A Morphological Study of Synaptic Reorganization in Mossy Fibers of the Dentate Gyrus according to Hippocampal Sclerosis in Temporal Lobe Epilepsy: A Comparison of Intraoperative ECoG Findings for Tailored Resection

ABSTRACT

This study was carried out to identify synaptic reorganization by mossy fibers of epileptic dentate gyrus by Timm sulphide silver histochemistry and to investigate degree of synaptic reorganization according to both hippocampal sclerosis and epileptiform discharge in human temporal lobe epilepsy(TLE). The control group was composed of two hippocampal tissues obtained from autopsied brain without neurological abnormalities. TLE group was composed of thirteen hippocampal tissues obtained from surgically resected temporal lobe. Among thirteen hippocampal tissues, five specimens were obtained both of two areas of each hippocampus with or without prominent epileptiform discharges on electrocorticogram(ECoG) for tailored hippocampal resection. Hippocampal cell density was quantitatively analyzed in TLE group and compared with that of control group. A portion of hippocampal tissue was observed under light microscopic and transmission electron microscopes after development with Danscher method. The results were as follows Hippocampal cell loss was noted in all TLE group. Hippocampal cell loss greater than 30% of control values was found in 12 cases and average hippocampal cell loss was 70%(range 39-88%). The remaining 1 case had 13% hippocampal cell loss. The supragranular Timm granules were noted in inner molecular layer of dentate gyrus and tended to significantly increase in proportion as severity of hippocampal sclerosis. Average of hippocampal cell loss in two areas of five hippocampal tissues with or without prominent epileptiform discharge on ECoG was 73.6%(range 53-90%) and 66.4%(range 50-86%), which showed statistically significant (p<0.05) difference between these two areas and the supragranular Timm granules also tended to increase in the hippocampal tissue with epileptiform discharge. On transmission electron microscope, there showed distinct supragranular Timm granules correspond to mossy fiber synaptic terminals. The results of this study demonstrated that mossy fiber synaptic reorganization seems to play a major role in pathogenesis of human TLE and the development of mossy fiber synaptic reorganization is closely related to severity of hippocampal sclerosis. The result also support the rationale for tailoring the extent of hippocampal resection by intraoperative acute recording(ECoG) according to individual pathophysiology.