Abstracts

Rationale: Patients with medial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis usually exhibit gray matter atrophy that involves not only the hippocampus, but also extra-hippocampal structures. Even though the preferential distribution of atrophy is consistent across different patients, it is unknown if the atrophy is a consequence of the excitotoxicity of seizures or secondary to deafferentation from loss of hippocampal connections. We aimed to investigate the relationship between loss of hippocampal connections and extra-hippocampal neuronal loss.Methods: We studied 16 consecutive patients with MTLE due to unilateral hippocampal atrophy (mean age=34±11years, 5 patients with right MTLE) ), and 34 age matched healthy controls. All subjects underwent MRI in a 3T Philips scanner. We employed a combination of two different MRI techniques. First, voxel based morphometry (VBM) of T1 images was performed with SPM5 and was used to quantify voxel-wise gray matter volume. Mean gray matter volumes were then extracted from limbic anatomical regions defined by the Anatomical Automatic Labeling. Secondly, diffusion tensor imaging (DTI) was performed with the software FSL and was used to quantify axonal integrity measured by fractional anisotropy (FA) and mean diffusivity (MD) of coherent water diffusion underlying the hippocampus (x=40, y=-24, z=-14, volume 976mm3, figure 1; the main fibers encompassed by this region are shown in figure 2). MRI data from patients were standardized as Z scores relative to the data from controls. Simple regression was then applied to investigate the relationship between relative loss of gray matter and relative temporal lobe axonal disruption.Results: We observed a significant reduction of gray matter volume in patients with MTLE involving the amygdala, caudate nuclei, cerebellum, anterior cingulate, fusiform gyrus, hippocampus, insula, parahippocampal gyrus, putamen, superior temporal gyrus and thalamus (p<0.01). Patients with MTLE also exhibited a significant reduction of FA ipsilateral (p=0.01) and contralateral (p=0.023) to the side of hippocampal atrophy, and a significant ipsilateral increase in MD (P<0.01). There was significant association between reduction of ipsilateral FA and reduction of gray matter in the ipsilateral anterior cingulate (p=0.039), fusiform gyrus (p=0.038) and superior temporal gyrus (p=0.038). There was also a significant relationship between increase in ipsilateral MD and reduction of gray matter in the ipsilateral (p=0.011) and contralateral (p=0.04) anterior cingulate.Conclusions: Extra-hippocampal neuronal loss in patients with MTLE possibly results from a combination of different factors. This study supports the theory that deafferentation from loss of hippocampal connections is a key component underlying extra-hippocampal atrophy in MTLE in some specific brain regions, particularly the temporal lobes and the anterior cingulate.