Hippocampal Sclerosis in Temporal Lobe Epilepsy

Abstract Hippocampal sclerosis (HS) is the most consistently observed histopathological finding in human temporal lobe epilepsy (TLE). Despite its long history, HS remains intriguing and continues to stimulate many questions about the functional significance of the histopathological alterations. Cell loss and gliosis have been hallmarks of HS since its earliest descriptions, and a classification system for subtypes of HS, based on the regions of predominant cell loss, was recently developed. These subtypes of HS are being studied in relation to clinical conditions and treatment planning, but the different patterns of histological changes could also inform studies of the basic mechanisms of TLE. While cell loss has been the focus of pathological studies of HS for many years, it has become increasingly important to consider the remaining neurons, as these are likely to be the sites of seizure initiation and propagation and thus the targets of treatment. Importantly, the major regions with remaining neurons (dentate gyrus, CA2, and the subiculum) all have unique morphological and functional changes that could influence epileptiform activity. Thus, the broad group of neuropathological changes in HS lead to numerous questions regarding their significance and functional effects, progressing from questions about the effects of different patterns of cell loss, to the influence of alterations in remaining neurons, and finally to consideration of the circuitry that could be established within the altered hippocampal formation. In this review, emphasis will be placed on studies of human HS, with inclusion of some related findings in animal models of epilepsy.