Table 2.

Definition of “diagnostic” lesions (see also Fig. 1)

Spongiform change	PrP+ amyloid deposits	Other PrP deposits
Small vacuoles (Fig. 1a): Small round to oval vacuoles located in the neuropil (most vacuoles are not larger than the nuclei of activated astrocytes and neuronal cells)	Of kuru type (Fig. 1d): Unicentric, rounded, amyloid plaques with a saw-like contour	“Synaptic” pattern (Fig. 1g): Diffuse or focal fine granular staining of the neuropil including focal areas with more dense staining and immunoreactive dot-like structures
Medium-sized vacuoles (Fig. 1b): Small to medium-sized round to oval vacuoles located in the neuropil (many vacuoles are larger than the nuclei of activated astrocytes and neuronal cells)	Of florid type (Fig. 1e, f): Large fibrillary amyloid plaques surrounded by a halo of spongiform change	Coarse or perivacuolar pattern (Fig. 1i, h): Diffuse or patchy staining of the neuropil characterized by coarse deposits (Fig. 1i) of irregular size and shape which are typically (but not always) associated with clusters of large confluent vacuoles (Fig. 1h). In the cerebellum (when present), these patchy/coarse deposits are not associated with spongiform change and are mostly found in the molecular layer (Fig. 1j)
Clusters of large, confluent vacuoles (Fig. 1c): Morula/grape-like clusters of coalescing large vacuoles		Plaque-like pattern (Fig. 1k, l): Focal, well-demarcated, rounded/oval extracellular deposits. In the cerebellum they are mainly located in the granular layer. Typically, some deposits are also found in the white matter. Their size varies but at least some of them exceed the size of the nucleus of cerebellar Purkinje cells. They are larger and more numerous in MV 2K (Fig. 1k) than in VV2 (Fig. 1i)
		Perineuronal pattern (Fig. 1m): Dot-like pattern of staining outlining the contour of the perikarya and/or the neurites of pyramidal neurons