Abstracts

Rationale: Recent studies suggest that hippocampal subfields (HSF) are vulnerable to age-related processes and differentially affected by pathological mechanisms. However, there is no information about the impact of epileptogenesis/hippocampal sclerosis (HS) on aging-related changes in the HSF. Here we analyzed 245 controls and 235 TLE patients (187 HS+, 48 MRI-Negative) aiming to investigate whether TLE patients, compared to controls, have faster volume loss in HSF.Methods: T1 weighted, isotropic images at 3T were acquired from controls (n=245, mean age±SD, 44±14y), TLE patients with unilateral HS (103 right, (RTLE, 44.5±10.9y), 84 left (LTLE, 46±11.3y)) and 48 TLE MRI-negative (43±13y). We used Freesurfer 5.3 to obtain bilateral HSF volumes: pre-subiculum (PRESUB), subiculum (SUB), CA1, CA2-3, CA4-dentate and fimbria. SPSS22 was used for statistical analysis. Repeated measures ANOVA (covariated for age and Bonferroni corrected) was applied for group comparisons. As an exploratory analysis, we tested both linear and quadratic models for curve fitting for all volumes and groups separately. Lastly, we applied a Potthoff analysis (Weaver & Wuensch 2013, PMID: 23344734) to compare the slopes between groups.Results: Compared to controls, LTLE HS+ group presented volumetric reduction of all SF, bilaterally (p<0.05, Bonferroni adjusted). RTLE HS+ had ipsilateral reductions of all SF, and only contralateral fimbria (p<0.05, Bonferroni adjusted). (Figure1). As expected, TLE MRI-negative presented volumes similar to controls. From curve fitting analysis, age-related changes were present in 12 HSF for LTLE HS+, 2 for RTLE HS+ (bilateral fimbria), and 6 HSF for both controls and TLE MRI-negative (bilateral PRESUB, SUB and fimbria). The Potthoff analysis revealed that compared to controls, only LTLE HS+ presented steeper trajectories, in 7/12 HSF (bilateral PRESUB, CA2-3, CA4-dentate and left CA1). Age-related curves for controls and LTLE HS+ are displayed in Figure2.Conclusions: Few studies analyzed such a large group of TLE and controls. MRI-negative groups had age-related HSF changes similar to controls. Interestingly, both RTLE and LTLE HS+ presented reduced volume in all ipsilateral HSF, in accordance with a recent meta-analysis of neuronal loss in subfields of HS studies (Steve et al.2014, PMID: 25017686). A more severe damage was observed in LTLE HS+, as it presented widespread atrophy of contralateral HSF. In addition, LTLE HS+ showed more pronounced age-related atrophy of several HSF, which is in line with studies indicating that in LTLE HS+ the worsening of several domains over the years, including cognition and seizure frequency, appears to be more intense than in RTLE HS+ and TLE with MRI-negative.