cells may represent an abortive or latent infection with JC virus (JCV).
- The findings contribute to understanding the neuropathology of PML in the context of HIV infection and highlight potential cellular tropism of JCV within the cerebellum.