Different mossy fiber sprouting patterns in ILAE hippocampal sclerosis types

Abstract

ObjectiveHippocampal sclerosis (HS) is the most prevalent pathology in temporal lobe epilepsy (TLE) characterized by segmental neuronal cell loss in the cornu ammonis (CA) 1–4. In addition, migration of granule cells and reorganization of their axons is observed, known as granule cell dispersion (GCD) and mossy fiber sprouting (MFS). The loss of mossy fibers` (MF) target cells in CA4 and CA3 was considered to be causative for MFS. The ILAE HS (International League Against Epilepsy) classification identifies three subtypes with different cell loss patterns in CA1-4. We studied the relation of ILAE HS subtypes to GCD and MFS to corroborate clinico-pathological subgroups in a large retrospective single-center series. Material and methodsHippocampal specimen of 319 patients were screened, 214 could be used for analysis. Immunohistochemical stainings for semi-quantitative analysis of neuronal cell loss (NeuN) and MFS (synaptoporin) were performed. Presurgical data were available from patient files and seizure outcome was classified according to Engel score after surgery. ResultsIn 39 patients (18%) no neuronal cell loss (ILAE no-HS), no GCD and no MFS was observed. In 154 patients (72%) severe neuronal cell loss was seen in CA1, CA4 and CA3 (ILAE HS 1, typical HS); in addition extensive GCD and MFS was observed. In 17 patients (8%) cell loss was seen predominantly in CA1 (ILAE HS 2); despite different cell loss pattern these hippocampi also showed GCD and MFS. In 4 patients (2%) cell loss was predominately detected in CA3 and CA4 (ILAE HS type 3), consecutively GCD and MFS were observed. Longer epilepsy duration and younger age at surgery was more often associated with ILAE HS 2 and febrile convulsions were completely absent in ILAE no-HS. Yet, seizure onset, age at initial precipitating injury and postsurgical seizure outcome did not show any significant association with ILAE HS subtypes. ConclusionGCD and MFS might develop independently from the neuronal cell loss of MF target cells.