Consensus recommendations on pathologic changes in the hippocampus: a postmortem multicenter inter-rater study.

There is no consensus on the pathologic conditions or severity implied by the term "hippocampal sclerosis" (HS). In this study, a panel of experienced neuropathologists evaluated inter-rater agreement for pathologic diagnoses in the hippocampus and proposes consensus recommendations on the use of the term "HS." In a group of 251 cases of HS selected from a large autopsy cohort (1,388; 18%), a coordinating group identified 5 patterns of degenerative or vascular pathology. Four independent neuropathologists assessed a single set of hematoxylin and eosin-stained sections following descriptive definitions to classify the appearances and assign the diagnosis of HS, if appropriate. Diagnostic agreement (range, 36%-70%) was highest for vascular lesions. Subsequent joint review of all cases highlighted the need to identify neurodegenerative lesions using immunohistochemistry. Initial agreement in assigning the diagnosis of HS varied from 0% to 86%. After a joint review, the group recommended that the term "HS" should be applied to all cases with complete/near-complete neuronal loss and gliosis in the subfields of the cornu Ammonis but not to hippocampal microinfarction. Therefore, the etiology of HS must be defined in association with a neurodegenerative process or as "lacking neurodegenerative markers," a pathologic condition presumed to arise from hypoxic/ischemic mechanisms.