Cellular pathology of hilar neurons in Ammon's horn sclerosis

In addition to functionally affected neuronal signaling pathways, altered a xonal, dendritic, and synaptic morphology may contribute to hippocampal hyp erexcitability in chronic mesial temporal lobe epilepsies (MTLE). The scler otic hippocampus in Ammon's horn sclerosis (AHS)-associated MTLE, which sho ws segmental neuronal cell loss, axonal reorganization, and astrogliosis, w ould appear particularly susceptible to such changes. To characterize the c ellular hippocampal pathology in MTLE, we have analyzed hilar neurons in su rgical hippocampus specimens from patients with MTLE. Anatomically well pre served hippocampal specimens from patients with AHS (n = 44) and from patie nts with focal temporal lesions (non-AHS; n = 20) were studied using confoc al laser scanning microscopy (CFLSM) and electron microscopy (EM). Hippocam pal samples from three tumor patients without chronic epilepsies and autops y samples were used as controls. Using intracellular Lucifer Yellow injecti on and CFLSM, spiny pyramidal, multipolar, and mossy cells as well as non-s piny multipolar neurons have been identified as major hilar cell types in c ontrols and lesion-associated MTLE specimens. In contrast, none of the hila r neurons from AHS specimens displayed a morphology reminiscent of mossy ce lls. In AHS, a major portion of the pyramidal and multipolar neurons showed extensive dendritic ramification and periodic nodular swellings of dendrit ic shafts. EM analysis confirmed the altered cellular morphology, with an a ccumulation of cytoskeletal filaments and increased numbers of mitochondria as the most prominent findings. To characterize cytoskeletal alterations i n hilar neurons further, immunohistochemical reactions for neurofilament pr oteins (NFP), microtubule-associated proteins, and tau were performed. This analysis specifically identified large and atypical hilar neurons with an accumulation of low weight NFP. Our data demonstrate striking structural al terations in hilar neurons of patients with AHS compared with controls and non-sclerotic MTLE specimens. Such changes may develop during cellular reor ganization in the epileptogenic hippocampus and are likely to contribute to the pathogenesis or maintenance of temporal lobe epilepsy. (C) 1999 Wiley- Liss, Inc.