gms | German Medical Science

Objective: Hippocampal sclerosis (HS) in Temporal Lobe Epilepsy is characterized by selective neuronal death, predominantly in the cornu ammonis (CA) 1-4. Granule cells (GC) survive but show two distinct pathologies; firstly, adult GCs migrate leading to granule cell dispersion (GCD) and secondly, GC axons, mossy fibers, sprout back to the GC layer (GCL). The natural MF projection towards the CA4 and CA3 region is thinned out, due to the loss of target neurons. We examined whether mossy fibers might project not only backwards but also forwards beyond the borders of CA3 into the CA2 and CA1 region. In addition, we compared a possible sprouting with clinical findings.

Methods: In total, 319 hippocampal specimen were analyzed. Immunohistochemical stainings for neuronal cell loss (NeuN) and MFS (synaptoporin) were performed and compared with clinical patient records.

Results: In a significant number of patients we found MF sprouting forward to CA1 and CA2. In these patients MF sprouting was significantly (p<0.05) associated with GCD and MF backward sprouting to GCL. However, there was no significant association with clinical histories including age at seizure onset, preoperative duration of epilepsy or with long-term seizure outcome.

Conclusion: This is the first description of mossy fiber sprouting in CA1 and CA2 in hippocampal sclerosis. The sprouting process seems to be one part of GC pathology with neuronal migration and multidirectional axonal sprouting.