Extent of mossy fiber sprouting in patients with mesiotemporal lobe epilepsy correlates with neuronal cell loss and granule cell dispersion

•Wyler I and II specimen reveal a natural projection of mossy fibers exclusively in CA3 and CA4.•Mossy fiber sprouting into the molecular layer and the decrease of mossy fibers in CA4 and CA3, seen in Wyler III and IV, might be due to target cell death in the CA4 and CA3 region.•Granule cell dispersion correlated with mossy fiber sprouting and neuronal cell death.•The extent of mossy fiber sprouting is correlated to preoperative epilepsy duration.•No correlation with postoperative seizure outcome.

ObjectiveThe most frequent finding in temporal lobe epilepsy is hippocampal sclerosis, characterized by selective cell loss of hippocampal subregions CA1 and CA4 as well as mossy fiber sprouting (MFS) towards the supragranular region and granule cell dispersion. Although selective cell loss is well described, its impact on mossy fiber sprouting and granule cell dispersion remains unclear.Materials and methodsIn a single center series, we examined 319 human hippocampal specimens, collected in a 15-years period. Hippocampal specimens were stained for neuronal loss, granule cell dispersion (Wyler scale I-IV, Neu-N, HE) and mossy fiber sprouting (synaptoporin-immunohistochemistry). For seizure outcome Engel score I-IV was applied.ResultsIn Wyler I and II specimens, mossy fibers were found along their natural projection exclusively in CA4 and CA3. In Wyler III and IV, sprouting of mossy fibers into the molecular layer and a decrease of mossy fibers in CA4 and CA3 was detected. Mean granule cell dispersion was extended from 121 μm to 185 μm and correlated with Wyler III-IV as well as mossy fiber sprouting into the molecular layer. Wyler grade, mossy fiber sprouting and granule cell dispersion correlated with longer epilepsy duration, late surgery and higher preoperative seizure frequency. Parameters analyzed above did not correlate with postoperative seizure outcome.DiscussionMossy fiber sprouting might be a compensatory phenomenon of cell death of the target neurons in CA4 and CA3 in Wyler III-IV. Axonal reorganization of granule cells is accompanied by their migration and is correlated with the severity of cell loss and epilepsy duration.