Multifocal varicella-zoster virus leukoencephalitis temporally remote from herpes zoster

Two patients with cancer, one with Hodkin's disease and the other with a granulosa cell tumor of the ovary, developed a progressive, eventually fatal infection of the central nervous system exhibiting multifocal symptoms and signs. Pathologically, gross abnormalities of the brain resembled those in progressive multifocal leukoencephalopathy (PML), with discrete and confluent plaque‐like lesions concentrated in the white matter, particularly along the gray‐white junction. Microscopically, pathological changes differed distinctly from those associated with PML; in addition to confluent foci of white matter injury characterized by early demyelination and subsequent necrosis, prominent Cowdry type A eosinophilic intranuclear inclusions were noted in oligodendrocytes, astrocytes, and neurons. By electron microscopy, intranuclear spherical particles consistent in size and appearance with herpesvirus nucleocapsids were found within the lesions. Immunoperoxidase studies detected varicella‐zoster virus (VZV) antigens in infected cells, implicating this virus as the responsible agent despite a lapse of many months between the cutaneous herpes zoster and onset of cerebral symptoms in both patients.