Members of the reference group (PP, AG, HK) prepared a draft of the assessment instructions, including a detailed description of the typical histopathological features as well as the major exclusion criteria for each CJD type (Table 1), a diagnostic flow chart to be followed during the assessment (Fig. 1), photographs and definitions of the pathology to be evaluated (Fig. 2; Table 2), and a standardized data sheet (Table 3). The latter aimed to collect information on the dominant vacuole size, on the main pattern of PrP deposition, and on whether or not kuru-type or florid amyloid plaques were seen. In addition, five specific questions concerning the distribution and severity of histopathological lesions in specific neuroanatomical structures were included (Table 3). Finally, an alternative nomenclature, more suitable for a histopathological diagnosis performed in the absence of molecular data, was proposed for each of the sporadic disease variants or subtypes (Table 4).
Assessors were then invited to a joint meeting to discuss the document drafts and simultaneously assess some exemplary cases using a multi-headed microscope.
The documents were then refined based on the most significant suggestions that emerged during the meeting, and a final version of each document (Tables 1, 2, 3, 4; Figs. 1, 2) was prepared by the reference group to be circulated among the participants.