Abstracts

Rationale: Neuropathological subtypes of hippocampal sclerosis (HS : ILAE types 1, 2 and 3) in temporal lobe epilepsy, are defined by the distribution of neuronal loss as assessed on NeuN immunostained sections (Blumcke, Thom et al. 2013). These subtypes have since been correlated with pre-operative memory deficits (Coras, Pauli et al. 2014) as well as outcome, supporting the utility of this classification. In some cases, HS may appear intermediate between type 1 and 2 (indeterminate HS [iHS]) and we sought to evaluate such cases with clinical-pathological correlations, including neuro-psychometric measurements.Methods: 93 HS cases were selected : 53 ILAE type 1, 15 ILAE type 2, 7 with no-HS and 18 with iHS. Quantitative analysis (labelling index [LI]) in hippocampal subfields: dentate gyrus, subgranular zone, CA4, CA3, CA2, CA1, subiculum) utilised whole slide scanning image analysis with NeuN and MAP2 to evaluate neuronal and dendritic loss and nestin for active gliosis. ZnT3 labelling was used for qualitative evaluation of the mossy fibre pathway (MFP). Pre- and post-operative clinical parameters were correlated between HS types and pathology measurements, including pre-operative verbal and visual memory scores.Results: There was significantly higher mean NeuN LI in CA4 in iHS compared to type 1 HS (p=0.001) and significantly lower LI compared to type 2 (p=0.0001). MAP2 LI were significantly higher in CA4 in iHS compared to type 1 HS (p<0.05) but were not significantly different from type 2 (Figure). No significant differences in LI were noted for CA1 with NeuN or MAP2 between iHS and either type 1 or 2 but significantly differences were noted from no-HS cases (p=0.01). MFP sprouting was present in all HS subtypes but the residual MFP was significantly better preserved in both type 2 and iHS cases (p=0.01). In the entire series there was a significant negative correlation between CA4 MAP2 LI and a pre-operative verbal memory deficit (p=0.01), with memory deficits noted in 29% of iHS cases compared to 52% of type 1 HS cases.Conclusions: HS cases that are indeterminate on NeuN more closely align with type 2 HS following MAP2 and ZnT3 evaluation. These additional markers prove to be helpful in the discrimination of HS types and for clinical-pathological correlations.