Progressive multifocal leukoencephalopathy - primary

Case Discussion

This is a rare case of primary progressive multifocal leukoencephalopathy (PML) confirmed at autopsy. This patient had no predisposing factors: HIV negative, no known immunosuppression or immunomodulation. 

This is a very severe case of progressive multifocal leukoencephalopathy in a patient with no underlying immunosuppressive illness. As such, this case has several atypical features including the absence of an underlying cause for immunosuppression, the presence of a cellular immune response (CD8-positive T lymphocytes and plasma cells) and microglial nodules and microglial activation in the cortex and thalamus in addition to the involved areas of the brainstem and cerebellum.

This case is therefore classified as a primary, versus classical, progressive multifocal leukoencephalopathy (PML).

Primary PML is rare with only five previously reported cases. The patients ranged in age from 63 to 86 and the disease had a protracted course of up to ten years in three out of the five cases. Therefore, immunocompetence is not an exclusion criterion for the diagnosis of PML. Inflammatory changes in PML are rare in typical PML but may develop after antiretroviral therapy in AIDS-associated PML.

The presence of inflammatory changes is usually associated with a favorable prognosis, but obviously not in this patient. The CD8-positive T cells predominate in both HIV-negative and HIV-positive patients and have been colocalized with JCV-infected oligodendrocytes previously. At present, the exact function of CD8-positive T cells in PML remains speculative.