[21] Due to the clinical suspicion of CJD, the autopsy was limited to the brain. The fresh brain weighed 1376 g and was cut after 2 weeks of fixation (CJD was excluded after preliminary examination of multiple brain samples). The cerebral hemispheres showed only mild ventricular

dilatation. The cerebellum displayed minimal atrophy of the superior vermis and large geographic areas of poorly demarcated, greyish discoloration of the white matter, more in the left hemisphere. Microscopic examination revealed extensive Ulixertinib loss of myelin involving the white matter of both cerebellar hemispheres, slightly more on the left side (Fig. 1). Demyelination was accompanied by a significant dropout of axons, numerous axonal retraction balls, accumulation of ferritin-positive microglia and CD68+ foamy macrophages, and a moderate Navitoclax supplier to severe degree of astrocytosis. These changes were most expressed in the centers of the lesions and gradually blended with relatively normal white matter with numerous small satellite foci of early myelin loss. The periphery of the demyelinated areas displayed

many oligodendroglial cells with enlarged nuclei filled by homogeneous, intensely purple intranuclear viral inclusions that were weakly immunoreactive for P53 and strongly positive for JCV antigens. Scattered vessels at the edge of the lesions were surrounded by mild CD8+ inflammatory infiltrations, with few CD3+ and CD4+ T-cells, and no CD20+ B-cells. The population of Purkinje cells and granule cells, as well as neurons in the dentate nucleus appeared normal. The cerebellar cortex contained scattered axonal torpedoes of Purkinje cells. The overall pathological changes were consistent with chronic PML lesions. The brainstem showed multiple small patches of demyelination with centrifugal

distribution of oligodendroglial intranuclear inclusions (Fig. 2A,B) and numerous foci of perivascular infiltrations by CD8+ T-cells, and less abundant PR 171 CD3+ and CD4+ T-cells (Fig. 3A,B). CD20+ B-cells were entirely absent. The perivascular myelin was not affected. Clusters of normal-appearing neurons outside of areas of demyelination were surrounded by CD8+ T-cells and microglia (Fig. 4A,B). In addition, the parenchyma of the pons was sprinkled with small collections or individual CD8+ cells without relation to the vessels or neurons. Very careful screening of sections of the brainstem revealed no direct contact of CD8+ T-cells with the oligodendroglial cells containing intranuclear inclusions. CD68+ macrophages and ferritin-positive microglia were massively increased in foci of demyelination and, to a lesser extent, diffusely throughout the entire brainstem. Scattered, well-formed microglial nodules were present as well.