Abstracts

Rationale: Memory dysfunction is a common disabling comorbidity in temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). While the role of hippocampus in memory is well-established, the importance of the rest of the Papez Circuit (including the fornix) in memory function is less clear. Bilateral fornix diffusion abnormalities in TLE patients with HS have been demonstrated with diffusion tensor imaging (DTI). However, the impact of fornix pathology on cognitive outcomes in TLE patients remains unclear. This study evaluated the relationships between fornix microstructure, hippocampal integrity and cognitive outcomes in TLE using DTI.

Methods: Twenty-two controls (mean age 43±14 years) and 33 TLE patients (43±13 years) were studied with fornix and hippocampus DTI on a Siemens Prisma 3T. FLAIR-DTI of the fornix was acquired with 35 slices, 1.2×1.2×2 mm³ interpolated to 0.64×0.64 mm² in-plane resolution, 5 b0, 20 directions with b=1000 s/mm² . Diffusion MRI of hippocampus was acquired with single shot EPI, 20 slices, 1×1×1 mm³, 10 directions at b=500 s/mm². Patients were subdivided into non-HS (n=10), unilateral HS (n=20) and bilateral HS (n=3) based on clinical MRI. Deterministic tractography was performed to extract left and right fornix volume, mean diffusivity (MD) and fractional anisotropy (FA) separately. Whole-hippocampi were manually segmented to compare with fornix measures. Twenty-one TLE patients underwent neuropsychology evaluation for potential TLE surgery. Age-normalized cognitive scores were correlated with MRI metrics, controlling for years of education.


Results: ANOVA demonstrated a significant effect of group for fornix volume (p< 0.01), FA (p< 0.01) and MD (p< 0.05). Ipsilateral fornix of unilateral HS and bilateral fornix of bilateral HS patients had 30% lower volume, 11% lower FA and 11% higher MD compared to the controls. Regions of elevated MD and reduced FA were observed in the ipsilateral fornix (body and crus) of HS patients compared to controls and non-HS fornix (Figure 1). In the HS group, a significant linear correlation was found between hippocampal volume and fornix FA (R=0.47, P=0.04), whereas no correlations were observed in controls and non-HS (Fig 2A-C). Left hippocampal volume correlated with verbal memory scores (R=0.72, p< 0.01) but not with processing speed index in TLE patients (Fig 2D, E). In contrast, fornix diffusion metrics did not show significant correlations with verbal memory (Fig 2F) or non-verbal memory scores in TLE patients. Fornix FA significantly correlated with processing speed index (R=0.42 p< 0.05, Fig 2G).