Asymmetric Gray Matter Volume Changes Associated with Epilepsy Duration and Seizure Frequency in Temporal-Lobe-Epilepsy Patients with Favorable Surgical Outcome

Abstract

Background and purpose: This study aimed to estimate the changes in gray matter volume (GMV) and their hemispheric difference in patients with mesial temporal lobe epilepsy (MTLE) using a voxel-based morphometry (VBM) methodology, and to determine whether GMV changes are correlated with clinical features.

Methods: VBM analysis of brain MRI using statistical parametric mapping 8 (SPM8) was performed for 30 left MTLE (LMTLE) and 30 right MTLE (RMTLE) patients and 30 age- and sex-matched healthy controls. We also analyzed the correlations between GMV changes and clinical features of MTLE patients.

Results: In SPM8-based analyses, MTLE patients showed significant GMV reductions in the hippocampus ipsilateral to the epileptic focus, bilateral thalamus, and contralateral putamen in LMTLE patients. The GMV reductions were more extensive in the ipsilateral hippocampus, thalamus, caudate, putamen, uncus, insula, inferior temporal gyrus, middle occipital gyrus, cerebellum, and paracentral lobule in RMTLE patients. These patients also exhibited notable reductions of GMV in the contralateral hippocampus, thalamus, caudate, putamen, and inferior frontal gyrus. We observed that GMV reduction was positively correlated with several clinical features (epilepsy duration and seizure frequency in RMTLE, and history of febrile seizure in LMTLE) and negatively correlated with seizure onset age in both the RMTLE and LMTLE groups.

Conclusions: Our study revealed GMV decreases in the hippocampus and extrahippocampal regions. Furthermore, the GMV reduction was more extensive in the RMTLE group than in the LMTLE group, since it included the contralateral hemisphere in the former. This difference in the GMV reduction patterns between LMTLE and RMTLE may be related to a longer epilepsy duration and higher seizure frequency in the latter.

Keywords: gray matter volume; hippocampal sclerosis; magnetic resonance imaging; mesial temporal lobe epilepsy; voxel-based morphometry.

Fig. 1. Statistical brain map revealing gray matter volume (GMV) reductions in the brains of patients with left mesial temporal lobe epilepsy (LMTLE) compared with controls. Decreased GMV in patients with LMTLE in the ipsilateral (left) hippocampus, bilateral thalamus, and contralateral (right) putamen. These findings were significant at a corrected false discovery rate (FDR) statistical threshold of p_FDR<0.05. The left side of the brain images corresponds to the right hemisphere.

Fig. 2. Statistical brain map revealing GMV reductions in the brains of patients with right mesial temporal lobe epilepsy (RMTLE) compared with control subjects. A: Decreased GMV in patients with RMTLE in the bilateral hippocampus, right parahippocampal gyrus, right uncus, right insula, bilateral thalamus, bilateral putamen, bilateral caudate, right inferior temporal gyrus, right superior/middle/inferior temporal gyrus, right middle occipital gyrus, right cerebellum, and left inferior frontal gyrus. These findings were significant at p_FDR<0.05. B: Brain regions with decreased GMV are shown on a rendered three-dimensional brain surface. The left side of the brain images corresponds to the right hemisphere. GMV: gray matter volume.

Fig. 3. Brain regions exhibiting significant correlations between changes in GMV and clinical parameters. A and B: Seizure onset age was positively correlated with the GMVs of the right middle temporal gyrus (A) and left parahippocampal gyrus (B) in patients with RMTLE. C and D: In LMTLE patients, seizure onset age was positively correlated with GMV changes in the right extranuclear (C) and right occipital (D) lobes. E and F: Febrile seizures were negatively correlated with GMV changes in the left middle frontal gyrus (E) and right superior temporal gyrus (F) in patients with LMTLE. These findings were significant at an uncorrected p value of <0.001. GMV: gray matter volume, LMTLE: left mesial temporal lobe epilepsy, RMTLE: right mesial temporal lobe epilepsy.